高危造血干细胞移植患者应用氟达拉滨替代环磷酰胺行预处理12例

目的 探讨氟达拉滨(Flu)替代环磷酰胺(Cy)的预处理方案在异基因造血干细胞移植(allo-HSCT)的安全性和疗效.方法 接受allo-HSCT治疗的高龄(≥55岁)和(或)合并脏器功能损害的恶性血液病患者12例,其中急性髓系白血病6例,急性淋巴细胞自血病1例,慢性粒细胞白血病2例,骨髓增生异常综合征3例.预处理时,HLA相合供者移植的9例采用改良白消安-氟达拉滨(BuFlu)方案,其中Flu为50 mg/d,用5 d;行HLA不相合移植的2例采用改良BuFlu联合兔抗人胸腺细胞球蛋白(ATG)方案;行二次移植的1例采用全身放疗(TBI)-Flu方案.采用环孢素A、吗替麦考酚酯及短程甲氨蝶呤预防移植物抗宿主病(GVHD).结果 患者输注单个核细胞的中位数为6.68× 10~8/kg,输注CD34~+细胞的中位数为1.502 × 10~6/kg.allo-HSCT后所有患者均达到白细胞植入,植入时间中位数为17.5 d;除1例外,其余11例患者均达到血小板植入,植入时间中位数为14 d;HSCT后30 d,11例患者为完全供者型,仅1例为供受者嵌合状态.患者对预处理方案的耐受性良好,未发生严重预处理相关并发症.12例中,6例出现Ⅰ度以上急性GVHD,其中Ⅰ度2例,Ⅱ度3例,Ⅲ度1例;10例存活100 d以上的患者中,8例发生慢性GVHD;无GVHD相关死亡.随访62～554 d,10例无原发病复发存活,存活时间中位数为424 d,2例患者死亡,其中1例死于原发病未缓解,另1例死于移植后淋巴系统增殖性疾病.结论 高龄和(或)脏器功能损害的患者对应用Flu替代Cy的预处理方案的耐受性较好,且异体造血干细胞的植入顺利,原发病复发率未见明显升高.

Outcomes following HSCT using fludarabine replacing cyclophosphamide as a new preconditioning regimen for treatment of hematologic malignancies

Objective To evaluate the hypothesis of fludarabine replacing cyclophosphamide as a new myeloablative preconditioning for the treatment of malignant hematologic diseases in aged and/or intolerable patients receiving allogeniec stem cell transplantation (allo-HSCT). Methods Between January 2008 and November 2008,12 patients, who were intolerant to standard conditioning regimen, received allo-HSCT with HLA identical sibling (n = 9) or mismatched family donors (n = 3),including 1 case of acute lymphoblastic leukemia with Ph chromosome (Ph+ ALL) ,6 cases of acute myelogenous leukemia (AMD,3 cases of myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) and 2 cases of chronic myelogenous leukemia (CML). Stem cell sources were G-CSF mobilized peripheral blood alone (n = 1) ,or with G-CSF mobilized bone marrow (n - 11), with a median of 6. 68 (4. 35 - 7. 86) × 10~8/kg MNC and 1. 50 (0. 31 - 3. 91) × 10~6/kg CD34~+ cells. Eleven patients received revised busulfan and fludarabine regimen with/without antithymocyteglobulin(ATG),and the rest one received TBI and fludarabine regimen. GVHD prophylaxis included cyclosporin A, mycophenolate mofetil and methotrexate. Results Results All patients were well tolerated to the regimen without serious regimen related toxicity. The median time of ANC≥0. 5 × 10~9/L was day 17. 5 (11 - 23), and that of BPC≥20. 0 ×10~9/L was day 14. All patients except one got donor engraftment successfully and attained CR. With a median follow-up of 418 (62-554) days, 10 of 12 patients were alive and disease-free. Conclusion Fludarabine replacing cyclophosphamide as a new preconditioning regimen is well tolerated and safe for allo-HSCT, especially in older patients or/and those with severe concurrent medical conditions.