异基因造血干细胞移植治疗复发难治性急性淋巴细胞白血病的临床研究

Clinical study of allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute lymphocytic leukemia

目的探讨异基因造血干细胞移植（allo-HSCT）对复发难治性急性淋巴细胞白血病（ALL）患者的疗效及治疗相关毒性。方法观察并分析47例复发难治性ALL患者对allo-HSCT治疗的耐受情况、移植相关并发症、总生存率以及无病存活率。其中HIA相合同胞间移植（sib-HSCT）19例，HLA相合的无血缘关系移植（URD-HSCT）18例，单倍型移植（Hi-HSCT）10例。预处理方案：42例采用改良TBI＋CY方案，5例采用改良BU／CY方案。移植物抗宿主病（GVHD）的预防：环孢素（CsA）联合短程甲氨蝶呤（MTX）、Hi-HSCT和URD-HSCT加用霉酚酸酯（MMF）及抗胸腺细胞免疫球蛋白（ATG）。定期监测微量残留病变（MRD），明确有分子生物学或细胞遗传学复发趋势的患者接受供者淋巴细胞输注（DLI）。结果所有患者均完成移植治疗，出现了不同程度黏膜炎；2例患者在应用CsA过程中有肾功能损害；1例患者发生药物性癫痫。移植后出现Ⅲ～Ⅳ度急性GVHD7例；慢性GVHD22例；致命性肺部感染9例（包括间质性肺炎3例）；出血性膀胱炎4例。有13例患者移植后再次复发。移植后造血重建的中位时间为移植后第17天。术后有19例接受DLI，6例疾病未再进展。中位随访期43（10～77）个月，预期5年总生存率为49．65％，无病存活率为46．55％。结论allo-HSCT能有效治疗复发难治性ALL，改善其预后，治疗失败的主要原因是移植后复发，其次为致命性肺部感染和重度急性GVHD。DLI可能有助于减少移植后复发。

Objective To explore the efficacy and toxicity of allogeneic hematopoietic stem cell transplantation （allo-HSCT） for relapsed/refractory acute lymphocytic leukemia （ALL）. Methods Fortyseven patients with relapsed/refractory ALL received allo-HSCT, which containing 19/47 from HLA-identical sibling donors （sib-HSCT）, 18/47 from HLA-identical unrelated donors（URD-HSCT） and 10/47 from haplo-identical donors（Hi-HSCT）. Conditioning regimens included ＂TBI plus Cyclophosphamidc （Cy） （42/ 47） ＂ or ＂busulfan （Bu） plus Cy（5/47 ） ＂. Cyclosporine （CsA） combined with a short-course Methotrexate （MTX） were used for graft versus host disease （GVHD） prophylaxis. In addition, patients receiving URD- HSCT or Hi-HSCT were given myeophenolate mofetil （MMF） and anti-thymocyte immunoglobuline （ATG）. Patients with molecular or cytogenetic relapse tendency on minimal residual disease （MRD） monitoring received donor lymphocyte infusion （DLI）. Results All patients tolerated the therapy well except for mucositis. Renal dysfuction occurred in 2 patients on CsA therapy. Epilepsy occurred in 1 patient, fatal infectious complications in 9 （including 3 interstitial pneumonia）, grade Ⅲ - Ⅳ acute GVHD（aGVHD） in 7, chronic GVHD（cGVHD） in 22 and hemorrhagic cystitis （HC） in 4 patients. Thirteen patients relapsed after transplantation. The median time of hematopoietic reconstitution was ＋ 17 ds. Nineteen patients received DLI, and 6 of them had no disease progression. With a median follow-up duration of 43 （10 -77） months, the estimated 5-year overall survival （OS） and disease free survival （DFS） rates were 49. 65% and 46.55%, respeetively. Conclusion Allo-HSCT is an effective therapy for relapsed/refraetory ALL. Relapse after transplantation, fatal infection, and severe acute GVHD are the main causes for failure. DLI might decrease the relapse rate after transplantation.