Galimberti S, Marasca R, Caracciolo F, Fazzi R, Papineschi F, Benedetti E, Guerrini F, Morabito F, Oliva E, Di Renzo N, Federico M, Petrini M, Torelli G
Department of Oncology, Transplant and Advances in Medicine - Section of Hematology, University of Pisa, Italy.
Bone Marrow Transplant. 2002 Apr;29(7):581-7. doi: 10.1038/sj.bmt.1703422.
Seventy-two patients with non-Hodgkin's lymphoma were evaluated for the presence of molecular markers (IgH, bcl-1, bcl-2 rearrangement) on bone marrow, at diagnosis and after PBSCT, and on harvests in order to find a possible predictive role of minimal residual disease on treatment outcome. At diagnosis, 41 (59%) out of 69 available bone marrows showed molecular involvement. Fifty-six percent of leukaphereses were involved, mainly indolent lymphoma (P = 0.001) or advanced disease (P = 0.01). Ex vivo purging cleared only one stem collection out of 31 PCR-positive leukaphereses. Aggressive lymphomas showed both a longer overall survival (OS) (P = 0.03) and relapse-free survival RFS (P = 0.02) when transplanted with unpurged stem cells, whereas indolent NHL survival was not influenced by ex vivo purging. Twenty out of 26 samples taken during follow-up had bone marrow involvement at diagnosis. Of these, 15 cleared their bone marrow; both OS and RFS were significantly longer in the PCR-negative cases (P = 0.05 and P = 0.005). At 1 year after PBSCT, 75% of patients were PCR negative, with 50% molecular remissions; the relapse rate was 55% for patients still PCR positive vs 29% for those who were PCR negative. Thus, after high-dose chemotherapy, close molecular monitoring of MRD using qualitative PCR techniques seems to represent a reliable prognostic indicator.
对72例非霍奇金淋巴瘤患者在诊断时、自体骨髓移植后及采集物中评估骨髓上分子标志物（IgH、bcl-1、bcl-2重排）的存在情况，以寻找微小残留病对治疗结果可能的预测作用。诊断时，69份可用骨髓中有41份（59%）显示有分子受累。56%的白细胞采集物受累，主要是惰性淋巴瘤（P = 0.001）或晚期疾病（P = 0.01）。体外净化仅清除了31份PCR阳性白细胞采集物中的1份干细胞采集物。侵袭性淋巴瘤在移植未净化的干细胞时，总生存期（OS）（P = 0.03）和无复发生存期（RFS）（P = 0.02）均较长，而惰性非霍奇金淋巴瘤的生存不受体外净化的影响。随访期间采集的26份样本中有20份在诊断时有骨髓受累。其中，15份清除了骨髓；PCR阴性病例的OS和RFS均显著更长（P = 0.05和P = 0.005）。自体骨髓移植后1年，75%的患者PCR阴性，分子缓解率为50%；仍为PCR阳性的患者复发率为55%，而PCR阴性的患者为29%。因此，在大剂量化疗后，使用定性PCR技术对微小残留病进行密切分子监测似乎是一个可靠的预后指标。
