Schultz K R, Ratanatharathorn V, Abella E, Eisenbrey A B, Karanes C, Lum L G, de Planque M M, Uberti J P, Ravindranath Y, Sensenbrenner L L
Detroit Medical Center Bone Marrow Transplantation Program: Department of Pediatrics, Wayne State University.
Bone Marrow Transplant. 1994 Jun;13(6):817-22.
Identifying risk factors that lead to graft failure may reduce morbidity and mortality after bone marrow transplantation (BMT) for hematologic malignancies. We evaluated engraftment of all patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and myelodysplastic syndrome (MDS) receiving an unmanipulated marrow allogeneic BMT at the Detroit Medical Center from 1987 to 1992 using a busulfan, cyclophosphamide +/- cytarabine preparative regimen. Three of 118 patients had graft failure (2.5%; (95% confidence interval (CI) 0.7%, 6.4%). Graft failure was high in patients < or = 15 years with 3 of 12 patients with failure (25.0%) compared with 0 of 106 patients > 15 years (p = 0.002). Failure to engraft was not seen in HLA-identical (related or unrelated) donor transplants (0 of 103) whereas 3 of 15 HLA-mismatched donors failed (p = 0.003). Patient diagnosis, locus of HLA-mismatch, cytarabine in the preparative regimen, marrow cell dose and the relative reactive index (RRI) were not significant factors. Altered busulfan kinetics secondary to young age was probably not a major factor since 8 of 8 HLA-identical donor transplants engrafted in children. These findings demonstrate that patients receiving an unmanipulated marrow graft using busulfan-containing regimens were at a high risk for graft failure only if they were < or = 15 years of age and had an HLA-mismatched donor. More immunosuppressive preparative regimens, possibly including total body irradiation, should be considered to prevent potential graft failure in children.
识别导致移植失败的风险因素可能会降低血液系统恶性肿瘤患者接受骨髓移植（BMT）后的发病率和死亡率。我们评估了1987年至1992年在底特律医疗中心接受未处理的异基因骨髓移植的所有急性髓性白血病（AML）、慢性髓性白血病（CML）和骨髓增生异常综合征（MDS）患者的植入情况，采用白消安、环磷酰胺+/-阿糖胞苷预处理方案。118例患者中有3例发生移植失败（2.5%；95%置信区间（CI）0.7%，6.4%）。年龄≤15岁的患者移植失败率较高，12例失败患者中有3例（25.0%），而15岁以上的106例患者中无一例失败（p = 0.002）。在HLA配型相同（亲属或非亲属）供体移植中未见植入失败（103例中0例），而15例HLA配型不合的供体中有3例失败（p = 0.003）。患者诊断、HLA配型不合位点、预处理方案中的阿糖胞苷、骨髓细胞剂量和相对反应指数（RRI）均不是显著因素。由于8例HLA配型相同的儿童供体移植中有8例植入成功，因此年轻导致的白消安动力学改变可能不是主要因素。这些发现表明，接受含白消安方案的未处理骨髓移植的患者，仅在年龄≤15岁且有HLA配型不合的供体时，移植失败风险较高。应考虑采用更强的免疫抑制预处理方案，可能包括全身照射，以预防儿童潜在的移植失败。
