Katsanis Emmanuel, Sapp Lauren N, Reid Susie Cienfuegos, Reddivalla Naresh, Stea Baldassarre
Department of Pediatrics, University of Arizona, Tucson, AZ, United States.
Department of Immunobiology, University of Arizona, Tucson, AZ, United States.
Front Pediatr. 2020 Jun 9;8:282. doi: 10.3389/fped.2020.00282. eCollection 2020.
Twenty-one pediatric and young adult patients (1.1-24.7 years) with hematologic malignancies underwent myeloablative T-cell replete haploidentical bone marrow transplant (haplo-BMT) between October 2015 to December 2019. Fifty-seven percent of the patients were ethnic or racial minorities. Thirteen patients had B-cell precursor acute lymphoblastic leukemia (B-ALL) with 10 receiving 1,200 cGy fractionated total body irradiation with fludarabine while the remaining 11 patients had targeted dose-busulfan, fludarabine, melphalan conditioning. Graft-vs.-host disease (GvHD) prophylaxis consisted of post-transplant cyclophosphamide (15 patients) or cyclophosphamide and bendamustine (six patients), with all patients receiving tacrolimus and mycophenolate mofetil. Twelve patients were in first or second remission at time of transplant with five in >2nd remission and four with measurable disease. Three patients had failed prior transplants and three CAR-T cell therapies. Only one patient developed primary graft failure but engrafted promptly after a second conditioned T-replete peripheral blood stem cell transplant from the same donor. An absolute neutrophil count of 0.5 × 10/L was achieved at a median time of 16 days post-BMT while platelet engraftment occurred at a median of 30 days. The cumulative incidence of grades III to IV acute GvHD and chronic GvHD was 15.2 and 18.1%, respectively. With a median follow-up of 25.1 months the relapse rate is 17.6% with an overall survival of 84.0% and a progression-free survival of 74.3%. The chronic graft-vs.-host-free relapse-free survival (CRFS) is 58.5% while acute and chronic graft-vs.-host-free relapse-free survival (GRFS) is 50.1%. Myeloablative conditioned T-replete haploidentical BMT is a viable alternative to matched unrelated transplantation for children and young adults with high-risk hematologic malignancies.
2015年10月至2019年12月期间，21例血液系统恶性肿瘤的儿科及青年患者（年龄1.1 - 24.7岁）接受了清髓性T细胞充足的单倍体相合骨髓移植（单倍体BMT）。57%的患者为少数族裔或种族。13例患者患有B细胞前体急性淋巴细胞白血病（B - ALL），其中10例接受了1200 cGy分次全身照射联合氟达拉滨，其余11例患者接受了靶向剂量的白消安、氟达拉滨、美法仑预处理。移植物抗宿主病（GvHD）预防方案包括移植后环磷酰胺（15例患者）或环磷酰胺与苯达莫司汀（6例患者），所有患者均接受他克莫司和霉酚酸酯。12例患者在移植时处于首次或第二次缓解期，5例处于第二次缓解期以上，4例有可测量的疾病。3例患者既往移植失败，3例接受过CAR - T细胞治疗。仅1例患者发生原发性移植失败，但在接受来自同一供体的第二次预处理的T细胞充足的外周血干细胞移植后迅速植入。BMT后中位16天时绝对中性粒细胞计数达到0.5×10⁹/L，血小板植入中位时间为30天。III至IV级急性GvHD和慢性GvHD的累积发生率分别为15.2%和18.1%。中位随访25.1个月时，复发率为17.6%，总生存率为84.0%，无进展生存率为74.3%。慢性无移植物抗宿主病无复发生存率（CRFS）为58.5%，急性和慢性无移植物抗宿主病无复发生存率（GRFS）为50.1%。清髓性预处理的T细胞充足的单倍体相合BMT是高危血液系统恶性肿瘤儿童和青年患者匹配无关供体移植的可行替代方案。
