Rubin C M, Mick R, Johnson F L
Department of Pediatrics, Pritzker School of Medicine, University of Chicago, IL, USA.
Bone Marrow Transplant. 1996 Sep;18(3):533-40.
We report 18 patients with Down's syndrome who underwent bone marrow transplantation, and review nine previously published patients. The indications for transplant in the combined group of 27 patients were acute lymphoblastic leukaemia in 14 cases (52%), acute myeloid leukaemia in 11 cases (41%) and aplastic anemia in two cases (7%). Transplants were autologous in five cases (19%) and allogeneic in 22 cases (81%); of the 22 allogeneic transplants, 16 donors were HLA-matched siblings. In all patients the conditioning regimen included total body irradiation of 7.5 Gy or more, and/or contained cyclophosphamide of 120 mg/kg or more. Seven patients (26%) had fatal pulmonary disease including pneumonitis and pulmonary hemorrhage. Five patients (19%) had significant airway problems including three with severe mucositis who required intubation for airway protection, one with severe mucositis with partial airway obstruction that required observation in the intensive care unit but did not require intubation, and one with Candida albicans laryngitis with development of a glottic web. Nineteen patients (70%) survived beyond 100 days post-transplant. There was no clear association between 100-day survival and the use of any particular agent or regimen used for conditioning or graft-versus-host disease prophylaxis, and the majority of patients tolerated high-dose cyclophosphamide, high-dose cytosine arabinoside, high-dose busulfan, total body irradiation, cyclosporin A, and methotrexate. There appeared to be more early deaths in patients who received the combination of cyclophosphamide and total body irradiation, compared with those receiving the combination of busulfan and cyclophosphamide or those receiving the combination of cytosine arabinoside and total body irradiation. Also, the use of methotrexate was associated with a greater number of early deaths, compared with cyclosporin A. At 3 years, life table estimates of freedom from relapse, relapse-free survival and survival were 75%, 44% and 48%, respectively. The estimated cumulative risk of death due to a non-leukaemic cause at 3 years was 39%. The data show that Down syndrome patients can tolerate the commonly used transplant conditioning regimens with acceptable toxicity; however, there is a strong suggestion in the data that the rates of life-threatening and fatal toxicity are higher than would be expected to occur in patients without Down's syndrome. Patients with Down's syndrome may have a predisposition to fatal pulmonary complications and reversible airway problems during the immediate post-transplant period.
我们报告了18例接受骨髓移植的唐氏综合征患者，并回顾了9例先前已发表的患者。在这27例患者的联合组中，移植的适应证为急性淋巴细胞白血病14例（52%）、急性髓细胞白血病11例（41%）、再生障碍性贫血2例（7%）。移植中有5例（19%）为自体移植，22例（81%）为异体移植；在22例异体移植中，16例供者为HLA匹配的同胞。所有患者的预处理方案均包括7.5 Gy或更高剂量的全身照射，和/或包含120 mg/kg或更高剂量的环磷酰胺。7例患者（26%）发生致命性肺部疾病，包括肺炎和肺出血。5例患者（19%）有明显的气道问题，其中3例有严重黏膜炎，需要插管以保护气道；1例有严重黏膜炎伴部分气道梗阻，需要在重症监护病房观察但无需插管；1例有白色念珠菌性喉炎并形成声门蹼。19例患者（70%）在移植后存活超过100天。100天生存率与用于预处理或预防移植物抗宿主病的任何特定药物或方案的使用之间没有明确关联，并且大多数患者耐受高剂量环磷酰胺、高剂量阿糖胞苷、高剂量白消安、全身照射、环孢素A和甲氨蝶呤。与接受白消安和环磷酰胺联合或接受阿糖胞苷和全身照射联合的患者相比，接受环磷酰胺和全身照射联合的患者似乎有更多早期死亡。此外，与环孢素A相比，甲氨蝶呤的使用与更多早期死亡相关。在第3年，无复发生存率、无病生存率和总生存率的生命表估计分别为75%、44%和48%。3年时非白血病原因导致的累积死亡风险估计为39%。数据表明，唐氏综合征患者能够耐受常用的移植预处理方案，毒性可接受；然而，数据强烈提示，危及生命和致命毒性的发生率高于预期在非唐氏综合征患者中发生的情况。唐氏综合征患者在移植后即刻可能易发生致命性肺部并发症和可逆性气道问题。
