title: Polymerase chain reaction is highly predictive of relapse in patients following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukemia.
abstract: In chronic myeloid leukemia (CML) the polymerase chain reaction (PCR) can be used to detect minimal residual disease after bone marrow transplantation (BMT). Previous studies have shown that PCR positivity is common following BMT. However, the clinical significance of this finding for any given individual who is PCR positive remains unclear, as many of these patients remain long-term disease-free survivors after allogeneic BMT. In the present study, we used PCR to detect BCR-ABL mRNA in 144 blood or marrow samples from 36 patients who received a T cell-depleted BMT for CML in first chronic phase. Six patients had no evidence of PCR-detectable residual disease at any time following transplant. The other 30 patients had at least one positive PCR result post-BMT. Once PCR positivity was found, it was usually sustained, with only four patients having a subsequent PCR negative assay. No patient who had two consecutive PCR-positive assays had a return to PCR negativity. None of the six patients with exclusively PCR-negative assays have developed either cytogenetic or hematologic relapse at a median follow-up of 42 months. Of the 30 patients with at least one PCR-positive assay post-BMT, 28 were PCR positive at last follow-up, and 22 have progressed to cytogenetic or hematologic relapse. If the PCR-positive assay occurred within 24 months of the transplant then the estimated probability of progression to cytogenetic or hematologic relapse was 65% at 24 months. Twenty of the 26 patients who were studied early (< or = 6 months) after BMT had at least one positive PCR assay. Fifteen of the 20 patients who were PCR positive < or = 6 months following transplant have progressed to either cytogenetic or hematologic relapse resulting in an estimated probability of relapse of 84% at 24 months. These results indicate that following T cell-depleted BMT for CML in first chronic phase, PCR is highly predictive of relapse and may identify a cohort of patients in need of therapeutic intervention before the onset of overt clinical relapse.
authors.affiliation: Bone Marrow Transplant Service Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mackinnon
authors.forename: L
authors.initials: L
authors.lastname: Barnett
authors.forename: G
authors.initials: G
authors.lastname: Heller
mesh_terms: D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000737:chemistry / Q000473:pathology; D016026:Bone Marrow Transplantation; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D015993:Life Tables; D008212:Lymphocyte Depletion; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D013601:T-Lymphocytes; D014184:Transplantation, Homologous
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016044:Fusion Proteins, bcr-abl