Spinelli Orietta, Peruta Barbara, Tosi Manuela, Guerini Vittoria, Salvi Anna, Zanotti Maria Cristina, Oldani Elena, Grassi Anna, Intermesoli Tamara, Micò Caterina, Rossi Giuseppe, Fabris Pietro, Lambertenghi-Deliliers Giorgio, Angelucci Emanuele, Barbui Tiziano, Bassan Renato, Rambaldi Alessandro
Hematology and Bone Marrow Transplantation Units of Ospedali Riuniti Bergamo, Bergamo, Italy.
Haematologica. 2007 May;92(5):612-8. doi: 10.3324/haematol.10965.
The molecular analysis of minimal residual disease (MRD) may provide information on the risk of recurrence in patients with acute lymphoblastic leukemia (ALL). The aim of this study was to correlate the kinetics of MRD clearance after allogeneic transplantation with the clinical outcome of adults with ALL.
MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) using probes derived from fusion chimeric genes (BCR/ABL and MLL/AF4) (n=22) or rearrangements of the T-cell receptor or immunoglobulin genes (n=21). Forty-three adult patients with ALL were studied to correlate the kinetics of MRD clearance before and after allogeneic hematopoietic stem cell transplantation.
At 36 months, the overall survival of patients who underwent transplantation in hematologic remission (n= 37) was 80% for those who were PCR-negative before transplantation (n= 12) compared to 49% for PCR-positive patients (n= 25)(p=0.17). For the same patients the cumulative incidence of relapse was 0% and 46%, respectively (p=0.027). Moreover, the relapse rate of patients who were PCR-negative at day +100 after transplantation was remarkably low (7%) compared to that among patients who were PCR-positive (80%, p=0.0006).
The kinetics of MRD clearance may help to identify patients at high risk of leukemia relapse after allogeneic stem cell transplantation. Patients not achieving an early molecular remission after transplantation require prompt and appropriate pre-emptive treatments such as infusions of donor lymphocytes or new experimental drugs.
微小残留病（MRD）的分子分析可为急性淋巴细胞白血病（ALL）患者的复发风险提供信息。本研究旨在将异基因移植后MRD清除的动力学与成人ALL患者的临床结局相关联。
采用实时定量聚合酶链反应（RQ-PCR），使用源自融合嵌合基因（BCR/ABL和MLL/AF4）（n = 22）或T细胞受体或免疫球蛋白基因重排（n = 21）的探针评估MRD。对43例成人ALL患者进行研究，以关联异基因造血干细胞移植前后MRD清除的动力学。
在36个月时，血液学缓解期接受移植的患者（n = 37）中，移植前PCR阴性者（n = 12）的总生存率为80%，而PCR阳性患者（n = 25）为49%（p = 0.17）。对于相同的患者，复发的累积发生率分别为0%和46%（p = 0.027）。此外，移植后第100天PCR阴性患者的复发率显著低于PCR阳性患者（7%对80%，p = 0.0006）。
MRD清除的动力学可能有助于识别异基因干细胞移植后白血病复发风险高的患者。移植后未实现早期分子缓解的患者需要迅速且适当的抢先治疗，如输注供体淋巴细胞或新的实验性药物。
