Patients with multiple myeloma transplanted with increased numbers of pbpc demonstrate early recovery of total lymphocytes

Patients with multiple myeloma (MM) are currently treated with autologous peripheral blood cell transplantation (PBCT). In most cases infusion of 5 x 10° CD34+ cells/kg is associated with timely engraftment of platelets and neutrophils. In some patients a much higher number of stem cells can be harvested. To assess the effects of infusing high doses of CD34+ progenitors we evaluated patients undergoing PBCT for MM between 10/97 and 6/ 00. Seventy patients were referred and 41 (58.6%) patients were considered eligible for transplant. Median age was 55 years. Patients received 4-6 cycles of V AD prior to Melphalan 140mg/m7TBI (N=34) or Melphalan 200mg/m2(N=7) as preparative regimens. PBPCs were mobilized with cyclophosphamide (2.5g/m:) and G-CSF 10 Jig/kg. Four patients received a combination of G-CSF (10 ig/kg) and SCF (20 Hg/kg). Large volume collections (25 L) were planned and completed on days 11 and 12 if necessary. The mean number of CD34+ stem cells collected was 17.7 + 2.3 x 10' cells/kg (range 2.0-73.2 x 106 cells/kg). 92.1% of patients collected a sufficient number of CD34+ cells in a single harvest. Patients receiving high doses of CD34+ cells (defined as >20 xlO'/kg) (N=14, mean 34.0 ±4.0 SEM) and patients receiving <20 xlO"/kg CD34+ (N=27, mean 9.310.9 SEM) were compared. No significant differences in early recovery of granulocytes or platelets were noted between groups (granulocyte count >0.5 xlO"/L day 8 and 7, platelet count >20 xlO'/L day 7 both groups). Patients in the high PBPC group demonstrated significantly higher WBC counts on days 8 and 9 post transplant (5.2 vs.1.8, p=0.0001, 10.5 vs. 4.6, p=0.009 respectively). The number of transfused blood products was significantly less in the high PBPC group (PRBC 2.6+0.5 vs. 3.3+0.5, pit 1.8±0.3 vs. 2.8±0.5, p<0.001). MM patients receiving high dose PBSCs demonstrated a remarkable recovery of total lymphocytes which occurred as early as day 21 (2.9 vs. 1.6, p=0.04). Linear regression modeling demonstrated a trend (P=0.07) towards faster recovery of lymphocytes that actually peaked to above normal values on day 42 (range 2.1-5.4, mean 3.8+1.0 xlO'/L) in the high PBSC group. No difference in survival was noted(92.9% vs. 81.5%, log rank 0.392, median follow-up 15.5 months). Further studies are required to delineate the functional state of these early recovering lymphocytes and potential responsiveness to immune stimulation. These data may identify an early optimal time for immunotherapy post transplant.