Kennedy Vanessa E, Savani Bipin N, Greer John P, Kassim Adetola A, Engelhardt Brian G, Goodman Stacey A, Sengsayadeth Salyka, Chinratanalab Wichai, Jagasia Madan
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplant, Department of Medicine, Veterans Affairs Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
Biol Blood Marrow Transplant. 2016 Oct;22(10):1801-1807. doi: 10.1016/j.bbmt.2016.06.029. Epub 2016 Jul 1.
Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab-containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined. We retrospectively analyzed 94 patients who received an allogeneic transplant for a B cell lymphoid malignancy. Of these, 33 received RIC with fludarabine, cyclophosphamide, and rituximab (FCR) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin inhibitor and mini-methotrexate, and 61 received RIC with fludarabine and busulfan (FluBu) and GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The 2-year overall survival was superior in patients who received FCR versus FluBu (72.7% versus 54.1%, P = .031), and in multivariable analysis adjusted for Disease Risk Index and donor type, only the conditioning regimen (FluBu versus FCR: HR, 2.06; 95% CI, 1.04 to 4.08; P = .037) and Disease Risk Index (low versus intermediate/high: HR, .38; 95% CI, .17 to .86; P = .02) were independent predictors of overall survival. The 2-year cumulative incidence of chronic GVHD was lower in patients who received FCR versus FluBu (24.2% versus 51.7%, P = .01). There was no difference in rate of relapse/progression or acute GVHD. Our results demonstrate that the use of RIC with FCR and GVHD prophylaxis with a calcineurin inhibitor and mini-methotrexate is associated with decreased chronic GVHD and improved overall survival.
减低强度预处理（RIC）已越来越多地用于异基因造血细胞移植，以在维持移植物抗肿瘤效应的同时，将移植相关死亡率降至最低。在B细胞淋巴系统恶性肿瘤中，含抗CD20抗体利妥昔单抗的减低强度方案与良好的生存率相关；然而，在B细胞淋巴系统恶性肿瘤的异基因造血细胞移植中，含利妥昔单抗方案与不含利妥昔单抗方案的长期结局仍有待确定。我们回顾性分析了94例接受异基因移植治疗B细胞淋巴系统恶性肿瘤的患者。其中，33例接受了含氟达拉滨、环磷酰胺和利妥昔单抗（FCR）的RIC，并使用钙调神经磷酸酶抑制剂和小剂量甲氨蝶呤预防移植物抗宿主病（GVHD），61例接受了含氟达拉滨和白消安（FluBu）的RIC，并使用钙调神经磷酸酶抑制剂和霉酚酸酯预防GVHD。接受FCR的患者2年总生存率优于接受FluBu的患者（72.7%对54.1%，P = 0.031），在针对疾病风险指数和供体类型进行校正的多变量分析中，只有预处理方案（FluBu对FCR：HR，2.06；95%CI，1.04至4.08；P = 0.037）和疾病风险指数（低对中/高：HR，0.38；95%CI，0.17至0.86；P = 0.02）是总生存的独立预测因素。接受FCR的患者慢性GVHD的2年累积发生率低于接受FluBu的患者（24.2%对51.7%，P = 0.01）。复发/进展率或急性GVHD无差异。我们的结果表明，使用含FCR的RIC并使用钙调神经磷酸酶抑制剂和小剂量甲氨蝶呤预防GVHD与慢性GVHD减少和总生存改善相关。
