Blood and Marrow Transplant Service, Westmead Hospital, Sydney, New South Wales, Australia.
Intern Med J. 2013 Feb;43(2):191-6. doi: 10.1111/j.1445-5994.2012.02843.x.
To demonstrate safety and efficacy of haploidentical bone marrow transplantation with non-myeloablative conditioning and high-dose post-transplant cyclophosphamide in adult patients with leukaemia or lymphoma.
Human leukocyte antigen haploidentical bone marrow transplantation is a treatment option in patients with haematological malignancies who have no available human leukocyte antigen-matched donor but is limited by conditioning regimen toxicity, graft failure, relapse and graft-versus-host disease (GvHD).
Twelve patients, median age of 51 years, underwent transplantation with T cell replete bone marrow from a haplotype-matched relative. The conditioning regimen consisted of cyclophosphamide, fludarabine and low-dose total body irradiation. Post-transplant immunosuppression consisted of a single dose of cyclophosphamide 50 mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes reported are overall survival, engraftment and chimerism, toxicity, and clinical outcome.
All patients had neutrophil recovery (median 14.5 days), and 11 of 12 had platelet engraftment (median 17 days). Two patients had autologous reconstitution. Seven of nine assessable patients had complete donor chimerism. Four patients had grades II-III GvHD, and none had grade IV GvHD. Four patients developed limited stage chronic GvHD. Five patients with acute myeloid leukaemia relapsed. Two patients died of nonrelapse causes, both from other malignancies, and five patients remain alive and relapse free. Median overall survival was 324 days (range 88-1163).
This regimen is feasible and well tolerated in older patients with high-risk leukaemia or lymphoma, with minimal short-term toxicity and low rates of GvHD. The proportion of disease-free survivors indicates a graft-versus-malignancy effect is present in survivors.
证明非清髓性预处理和高剂量移植后环磷酰胺在成人白血病或淋巴瘤患者中进行单倍体相合骨髓移植的安全性和有效性。
人类白细胞抗原单倍体相合骨髓移植是血液系统恶性肿瘤患者的一种治疗选择，这些患者没有可用的人类白细胞抗原匹配供体，但受到预处理方案毒性、移植物失败、复发和移植物抗宿主病（GvHD）的限制。
12 名患者，中位年龄 51 岁，接受来自单倍型匹配亲属的 T 细胞丰富骨髓移植。预处理方案包括环磷酰胺、氟达拉滨和低剂量全身照射。移植后免疫抑制方案包括在第 3 天给予单次 50mg/kg 的环磷酰胺，随后口服他克莫司和吗替麦考酚酯。报告的结果是总生存率、植入和嵌合状态、毒性和临床结果。
所有患者均有中性粒细胞恢复（中位时间 14.5 天），12 例中有 11 例血小板植入（中位时间 17 天）。2 例患者有自体重建。9 例可评估患者中有 7 例完全供者嵌合。4 例患者发生 2-3 级 GvHD，无 4 级 GvHD。4 例患者发生局限性慢性 GvHD。5 例急性髓系白血病复发。2 例患者死于非复发原因，均为其他恶性肿瘤，5 例患者存活且无复发。中位总生存期为 324 天（范围 88-1163 天）。
该方案在年龄较大、患有高危白血病或淋巴瘤的患者中是可行且耐受良好的，具有最小的短期毒性和低 GvHD 发生率。无病生存者的比例表明，在幸存者中存在移植物抗恶性肿瘤效应。
