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High leukemia-free survival after TBI-based conditioning and mycophenolate mofetil-containing immunosuppression in patients allografted for chronic myelomonocytic leukemia: a single-center experience.
Annals of Hematology ( IF 3.5 ) Pub Date : 2020-02-08 , DOI: 10.1007/s00277-020-03952-4
Aleksandar Radujkovic 1 , Ute Hegenbart 1 , Carsten Müller-Tidow 1 , Klaus Herfarth 2 , Peter Dreger 1 , Thomas Luft 1
Affiliation  

This retrospective single-center analysis studied the impact of the conditioning and the graft-versus-host disease (GVHD) prophylaxis on outcome in unselected patients allografted for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) secondary to documented prior CMML. A total of 44 patients (median age 61 years) allografted between 2002 and 2019 in our institution were analyzed. Fifteen patients had secondary AML. The conditioning regimen was fractionated 6-8 Gy total body irradiation (TBI) in combination with fludarabine in 33 (75%) patients. Eleven patients (25%) received alkylator-based conditioning therapy without TBI. For GVHD prophylaxis, a calcineurin inhibitor (CNI) backbone in combination with methotrexate (MTX) or mycophenolate mofetil (MMF) was applied in 21 and 23 patients, respectively. All patients allografted from an unrelated donor (UD) received antithymocyte globuline. In univariate analysis of the entire cohort, TBI-based conditioning and MMF-containing immunosuppression were associated with improved leukemia-free survival (LFS, HR 0.16, P < 0.001 and HR 0.41, P = 0.030, respectively). After stratification according to conditioning and GVHD prophylaxis into four groups (TBI-MMF [n = 17], TBI-MTX [n = 16], alkylator-MMF [n = 6], alkylator-MTX [n = 5]), TBI-MMF was associated with improved overall survival (OS) and LFS (P = 0.001 and P < 0.001, respectively). Patient and disease characteristics did not differ between the groups. The associations of TBI-based conditioning and MMF with prolonged LFS were observed across the CMML (n = 29), secondary AML (n = 15), and UD allograft (n = 34) subgroups. In summary, our study suggests that allografting based on intermediate-dose TBI conditioning and MMF-containing GVHD prophylaxis is associated with increased disease control in CMML. Larger (registry-based) studies are warranted to confirm our findings.

中文翻译:

在同种异体移植慢性粒细胞单核细胞白血病患者中,基于TBI的调理和含麦考酚酸酯的免疫抑制后高无白血病生存:单中心经验。

这项回顾性单中心分析研究了条件和移植物抗宿主病(GVHD)预防对未选患者的继发于先前CMML继发的慢性粒细胞单核细胞白血病(CMML)和急性髓细胞性白血病(AML)的未选患者结局的影响。分析了我院2002年至2019年间共移植的44例患者(中位年龄61岁)。15例患者患有继发性AML。在33名(75%)患者中,联合氟达拉滨对6-8 Gy全身辐射(TBI)进行了分级分级治疗。11名患者(25%)接受了基于烷基化的无TBI调理治疗。为了预防GVHD,分别在21和23例患者中应用了钙调神经磷酸酶(CNI)骨架与甲氨蝶呤(MTX)或霉酚酸酯(MMF)组合。从无关供体(UD)同种异体移植的所有患者均接受抗胸腺细胞球蛋白。在整个队列的单变量分析中,基于TBI的调节和含MMF的免疫抑制与无白血病生存期改善相关(LFS,HR 0.16,P <0.001和HR 0.41,P = 0.030)。根据条件分层和GVHD预防分为四组(TBI-MMF [n = 17],TBI-MTX [n = 16],烷基化剂-MMF [n = 6],烷基化剂-MTX [n = 5]),TBI -MMF与总生存期(OS)和LFS改善有关(分别为P = 0.001和P <0.001)。两组之间的患者和疾病特征无差异。在CMML(n = 29),继发性AML(n = 15)和UD同种异体移植(n = 34)子组中观察到基于TBI的调节和MMF与LFS延长的关联。综上所述,我们的研究表明,基于中剂量TBI调节和含MMF的GVHD预防的同种异体移植与CMML中疾病控制的增加有关。较大的(基于注册表的)研究必须确认我们的发现。
更新日期:2020-02-10
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