Zikos P, Van Lint M T, Lamparelli T, Gualandi F, Occhini D, Bregante S, Berisso G, Mordini N, Incagliato M, Fugazza G, Sessarego M, Bacigalupo A
Divisione Ematologia Il, Ospedale San Martino, Genoa, Italy.
Haematologica. 1998 Oct;83(10):896-903.
The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoietic stem cell transplantation (HSCT) is one therapeutic option. The goal of this study is to describe long term results of HSCT in high risk ALL patients.
Between 1978 and 1996, 170 patient with ALL and a median age of 22 years (1-49), underwent an allogeneic HSCT from HLA-identical siblings (n = 149), family mismatched donors (n = 18) or unrelated HLA matched donors (n = 3); 92% of patients had at least one adverse prognostic factor for high risk ALL at diagnosis; one third (33%) were in first remission (CR1) and the majority (85%) received an unmanipulated HSCT with cyclosporin-methotrexate prophylaxis of graft-versus-host disease (GvHD).
After a median follow-up of over 6 years, 59 patients are alive and 111 patients have died of leukemia (46%) or transplant related complications (54%). The actuarial 10 year survival is 53%, 38% and 20%, for patients in CR1, CR2 or advanced phase, respectively. The actuarial survival of patients with (n = 24) of without (n = 46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45% and 48% (p = 0.5). The year of transplant had a significant impact in multivariate analysis on transplant related mortality (TRM) (p = 0.0009) but not on relapse (p = 0.3). Chronic GvHD was the most important favorable prognostic factor for survival (p = 0.0014) and relapse (p = 0.0019).
This study confirms that long term survival can be achieved with HSCT in ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been significantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chronic GvHD. Immune intervention post-HSCT may be considered to address this problem.
急性淋巴细胞白血病（ALL）患者缓解后的最佳治疗方案存在争议，造血干细胞移植（HSCT）是一种治疗选择。本研究的目的是描述高危ALL患者HSCT的长期结果。
1978年至1996年间，170例ALL患者，中位年龄22岁（1 - 49岁），接受了来自 HLA 相同同胞（n = 149）、家族配型不合供者（n = 18）或无关 HLA 配型相合供者（n = 3）的异基因HSCT；92%的患者在诊断时至少有一项高危ALL的不良预后因素；三分之一（33%）处于首次缓解期（CR1），大多数（85%）接受了未处理的HSCT，并采用环孢素 - 甲氨蝶呤预防移植物抗宿主病（GvHD）。
中位随访超过6年后，59例患者存活，111例患者死于白血病（46%）或移植相关并发症（54%）。CR1、CR2或晚期患者的10年精算生存率分别为53%、38%和20%。在CR1/CR2期进行移植的有（n = 24）和无（n = 46）细胞遗传学异常患者的精算生存率分别为45%和48%（p = 0.5）。移植年份在多因素分析中对移植相关死亡率（TRM）有显著影响（p = 0.0009），但对复发无影响（p = 0.3）。慢性GvHD是生存（p = 0.0014）和复发（p = 0.0019）最重要的有利预后因素。
本研究证实，ALL患者即使是有细胞遗传学异常的患者，通过HSCT也可实现长期生存。近年来移植死亡率显著降低，而白血病复发率保持不变：后者受慢性GvHD发生情况的影响。HSCT后可考虑进行免疫干预以解决这一问题。
