Reduced intensity thiotepa-cyclophosphamide conditioning for allogeneic haemopoietic stem cell transplants (HSCT) in patients up to 60 years of age
Reduced intensity thiotepa-cyclophosphamide conditioning for allogeneic haemopoietic stem cell transplants (HSCT) in patients up to 60 years of age
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DOI：
10.1046/j.1365-2141.2000.02123.x
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发表时间：
2000-06-01
影响因子：
6.5
通讯作者：
Bacigalupo, A
中科院分区：
文献类型：
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作者：
Raiola, AM;Van Lint, MT;Bacigalupo, A
移植相关死亡率（TRM）仍然是接受异基因造血干细胞移植（HSCT）的老年患者的主要问题。因此，我们在33例中位年龄为52岁（范围43-60）的移植自人类白细胞抗原（HLA）相同同胞的患者中探索了一种强度较低的预处理。基础疾病为慢性髓性白血病（n = 15）、急性髓性白血病（n = 6）、骨髓增生异常（n = 7）或慢性淋巴组织增生性疾病（n = 5）; 15例患者（45%）为晚期疾病。该方案由第-5天的塞替派（THIO; 10 mg/kg）和第-3天和第-2天的环磷酰胺（CY; 50 mg/kg）（总剂量100 mg/kg）组成。来源是骨髓（BM）（n = 17）或粒细胞集落刺激因子（G-CSF）动员的外周血（PB）（n = 16），无需操作即可输注。移植物抗宿主病（GVHD）预防包括环孢菌素A（CyA）和短期甲氨蝶呤。中性粒细胞计数达到0.5 × 10（9）/l的平均时间为17天（范围11-23），到第100天，79%的患者检测到完全供体嵌合体。3%的患者发生急性GVHD III或IV级。慢性GVHD见于45%的患者，PB（69%）与BM移植（23%）相比有显著差异（P = 0.009）。对于BM移植物，精算2年TRM为6%，复发率为56%，生存率为87%;对于PB移植物，这些数字分别为27%，33%和68%。25例患者在中位随访762天（范围216-1615）时存活，20例患者（60%）保持无疾病。13例（39%）接受供者淋巴细胞输注（DLI）治疗持续或复发性疾病，6例患者完全缓解。最后总结：（i）年龄不超过60岁的患者可以在降低强度的条件下进行同种异体移植;（ii）由于慢性GVHD的风险较低，该手术与移植相关的死亡率较低相关，特别是骨髓移植;（iii）一半患者在移植后需要DLI治疗持续疾病或复发。
Transplant-related mortality (TRM) remains a major problem in older patients undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have therefore explored a less intensive conditioning in 33 patients with a median age of 52 years (range 43-60) transplanted from human leucocyte antigen (HLA)-identical siblings. The underlying disease was chronic myeloid leukaemia (n = 15), acute myeloid leukaemia (n = 6), myelodysplasia (n = 7) or a chronic lymphoproliferative disorder (n = 5); 15 patients (45%) had advanced disease. The regimen consisted of thiotepa (THIO; 10 mg/kg) on day -5 and cyclophosphamide (CY; 50 mg/kg) on days -3 and -2 (total dose 100 mg/kg). The source was bone marrow (BM) (n = 17) or granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) (n = 16), which were infused without manipulation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and a short course of methotrexate. Mean time to achieve a neutrophil count of 0.5 x 10(9)/l was 17 d (range 11-23) and full donor chimaerism was detected in 79% of patients by day 100. Acute GVHD grade III or IV occurred in 3% of patients. Chronic GVHD was seen in 45% of patients, with a significant difference for PB (69%) compared with BM transplants (23%) (P = 0.009). For BM grafts, the actuarial 2-year TRM was 6%, the relapse 56% and survival 87%; for PB grafts, these figures were, respectively, 27%, 33% and 68%. Twenty-five patients are alive at a median follow-up of 762 d (range 216-1615) and 20 patients (60%) remain free of disease. Thirteen patients (39%) received donor lymphocyte infusion (DLI) either for persisting or relapsing disease and six patients had complete remission. In conclusion: (i) patients up to the age of 60 years can be allografted with reduced intensity conditioning; (ii) the procedure was associated with a low transplant-related mortality, particularly for bone marrow grafts, because of a lower risk of chronic GVHD; and (iii) DLI were required after transplant in half the patients for persisting disease or relapse.