Chimerism status is a useful predictor of relapse after allogeneic stem cell transplantation for acute leukemia

Abstract

BACKGROUND AND OBJECTIVES: The role of hematopoietic chimerism after allogeneic stem cell transplantation (SCT) for acute leukemia remains controversial. We studied the relationship between hematopoietic chimerism and several prognostic variables on the outcome of SCT in patients with acute leukemia. DESIGN AND METHODS: Chimerism was determined by a semiquantitative method, based on polymerase chain reaction (PCR) amplification of variable number tandem repeat (VNTR) minisatellites, in 133 consecutive patients who underwent allogeneic SCT for acute leukemia (68 myeloid, 58 lymphoid and 7 biphenotypic), all receiving a myeloablative conditioning regimen. RESULTS: The median follow-up for the surviving patients was 44.8 months (range: 12.0-129.0). Recipient hematopoiesis (mixed chimerism, MC) was detected in 40 cases (30.1%). Two types of patients could be distinguished in this MC group: 29 with increasing MC and 9 with decreasing MC. The remaining 93 cases maintained complete donor chimerism (CC) over the whole follow-up period. Patients with increasing MC showed a significantly higher (p<0.001) rate of relapse (93.1%) and death (89.7%) in comparison to both those with CC (26.9% relapse, 44.1% dead) or decreasing MC (11.1% relapse, 44.4% dead). The detection of increasing MC preceded relapse by a median of 74 days (range: 5-434) and was significantly related with the absence of chronic graft-versus-host disease. Univariate and multivariate analysis confirmed that chimerism was the most significant variable involved in relapse, leukemia-free survival and overall survival after SCT. INTERPRETATION AND CONCLUSIONS: These results demonstrate that sequential determination of chimerism allows the prediction of relapse and death after SCT for acute leukemia. The interval between detection of increasing MC and relapse may permit timely implementation of therapeutic measures.