MOBILIZATION OF PERIPHERAL-BLOOD STEM-CELLS WITH CHEMOTHERAPY AND CYTOKINES IN MULTIPLE-MYELOMA

In an attempt to offset the impaired hematopoietic progenitors' mobili zation and collection which are frequently encountered in multiple mye loma (MM), we have started a pilot study to evaluate the ability of a combination of high-dose melphalan (HDM) and sequential s.c. administr ation of recombinant human interleukin 3 (rhIL-3) and rh-granulocyte c olony-stimulating factor (G-CSF) to mobilize blood cells (BC) in MM pa tients, Two different schedules for administration were successively t ested, Schedule A consisted of IL-3 (5 mu g/kg/d) from day 7 to day 11 after HDM followed by G-CSE (5 mu g/kg/d) from day 12 to day 20. Unde r schedule B, HDM was followed by IL-3 alone at the same dosage from d ay 1 to day 3, IL-3 and G-CSF (idem) from day 4 to day 7 and G-CSF alo ne from day 8 until completion of apheresis, Two patients (one previou sly untreated, one having received prior chemotherapy for one year) un derwent schedule A; three patients (one previously untreated, two pret reated) underwent schedule B, The post-HDM aplasia was not shortened i n schedule B patients in comparison to what we usually observed follow ing HDM alone (25 days) correlated with a very moderate two- to three- fold CD34(+) cell increase, Only one patient was further transplanted with apheresis products: the post-transplant granulocyte recovery was slower than usual (16 days versus 12 days) while platelet count never recovered over 20 x 10(9)/I. In contrast, the post-HDM aplasia was sig nificantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25- to 165-fold increase in CD34(+) cells. These two patients underwent further BC transplant which was characterized by shortened granulocyte count nadir (9 days) and accelerated sustaine d platelet recovery (10 to 14 days), In the third patient, the hematop oietic recovery was delayed longer after schedule B and was preceded b y a transient appearance of consistent rates of plasmacytoid cells in peripheral blood, suggesting a cytokine-related mobilization of myelom a cells, However, schedule B, comprising an IL-3/G-CSF overlap, seems to better enhance BC mobilization than schedule A does and may offset the inhibition (induced by either the disease or melphalan) of hematop oiesis in high-grade MM. Yet, the risk of concomitant tumor cell mobil ization will require extreme caution when developing cytokine mobiliza tion in the future.