Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors
Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors
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DOI：
10.1182/blood-2004-03-0804
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发表时间：
2004-09-01
期刊：
影响因子：
20.3
通讯作者：
Storb, R
中科院分区：
文献类型：
--
作者：
Diaconescu, R;Flowers, CR;Storb, R
异基因造血细胞移植（HCT）的非清髓性方案已开发用于不适合清髓性预处理的患者。我们使用美国国家癌症研究所（NCI）的通用毒性标准，比较了73例非清髓性和73例清髓性HILA匹配的相关供者HCT接受者的方案相关毒性（RRT）和非复发死亡率（NRM）。非清髓方案为2戈伊全身照射（TBI），单独（n = 40）或联合氟达拉滨，30 mg/m2/d，共3天（n = 33）。移植后免疫抑制剂包括吗替麦考酚酯和环孢素。清髓方案主要包括环磷酰胺+TBI或白消安+环磷酰胺，其次是移植后甲氨蝶呤和环孢菌素。非清髓性患者比清髓性患者风险更高，因为年龄更大，从诊断到HCT的时间更长，更频繁的高剂量HCT，以及更高的移植前Charlson合并症评分。然而，他们在7个器官/系统中发生的毒性严重程度显著较低：血液学、胃肠道、肝脏、出血、感染、代谢和肺。这转化为第100天（3% vs 23%，P = 10（-4））和1年（116% vs 30%，P = 0.04）时的NRM更少。在多变量分析中，预测RRT和NRM减少的最强因素是非清髓性预处理，而高移植前合并症评分预测较高的NRM。总之，非清髓性方案的RRT和NRM较低，可以考虑用于比较研究，包括Charlson合并症评分更有利的年轻患者。(C)2004年，美国血液学会。
Nonmyeloablative regimens for allogeneic hematopoietic cell transplantation (HCT) have been developed for patients ineligible for myeloablative conditioning. We compared regimen-related toxicities (RRTs) and nonrelapse mortality (NRM) in 73 nonmyeloablative and 73 myeloablative recipients of HILA-matched related donor HCT, using the National Cancer Institute (NCI) Common Toxicity Criteria. Nonmyeloablative regimens were 2 Gy total body irradiation (TBI), either alone (n = 40) or combined with fludarabine, 30 mg/m(2)/d for 3 days (n = 33). Posttransplantation immunosuppression included mycophenolate mofetil and cyclosporine. Myeloablative regimens consisted mostly of cyclophosphamide + TBI or busulfan + cyclophosphamide, followed by posttransplantation methotrexate and cyclosporine. Nonmyeloablative patients were at higher risk than ablative patients because of greater age, longer time from diagnosis to HCT, more frequent preceding high-dose HCT, and higher pretransplantation Charlson comorbidity scores. Nevertheless, they experienced significantly less severe toxicities in 7 organs/ systems: hematologic, gastrointestinal, hepatic, hemorrhage, infection, metabolic, and pulmonary. This translated into less NRM at day 100 (3% versus 23%, P = 10(-4)) and 1 year (116% versus 30%, P = .04). In multivariate analysis, the strongest factor predicting lessened RRT and NRM was nonmyeloablative conditioning, whereas high pretransplantation comorbidity scores predicted higher NRM. In conclusion, nonmyeloablative regimens had lower RRT and NRM and could be considered for comparative studies, including younger patients with more favorable Charlson comorbidity scores. (C) 2004 by The American Society of Hematology.