Mengarelli Andrea, Iori AnnaPaola, Guglielmi Cesare, Romano Atelda, Cerretti Raffaella, Torromeo Concetta, Micozzi Alessandra, Fenu Susanna, Laurenti Luca, Donato Vittorio, De Felice Lidia, Arcese William
Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy.
Haematologica. 2002 Jan;87(1):52-8.
To analyze the results of standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia.
From October 1986 to February 2000, 104 consecutive patients (male: n = 63; median age: 21, range 1.3-44.2 years) with high-risk acute leukemia underwent a non-T-cell depleted graft from an HLA-identical sibling following a standard or alternative myeloablative conditioning regimen. Sixty patients were affected by acute lymphoblastic leukemia (ALL) and 44 by acute myeloid leukemia (AML); the phase at transplant was >= 2nd complete remission (CR) in 76, untreated 1st relapse with < 20% blasts in 11, refractory leukemia or overt resistant relapse in 17. Pre-transplant regimens consisting of either 12 Gy fractionated total body irradiation (TBI) or 16 mg/kg busulphan (BU) combined with cyclophosphamide (CY) were defined standard (n = 38), whereas all other myeloablative regimens (TBI plus 60 mg/kg etoposide and three-drug combinations) were considered alternative (n = 66).
No significant differences in terms of baseline characteristics, incidence and severity of either acute or chronic graft-versus-host disease (GVHD) were observed between the two groups, but a significantly higher proportion of patients prepared with an alternative regimen were not evaluable for chronic GVHD (36% vs 16%) (p = 0.026). Sixty-six patients died, 38 of relapse, 26 of transplant-related mortality (TRM) and 2 of other causes. Thirty-eight patients are still alive with a follow-up ranging from 0.7 to 13.8 years (median, 7.1 years); only 1 of 39 patients who relapsed after transplant is alive in CR at 5.7 years from relapse. At the median follow-up, the actuarial probabilities of overall survival, relapse and TRM for patients conditioned with standard and alternative regimens are respectively 52% vs 25% (95% CI, 36-68% vs 13-37%; p = 0.0163), 34% vs 58% (95% CI, 18-51% vs 43-73%; p = 0.0377) and 25% vs 32% (95% CI, 9-40% vs 19-44%; p = ns). After adjustment for diagnosis, age, period, leukemia phase, duration of 1st CR, GVHD prophylaxis and donor-recipient sex combination, the multivariate analysis showed that alternative regimens are associated with a significantly worse survival (hazard ratio 2.31; p = 0.0071) and relapse rate (hazard ratio 2.75; p = 0.0187).
From this retrospective analysis we can conclude that the alternative myeloablative conditioning regimens we used did not improve the outcome of patients transplanted for high-risk acute leukemia.
分析标准与替代清髓性预处理方案在高危急性白血病异基因造血干细胞移植中的效果。
1986年10月至2000年2月，104例连续的高危急性白血病患者（男性63例；中位年龄21岁，范围1.3 - 44.2岁）在接受标准或替代清髓性预处理方案后，接受来自 HLA 相合同胞的非 T 细胞去除移植物。60例为急性淋巴细胞白血病（ALL）患者，44例为急性髓系白血病（AML）患者；移植时处于≥第二次完全缓解（CR）期的有76例，未治疗的首次复发且原始细胞<20%的有11例，难治性白血病或明显耐药复发的有17例。由12 Gy 分次全身照射（TBI）或16 mg/kg 白消安（BU）联合环磷酰胺（CY）组成的预处理方案被定义为标准方案（n = 38），而所有其他清髓性方案（TBI 加60 mg/kg 依托泊苷和三药联合方案）被视为替代方案（n = 66）。
两组在基线特征、急性或慢性移植物抗宿主病（GVHD）的发生率和严重程度方面均未观察到显著差异，但接受替代方案预处理的患者中不可评估慢性 GVHD 的比例显著更高（36%对16%）（p = 0.026）。66例患者死亡，38例死于复发，26例死于移植相关死亡率（TRM），2例死于其他原因。38例患者仍存活，随访时间为0.7至13.8年（中位，7.1年）；移植后复发的39例患者中，仅1例在复发后5.7年处于CR状态存活。在中位随访时，接受标准和替代方案预处理患者的总生存、复发和TRM的精算概率分别为52%对25%（95%CI，36 - 68%对13 - 37%；p = 0.0163），34%对58%（95%CI，18 - 51%对43 - 73%；p = 0.0377）和25%对32%（95%CI，9 - 40%对19 - 44%；p = 无显著性差异）。在对诊断、年龄、时期、白血病阶段、首次CR持续时间、GVHD预防和供受者性别组合进行调整后，多变量分析显示替代方案与显著更差的生存率（风险比2.31；p = 0.0071）和复发率（风险比2.75；p = 0.0187）相关。
从这项回顾性分析中我们可以得出结论，我们使用的替代清髓性预处理方案并未改善高危急性白血病移植患者的结局。
