Cytogenetic response to autografting in chronic myelogenous leukemia correlates with the amount of BCR-ABL positive cells in the graft

Abstract

Objective. An objective of autologous transplant in chronic myelogenous leukemia is to reinfuse the patient stem cells with the lowest amount of leukemic progenitors. We analyzed if the cytogenetic response after autografting was correlated with the amount of BCR ABL–positive cells present in the graft. Materials and Methods. By BCR-ABL mRNA quantification, we studied the serial pheresis product from 40 Philadelphia (Ph)-positive patients who received ICE/mini-ICE mobilization therapy and underwent autologous stem cell transplant in our unit. Therefore, we correlated the residual disease in the graft reinfused to the patients with the cytogenetic response after autografting, taking into consideration only those responses that lasted 12 months or more. Results. Thirty-two patients had a graft with 0–35% Ph-metaphases and 19 had a graft with BCR-ABL/ABL ratio ≤0.01. After a median of 27 months (range, 12–50) from transplant, 18 patients achieved complete or major cytogenetic response lasting at least 12 months and 14 of them (78%) had a graft with BCR-ABL/ABL ratio ≤0.01 (range, 0.0003–0.01). Twenty-two patients had short-lived response or showed to be >35% Ph-positive in the marrow after transplant, but only 5 of them (23%) had a graft with BCR-ABL/ABL ratio ≤0.01 (range, 0.001–0.01). Therefore, we found a strong association between BCR-ABL/ABL ratio ≤0.01 in the reinfused progenitor collections and the achievement of complete or major cytogenetic remission after autografting ( χ 2 test, p = 0.0001). Patients reinfused with low contaminated grafts also showed a longer duration of the response (logrank test, P = 0.0009). Eleven patients were reinfused with the lowest-contaminated stem cell collections, according to the BCR-ABL/ABL ratio. None of these patients had prolonged neutropenia or thrombocytopenia following stem cell reinfusion and 9 of them had long-lasting complete or major cytogenetic response after transplant. Conclusion. This study demonstrates that the amount of BCR-ABL positive cells present in the graft is an important predictive factor for the achievement and the duration of cytogenetic response after autografting.