Chao M M, Kuehl J S, Strauss G, Hanenberg H, Schindler D, Neitzel H, Niemeyer C, Baumann I, von Bernuth H, Rascon J, Nagy M, Zimmermann M, Kratz C P, Ebell W
Department of Pediatric Hematology Oncology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany,
Ann Hematol. 2015 Aug;94(8):1311-8. doi: 10.1007/s00277-015-2370-7. Epub 2015 Apr 12.
Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.
范可尼贫血（FA）是一种基因组不稳定综合征，与骨髓衰竭、骨髓增生异常综合征（MDS）和/或急性髓系白血病（AML）相关，需要进行造血干细胞移植（HSCT）以恢复正常造血功能。尽管基于氟达拉滨的低强度预处理方案（不进行放疗）在 HLA 匹配的同胞供体的 FA HSCT 中能取得优异的效果，但对于使用替代供体的 FA 患者，其治疗效果虽在改善，但仍不太理想。我们介绍了 17 例 FA 患者的治疗经验，这些患者在柏林夏里特大学医学中心采用了基于氟达拉滨的非放疗预处理方案，完成了不匹配的相关或无关供体 HSCT。所有患者均实现了造血干细胞植入；然而，有 1 例患者在多种病毒感染的情况下出现嵌合体不稳定，需要进行干细胞强化以恢复完全供体嵌合体状态。47%的患者发生了 I 级急性移植物抗宿主病（aGVHD）。未发生任何严重程度的 II-IV 级 aGVHD 或慢性移植物抗宿主病。在中位随访 30 个月时，88%的患者存活且造血功能正常。2 例患者在移植后 4 个月死于感染。这些结果表明，对于 FA 患者，仅使用化疗进行预处理的不匹配和无关供体 HSCT 的短期疗效可能非常好。然而，病毒再激活是一种主要的治疗相关并发症。
