DETECTION OF BCR ABL RNA TRANSCRIPTS USING THE POLYMERASE CHAIN-REACTION IS HIGHLY PREDICTIVE FOR RELAPSE IN PATIENTS TRANSPLANTED WITH UNRELATED MARROW GRAFTS FOR CHRONIC MYELOGENOUS LEUKEMIA/

Relapse after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia (CML) is thought to result from residual leukae mia cells which survive the intensive conditioning regimen and are not eradicated by donor-derived immune effector cells capable of mediatin g a graft-versus-leukaemia (GVL) effect. Early relapse can be detected using highly sensitive assays such as the polymerase chain reaction ( PCR) which have been shown to have predictive value for subsequent rel apse in selected patient populations. The validity of PCR for predicti ng CML relapse in unrelated marrow transplant recipients where the GVL effect appears to be augmented due to increased HLA disparity between donor and recipient, however, has not been well defined. In this stud y we assessed the prognostic value of PCR in a cohort of 52 patients t ransplanted with T-cell-depleted unrelated marrow grafts for CML, The actual probability of relapse at 3 years was 71% in patients with at l east one positive assay versus 6% in patients with no positive assays post-transplant. Patients with one or more positive assays at any time post-transplant had a 56-fold increased risk of relapse which was sig nificantly higher (P=0.0002) than that observed in patients who remain ed persistently PCR negative, Moreover, PCR detected relapse a median of 5 months earlier than cytogenetic analysis in a subgroup of patient s in whom concurrent sampling had been performed, These data validate the use of PCR as a prognostic test in this patient population and may help to identify a cohort of patients to be considered as candidates for pre-emptive adoptive immunotherapy.