Chimeric antigen receptor (CAR) T cell immunotherapies targeting CD19 or CD22 induce remissions in the majority of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), although relapse due to target antigen loss or downregulation has emerged as a major clinical dilemma. Accordingly, great interest exists in developing CAR T cells directed against alternative leukemia cell

CD19-specific chimeric antigen receptor (CD19-CAR)-T cell therapies mediate durable responses in late-stage B-cell malignancies, but can be complicated by a potentially severe immune effector cell-associated neurotoxicity syndrome (ICANS). Despite broad efforts, the precise mechanisms of ICANS are not entirely known, and resistance to current ICANSdirected therapies (especially corticosteroids) has

Remodeling of the bone marrow microenvironment in chronic inflammation and in aging reduces hematopoietic stem cell (HSC) function. To assess the mechanisms of HSC functional decline and find strategies to counteract these, we established a model in which Sfrp1 gene was deleted in Osterix+ osteolineage cells (OS1Δ/Δ mice). HSCs from these mice showed severely diminished repopulating activity with associated

Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy. However relapse of malignant disease is the primary cause of treatment failure and reflects loss of immunological graft versus leukaemia effect. We studied the transcriptional and phenotypic profile of CD8+ T cells in the first month following transplantation and related this to risk of subsequent relapse

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There is growing evidence for an inherited basis of susceptibility to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies by us and others have identified non-coding ALL risk variants at the ARID5B gene locus, but the molecular mechanisms linking ARID5B to normal and malignant hematopoiesis remain largely unknown. Using a Vav1-driven transgenic mouse model, we characterized

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Chemotherapy resistance is the main cause of treatment failure in acute myeloid leukemia (AML) and has been related to ATP-binding cassette (ABC) transporter activity. However, the links between ABC activity, immunophenotype, and molecular AML parameters have been poorly evaluated. Moreover, the prognostic value of ABC activity, when compared to new molecular markers, is unknown. Here we investigated

In hemophilia A (HA), F8 nonsense variants, and particularly those affecting the large factor VIII (FVIII) B domain that is dispensable for coagulant activity, display lower association with replacement therapy-related anti-FVIII inhibitory antibodies as retrieved from multiple international databases. Since null genetic conditions favour inhibitor development, we hypothesized that translational readthrough

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Measurable residual disease (MRD) before hematopoietic cell transplantation (HCT) is an independent established prognostic factor in patients with acute myeloid leukemia (AML). Several methods exist to evaluate the presence of residual leukemia cells, but how these are used best in combination is unclear. To examine how residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry

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The outcome of acute myeloid leukemia (AML) remains poor, and immunotherapy has the potential to improve this. T cells expressing chimeric antigen receptors (CARs) or bispecific T cell engagers targeting CD123 are actively being explored in preclinical and/or early phase clinical studies. We have shown that T cells expressing CD123-specific bispecific T cell engagers (CD123.ENG T cells) have anti-AML

Elucidating genetic aberrations in pediatric acute myeloid leukemia (AML) provides insight in biology and may impact on risk-group stratification and clinical outcome. This study aimed to detect such aberrations in a selected series of samples without known (cyto)genetic aberration using molecular profiling. A cohort of 161 patients was selected from various study groups: DCOG, BFM, SJCRH, NOPHO and

Phosphatidylinositol 3-kinase (PI3K) inhibitors are effective in chronic lymphocytic leukemia (CLL). However, the severe toxicity profile associated with the first-generation inhibitors idelalisib and duvelisib, combined with the availability of other more tolerable agents, have limited their use. CLL is still considered incurable, and relapse after treatment, development of resistance, and treatment

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Although human cultures stimulated with dexamethasone suggest that the glucocorticoid receptor (GR) activates stress erythropoiesis, the effects of GR activation on erythropoiesis in vivo remains poorly understood. We characterized the phenotype of a large cohort of patients with Cushing's Disease, a rare condition associated with elevated cortisol levels. Results from hypercortisolemic patients with

Time at home is a critically important outcome to adults with acute myeloid leukemia (AML) when selecting treatment; however, no study to date has adequately described the amount of time older adults spend at home following initiation of chemotherapy. We queried records from a multi-institution health system to identify adults age ≥60 newly diagnosed with AML treated with azacitidine (AZA) or venetoclax

The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved the outcomes of patients but, in parallel, has changed the frequency and epidemiology of thrombotic events. Now, thrombosis is a significant cause of morbidity and mortality in MM patients, and optimal thromboprophylaxis is far from being

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Classical Hodgkin Lymphoma (CHL) is unusually sensitive to PD1 inhibition and PDL1 is highly expressed on CHL cells and in the tumor microenvironment. This could be interpreted as evidence of exhaustion, but paradoxically, PD1+ lymphocyte infiltration does not predict PD1 inhibitor response and no increase in cytotoxic markers is seen after PD1 therapy as might be expected with reversal of exhaustion

The Philadelphia (Ph) 9;22 chromosome translocation has two common isoforms that are preferentially associated with distinct subtypes of leukemia. The p210 variant is the hallmark of CML whereas p190 is frequently associated with B-ALL. The only sequence difference between the two isoforms is the guanidine exchange factor (GEF) domain. This GEF is reported to activate RHO family GTPases in response

We have previously shown that complete response (CR) rates and overall survival (OS) of patients with acute myeloid leukemia (AML) have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients age 65 or younger randomized to 7+3 arms from 5 SWOG studies: S8600 (n=530), S9031 (n=98)

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Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR-T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR-T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT

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Anemia is a major health issue and associated with increased morbidity. Iron deficiency anemia (IDA) is the most prevalent, followed by anemia of chronic disease (ACD). IDA and ACD often coexist, challenging diagnosis and treatment. While iron supplementation is the first-line therapy for IDA, its optimal route of administration and the efficacy of different repletion strategies in ACD are elusive

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Hepatitis E virus is increasingly being reported to cause chronic infection in immunocompromised patients. However, less is known about patients with underlying hematologic disease. In particular, the impact of hepatitis E infection on oncologic therapy has been poorly described. In this retrospective single-center analysis, we analyzed 35 hematological patients with hepatitis E, including 20 patients

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Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T-cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel

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IgM monoclonal gammopathy of undetermined significance is a pre-malignant condition for Waldenstrom Macroglobulinaemia (WM) and other B-cell malignancies, defined by asymptomatic circulating IgM monoclonal protein below 30 g/l with a lymphoplasmacytic bone marrow infiltration of less than 10%. A significant proportion, however develop unique immunological and biochemical manifestations related to the

Primary Plasma Cell Leukaemia (pPCL) is a rare and challenging malignancy. There is limited data regarding optimum transplant approaches. Therefore we undertook a retrospective analysis from 1998-2014 of 751 patients with Primary Plasma Cell Leukaemia (pPCL) undergoing one of four transplant strategies; single autologous transplant (single-auto), single allogeneic transplant (allo-first) or a combined

We aim to identify predictors of therapy-related myeloid neoplasms (t-MN) in patients with breast cancer (BC) and cytopenias to determine the timing of bone marrow biopsy (BMBx). Patients with BC and cytopenias who were referred for BMBx between 2002-2018 were identified using the Memorial Sloan Kettering Cancer Center institutional database. Characteristics associated with the risk of t-MN were evaluated

Patients with refractory relapsed multiple myeloma (RRMM) respond to Elotuzumab (Elo) and lenalidomide (Len) combination treatment. The mechanisms underlying this observation are not fully understood. Furthermore, predictive biomarkers of response have not been revealed to date. To address these issues, we used a humanized myeloma mouse model and adoptive transfer of human NK cells to show that Elo

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSCs populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSCs are impaired in AA

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Intratumoral heterogeneity (ITH) provides the substrate for tumor evolution and treatment resistance, yet is remarkably understudied in lymphoma, due to the often limited amount of tissue that gets sampled during the routine diagnostic process, generally from a single nodal or extranodal site. Furthermore, the trajectory of how lymphoma, and especially non-Hodgkin lymphoma, spreads throughout the human

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Physiologic and pathogenic IL7-receptor (IL7R) induced signaling provokes glucocorticoid resistance in a subset of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. Activation of downstream STAT5 has been suggested to cause steroid resistance through upregulation of anti-apoptotic BCL2, one of its downstream target genes. Here, we demonstrate that isolated STAT5 signaling in various T-ALL