Very primitive hemopoietic cells (LTC-IC) are present in Philadelphia negative cytaphereses collected during early recovery after chemotherapy for chronic myeloid leukemia (CML)

Abstract

We have previously demonstrated that Philadelphia negative (Ph-ve) hemopoietic cells can be collected by leukaphereses after an acute leukemia-like chemotherapy during the early hemopoietic recovery in patients with chronic myeloid leukemia (CML). In this study we have evaluated whether these collections contain very primitive hemopoietic cells defined as 'long-term culture initiating cells' (LTC-IC) and whether these cells belong to the Ph-positive or Ph-negative population. Twenty-eight out of 76 cytaphereses collected in 15 patients with CML proved to contain Ph-ve cells only (six patients), 21 showed only Ph+ve cells (five patients), and 27 a mixture of Ph+ve and Ph-ve cells (four patients). In cytaphereses containing Ph-ve cells only, we found variable numbers of LTC-ICs, more consistently when we mobilized patients in the first 3 months from diagnosis. In three cases cytogenetic analysis on LTC-ICs and CFU-GM confirmed results obtained on fresh samples. Ph-positive collections were devoid of LTC-ICs except for 2/21 samples. However, their cytogenetic analysis revealed a small number of Ph-negative progenitors. LTC-ICs were randomly detected in mixed (Ph+ve and Ph-ve) collections. In conclusion these data indicate that, in a consistent proportion of chronic myeloid leukemia patients, intensive chemotherapy is able to recruit Ph-ve LTC-ICs in to the peripheral blood. Moreover these data provide the biological basis for developing autografting programs with Ph-negative cells.