Kinetics of Increasing BCR-ABL Transcript Numbers in Chronic Myeloid Leukemia Patients Who Relapse After Bone Marrow Transplantation

• Published in: Blood Vol. 87; no. 10; pp. 4473 - 4478
• Main Authors: Lin, Feng, Rhee, Frits van, Goldman, John M., Cross, Nicholas C.P.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.05.1996; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers, Tumor - analysis; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Fusion Proteins, bcr-abl - biosynthesis; Fusion Proteins, bcr-abl - genetics; Humans; Kinetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Leukemia, Myeloid, Accelerated Phase - genetics; Leukemia, Myeloid, Accelerated Phase - pathology; Leukemia, Myeloid, Chronic-Phase - genetics; Medical sciences; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm, Residual; Polymerase Chain Reaction; Prognosis; Prospective Studies; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Treatment Outcome; Human; Relapse; Transfusion; RNA-directed DNA polymerase; Enzyme; Transferases; Homograft; Exploration; Malignant hemopathy; Polymerase chain reaction; Myeloproliferative syndrome; Nucleotidyltransferases; Chronic; Messenger RNA; Treatment; C-Onc gene; Chronic myelocytic leukemia; Bone marrow; Graft; Kinetics; Molecular biology; Hybrid gene; Protooncogene
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.10.4473.bloodjournal87104473

We prospectively studied 98 chronic myeloid leukemia (CML) patients after bone marrow transplantation by competitive polymerase chain reaction to detect and quantify leukemia-specific BCR-ABL mRNA. Of 69 patients who had persistently undetectable, decreasing, or low BCR-ABL levels (< 50 transcripts/μg RNA) on sequential analysis, one (1%) subsequently relapsed. Of 29 patients who had increasing or persistently high BCR-ABL (>50 transcripts/μg RNA) on sequential analysis, 21 (72%) have relapsed (P < .00001). In 19 patients studied sequentially, a constant logarithmic increase in the number of BCR-ABL transcripts was found before relapse, indicating a constant BCR-ABL transcript doubling time. The doubling time for patients relapsing cyto-genetically or into chronic phase (median, 24.7 days) was significantly longer than that of patients relapsing into advanced phases (median, 14.7 days; P = .005). Eight patients were treated for relapse by donor leukocyte transfusions. The doubling time of responders was significantly longer than that of nonresponders (P = .017). We conclude that quantification of BCR-ABL transcripts after bone marrow transplantation (BMT) is valuable in predicting relapse: a more rapid BCR-ABL transcript doubling time before relapse might indicate a more aggressive disease.