Abstract

CML relapse after allogeneic SCT is a relatively frequent situation and is clearly correlated to disease status, time from diagnosis to transplant and T cell depletion. Defining other risk factors could help modulate post transplant immunosuppression. We evaluated the value of early minimal residual disease (MRD) quantification to predict relapse of CML patients receiving standard allogeneic SCT. MRD was analysed by RQ-PCR at Day 100 in 38 patients with a follow up after transplant > 1 year and was expressed as BCR-ABL/ABL, qualified by objective evaluation of RNA amplifiability relative to local normal values for MRD samples (the Quality Index or QI). This QI allows objective evaluation of the degree of correction for positive results and modification of the limits of detection for negative results. Thirty six of 38 patients received conventional conditioning regimen with either BU/CY or TBI/CY and classical prevention of GVHD based on cyclosporin and methotrexate. The median time from diagnosis to transplant was 21 months and median follow up of the cohort was 76.8 months. Patients were allocated to two groups according to their Day 100 RQ PCR level. We compared the characteristics and evolution of the 14 patients with a high MRD level (Day 100 RQ PCR >10−4) to that of the 24 patients with a low MRD level (Day 100 RQ PCR <10−4). There were no significant differences in terms of disease status at transplant, median age at transplant, time from diagnosis to transplant, type of conditioning regimen, source of stem cells, sex mismatch, grade of acute GVHD or incidence of chronic GVHD between the two groups. We show that Day 100 BCR-ABL transcript levels >10−4 by RQ-PCR represents an independent risk factor of relapse after conventional non T cell depleted SCT. These data should favour risk-adapted post transplant immunosuppression based on a single time point early evaluation of MRD.

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