Klein Orly R, Buddenbaum Jessica, Tucker Noah, Chen Allen R, Gamper Christopher J, Loeb David, Zambidis Elias, Llosa Nicolas J, Huo Jeffrey S, Robey Nancy, Holuba Mary Jo, Kasamon Yvette L, McCurdy Shannon R, Ambinder Richard, Bolaños-Meade Javier, Luznik Leo, Fuchs Ephraim J, Jones Richard J, Cooke Kenneth R, Symons Heather J
Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Biol Blood Marrow Transplant. 2017 Feb;23(2):325-332. doi: 10.1016/j.bbmt.2016.11.016. Epub 2016 Nov 22.
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.
低强度预处理方案用于单倍体相合造血干细胞移植(BMT)对患有血液系统恶性肿瘤的成年患者安全且有效。我们报告了2003年至2015年期间接受非清髓性单倍体相合BMT并在移植后使用环磷酰胺治疗的高危血液系统恶性肿瘤儿童/年轻成年患者(n = 40)的数据。患者接受了氟达拉滨、环磷酰胺和全身照射的预处理方案。移植后免疫抑制包括环磷酰胺、霉酚酸酯和他克莫司。32例患者中有29例(91%)实现供体植入,中性粒细胞>500/µL的中位植入时间为16天(范围13至22天),血小板>20,000/µL且无需输血的中位植入时间为18天(范围12至62天)。100天时急性移植物抗宿主病(GVHD)II至IV级和III至IV级的累积发生率分别为33%和5%。根据美国国立卫生研究院的共识标准,慢性GVHD的累积发生率为23%,中度至重度慢性GVHD为7%。1年时移植相关死亡率(TRM)为13%。2年时复发的累积发生率为52%。中位随访20个月(范围3至148个月),1年精算总生存率和无事件生存率分别为56%和43%。因此,我们证明了采用该方案治疗的儿童/年轻成年患者具有优异的植入率、GVHD和TRM。这种方法对于患有高危血液系统恶性肿瘤的儿童和年轻成年患者是一种广泛可用、安全且可行的选择,包括那些既往有清髓性BMT病史和/或那些有合并症或器官功能障碍而不符合清髓性BMT条件的患者。