Estimations of BCR-ABL/ABL transcripts by quantitative PCR in chronic myeloid leukaemia after allogeneic bone marrow transplantation and donor lymphocyte infusion.
Serial assays of qualitative (multiplex and nested) and quantitative PCR were carried out for detecting and estimating the level of BCR-ABL transcripts in 39 CML patients following bone marrow transplantation. Seven of these patients, who received donor lymphocyte infusions (DLIs) following to relapse, were also monitored. Quantitative estimates of BCR-ABL transcripts were obtained by co-amplification with a competitor sequence. Estimates of ABL transcripts were used, an internal control and the ratio BCR-ABL/ABL was thus estimated for evaluating the kinetics of residual clones. Twenty four patients were followed shortly after BMT; two of these patients were in cytogenetic relapse coexisting with very high BCR-ABL levels while other 22 were in clinical, haematologic and cytogenetic remission 2-42 months after BMT. In this latter group, seven patients showed a favourable clinical-haematological progression in association with molecular remission while in 14 patients quantitative PCR assays indicated molecular relapse that was not associated with an early cytogenetic-haematologic relapse. BCR-ABL/ABL levels could not be correlated with presence of GVHD in 24 patients after BMT. In all seven patients treated with DLI, high levels of transcripts were detected at least 4 months before the appearance of clinical haematological relapse. Following DLI, five of these patients showed decreasing transcript levels from 2 to 5 logs between 4 and 12 months. In eight other patients studied long after BMT, five showed molecular relapse up to 117 months post-BMT and only one showed cytogenetic relapse. Our findings indicated that quantitative estimates of BCR-ABL transcripts were valuable for monitoring minimal residual disease in each patient.
Otazú
Ivone B
IB
Division of Genetics, Instituto Nacional de Câncer, Praça da Cruz Vermelha, 23, 20230-130, Rio de Janeiro, Brazil. iotazu@ufrj.br
Tavares
Rita de Cassia B
Rde C
Hassan
Rocío
R
Zalcberg
Ilana
I
Tabak
Daniel G
DG
Seuánez
Héctor N
HN
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D016026:Bone Marrow Transplantation; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics*; D006082:Graft Enhancement, Immunologic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis* / Q000096:biosynthesis; D012008:Recurrence; D012074:Remission Induction; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl