Woolfrey A E, Gooley T A, Sievers E L, Milner L A, Andrews R G, Walters M, Hoffmeister P, Hansen J A, Anasetti C, Bryant E, Appelbaum F R, Sanders J E
Fred Hutchinson Cancer Research Center and University of Washington Departments of Pediatrics and Medicine, Seattle, WA, USA.
Blood. 1998 Nov 15;92(10):3546-56.
We analyzed results of 40 infants less than 2 years of age who received bone marrow transplants (BMT) between May 1974 and January 1995 for treatment of acute myelogenous leukemia (AML; N = 34) or myelodysplastic syndrome (MDS; N = 6) to determine outcome and survival performance. Among the AML patients, 13 were in first remission, 9 were in untreated first relapse or second remission, and 12 were in refractory relapse. Patients were conditioned with cyclophosphamide in combination with either total body irradiation (TBI; N = 29) or busulfan (N = 11). Source of stem cells included 6 autologous donors, 15 HLA genotypically identical siblings, 14 haploidentical family members, and 5 unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was methotrexate (MTX) for 17, MTX plus cyclosporine (CSP) for 14, or CSP plus prednisone for 3. Incidence of severe (grade 3-4) regimen-related toxicity was 10% and transplant-related mortality was 10%. Acute GVHD (grades II-III) occurred in 39% of allogeneic patients, and chronic GVHD developed in 40%. Relapse, the most significant problem for patients in this study, occurred in 1 MDS patient and 23 AML patients and was the cause of death for 19 patients. The 2-year probabilities of relapse are 46%, 67%, and 92%, respectively, for patients transplanted in first remission, untreated first relapse or second remission, and relapse. One MDS and 8 AML patients received second marrow transplants for treatment of relapse, and 5 of these survive disease-free for more than 1.5 years. All 6 MDS patients and 11 of 34 AML patients survive more than 1.5 years later. The 5-year probabilities of survival and disease-free survival are 54% and 38% for patients transplanted in first remission and 33% and 22% for untreated first relapse or second remission. None of the patients transplanted with refractory relapse survive disease-free. Outcome was significantly associated with phase of disease at transplantation and pretransplant diagnosis of extramedullary disease. Long-term sequelae included growth failure and hormonal deficiencies. Survival performance was a median of 100% (80% to 100%) and neurologic development for all survivors was appropriate for age. This study indicates that infants with AML have similar outcome after BMT compared with older children and that BMT should be performed in first remission whenever possible. In addition, allogeneic BMT provides effective therapy for the majority of infants with MDS.
我们分析了1974年5月至1995年1月期间接受骨髓移植（BMT）的40名2岁以下婴儿的结果，这些婴儿因治疗急性髓性白血病（AML；n = 34）或骨髓增生异常综合征（MDS；n = 6）而接受移植，以确定结局和生存情况。在AML患者中，13例处于首次缓解期，9例处于未经治疗的首次复发或第二次缓解期，12例处于难治性复发期。患者接受环磷酰胺联合全身照射（TBI；n = 29）或白消安（n = 11）进行预处理。干细胞来源包括6名自体供者、15名HLA基因型相同的同胞、14名单倍体家庭成员和5名无关供者。移植物抗宿主病（GVHD）预防方案为17例使用甲氨蝶呤（MTX），14例使用MTX加环孢素（CSP），3例使用CSP加泼尼松。严重（3 - 4级）方案相关毒性的发生率为10%，移植相关死亡率为10%。急性GVHD（II - III级）发生在39%的异基因患者中，慢性GVHD发生在40%的患者中。复发是本研究中患者最主要的问题，发生在1例MDS患者和23例AML患者中，是19例患者死亡的原因。对于在首次缓解期、未经治疗的首次复发或第二次缓解期以及复发期接受移植的患者，2年复发概率分别为46%、67%和92%。1例MDS患者和8例AML患者因复发接受了第二次骨髓移植，其中5例无病存活超过1.5年。所有6例MDS患者和34例AML患者中的11例在1.5年后存活。对于在首次缓解期接受移植的患者，5年生存概率和无病生存概率分别为54%和38%；对于未经治疗的首次复发或第二次缓解期的患者，分别为33%和22%。难治性复发患者接受移植后无一例无病存活。结局与移植时疾病阶段和移植前髓外疾病诊断显著相关。长期后遗症包括生长发育迟缓以及激素缺乏。所有幸存者的生存情况中位数为100%（80%至100%），神经发育与年龄相符。本研究表明，AML婴儿接受BMT后的结局与大龄儿童相似，并且只要有可能应在首次缓解期进行BMT。此外，异基因BMT为大多数MDS婴儿提供了有效的治疗方法。
