Autologous transplantation for chronic myelogenous leukemia with mafosfamide-treated marrow

Ten adult patients with Ph-positive chronic myelogenous leukemia (CML) received autologous bone marrow transplantation (ABMT) using marrow treated ex vivo with mafosfamide. At the time of ABMT, six patients were in chronic phase and four in accelerated phase. Seven of ten patients reported herein were selected on the basis of a previous laboratory assessment of the numbers of normal and leukemic stroma-adherent progenitor cells within mafosfamide-treated marrow. Only patients showing ≥50% Ph-negative stroma-adherent progenitor cells within mafosfamide-treated marrow were considered eligible for autografting. In nine out of ten evaluable patients, the median time to achieve 500 neutrophils/μl was 32 days (range: 25–72). A platelet count of 2 × 104/μl was achieved at a median of 40 days (range: 27–97). Six out of nine analyzable patients engrafted Ph-negative. The median duration of the Ph-negative hematopoiesis, confirmed also by Southern blot analysis, was 6.5 months (range: 4–30). A good correlation was evident between the results of the in vitro preharvest screening test and the in vivo occurrence of normal hematopoiesis post-transplant. Two patients who showed 75% and 89% Ph-negative stroma-adherent progenitors engrafted Ph-positive, whereas four out of five evaluable patients who had 100% Ph-negative stroma-adherent progenitors engrafted Ph-negative. After a median follow-up of 16 months (range: 3–31), five patients evolved into blast crisis, three are alive in hematologic and cytogenetic relapse, and one died without evolving into blast crisis. In conclusion, our results demonstrate that: 1) engraftment can occur from Ph-negative stem cells selected by mafosfamide purging; 2) in selected CML patients, mafosfamide is effective in reducing the size of the malignant clone and inducing a transient period of Ph-negative hematopoiesis; and 3) modifications of the purging procedure as well as post-transplant manipulation of the immune-hematopoietic system are required to prolong cytogenetic remission or cure CML patients ineligible for allogeneic or unrelated bone marrow transplantation (BMT).