COMPARATIVE-ANALYSIS OF AUTOGRAFTING IN CHRONIC MYELOGENOUS LEUKEMIA - EFFECTS OF PRIMING REGIMEN AND MARROW OR BLOOD-ORIGIN OF STEM-CELLS

The aims of this study were (1) to evaluate the effect of intermediate (cyclophosphamide alone) or intensive (mitoxantrone, cytosine arabino side, cyclophosphamide) priming on the cytogenetic response in mobiliz ed bone marrow (BM) or peripheral blood (PB) progenitors in patients w ith chronic myelogenous leukemia (CML), (2) to determine the incidence of cytogenetic remissions after mobilized progenitor transplantation in CML, and (3) to determine the effect of in vivo priming on the abil ity to select Philadelphia chromosome-negative (Ph-negative) CD34(+)HL A-DR- cells from mobilized BM or PB in quantities sufficient for trans plantation. Between February 1994 and March 1997, 44 patients were enr olled in three sequential protocols. Although the duration of neutrope nia after only cyclophosphamide mobilization was shorter, clinical mor bidity for the intermediate and intensive priming protocols was simila r. Cytogenetic responses in mobilized PB progenitors were similar afte r mobilization with either intermediate or intensive chemotherapy. The degree of Ph negativity in the mobilized product correlated with dise ase stage at the time of mobilization (early chronic phase [ECP] > lat e CP > accelerated phase). Cytogenetic responses after transplantation with mobilized progenitors obtained after the different regimens were similar. The cytogenetic status of the graft predicted the cytogeneti c status of marrow obtained 3 weeks after transplantation whereas cyto genetic responses 3, 6, and 12 months after transplantation correlated with the number of BCR/ABL-negative CD34(+)HLA-DR- cells, but not the number of Ph-negative metaphases in the graft. In patients with ECP C ML, mobilized PB collections yielded significantly more CD34(+)HLA-DR- cells than from steady state or mobilized BM. CD34(+)HLA-DR- cells we re Ph negative and polyclonal (X-chromosome inactivation) in the major ity of ECP CML patients, before and after mobilization and irrespectiv e of the mobilization regimen. Because infusion of large numbers of Ph -negative CD34(+)HLA-DR- cells predicted superior outcome after transp lantation, approaches in which CD34(+)HLA-DR- cells are selected from mobilized PB may result in longer lasting and clinically significant c ytogenetic responses after transplantation. (C) 1998 by The American S ociety of Hematology.