AUTOLOGOUS TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA WITH MAFORSFAMIDE-TREATED MARROW

Ten adult patients with Ph-positive chronic myelogenous leukemia (CML) received autologous bone marrow transplantation (ABMT) using marrow t reated ex vivo with mafosfamide. At the time of ABMT, six patients wer e in chronic phase and four in accelerated phase. Seven of ten patient s reported herein were selected on the basis of a previous laboratory assessment of the numbers of normal and leukemic stroma-adherent proge nitor cells within mafosfamide-treated marrow. Only patients showing g reater-than-or-equal-to 50% Ph-negative stroma-adherent progenitor cel ls within mafosfamide-treated marrow were considered eligible for auto grafting. In nine out of ten evaluable patients, the median time to ac hieve 500 neutrophils/mul was 32 days (range: 25-72). A platelet count of 2 x 10(4)/mul 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 ev ident between the results of the in vitro preharvest screening test an d the in vivo occurrence of normal hematopoiesis post-transplant. Two patients who showed 75% and 89% Ph-negative stroma-adherent progenitor s engrafted Ph-positive, whereas four out of five evaluable patients w ho had 100% Ph-negative stroma-adherent progenitors engrafted Ph-negat ive. After a median follow-up of 16 months (range: 3-31), rive patient s evolved into blast crisis, three are alive in hematologic and cytoge netic relapse, and one died without evolving into blast crisis. In con clusion, our results demonstrate that: 1) engraftment can occur from P h-negative stem cells selected by mafosfamide purging; 2) in selected CML patients, mafosfamide is effective in reducing the size of the mal ignant clone and inducing a transient period of Ph-negative hematopoie sis; and 3) modifications of the purging procedure as well as post-tra nsplant manipulation of the immune-hematopoietic system are required t o prolong cytogenetic remission or cure CML patients ineligible for al logeneic or unrelated bone marrow transplantation (BMT).