MOBILIZATION OF CYTOGENETICALLY NORMAL BLOOD PROGENITORS CELLS BY INTENSIVE CONVENTIONAL CHEMOTHERAPY FOR CHRONIC MYELOID AND ACUTE LYMPHOBLASTIC-LEUKEMIA

Various lines of evidence suggest that substantial numbers of very pri mitive normal hematopoietic cells persist in the marrow of most patien ts with CML, despite the presence of an expanded Philadelphia-Chromoso me (Ph) positive population, and that normal clones might, in certain circumstances, have a proliferative advantage over leukemic population s. We have recently demonstrated in 5/8 CML patients with blastic phas e (BP) that the blood progenitor cells/(BPC) harvested during early re covery from marrow aplasia were Ph-negative on cytogenetic analysis, s uggesting that leukapheresis may provide a useful source of 'normal' p rogenitors for subsequent reinfusions. We report here an update on 40 patients with Ph + CML and 9 patients with ALL in first or subsequent relapses with associated cytogenetic translocations including t(8; 14) t(4;8) t(4; 11) and t(9;22). All these patients received intensive co nventional chemotherapy and during early recovery from marrow aplasia, when the WBC reached 0.5-2.0 x 10(9)/L, BPC were collected by 4-8 leu kapheresis and tested for the persistence of the marker translocations and, when possible, for the presence of the hybrid bcr/abl transcript s by polymerase chain reaction (PCR). In seven out of 10 patients with chronic phase CML, BPC were Ph-negative and in 5 PCR negative. In bot h accelerated phase patients, BPC were Ph-negative but PCR-positive an d in eight out of 28 blastic CML patients, BPC were Ph-negative and in two cases also PCR-negative. Six out of 9 ALL patients, lost the cyto genetic translocations. After complete recovery, 16 patients were subs equently given high-dose therapy followed by reinfusion of 'normal' BP C. Two patients in CP-CML and 2 out of six patients with ALL maintain clinical and cytogenetic remission at 3 and 10 months and 16 months re spectively. All the patients transplanted in BP-CML relapsed 5-18 mont hs post-transplant. These data suggest that intensive conventional che motherapy can lead to a precocious overshoot of cytogenetically normal BPC.