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目的:探讨异基因造血干细胞移植(allo-HSCT)治疗成人费城染色体阳性(Ph+)的急性淋巴细胞白血病(ALL)的疗效。方法:回顾性分析经VDP(长春新碱、蒽环类、糖皮质激素)±C(环磷酰胺或异环磷酰胺)±L(左旋门冬酰胺酶或培门冬酶)方案诱导化学治疗(化疗)的12例Ph+ALL患者。初始诱导缓解患者在等待移植期间进行巩固化疗,并加用伊马替尼(400～800 mg/d),与化疗同步或交替应用。初始诱导失败患者及巩固治疗期间复发患者应用Hyper-CVAD/LALA(大剂量环磷酰胺、长春新碱、多柔比星、地塞米松或米托蒽醌、阿糖胞苷)方案联合伊马替尼或达沙替尼进行再次诱导。所有患者缓解后经白消安联合环磷酰胺(Bu-Cy)或改良Bu-Cy方案预处理后进行allo-HSCT。部分患者干细胞回输后2～3个月始继续服用酪氨酸激酶抑制剂。结果:12例患者移植前均获得血液学缓解、7例获得分子学缓解。其中完全缓解(CR)1期9例、CR 2期2例、初发难治性1例。移植前11例患者应用伊马替尼;移植后5例患者应用酪氨酸激酶抑制剂,其中4例应用伊马替尼、1例应用达沙替尼。中位随访时间12.7(3～54)个月,7例患者生存,3例患者死于疾病复发,2例患者死于治疗相关并发症。所有患者均植入,移植后2年总生存率66.7%±13.6%;2年累计复发率40.6%±16.0%;2年累计非复发病死率16.7%±10.8%。首次缓解(CR1)后移植治疗的2年总生存率70.0%±14.5%;2年累计复发率40.0%±18.2%;2年累计非复发病死率20.0%±12.6%。结论:酪氨酸激酶抑制剂可能会使更多患者获得缓解,从而有机会进行allo-HSCT。CR1的生存获益更大。allo-HSCT联合酪氨酸激酶抑制剂为Ph+ALL患者有前景的治疗方案。
Objective: To investigate the efficacy of allo-HSCT in the treatment of Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL). Methods: A retrospective analysis of chemotherapy induced by VDP (vincristine, anthracycline, glucocorticoids) ± C (cyclophosphamide or ifosfamide) ± L (L-asparaginase or pegaspargase) (Chemotherapy) in 12 patients with Ph + ALL. Patients with initial induction remission undergo consolidation chemotherapy while waiting for a transplant, and add imatinib (400-800 mg / d) concurrently or alternately with chemotherapy. Hyper-CVAD / LALA (high-dose cyclophosphamide, vincristine, doxorubicin, dexamethasone or mitoxantrone, cytarabine) regimens were used in combination with Imam in patients with initial induction of failure and in relapsed patients during consolidation therapy Tenney or dasatinib was induced again. All patients were relieved and allo-HSCT was performed after pretreatment with busulfan combined with cyclophosphamide (Bu-Cy) or modified Bu-Cy protocol. Some patients continue to take tyrosine kinase inhibitors 2 to 3 months after the return of stem cells. RESULTS: All 12 patients achieved hematologic remission before transplantation and 7 received molecular remission. Among them, 9 were in stage 1 of complete remission (CR), 2 were in stage CR 2, and 1 was refractory to initial onset. Imatinib was administered to 11 patients before transplantation; tyrosine kinase inhibitors were used in 5 patients after transplantation, of which 4 were imatinib and 1 was dasatinib. The median follow-up time was 12.7 (range, 3 to 54) months. Seven patients survived, three died of disease recurrence, and two died of treatment-related complications. All patients were implanted. After 2 years of transplantation, the overall survival rate was 66.7% ± 13.6%. The 2-year cumulative recurrence rate was 40.6% ± 16.0%. The 2-year cumulative non-recurrence mortality rate was 16.7% ± 10.8%. The 2-year overall survival rate was 70.0% ± 14.5% after 2 years of initial CR (CR1) transplantation, 40.0% ± 18.2% after 2 years of CRI, and 20.0% ± 12.6% of 2 years. CONCLUSIONS: Tyrosine kinase inhibitors may result in more patients being remitted, giving the opportunity for allo-HSCT. CR1 survival benefit more. Allo-HSCT combined with tyrosine kinase inhibitors is a promising treatment for patients with Ph + ALL.