title: Estimations of BCR-ABL/ABL transcripts by quantitative PCR in chronic myeloid leukaemia after allogeneic bone marrow transplantation and donor lymphocyte infusion.
abstract: 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.
authors.affiliation: Division of Genetics, Instituto Nacional de Câncer, Praça da Cruz Vermelha, 23, 20230-130, Rio de Janeiro, Brazil. iotazu@ufrj.br
authors.forename: Ivone B
authors.initials: IB
authors.lastname: Otazú
authors.forename: Rita de Cassia B
authors.initials: Rde C
authors.lastname: Tavares
authors.forename: Rocío
authors.initials: R
authors.lastname: Hassan
authors.forename: Ilana
authors.initials: I
authors.lastname: Zalcberg
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tabak
authors.forename: Héctor N
authors.initials: HN
authors.lastname: Seuánez
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl