Charité Universitätsmedizin Berlin, Department of Pediatric Oncology/Hematology, Augustenburger Platz 1, 13353 Berlin, Germany.
J Clin Oncol. 2013 Jul 20;31(21):2736-42. doi: 10.1200/JCO.2012.48.5680. Epub 2013 Jun 17.
In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).
In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.
The probability of event-free survival for patients with MRD ≥ 10(-3) was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10(-3) could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) -ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).
Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.
在急性淋巴细胞白血病（ALL）复发风险中等的儿童中，确定需要强化治疗的患者至关重要。我们假设，通过异基因造血干细胞移植（HSCT）可以改善微小残留病（MRD）缓解不佳的患者的预后。
在柏林-法兰克福-明斯特组（ALL-REZ BFM）2002 年急性淋巴细胞白血病复发研究中，诱导治疗结束时 MRD 水平≥10(-3)（n=99）的患者被分配接受 HSCT，而 MRD 水平<10(-3)（n=109）的患者继续接受化疗。通过实时聚合酶链反应定量检测克隆特异性 T 细胞受体/免疫球蛋白基因重排。
在 ALL-REZ BFM 2002 中，MRD≥10(-3)的患者无事件生存概率为 64%±5%，而前一研究 ALL-REZ BFM P95/96 中的概率为 18%±7%（P<0.001）。这主要是通过将 8 年时的累积复发率（CIR）从 59%±9%降至 27%±5%（P<0.001）来实现的。在晚期联合或孤立骨髓 B 细胞前体（BCP）-ALL 复发的患者中（CIR，20%±5%），MRD<10(-3)的患者预后良好可以得到证实，而早期联合 BCP-ALL 复发的患者预后不良（CIR，63%±13%；P<0.001）。
异基因 HSCT 显著改善了中危复发 ALL 患者和 MRD 反应不佳患者的预后。结果，该组患者的预后接近 MRD 反应良好的患者。即使在 MRD 反应良好的情况下，早期联合复发的患者仍需要强化治疗，这表明复发时间的预后影响。
