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  • Long-term results of brentuximab vedotin in relapsed and refractory Hodgkin lymphoma: multi-center real-life experience
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-17
    Murat Özbalak, Ayşe Salihoğlu, Teoman Soysal, İhsan Karadoğan, Semra Paydaş, Evren Özdemir, Birol Yıldız, Nuri Karadurmuş, Leylagül Kaynar, Münci Yagci, Vildan Özkocaman, Pervin Topçuoğlu, Muhit Özcan, Elif Birtaş, Hakan Göker, Burhan Ferhanoglu

    Abstract Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4–84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05–0.22) and 26% (95% CI, 0.16–0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13–0.54) and 60% (95% CI, 0.33–0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

    更新日期:2020-01-22
  • In the South African setting, HIV-associated Burkitt lymphoma is associated with frequent leukaemic presentation, complex cytogenetic karyotypes, and adverse clinical outcomes
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-18
    Jessica Opie, Katherine Antel, Ania Koller, Nicolas Novitzky

    Abstract South Africa (SA) has a high prevalence of human immunodeficiency virus (HIV) infection. People living with HIV are at markedly increased risk of developing Burkitt lymphoma (BL), which is characterized by the MYC translocation. There is a paucity of survival data of HIV-associated Burkitt lymphoma/leukaemia (HIV-BL) cases from SA, and the relationship between karyotype and outcomes has not been widely reported. Here we report the clinico-pathological characteristics of a cohort of cytogenetically confirmed HIV-BL cases. A retrospective, descriptive review was conducted of clinico-pathological features of HIV-BL patients newly diagnosed and treated between 2005 and 2014 at our tertiary academic institution in Cape Town. Only HIV-BL patients with cytogenetic evidence of a MYC translocation were included for analysis. A multivariable Cox proportional hazards model assessed the impact of variables on overall survival (OS). Forty-nine patients met inclusion criteria. Their median age was 37 years (IQR 30–43 years) and 57% (n = 28) were females. Their median CD4 count was 240 cells/μl (IQR 103–423 cells/μl). The majority, 61% (n = 30), had leukaemic presentation, and 20% (n = 10) had a complex karyotype on conventional karyotyping. Seventy-seven percent (n = 36) received various protocols of combination intensive chemotherapy, excluding rituximab. Their OS was 64% (95% CI 45–77%) at 6 months, and 34% (95%CI 17–51%) at 5 years. Leukaemic presentation and a complex karyotype gave a 2.7-fold (95% CI 1.0–6.7) and 2.6-fold (95% CI 1.1–6.6) increased risk of mortality respectively, which were statistical significant (p < 0.05). We report 49 newly diagnosed, cytogenetically confirmed HIV-BL patients at our institution over a 10-year period. There was a high proportion of complex karyotypes and leukaemic presentation, which both independently adversely affected survival. This may be due to differences in the pathobiology of HIV-BL that requires further study and could lead to therapeutic advances in this patient group.

    更新日期:2020-01-21
  • Phenotypic characterization of macrophages in the BMB sample of human acute leukemia
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-18
    Jian-Xin Song, Yan Wen, Rui-Wei Li, Ting Dong, Yi-Fei Tang, Juan-Juan Zhang, Ya-Lian Sa

    Abstract Macrophages within tissues display a strong plastic ability in respond to environmental cues in both physiologic influences and disease. However, the macrophage phenotype and its distribution in the bone marrow biopsies (BMB) samples of human acute leukemia (AL) remain poorly understood. In this study, 97 BMB samples of patients with acute leukemia and 30 iron-deficiency anemias (IDA) as control group were evaluated with immunohistochemistry. In comparison with controls, the counts of CD68+, CD163+, and CD206+macrophages were remarkably increased in BMB samples of acute leukemia (P < 0.01), as well as their infiltration density was roaring up-regulation (P < 0.01). The expression levels of CD68+, CD163+, and CD206+macrophages were decreased in patients with complete remission, but there still existed statistically significant contrast to the control group (P < 0.01). The ratios of the CD163-positive cells or CD206-positive cells to CD68-positive cells were most prevalent in the BMB samples of human acute leukemia compared with the control group (P < 0.01), which support that macrophages were polarized to M2 macrophages.

    更新日期:2020-01-21
  • MicroRNAs: pivotal regulators in acute myeloid leukemia
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-13
    Mingyu Li, Xianglun Cui, Hongzai Guan

    Abstract MicroRNAs are a class of small non-coding RNAs that are 19–22 nucleotides in length and regulate a variety of biological processes at the post-transcriptional level. MicroRNA dysregulation disrupts normal biological processes, resulting in tumorigenesis. Acute myeloid leukemia is an invasive hematological malignancy characterized by the abnormal proliferation and differentiation of immature myeloid cells. Due to the low 5-year survival rate, there is an urgent need to discover novel diagnostic markers and therapeutic targets. In recent years, microRNAs have been shown to play important roles in hematological malignancies by acting as tumor suppressors and oncogenes. MicroRNAs have the potential to be a breakthrough in the diagnosis and treatment of acute myeloid leukemia. In this review, we summarize the biology of microRNAs and discuss the relationships between microRNA dysregulation and acute myeloid leukemia in the following aspects: signaling pathways, the abnormal biological behavior of acute myeloid leukemia cells, the clinical application of microRNAs and competing endogenous RNA regulatory networks.

    更新日期:2020-01-13
  • Evaluation of dsDNA from extracellular vesicles (EVs) in pediatric AML diagnostics
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-13
    Evangelia Kontopoulou, Sarah Strachan, Katarina Reinhardt, Fabienne Kunz, Christiane Walter, Bernd Walkenfort, Holger Jastrow, Mike Hasenberg, Bernd Giebel, Nils von Neuhoff, Dirk Reinhardt, Basant Kumar Thakur

    Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by a collection of genetic and epigenetic changes. As a consequence, AML can evolve towards more aggressive subtypes during treatment, which require additional therapies to prevent future relapse. As we have previously detected double-stranded DNA (dsDNA) in tumor-derived extracellular vesicles (EVs), in this current study we attempted to evaluate the potential diagnostic applications of AML EV-dsDNA derived from primary bone marrow and peripheral blood plasma samples. EVs from plasma of 29 pediatric AML patients (at initial diagnosis or during treatment) were isolated by ultracentrifugation, after which dsDNA was extracted from obtained EVs and analyzed for leukemia-specific mutations using next generation sequencing (NGS) and GeneScan-based fragment-length analysis. In 18 out of 20 patients, dsDNA harvested from EVs mirrored the (leukemia-specific) mutations found in the genomic DNA obtained from primary leukemia cells. In the nanoparticle tracking analysis (NTA), a decrease in EV numbers was observed in patients after treatment compared with initial diagnosis. Following treatment, in 75 samples out of the 79, these mutations were no longer detectable in EV-dsDNA. In light of our results, we propose the use of leukemia-derived EV-dsDNA as an additional measure for mutational status and, potentially, treatment response in pediatric AML.

    更新日期:2020-01-13
  • Platelet counts of adults upon acute hospital admission to internal medicine units are a predictor of mortality
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-13
    Guillaume Moulis, Christian Fynbo Christiansen, Bianka Darvalics, Ina Trolle Andersen, Henrik Toft Sørensen, Mette Nørgaard

    Abstract The objective of this cohort study was to examine the association between platelet counts upon acute hospitalization and mortality. The study included all adults in North and Central Denmark Regions with a first acute admission to an internal medicine unit during 2006–2012, categorized by first platelet count within +/−24 hours of admission. We assessed the association between platelet count and in-hospital, 30-day, 90-day, and 365-day mortality using age- and sex-adjusted Cox models. We also stratified analyses by presence/absence of comorbidity and performed additional analyses restricted to patients with a primary discharge diagnosis of cardiovascular disease or infection. Among the 274,148 study patients, the 1-year mortality was 12.6%. The association between platelet count and mortality took the form of an asymmetric U-shaped curve. For 30-day mortality, hazard ratios (HRs) were 5.24 (95% CI: 4.60–5.97) for platelet count < 50 × 109/L and 2.50 (95% CI: 2.33–2.69) for platelet count ≥ 500 × 109/L, compared with a normal platelet count (150–400 × 109/L). A slightly increased risk of mortality was observed for platelet counts < 200 × 109/L and ≥ 250 × 109/L. A similar pattern was observed for 30-day, 90-day, and 365-day mortality and in all subgroups except patients with a primary discharge diagnosis of infection. In this case, patients with a platelet count between 150 × 109/L and 199 × 109/L had the lowest mortality. Platelet counts in adults upon acute hospital admission to internal medicine units, including counts within the normal range, are a predictor of mortality.

    更新日期:2020-01-13
  • Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-06
    Nicolas Vallet, Marjan Ertault, Jean-Baptiste Delaye, Thomas Chalopin, Alban Villate, Laurianne Drieu La Rochelle, Julien Lejeune, Amélie Foucault, Martin Eloit, Chantal Barin-Le Guellec, Olivier Hérault, Philippe Colombat, Emmanuel Gyan

    Abstract The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3–41.9) vs 63.9% (95% CI 5.1–72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1–53.1) and 77.7% (95% CI 70.1–85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4–3.5)] and OS [HR = 4.7 (95% CI 2.8–7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1–89.9) vs 88.0 (95% CI 75.3–100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.

    更新日期:2020-01-06
  • Correction to: Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-16
    Hyewon Lee, Yu Ri Kim, Soo-Jeong Kim, Yong Park, Hyeon-Seok Eom, Sung Yong Oh, Hyo Jung Kim, Hye Jin Kang, Won-Sik Lee, Joon Ho Moon, Young-Woong Won, Tae-Sung Kim, Jin Seok Kim

    An additional affiliation for the first author was not indicated. Hyewon Lee is also affiliated with: Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea.

    更新日期:2020-01-06
  • Correction to: The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Sophie Park,Charikleia Kelaidi,Mathieu Meunier,Nicole Casadevall,Aaron T Gerds,Uwe Platzbecker

    This article was originally published without an Open Access but due to the authors final decision to opt for Open Choice this correction was created.

    更新日期:2020-01-06
  • Overexpressed WT1 exhibits a specific immunophenotype in intermediate and poor cytogenetic risk acute myeloid leukemia
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-04
    Xiao-Rui Wang, Yan Chang, Xiao-Ying Yuan, Ya-Zhe Wang, Ya-Zhen Qin, Guo-Rui Ruan, Yue-Yun Lai, Yan-Rong Liu

    Many studies have confirmed that overexpressed WT1 exists in leukemic cells, especially in AML. However, the immunophenotypic features of this sort of leukemic cells remain to be unclarified. We retrospectively analyzed the immunophenotype of 283 newly diagnosed AML patients with intermediated and poor cytogenetic risk to evaluate the correlation between phenotype and WT1 overexpression. EVI1 transcripts, KMT2A-PTD, FLT3-ITD, and NPM1 mutations were simultaneously assessed. Our results revealed that overexpressed WT1 was significantly associated with the expression of CD117, CD13, and CD123. Besides, leukemic cells with WT1 overexpression also lacked lymphoid and myeloid differentiation-related markers. FAB subtype M2 patients had higher WT1 levels, compared with other FAB subtype. Multivariate analysis was proved that NPM1 mutation, M2 subtype, and the expression of CD123 were independently associated with WT1 overexpression. These indicated that AML with overexpressed WT1 was proliferated and blocked in the early stage of AML development. It presumably provided some clues to detect overexpressed WT1 cells via multiparameter flow cytometry. CD123-targeted drugs might become one of the alternative treatments for patients with WT1 overexpression.

    更新日期:2020-01-04
  • The prognostic significance of ΔSUV max assessed by PET/CT scan after 2 cycles of chemotherapy in patients with classic Hodgkin’s lymphoma
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-03
    Shenmiao Yang, Liheng Qiu, Xiaojun Huang, Qian Wang, Jin Lu

    Abstract The objective of this study is to investigate the prognostic value of the percentage change of maximum standardized uptake value (ΔSUVmax) assessed by PET/CT scan after 2 cycles of chemotherapy (iPET2) in patients with classic Hodgkin’s lymphoma (CHL). ΔSUVmax was calculated as follows: the ratio of (SUVmax at baseline-SUVmax at iPET2)/SUVmax at baseline which was determined before initiation of ABVD chemotherapy. The median ΔSUVmax of 46 patients at iPET2 was 87.9% (range − 6.1–100.0%). The optimal ΔSUVmax cutoff value for progression-free survival (PFS) was 83.0% with the receiver operating characteristic curve. The area under the curve for PFS was 0.886 (95% CI 0.788–0.984, p < 0.001). The median PFS of 29 (63.0%) patients who achieved a SUVmax reduction of more than 83.0% was 34 months. The median PFS of 17 (37.0%) patients with ΔSUVmax < 83.0% was 9 months. This difference was significant (p < 0.001). Cohen’s kappa coefficient of Deauville Score (DS)- and ΔSUVmax-judged positivity was 0.752 (95% CI 0.592–0.992, p < 0.001), suggesting a strong consistency. Multivariate analysis showed that ΔSUVmax at iPET2 less than 83.0% of SUVmax at diagnosis was an independent factor predicting PFS [HR = 11.339, 95% CI 2.485–51.742, p = 0.002]. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ΔSUVmax<83.0% was 84.6%, 81.8%, 67.7%, 93.1%, and 82.6%, which was similar to that of DS as 61.5%, 87.9%, 66.7%, 85.3%, and 80.4%, respectively. ΔSUVmax<83.0% of iPET2 effectively predicts prognosis of patients with CHL treated with ABVD.

    更新日期:2020-01-04
  • Outcome after autologous stem cell transplantation in primary refractory or relapsed Hodgkin lymphoma—a long-term follow-up single center experience
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-02
    Malte Roerden, Martin Sökler, Lothar Kanz, Wolfgang Bethge, Wichard Vogel, Juliane S. Walz

    Autologous stem cell transplantation (autoSCT) can achieve long-term remission in primary refractory or relapsed Hodgkin lymphoma (r/r HL); however, still up to 50% of patients relapse after autoSCT. In this retrospective analysis, we investigated the impact of autologous stem cell transplantation in a consecutive, unselected cohort of primary refractory and relapsed Hodgkin lymphoma patients (n = 66) with the majority of patients treated in the pre-brentuximab vedotin and immune checkpoint inhibitor era. In our cohort, a 5-year overall survival (OS) from autoSCT of 59.5% and a 5-year progression-free survival (PFS) after autoSCT of 46.1% was achieved. Multivariate analysis revealed primary refractory disease and early relapse (< 12 months) after initial therapy as well as the presence of B symptoms at relapse as independent risk factors associated with a higher risk for relapse and an inferior PFS and OS. Several other clinical factors, including the presence of extranodal disease at relapse and failure to achieve a complete response to salvage chemotherapy, were associated with a trend towards an inferior survival. Patients relapsing after autoSCT had a particularly poor outcome, regardless of eligibility to undergo allogeneic stem cell transplantation (alloSCT). We further evaluated recently published prognostic models for r/r HL patients undergoing autoSCT and could validate several risk scores in our independent “real world” cohort.

    更新日期:2020-01-04
  • A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-02
    Young-Woong Won, Hyewon Lee, Hyeon-Seok Eom, Jin Seok Kim, Cheolwon Suh, Dok Hyun Yoon, Jung Yong Hong, Hye Jin Kang, Jae Hoon Lee, Won Seog Kim, Seok Jin Kim, Won-Sik Lee, Myung Hee Chang, Young Rok Do, Jun Ho Yi, Inho Kim, Jong-Ho Won, Kyoungha Kim, Sung Yong Oh, Jae-Cheol Jo

    Abstract We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin’s lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1–46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156

    更新日期:2020-01-04
  • Clinicopathological features of in situ follicular neoplasm and relations with follicular lymphoma in Japan
    Ann. Hematol. (IF 2.850) Pub Date : 2020-01-02
    Satoko Ogata, Hiroaki Miyoshi, Fumiko Arakawa, Joji Shimono, Kyohei Yamada, Eriko Yanagida, Masami Nambu, Akinori Iwashita, Seiji Haraoka, Koichi Ohshima

    Abstract This study aims to investigate the clinicopathological features of in situ follicular neoplasm (ISFN) in Japan. ISFN is a rare condition formerly considered as an early precursor of follicular lymphoma (FL). This is a first original report of ISFN from Asian country. We reviewed 19 biopsy samples of ISFN. ISFNs were categorized into two groups: (1) ISFN, consisting of ISFN with strong positivity for BCL-2 immunohistochemical staining (IHC), and obvious translocation of BCL-2; and (2) ISFN-like FL, featuring cases without obvious translocation but having morphological features and characteristic IHC findings of ISFN. As control, we adopted obvious FL. For some cases showing coexisting ISFN and FL lesions in the same lymph node, we could conduct further clonality analysis for each lesion. Nine of the 19 cases of ISFN coexisted with FL or had a history of overt B- or T-cell lymphoma including FL. Statistical comparison among ISFN-like FL and FL showed no significant differences in pathological features. Molecular analysis suggested that ISFN lesion and FL lesion in the same lymph node each have a different clonality. ISFN coexists or associates with other overt lymphomas frequently.

    更新日期:2020-01-04
  • Ruxolitinib treatment for SR-aGVHD in patients with EBV-HLH undergoing allo-HSCT
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-26
    Guangqiang Meng, Jingshi Wang, Xinkai Wang, Yini Wang, Zhao Wang

    Abstract Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.

    更新日期:2020-01-04
  • Clinical characteristics of interim-PET negative patients with a positive end PET from the prospective HD08-01 FIL study
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-23
    Luigi Rigacci, Benedetta Puccini, Alessandro Broccoli, Manjola Dona, Manuel Gotti, Andrea Evangelista, Armando Santoro, Maurizio Bonfichi, Alessandro Re, Michele Spina, Barbara Botto, Alessandro Pulsoni, Chiara Pagani, Caterina Stelitano, Flavia Salvi, Luca Nassi, Lara Mannelli, Sofia Kovalchuk, Daniela Gioia, Pier Luigi Zinzani

    Abstract FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18–4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.

    更新日期:2020-01-04
  • The effectiveness and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world clinical practice: a study of the Korean Multiple Myeloma Working Party (KMMWP-151 study)
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-23
    Jae-Cheol Jo, Ho Sup Lee, Kihyun Kim, Je-Jung Lee, Sung-Soo Yoon, Soo-Mee Bang, Jin Seok Kim, Hyeon-Seok Eom, Dok Hyun Yoon, Yoojin Lee, Ho-Jin Shin, Yong Park, Won Sik Lee, Young Rok Do, Yeung-Chul Mun, Mark Hong Lee, Hyo Jung Kim, Sung-Hyun Kim, Min Kyoung Kim, Sung-Nam Lim, Su-Hee Cho, Seong Kyu Park, Jun Ho Yi, Jae Hoon Lee, Jinmi Kim, Chang-Ki Min

    Abstract Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

    更新日期:2020-01-04
  • The classic prognostic factors in advanced Hodgkin’s lymphoma patients are losing their meaning at the time of Pet-guided treatments
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-23
    Alessia Bari, Raffaella Marcheselli, Stefano Sacchi, Alessandro Re, Chiara Pagani, Alessandra Tucci, Barbara Botto, Umberto Vitolo, Anna Lia Molinari, Benedetta Puccini, Alessandro Pulsoni, Armando Santoro, Monica Tani, Luca Nassi, Erika Meli, Vincenzo Pavone, Maurizio Bonfichi, Andrea Evangelista, Daniela Gioia, Alessandro Levis, Pierluigi Zinzani

    Abstract The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.

    更新日期:2020-01-04
  • A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-18
    Massimo Martino, Mercedes Gori, Giovanni Tripepi, Anna Grazia Recchia, Michele Cimminiello, Pasquale Fabio Provenzano, Virginia Naso, Anna Ferreri, Tiziana Moscato, Giuseppe Console, Barbara Loteta, Giuseppe Alberto Gallo, Massimo Gentile, Vanessa Innao, Marco Rossi, Antonella Morabito, Iolanda Donatella Vincelli, Donato Mannina, Annalisa Pitino

    G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.

    更新日期:2020-01-04
  • Clinical features and treatment outcomes of limited-stage mantle cell lymphoma: Consortium for Improving Survival of Lymphoma report
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-18
    Jae-Cheol Jo, Seok Jin Kim, Ho Sup Lee, Hyeon-Seok Eom, Soon Il Lee, Yong Park, Jeong-Ok Lee, Yoojin Lee, Ho-Young Yhim, Deok-Hwan Yang, Ja Min Byun, Hye Jin Kang, Hyo Jung Kim, Ho-Jin Shin, Kwai Han Yoo, Cheolwon Suh

    Abstract Limited-stage (Ann Arbor stage I or II) mantle cell lymphoma (MCL) is an extremely rare disease. Thus, there is little data on the clinical features and treatment outcomes of patients with early-stage MCL. We examined consecutive stage I or II MCL 41 cases diagnosed between 2000 and 2016 in 16 institutions of the Consortium for Improving Survival of Lymphoma group. All cases were pathologically confirmed and systemic evaluation was performed for staging. The clinical features were reviewed, and the treatment outcomes were analyzed. The median age of patients was 66 years (range 19–85 years); there were more men (n = 31, 75.6%) than women. Most patients (n = 28, 68.3%) had stage 2 disease, and 29 (70.7%) were symptomatic. The elevation of lactate dehydrogenase (n = 2, 4.9%) was not common; thus, 39 patients (95.1%) had a low-risk score (0 or 1) for the International Prognostic Index, and 28 (68.3%) had a low-risk score (1–3) for the MCL International Prognostic Index. Most patients (n = 37, 90.1%) received chemotherapy as the first therapeutic strategy, while some received radiotherapy (n = 2), surgical resection (n = 1), or no treatment (n = 1). Of the patients who received chemotherapy, 23 (56.9%) received a rituximab-containing regimen, and R-CHOP (n = 17) and R-bendamustine (n = 5) were commonly used. The best response was noted in 97.4% (n = 38) of patients, including 32 who showed a complete response (78%). With a median follow-up duration of 40.6 months, the 42 months relapse-free survival was 59.1%, and the 5-year overall survival rate was 80.4%. Limited-state MCL showed indolent clinical and low-risk prognostic features. Chemotherapy could be effective for controlling localized MCL lesions, with high complete response rates.

    更新日期:2020-01-04
  • Evaluation of thrombotic events in patients with immune thrombocytopenia
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-18
    Shoko Ito, Shin-ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda

    Abstract Immune thrombocytopenia (ITP) has been reported to be associated with thrombotic events. The incidence of thrombosis in 303 newly diagnosed ITP patients in our institute between 2000 and 2016 was retrospectively reviewed. During a median follow-up of 3.6 years, 16 thrombotic events (12 arterial and four venous) occurred. The median platelet count at thrombotic events was 102 × 109/l. At 10 years, the cumulative thrombosis incidence was 10%. A univariate analysis showed that smoking, hypertension, male gender, a history of thrombosis, and atrial fibrillation (Af) were significantly associated with the occurrence of thrombosis, and a multivariate analysis identified smoking and Af as independent risk factors. The thrombotic risk was not increased by lupus anticoagulant positivity or ITP treatment. At 5 years, the cumulative incidence of bleeding and overall survival probability was 5.6% and 92%, respectively. This study demonstrates that smoking and Af were associated with an increased risk of thrombosis. Previously identified risk factors were not confirmed in these Japanese ITP patients.

    更新日期:2020-01-04
  • An uncommon presentation of chronic myeloid leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Joseph S Christiansen,Manila Gaddh,Jill Wells

    更新日期:2019-11-01
  • Unmanipulated haploidentical hematopoietic stem cell transplantation using very low-dose antithymocyte globulin and methylprednisolone in adults with relapsed/refractory acute leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-12-02
    Tatsuya Konishi,Noriko Doki,Akihito Nagata,Yuta Yamada,Toshiaki Takezaki,Satoshi Kaito,Shuhei Kurosawa,Masahiro Sakaguchi,Kaito Harada,Shunichiro Yasuda,Kosuke Yoshioka,Kyoko Inamoto,Takashi Toya,Aiko Igarashi,Yuho Najima,Takeshi Kobayashi,Kazuhiko Kakihana,Hisashi Sakamaki,Kazuteru Ohashi

    Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT.

    更新日期:2019-11-01
  • The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-10-28
    Sophie Park,Charikleia Kelaidi,Mathieu Meunier,Nicole Casadevall,Aaron T Gerds,Uwe Platzbecker

    Myelodysplastic syndromes (MDS) are hematopoietic stem cell malignancies associated with an erythroid maturation defect, resulting in anemia. Treatments for MDS include erythropoiesis-stimulating agents (ESAs). The identification of prognostic markers is important to help predict response and improve outcomes. Various scoring systems have been developed to help predict response to ESAs. Despite limitations in its assessment, serum erythropoietin (sEPO) level is an important predictor of hematologic response to ESAs in patients with lower-risk MDS. Numerous studies have reported significantly lower sEPO levels among responders versus non-responders. Furthermore, treatment response is significantly more likely among those with sEPO levels below versus those above various cutoffs. Other prognostic indicators for response to ESAs include lower transfusion requirement, fewer bone marrow blasts, higher hemoglobin, lower serum ferritin, lower-risk MDS, and more normal cytogenetics. Studies of other MDS therapies (e.g., lenalidomide and luspatercept) have also reported that lower sEPO levels are indicative of hematologic response. In addition, lower sEPO levels (up to 500 IU/L) have been included in treatment algorithms for patients with lower-risk MDS to define whether ESAs are indicated. Lower sEPO levels are predictive of hematologic response-particularly to ESAs. Further, clinical trials should use sEPO thresholds to ensure more homogeneous cohorts.

    更新日期:2019-11-01
  • Proportion of anemia attributable to iron deficiency in high-altitude infant populations.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-11-02
    B Maritza Choque-Quispe,Valeria Paz,Gustavo F Gonzales

    更新日期:2019-11-01
  • Pixantrone demonstrates significant in vitro activity against multiple myeloma and plasma cell leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-10-20
    Ella Willenbacher,Karin Jöhrer,Wolfgang Willenbacher,Brigitte Flögel,Richard Greil,Brigitte Kircher

    Treatment results for multiple myeloma and plasma cell leukemia have considerably improved, but cure remains elusive and establishing new therapeutic approaches constitutes a major unmet clinical need. We analyzed the anti-myeloma properties of the aza-anthracenedione pixantrone which has been successfully used in a phase III study for the treatment of patients with aggressive non-Hodgkin's lymphoma as monotherapy as well as in combination regimes in vitro and in an adapted in vivo model (ex ovo chicken chorioallantoic membrane (CAM) assay). Pixantrone significantly inhibited proliferation and metabolic activity of all investigated myeloma cell lines. Importantly, anti-myeloma effects were more pronounced in tumor cell lines than in stromal cells, mesenchymal stem cells, and peripheral blood mononuclear cells of healthy controls. Apoptosis of myeloma cell lines was observed only after a 7-day incubation period, indicating a fast cytostatic and a slower cytotoxic effect of this drug. Pixantrone reduced the viability of primary plasma cells of patients and induced downregulation of myeloma-cell growth in the CAM assay. Additionally, we demonstrate in vitro synergism between pixantrone and the histone deacetylase inhibitor panobinostat with respect to its anti-proliferative features. From these data, we conclude that systematic investigations of the clinical usefulness of pixantrone in the framework of controlled clinical trials are clearly indicated (e.g., in penta-refractory patients).

    更新日期:2019-11-01
  • MEF2D-rearranged acute lymphoblastic leukemia resembles Burkitt lymphoma/leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Jiewen Sun,Wenjuan Yu,Xiang Zhang

    更新日期:2019-11-01
  • A novel SNP rs11759328 on Rho GTPase-activating protein 18 gene is associated with the expression of Hb F in hemoglobin E-related disorders.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Wittaya Jomoui,Wanicha Tepakhan,Supawadee Yamsri,Hataichanok Srivorakun,Goonnapa Fucharoen,Supan Fucharoen

    Hemoglobin (Hb) F has a modulatory effect on the clinical phenotype of β-thalassemia disease. High expression of Hb F in Hb E-related disorders has been noted, but the mechanism is not well understood. We have examined the association of a novel SNP rs11759328 on ARHGAP 18 gene and other known modulators with a variability of Hb F in Hb E-related disorders. Genotyping of SNP rs11759328 (G/A) was performed based on high-resolution melting analysis. The rs11759328 (A allele) was shown to be significantly associated with Hb F levels (p < 0.05) in heterozygous and homozygous Hb E. High levels of Hb F in both heterozygous and homozygous Hb E were also found to be associated with SNPs in the study of other modifying genes including KLF 1 mutation, rs7482144 (Gγ-XmnI), rs4895441, rs9399137 of (HBS1L-MYB), and rs4671393 (BCL11A). Multivariate analysis showed that KLF1 mutation and SNP rs11759328 (GA) (ARHGAP18) modulated Hb F expression in heterozygous Hb E. For homozygous Hb E, this was found to be related to five modifying factors, i.e., KLF1 mutation, rs4895441 (GG), rs9399137 (CC), rs4671393 (AA), and rs4671393 (GA). These results indicate that a novel SNP rs11759328 is a genetically modifying factor associated with increased Hb F in Hb E disorder.

    更新日期:2019-11-01
  • R-GEM-Lenalidomide versus R-GEM-P as second-line treatment of diffuse large B-cell lymphoma: results of the UK NRCI phase II randomised LEGEND trial.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Andrea Kühnl,Clare Peckitt,Bijal Patel,Kirit M Ardeshna,Marian P Macheta,John Radford,Rod Johnson,Shankaranarayana Paneesha,Sarah Barton,Ian Chau,Ruwaida Begum,Nicola Valeri,Andrew Wotherspoon,Yong Du,Imene Zerizer,David Cunningham

    Outcome of patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) remains poor, highlighting the need for novel treatment approaches. The multicentre randomised phase II LEGEND trial evaluated lenalidomide in combination with rituximab, methylprednisolone and gemcitabine (R-GEM-L) vs. standard R-GEM-P as second-line treatment of DLBCL. The study closed early to recruitment after the planned interim analysis failed to demonstrate a complete response (CR) rate of ≥ 40% in either arm. Among 34 evaluable patients, 7/18 (38.9%) achieved CR with R-GEM-L and 3/16 (18.8%) with R-GEM-P. Median event-free and overall survival was 3.5/3.8 months and 10.8/8.3 months for R-GEM-L and R-GEM-P, respectively. The incidence of grade ≥ 3 toxicities was 52% in R-GEM-L and 83% in R-GEM-P. Efficacy and tolerability of R-GEM-L seem comparable with R-GEM-P and other standard salvage therapies, but a stringent design led to early trial closure. Combination of lenalidomide with gemcitabine-based regimens should be further evaluated in r/r DLBCL.

    更新日期:2019-11-01
  • Visual and volumetric parameters by 18F-FDG-PET/CT: a head to head comparison for the prediction of outcome in patients with multiple myeloma.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Rosa Fonti,Sara Pellegrino,Lucio Catalano,Fabrizio Pane,Silvana Del Vecchio,Leonardo Pace

    In multiple myeloma (MM) patients, 18F-FDG-PET/CT allows either the detection of disease spread by using visual parameters based on the Italian Myeloma criteria for PET Use (IMPeTUs) or the direct measurement of metabolic tumor burden by volume-based parameters such as metabolic tumor volume (MTV). The purpose is to evaluate the contribution of visual and volumetric parameters in the prediction of progression-free survival (PFS) and overall survival (OS) in MM patients. Forty-seven patients in stage IIIA who had undergone whole-body 18F-FDG-PET/CT were retrospectively evaluated. In each patient, visual parameters were determined and compared with volumetric parameters for PFS and OS prediction after a mean follow-up period of 53 months. Among the visual and volumetric parameters tested, a statistically significant difference was found between maximum standardized uptake value, MTV, total lesion glycolysis, and number of lytic lesions of patients with (n = 26) or without (n = 21) progression (p = 0.0400, p = 0.0065, p = 0.015, and p = 0.0220, respectively) and of dead (n = 24) vs survivors (n = 23) (p = 0.0171, p = 0.0037, p = 0.0060, and p = 0.0270, respectively). At univariate and multivariate analysis, MTV and hemoglobin were predictive of both PFS (p = 0.008) and OS (p = 0.0026). The best MTV discriminative value assessed by receiver operating characteristic curve analysis for predicting both PFS and OS was 39.4 ml. By Kaplan-Meier analysis and log-rank test, PFS and OS were significantly better in patients with MTV ≤ 39.4 ml (p = 0.0004 and p = 0.0001, respectively) as compared with those having an MTV higher than the cutoff. The volume-based parameter MTV determined by 18F-FDG-PET/CT may be used in the prediction of PFS and OS in myeloma patients.

    更新日期:2019-11-01
  • The incidence of thromboembolism for lenalidomide versus thalidomide in older patients with newly diagnosed multiple myeloma.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Ang Li,Qian Wu,Greg Warnick,Shan Li,Edward N Libby,David A Garcia,Gary H Lyman

    It is uncertain if different immunomodulatory drugs (IMID) pose distinct thrombotic risk in patients with newly diagnosed multiple myeloma (MM). Among 2397 MM patients from the SEER-Medicare database from 2007 to 2013, 78% received lenalidomide, and 22% received thalidomide. After inverse probability weighting to balance confounders, the 12-month incidences of venous thromboembolism (VTE 10%) and arterial thromboembolism (ATE 5%) were similarly high in both groups. Lenalidomide versus thalidomide had a subdistribution hazard ratio of 1.11 (0.59-2.02) for VTE and a subdistribution hazard ratio of 0.96 (0.45-1.98) for ATE. Overall survival was not significantly different with a hazard ratio of 0.88 (0.60-1.18) for lenalidomide versus thalidomide. Concurrent anticoagulant prophylaxis was infrequently prescribed in < 20% of both groups. Our study demonstrates that despite improvement in myeloma-directed therapy and supportive care, thrombosis remains an important consideration for all IMID-treated MM patients. Appropriate risk stratification and vigilant thromboprophylaxis remain essential to prevent this complication.

    更新日期:2019-11-01
  • Prognostic significance of hyperfibrinogenemia in patients with lower-risk myelodysplastic syndromes.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Shinji Ogura,Shoichiro Yonei,Tomohiko Tanigawa,Masahiro Akimoto,Aki Sakurai,Yuriko Fujita,Chisako Ito,Yoshinobu Aisa,Tomonori Nakazato

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Clinical impact of the CONUT score in patients with multiple myeloma.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Sho Okamoto,Hiroshi Ureshino,Keisuke Kidoguchi,Kana Kusaba,Haruna Kizuka-Sano,Haruhiko Sano,Atsujiro Nishioka,Kyosuke Yamaguchi,Kazuharu Kamachi,Hidekazu Itamura,Mariko Yoshimura,Masako Yokoo,Takero Shindo,Yasushi Kubota,Toshihiko Ando,Kensuke Kojima,Atsushi Kawaguchi,Eisaburo Sueoka,Shinya Kimura

    Novel anti-myeloma drugs have significantly improved the overall survival (OS) of patients with multiple myeloma (MM). However, not all MM patients treated with these drugs show survival benefits, and biologic and genetic prognostic factors are insufficient to predict the response to treatment. Decreasing treatment-related complications is important to improve the efficacy of treatment in patients with MM. The Controlling Nutritional Status (CONUT) score is a screening method for poor nutritional status, which is associated with poor prognosis in several cancers because it increases the rate of treatment-related complications. We retrospectively analyzed the OS of 64 patients with symptomatic MM and evaluated the correlation between the CONUT score and patient prognosis in MM. The median age at diagnosis was 66 years, and multivariate analysis showed that a high CONUT score (≥ 5; hazard ratio, 3.937; 95% confidence interval, 1.214-12.658; P = 0.022) was an independent prognostic risk factor. Subgroup analysis was performed according to patient age because the choice of treatment strategy, particularly autologous peripheral blood stem cell transplantation (auto-PBSCT), can vary depending on age in MM patients. Younger patients (< 65 years old) who received auto-PBSCT and had a lower CONUT score (0-3) showed a significantly better survival outcome than those with a higher CONUT score (≥ 4) (median OS, not reached vs. 64.1 months; P = 0.011). The CONUT score is simple to calculate and provides a useful prognostic indicator in patients with MM, especially transplant-eligible patients.

    更新日期:2019-11-01
  • The predictive value of minimal residual disease when facing the inconsistent results detected by real-time quantitative PCR and flow cytometry in NPM1-mutated acute myeloid leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Meng-Ge Gao,Guo-Rui Ruan,Ying-Jun Chang,Yan-Rong Liu,Ya-Zhen Qin,Qian Jiang,Hao Jiang,Xiao-Jun Huang,Xiao-Su Zhao

    For acute myeloid leukemia (AML) with nucleophosmin 1 mutation (NPM1m), multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) are used to monitor minimal residual disease (MRD). However, the results of the two methods are sometimes inconsistent. This study was designed to analyze how to address the discordant results of FCM and RQ-PCR in AML patients undergoing chemotherapy, especially when positive FCM (FCM+) and negative NPM1m (NPM1m-) results are detected in the same sample. Our study included 93 AML patients with NPM1m positive (NPM1m+) who received chemotherapy but did not undergo hematopoietic stem cell transplantation. We monitored NPM1m and leukemia-associated immunophenotypes (LAIPs) by RQ-PCR and FCM, respectively, to assess MRD after each chemotherapy course. After each course of chemotherapy, all patients were classified into four groups based on the results of FCM and RQ-PCR: both negative (group 1, FCM-NPM1m-), single positive (group 2, FCM-NPM1m+; group 3, FCM+NPM1m-), or both positive (group 4, FCM+NPM1m+). The results showed that there was not a significant difference in the 2-year cumulative incidence of relapse (CIR) after each course of chemotherapy between group 2 and group 3. Furthermore, patients in groups 2 and 3 had a lower 2-year CIR than those in group 4 and a significantly higher 2-year CIR than those in group 1 after the first two courses. The patients in group 4 had a significantly higher 2-year CIR than those in group 1 after the first two courses. These results suggested that in the MRD monitoring process of AML patients, when the results of FCM and RQ-PCR are inconsistent (especially when FCM is positive and NPM1m is negative), these single-positive results still have predictive significance for relapse.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Sequential therapy of four cycles of bortezomib, melphalan, and prednisolone followed by continuous lenalidomide and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Reiko Isa,Nobuhiko Uoshima,Ryoichi Takahashi,Sonoko Nakano-Akamatsu,Eri Kawata,Hiroto Kaneko,Kazuho Shimura,Yuri Kamitsuji,Tomoko Takimoto-Shimomura,Shinsuke Mizutani,Yoshiaki Chinen,Muneo Ohshiro,Takahiro Fujino,Yuka Kawaji,Hitoji Uchiyama,Nana Sasaki,Taku Tsukamoto,Yuji Shimura,Tsutomu Kobayashi,Masafumi Taniwaki,Junya Kuroda,

    The combinations of melphalan, bortezomib, and prednisolone (VMP) and of lenalidomide and dexamethasone (Rd) are standard treatment strategies for transplant-ineligible newly diagnosed multiple myeloma (NDMM). To make the most of these two strategies, we investigated the efficacy and feasibility of first-line treatment with 4 cycles of VMP followed by continuous Rd therapy in a multi-institutional phase 2 study in Japanese patients with transplant-ineligible NDMM. Thirty-six patients of median age 74 years old with NDMM initially received 35-day cycles of VMP: oral melphalan (6 mg/m2) and prednisolone (60 mg/m2) on days 1 to 4 and bortezomib (1.3 mg/m2) on days 1, 8, 15, and 22. After 4 cycles of VMP, treatment was switched to 28-day cycles of Rd, which was continued until disease progression or emergence of an unacceptable adverse event (AE) in 33 patients, while one patient who achieved CR after VMP continued VMP at the physician's discretion. The overall response rates after VMP and after Rd were 66.7% and 86.1%, including CR rates of 5.6% and 36.1%, respectively. In a median follow-up period of 34.3 months, the progression-free survival and overall survival rates at 3 years were 43.2% and 81.3%, respectively. Grade 3-4 hematological AEs included neutropenia (39% with VMP and 24% with Rd) and thrombocytopenia (11% with VMP and 3% with Rd). There was no death due to an AE. In conclusion, sequential therapy with VMP followed by Rd is effective and mostly feasible for transplant-ineligible NDMM. The study is registered as UMIN000034815.

    更新日期:2019-11-01
  • Systemic mastocytosis associated with acute myeloid leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Frederico Lisboa Nogueira,Naira Neves Neto Martins,Patrícia Santos Resende Cardoso,Mitiko Murao,Frederico Henrique Correa de Melo,Ana Beatriz Firmato Glória,Evandro Maranhão Fagundes

    更新日期:2019-11-01
  • Multiple cytokine-producing aggressive EBV-positive diffuse large B cell lymphoma, not otherwise specified with hemophagocytic syndrome.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Shoko Nakayama,Yasuyoshi Morita,Jorge Luis Espinoza,Shinya Rai,Yasuhiro Taniguchi,Takahide Taniguchi,Yoshiaki Miyake,Hirokazu Tanaka,Takashi Ashida,Itaru Matsumura

    更新日期:2019-11-01
  • Hematocrit levels and thrombotic events in patients with polycythemia vera: an analysis of Veterans Health Administration data.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-26
    Shreekant Parasuraman,Jingbo Yu,Dilan Paranagama,Sulena Shrestha,Li Wang,Onur Baser,Robyn Scherber

    Patients with polycythemia vera (PV) have a high incidence of thrombotic events (TEs), contributing to a greater mortality risk than the general population. The relationship between hematocrit (HCT) levels and TE occurrence among patients with PV from the Veterans Health Administration (VHA) was evaluated to replicate findings of the CYTO-PV trial with a real-world patient population. This retrospective study used VHA medical record and claims data from the first claim with a PV diagnosis (index) until death, disenrollment, or end of study, collected between October 1, 2005, and September 30, 2012. Patients were aged ≥ 18 years at index, had ≥ 2 claims for PV (ICD-9-CM code, 238.4) ≥ 30 days apart during the identification period, continuous health plan enrollment from 12 months pre-index until end of study, and ≥ 3 HCT measurements per year during follow-up. This analysis focused on patients with no pre-index TE, and with all HCT values either < 45% or ≥ 45% during the follow-up period. The difference in TE risk between HCT groups was assessed using unadjusted Cox regression models based on time to first TE. Patients (N = 213) were mean (SD) age 68.9 (11.5) years, 98.6% male, and 61.5% white. TE rates for patients with HCT values < 45% versus ≥ 45% were 40.3% and 54.2%, respectively. Among patients with ≥ 1 HCT before TE, TE risk hazard ratio was 1.61 (95% CI, 1.03-2.51; P = 0.036). This analysis of the VHA population further supports effective monitoring and control of HCT levels < 45% to reduce TE risk in patients with PV.

    更新日期:2019-11-01
  • Congenital dyserythropoietic anemia type I mimicking myelodysplasia syndrome with a novel CDAN1 mutation.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-11-25
    Xueyan Lv,Shanwu Dong,Fengli Lan,Bingyu Zhang,Hongbo Chen,Runming Jin

    更新日期:2019-11-01
  • The increased neopterin content in turkish pediatric patients with sickle cell anemia.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-11-25
    Suna Sabuncuoğlu,Yeşim Öztaş,Ahmet Yalcinkaya,Selma Ünal,Terken Baydar,Gözde Girgin

    In the present study, the possible activation of cellular immunity in SCD patients was investigated. As immune activation parameters, neopterin concentrations and kynurenine/tryptophan ratio for tryptophan degradation in 35 pediatric patients with sickle cell disease (31 HbSS and 4 HbSß) were determined. Our results have shown that neopterin levels (both urinary and serum) are increased in pediatric patients with sickle cell disease. The increase in neopterin concentration was accompanied by significantly increased biopterin, kynurenine concentration and kynurenine/tryptophan ratio. The mechanism of immune activation and the effects of inflammatory mediators in sickle cell disease are poorly understood, especially in terms of cell-mediated immunity. Further in-vivo and in-vitro studies are required to illuminate the association between neopterin levels and neutrophil activation in sickle cell disease.

    更新日期:2019-11-01
  • Primary central nervous system lymphoma in China: a single-center retrospective analysis of 167 cases.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Xiang-Gui Yuan,Yu-Rong Huang,Teng Yu,Yang Xu,Yun Liang,Xiao-Hong Zhang,Chong-Ran Sun,Xiao-Ying Zhao

    Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17-96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1-152 ), the median OS and PFS were 37 months (95% CI, 25-49) and 17 months (95% CI, 13-20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.

    更新日期:2019-11-01
  • A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Jin-Hua Liang,Hua-Yuan Zhu,Dan-Min Xu,Li Wang,Yan Wang,Chun Qiao,Yu-Jie Wu,Rong Wang,Jian-Yong Li,Wei Xu

    更新日期:2019-11-01
  • Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Huifang Wang,Nanchen Zhang,Xia Wu,Xue Zheng,Yantao Ling,Yuping Gong

    U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes. Some studies have reported the prognostic impact of U2AF1 mutant in patients with de novo MDS, with discrepant results, so we do a meta-analysis about the relevant literatures to further investigate their prognostic impact on patients with de novo MDS. We conducted a literature search on databases such as PubMed, Embase, and the Cochrane Library to obtain studies on the prognosis of U2AF1 mutant in patients with de novo MDS published up to August 9, 2018. The primary endpoint was overall survival (OS), and the secondary endpoint was acute myeloid leukemia (AML) transformation. We extracted the hazard ratios (HRs) of OS and AML transformation and their 95% confidence intervals (CIs). Meta-analysis was performed by selecting a fixed-effect model or a random-effects model based on the heterogeneity between studies. A total of 14 cohort studies were included in the final meta-analysis, including 3322 patients with de no MDS, in which 390 patients were associated with U2AF1 mutant. The results showed that U2AF1 mutant had an adverse prognostic impact on OS (HR = 1.84, 95% CI: 1.45-2.33, P < 0.00001) and AML transformation (HR = 2.47, 95% CI: 1.50-4.06, P = 0.0004). U2AF1 mutant was associated with shorter OS in subgroup analyses of low- or intermediate-1-IPSS, U2AF1S34 and U2AF1Q157/R156. Out meta-analysis indicates that U2AF1 mutants are independent, detrimental prognostic factors for OS and AML transformation in patients with de novo MDS, as well as associating with shorter OS in subgroups of low- or intermediate-1-IPSS, U2AF1S34 and U2AF1Q157/R156. Further prospective studies are needed in the future, and subgroup analysis of U2AF1 subgroups is needed to obtain a more reliable basis for the impact of U2AF1 mutant on the prognosis of de novo MDS.

    更新日期:2019-11-01
  • Efficacy and safety of bosutinib in chronic phase CML patients developing pleural effusion under dasatinib therapy.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-19
    Mario Tiribelli,Elisabetta Abruzzese,Isabella Capodanno,Federica Sorà,Elena Trabacchi,Alessandra Iurlo,Luigiana Luciano,Gianni Binotto,Massimiliano Bonifacio,Mario Annunziata,Monica Crugnola,Renato Fanin

    更新日期:2019-11-01
  • Evaluation of cerebrospinal clonal gene rearrangement in newly diagnosed non-Hodgkin's lymphoma patients.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-14
    Boaz Nachmias,Veronica Sandler,Elena Slyusarevsky,Galina Pogrebijski,Svetlana Kritchevsky,Dina Ben-Yehuda,Neta Goldschmidt,Moshe E Gatt

    Overt central nervous system (CNS) involvement in aggressive non-Hodgkin's lymphoma (NHL) is rare at diagnosis. Much effort is put to identify risk factors for occult CNS involvement, and the risk assessment of CNS relapse. Prophylactic treatment carries risk of adverse events and its efficacy is not clear. Detection of cerebrospinal fluid molecular gene rearrangement (GRR) as a method to detect occult disease has been studied in acute leukemia and primary CNS lymphoma. To date, the capacity of a positive GRR in newly diagnosed NHL patients to predict CNS relapse has not been addressed. We retrospectively studied the prognostic value of GRR in cerebrospinal fluid samples of 148 newly diagnosed patients with high grade NHL. We demonstrate that positive GRR at diagnosis does not affect PFS or OS and did not predict CNS relapse. However, although numbers were small, repeated positive samples (≥ 2) correlated with a higher risk for CNS relapse (p = 0.048), possibly stressing the need for an aggressive preventive approach.

    更新日期:2019-11-01
  • Efficacy and safety of micafungin in unrelated cord blood transplant recipients.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-09
    Takeo Yasu,Takaaki Konuma,Maki Oiwa-Monna,Mai Mizusawa,Masamichi Isobe,Seiko Kato,Satoshi Takahashi,Arinobu Tojo

    Micafungin (MCFG) is an echinocandin antifungal drug used for prophylaxis and treatment of fungal infections after allogeneic hematopoietic cell transplantation (HCT). However, its efficacy and safety in patients undergoing cord blood transplantation (CBT) has not been clarified. We retrospectively analyzed the efficacy and safety of MCFG in 92 adult patients undergoing CBT in our institute. Of the entire cohort, 83 patients (90%) received MCFG for empirical or preemptive therapy. Documented breakthrough fungal infection occurred in 2 patients during MCFG treatment. Among the 49 patients who received MCFG as empirical therapy for febrile neutropenia, 41 (84%) patients had resolution of fever during neutropenia. Elevation of serum levels of hepatobiliary parameters during MCFG treatment was commonly observed, but grade 3 or higher elevation was rare. We also compared the efficacy and safety of 2 different initial daily doses of MCFG (150 mg vs. 300 mg). There were no significant differences of efficacy and safety between the two groups. These data suggest that MCFG was effective and safe for adult patients undergoing CBT. The optimal daily dose of MCFG treatment is a matter of future investigation for adult patients undergoing CBT.

    更新日期:2019-11-01
  • Red blood cells microparticles are associated with hemolysis markers and may contribute to clinical events among sickle cell disease patients.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-08
    Oladele Simeon Olatunya,Carolina Lanaro,Ana Leda Longhini,Carla Fernanda Franco Penteado,Kleber Y Fertrin,Adekunle Adekile,Sara T O Saad,Fernando Ferreira Costa

    Microparticles are sub-micron vesicles possessing protein and other materials derived from the plasma membrane of their parent cells, and literature suggests that they may have a role in the pathophysiology and downstream manifestations of sickle cell disease (SCD). The contributions of red blood cells microparticles (RMP) to the pathogenic mechanisms and clinical phenotypes of SCD are largely unknown. There is a controversy as to whether the proportions of intravascular hemolysis (approximately ≤ 30% of total hemolysis) would be enough to explain some complications seen in patients with SCD. We investigated RMP among 138 SCD patients and 39 HbAA individuals. Plasma RMPs were quantified by flow cytometry, plasma hemoglobin and heme by colorimetric assays, and haptoglobin and hemopexin by ELISA. The patients had higher RMP, plasma hemoglobin, and heme compared to the controls. On the contrary, haptoglobin and hemopexin were depleted in the patients. The RMP correlated positively with heme, lactate dehydrogenase, plasma hemoglobin, serum bilirubin, reticulocyte counts, and tricuspid regurgitant jet velocity of the patients. Contrarily, it correlated negatively with HbF, hemopexin, red blood cells counts, hemoglobin concentration, and haptoglobin. Although patients treated with hydroxyurea had lower RMP, this did not attain statistical significance. Patients with sickle leg ulcer and elevated tricuspid regurgitant jet velocity had higher levels of RMP. In conclusion, these data suggest that RMPs are associated with hemolysis and may have important roles in the pathophysiology and downstream complications of SCD.

    更新日期:2019-11-01
  • The prognostic significance of Wilms' tumor gene 1 (WT1) expression at diagnosis in adults with Ph-negative B cell precursor acute lymphoblastic leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-08
    Ya-Zhen Qin,Qian Jiang,Lan-Ping Xu,Hao Jiang,Yu Wang,Xiao-Su Zhao,Zong-Ru Li,Yue-Yun Lai,Yan-Rong Liu,Xiao-Hui Zhang,Kai-Yan Liu,Xiao-Jun Huang

    The prognostic significance of Wilms' tumor gene 1 (WT1) expression at diagnosis in adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly understood. A total of 257 adults with Ph-negative BCP-ALL who were consecutively diagnosed and received at least 1 course of induction therapy at our institute were retrospectively analyzed. The WT1 expression patterns were significantly different among the molecularly and cytogenetically defined groups (E2A-PBX1, TEL-AML1, and MLL rearrangements; high hyperdiploidy and B-other). By considering the WT1 expression pattern and the relapse status, 2 cutoff values, 1.8% and 7.2%, were arbitrarily selected to place patients into WT1-low, WT1-inter, and WT1-high groups. In the B-other patients who achieved complete remission (CR), WT1-low and WT1-high patients had similar 3-year relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS) rates, which were all significantly lower than those of WT1-inter patients. The combined WT1-low/high expression group (n = 132) had significantly lower 3-year RFS, DFS, and OS rates compared with the WT1-inter group (n = 63) of B-other patients (RFS and DFS all P < 0.0001; OS P = 0.0018 and 0.0008). WT1 low/high expression as well as treating with chemotherapy only was independent poor prognostic factors for RFS, DFS, and OS in the B-other patients who achieved CR. Therefore, the molecularly and cytogenetically defined adult Ph-negative BCP-ALL groups have characteristic WT1 expression patterns, and WT1 low/high expression at diagnosis predicts poor outcome in B-other patients.

    更新日期:2019-11-01
  • Multicenter retrospective analysis of the clinicopathologic features of monomorphic epitheliotropic intestinal T-cell lymphoma.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-08
    Jun Ho Yi,Gyeong-Won Lee,Young Rok Do,Hye Ra Jung,Jung Yong Hong,Dok Hyun Yoon,Cheolwon Suh,Yoon Seok Choi,Seong Yoon Yi,Byeong Seok Sohn,Byung-Su Kim,Sung Yong Oh,Jinny Park,Jae-Cheol Jo,Seung-Sook Lee,Young-Ha Oh,Seok Jin Kim,Won Seog Kim

    Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE-IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.

    更新日期:2019-11-01
  • Prognostic significance of the EVI1 gene expression in patients with acute myeloid leukemia: a meta-analysis.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-09-05
    Xia Wu,Huifang Wang,Jili Deng,Xue Zheng,Yantao Ling,Yuping Gong

    Ecotropic virus integration site-1 (EVI1) is frequently expressed in patients with acute myeloid leukemia (AML). Many studies have reported the potential poor prognostic impact of EVI1 higher expression (EVI1H) in the AML patients; however, the conclusions previously reported have not been fully assessed and are still controversial. Therefore, we performed a meta-analysis to evaluate the prognostic significance of EVI1H in patients with AML. The primary endpoint was overall survival (OS), and the event-free survival (EFS) was selected as the secondary endpoint. We extracted the hazard ratio (HR) and their 95% confidence interval (CI) for the OS and EFS from the multivariate COX proportional hazard models. A total of 4767 AML patients from 11 studies up to 23 February 2019 were subjected to our meta-analysis. Pooled HRs suggested that EVI1H had an adverse impact on OS (HR = 1.52, 95%CI 1.24-1.86) and EFS (HR = 1.41, 95%CI 1.14-1.74) in AML patients. EVI1H was also associated with a shorter OS (HR = 1.73, 95%CI 1.43-2.11) and EFS (HR = 1.17, 95%CI 1.05-1.31) in AML patients with the intermediate cytogenetic risk (ICR) according to the National Comprehensive Cancer Network (NCCN), European leukemia network (ELN), or International System for Human Cytogenetic Nomenclature (ISCN). Furthermore, EVI1H appeared to be a poor prognosis indicator in patients with normal cytogenetics (NC) (HR for OS:2.01, 95%CI 1.32-3.05; HR for EFS 1.54, 95%CI 1.09-2.17) and young patients (HR for OS 1.30, 95%CI 1.09-1.55), respectively. This meta-analysis indicates EVI1H has an independent and significantly adverse prognostic impact on AML patients in the entire population, and this conclusion same applies to some subgroups like AML patients with ICR, NC, and young AML patients.

    更新日期:2019-11-01
  • Characteristics and course of patients with advanced hematologic malignancies receiving specialized inpatient palliative care at a German university hospital.
    Ann. Hematol. (IF 2.850) Pub Date : 2019-06-30
    Dennis A Eichenauer,Heidrun Golla,Indra Thielen,Michael Hallek,Raymond Voltz,Klaus Maria Perrar

    更新日期:2019-11-01
  • Enrichment of circulating myeloma cells by immunomagnetic beads combined with flow cytometry for monitoring minimal residual disease and relapse in patients with multiple myeloma.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Ningning Wang,Nahom Tesfaluul,Jia Li,Xiaojuan Gao,Shuai Liu,Baohong Yue

    Difficulty in regularly analyzing marrow myeloma cells (MMCs) and low frequency of circulating myeloma cells (CMCs) in blood presents challenges for monitoring minimal residual disease (MRD) in multiple myeloma (MM). We have developed a set of method for enrichment of CMCs by immunomagetic beads (IMB) combined with flow cytometry (IMB-FCM) based on CD38-APC/CD138-APC antibodies in U266-spiked samples and in 122 patient samples. U266 cell capture efficiency of CD38/CD138-IMB-FCM (6.960, 2.574) was 6- and 2-fold higher than that of FCM (1.032), and the sensitivity of FCM and IMB-FCM was 0.01% and 0.001%, respectively. In MM cohort, the positive rate of CMCs by IMB-FCM increased from 60.5~70.0 to 85~87.2% in newly diagnosed/relapsed and partial remission (PR) patients compared with by FCM (P < 0.05). Two complete remission (CR) patients contain certain amounts of CMCs by IMB-FCM while no CMCs and MMCs were detectable by FCM. Patients exhibiting PR and CR upon therapy had much lower CMC and MMC counts than newly diagnosed/relapsed patients (P < 0.005). Based on MRD measurement in BM and PB samples, all FCM-negative BM samples were also paired with FCM/IMB-FCM-negative PB samples among newly diagnosed, relapsed, and PR patients, and FCM-positive BM samples were accompanied by IMB-FCM-positive results in 88% of corresponding PB samples. CMCs strongly associated with other clinical biomarkers of disease burden, including elevated MMCs, β2-MG, sCrea, and DS and ISS stages, and more serious anemia, bone destruction, and renal impairment (P < 0.05). Logistic regression analysis revealed that elevated β2-MG and moderate-to-more anemia were significant risk factors for the presence of CMCs (P < 0.05). As a noninvasive "liquid biopsy" of monitoring MRD, the potential of IMB-FCM for CMC detection may complement or minimize bone marrow aspiration in future treatment of MM patients.

    更新日期:2019-11-01
  • Transcriptional alteration of DNA repair genes in Philadelphia chromosome negative myeloproliferative neoplasms.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Martin Kirschner,Anne Bornemann,Claudia Schubert,Deniz Gezer,Kim Kricheldorf,Susanne Isfort,Tim H Brümmendorf,Mirle Schemionek,Nicolas Chatain,Tomasz Skorski,Steffen Koschmieder

    Philadelphia negative (Ph-neg) myeloproliferative neoplasms (MPN) are a heterogenous group of clonal stem cell disorders. Approved treatment options include hydroxyurea, anagrelide, and ruxolitinib, which are not curative. The concept of synthetic lethality may become an additional therapeutic strategy in these diseases. In our study, we show that DNA repair is altered in classical Ph-neg MPN, as analyzed by gene expression analysis of 11 genes involved in the homologous recombination repair pathway (HRR), the non-homologous end-joining pathway (NHEJ), and the single-strand break repair pathway (SSB). Altogether, peripheral blood-derived cells from 57 patients with classical Ph-neg MPN and 13 healthy controls were analyzed. LIG3 as an essential part of the SSB was significantly lower expressed compared to controls in all three entities (essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)). In addition, while genes of other DNA-repair pathways showed-possibly compensatory-increased expression in ET (HRR, NHEJ) and PV (NHEJ), MF samples displayed downregulation of all genes involved in NHEJ. With regard to the JAK2 mutational status (analyzed in ET and MF only), no upregulation of the HRR was detected. Though further studies are needed, based on these findings, we conclude that synthetic lethality may become a promising strategy in treating patients with Ph-neg MPN.

    更新日期:2019-11-01
  • Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Gilles Salles,Emmanuel Bachy,Lukas Smolej,Martin Simkovic,Lucile Baseggio,Anna Panovska,Hervé Besson,Nollaig Healy,Jamie Garside,Wafae Iraqi,Joris Diels,Corinna Pick-Lauer,Martin Spacek,Renata Urbanova,Daniel Lysak,Ruben Hermans,Jessica Lundbom,Evelyne Callet-Bauchu,Michael Doubek

    After analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab-containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14-0.37; p < 0.0001) and 0.40 (0.22-0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16-0.27; p < 0.0001) and 0.29 (0.21-0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22-0.63; p = 0.0003) for PFS and 0.53 (0.27-1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.

    更新日期:2019-11-01
  • Acute porphyrias: a German monocentric study of the biochemical, molecular genetic, and clinical data of 62 families.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Olivia Bronisch,Thomas Stauch,Thomas Haverkamp,Maria K Beykirch,Petro E Petrides

    In Germany, analyses of clinical and laboratory features of patients with acute porphyrias are only available for hereditary coproporphyria (HCP) but not with other acute porphyrias, acute intermittent porphyria (AIP) and variegate porphyria (VP). The aim of the study was to analyze a large cohort of patients with particular focus upon quality of life aspects. Sixty-two individuals from separate families with acute porphyrias (57 AIP, 5 VP) were included into an observational study collecting biochemical, genetic, and clinical data. A questionnaire was designed to complete anamnestic information and to assess the influence on quality of life. Most frequent signs and symptoms or laboratory abnormalities were abdominal colicky pain, red coloration of urine, and hyponatremia. Depression or anxiety was reported by 61% or 52% individuals, respectively. Fatigue was mentioned as the most quality of life-limiting symptom. In 59/61 patients, mutations could be identified. 44% (20/45) had to be admitted to an intensive care unit. Heme arginate was used in 64% (29/45) of patients for treatment of acute attacks at least once and in 33% for long-term treatment with high frequency of administration. Serum creatinine values increased in 47% (7/17) of the patients with recurrent attacks. Our analysis confirms a substantial influence of the diseases on the quality of life on patients. Percentages of urine discoloration and intensive care unit admissions were much higher than in other reports. Long-term treatment with heme arginate requires careful monitoring of iron status and renal values.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • New insights inside the interdigitating dendritic cell sarcoma-pooled analysis and review of literature.
    Ann. Hematol. (IF 2.850) Pub Date : null
    Amr Muhammed,Ahmed R H Ahmed,Hashem Maysa,Ahmed E S Mohamed,Asmaa Abd-ElGhany Abd-ElLateef,Esraa Elnakib

    Interdigitating dendritic cell sarcoma is a rare haematological neoplasm with high debatable management protocols. The data extracted from 127 case reports published between 1981 and 2018 were analysed. The median age at diagnosis was 58 years with a male to female ratio of 1.65:1. The median OS and PFS of IDCS were 12 and 6 months, respectively, with a disease-specific mortality rate of 36.4%. Two-thirds of patients had a localised disease, while 30% had a disseminated form with 1-year mortality rates of 21.1% and 78.9%, respectively. Twenty per cent of cases were associated with other malignancies. Histologically, the proliferation of large spindle-shaped cells with fascicular growth was described in 84.3% of cases. Based on Cox-regression model, surgical resection was the only treatment modality linked to survival improvement with no recorded survival benefits of radiotherapy and chemotherapy. The 1-year mortality rates in resected and non-resected disease were 17.8% and 63.2%, respectively (P < 0.0001).

    更新日期:2019-11-01
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