Summary:Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in non-Hodgkin's lymphoma (NHL). Factors affecting ALC-15 remain unknown. We hypothesized that dose of infused autograft lymphocytes (A-ALC) directly impacts upon ALC-15. A total of 190 consecutive NHL patients received A-ALC between 1993 and 2001. The primary end point was correlation between A-ALC and ALC-15. A strong correlation was identified (r ¼ 0.71). A higher A-ALC was infused into patients achieving an ALC-15 X500/ll vs ALC-15 o500/ll (median of 0.68 Â 10 9 /kg (0.04-2.21 Â 10 9 /kg), vs 0.34 Â 10 9 /kg (0.04-1.42 Â 10 9 /kg), Po0.0001). The median follow-up for all patients was 36 months (maximum of 109 months). The A-ALC threshold was determined at 0.5 Â 10 9 /kg. The median overall survival (OS) and progression-free survival (PFS) times were longer in patients who received an A-ALC X0.5 Â 10 9 /kg vs A-ALC o0.5 Â 10 9 /kg (76 vs 17 months, Po0.0001; 49 vs 10 months, Po0.0001, respectively). Multivariate analysis demonstrated A-ALC to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that ALC-15 and survival are dependent upon the dose of infused A-ALC in NHL.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in multiple myeloma (MM); however, factors affecting ALC-15 in MM remain unknown. We hypothesized that the dose of infused peripheral blood autograft lymphocytes (autograft absolute lymphocyte count: A-ALC) impacts ALC-15 recovery. Between 1989 and 2001, 267 consecutive MM patients underwent APHSCT. We set out to determine the correlation between A-ALC and ALC-15 and the utility of A-ALC as a marker for ALC-15 recovery. A-ALC was found to be both a strong predictor for area under curve (AUC ¼ 0.93; P ¼ 0.0001) and strongly correlated with (r s ¼ 0.83; P ¼ 0.0001) ALC-15 recovery. Higher infused A-ALC was significantly correlated with an ALC-15X500/ll. In addition, median post-transplant overall survival (OS) and time to progression (TTP) were longer in patients who received an A-ALCX0.5 Â 10 9 lymphocytes/kg versus A-ALC o0.5 Â 10 9 lymphocytes/kg (58 vs 30 months, P ¼ 0.00022; 22 vs 15 months, Po0.00012, respectively). Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM.

Early absolute lymphocyte count (ALC) has been reported to be a powerful prognostic indicator of survival after autologous stem cell transplantation (ASCT). One possible source affecting ALC recovery includes the re-infused autologous graft lymphocytes (AGL). To assess if the re-infused AGL correlate with ALC recovery post-ASCT, we conducted a pilot study to identify which of the re-infused AGL subsets is most associated with day 15 ALC recovery in three patients with multiple myeloma and four patients with non-Hodgkin's lymphoma. Using the Spearman rank correlation coefficient analysis (r), we compared absolute numbers of CD3, CD4, CD8, CD19, and CD16+/CD56+ cells/kg of body weight from the apheresis product with ALC (cells/microl) at day 15 post-ASCT. The main lymphocyte subsets identified in the apheresis product were T cells and NK cells. There was no strong correlation between T or B cells from the apheresis product compared with the ALC at day 15 post-ASCT (CD3, r = 0.21; CD4, r = 0.32; CD8, r = 0.39; and CD19, r = 0.14). However, there was good correlation between NK cells from the apheresis product compared with ALC at day 15 post-ASCT (CD16+/CD56+/CD3-, r = 0.77). These data provide preliminary evidence that the number of re-infused autologous graft NK cells in the apheresis product significantly affect ALC recovery early post-ASCT. However, given the small sample size, our results are primarily hypothesis generating and subject of further research.

Summary:The purpose of this study was to determine the effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. We performed a retrospective review of 67 patients newly diagnosed with multiple myeloma at Mayo Clinic and treated with a single regimen prior to stem cell transplantation between January of 2000 and September of 2001. Stem cells were collected from 24 patients who received thalidomide, 200 mg/day, with dexamethasone as initial therapy before stem cell collection. These patients were compared with 43 control patients seen during the same period who had received only one previous regimen before stem cell collection and transplantation. The cumulative thalidomide dose before stem cell collection was 17 000 mg over a median of four cycles (range, 2-7 cycles). The thalidomide and control groups were not significantly different in their baseline characteristics, number of stem cells collected, time to collection, or time to engraftment of neutrophils or platelet count of 50 000/ll. Time to platelet count of 20 000/ll was delayed by a median of 4 days (P ¼ 0.008), but platelet transfusion requirements did not differ (P ¼ 0.95). We concluded that thalidomide does not substantially affect peripheral cell mobilization or engraftment.

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