Kothari Alok, Ngwube Alexander, Hayashi Robert, Murray Lisa, Davis Jeffrey, Haut Paul, Loechelt Brett J, Shenoy Shalini
Department of Pediatrics, Washington University, St. Louis, Missouri.
Department of Pediatrics, Children's and Women's Health Centre of BC, Vancouver, BC, Canada.
Biol Blood Marrow Transplant. 2015 Jul;21(7):1321-5. doi: 10.1016/j.bbmt.2015.03.019. Epub 2015 Mar 31.
Genetically derived hematologic cytopenias are a rare heterogeneous group of disorders. Allogeneic hematopoietic cell transplantation (HCT) is curative but offset by organ toxicities from the preparative regimen, graft rejection, graft-versus-host disease (GVHD), or mortality. Because of these possibilities, consideration of HCT can be delayed, especially in the unrelated donor setting. We report a prospective multicenter trial of reduced-intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan and HCT in 11 children with marrow failure of genetic origin (excluding Fanconi anemia) using the best available donor source (82% from unrelated donors). The median age at transplantation was 23 months (range, 2 months to 14 years). The median times to neutrophil (>500 × 10(6)/L) and platelet (>50 × 10(9)/L) engraftment were 13 (range, 12 to 24) and 30 (range, 7 to 55) days, respectively. The day +100 probability of grade II to IV acute GVHD and the 1-year probability of limited and extensive GVHD were 9% and 27%, respectively. The probability of 5-year overall and event-free survival was 82%; 9 patients were alive with normal blood counts at last follow-up and all were successfully off systemic immunosuppression. In patients with genetically derived severe hematologic cytopenias, allogeneic HCT with this RIC regimen was successful in achieving a cure. This experience supports consideration of HCT early in such patients even in the absence of suitable related donors.
遗传性血液系统血细胞减少症是一组罕见的异质性疾病。异基因造血细胞移植（HCT）具有治愈性，但会被预处理方案的器官毒性、移植物排斥、移植物抗宿主病（GVHD）或死亡率所抵消。由于存在这些可能性，HCT的考虑可能会延迟，尤其是在无关供体的情况下。我们报告了一项前瞻性多中心试验，对11名遗传性骨髓衰竭（不包括范可尼贫血）儿童使用最佳可用供体来源（82%来自无关供体）进行阿仑单抗、氟达拉滨和马法兰的减低强度预处理（RIC）及HCT。移植时的中位年龄为23个月（范围为2个月至14岁）。中性粒细胞（>500×10⁶/L）和血小板（>50×10⁹/L）植入的中位时间分别为13天（范围为12至24天）和30天（范围为7至55天）。II至IV级急性GVHD的+100天概率和局限性及广泛性GVHD的1年概率分别为9%和27%。5年总生存率和无事件生存率的概率为82%；9名患者在最后一次随访时血细胞计数正常且存活，所有患者均成功停用全身免疫抑制。在患有遗传性严重血液系统血细胞减少症的患者中，采用这种RIC方案的异基因HCT成功实现了治愈。这一经验支持即使在没有合适的相关供体的情况下，也应在此类患者早期考虑HCT。
