The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma

Abstract

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.

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

“…In previous studies, 21,22 the same group reported a strong correlation between infused A-ALC and both T and NK cell counts at day +15; interestingly, no association was found between CD34+ stem cells and ALC-15.…”

“…• A-ALC40.5 × 10 9 /kg predicts better OS and PFS A-ALC independent prognostic factor for OS and DFS 22 Porrata et al 21 • a A-ALC40.5 × 10 9 /kg predicts better OS and PFS A-ALC independent prognostic factor for OS and PFS 21 Holtan et al, 32 Varmavuo et al 33 and Gaugler et al 27 •…”

Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens

“…The number of lymphocytes within the graft infused seems to have prognostic significance potentially by affecting early lymphocyte recovery. 38,40,41 Numbers of NK cells in the graft may be important to ensure rapid immune reconstitution. 42 Further, the number of CD8 þ cells in the graft seems to be important for early lymphocyte recovery.…”

“…Two studies have reported an association between the number of lymphocytes infused and outcome in myeloma patients 38,41 and one study in NHL patients. Further, the study of Holtan et al 47 suggested that mobilization with G-CSF plus plerixafor was associated with more effective mobilisation of lymphocytes.…”

The relationship between absolute lymphocyte count with PFS in patients with Hodgkin's lymphoma undergoing autologous hematopoietic cell transplant

“…23 Our study that noted an association between pre-apheresis ALC and PFS does provide some support that overall immune recovery may be important in survival and that the ALC may represent a crude marker for immune reconstitution. 8 Other studies have also identified the importance of the infused lymphocyte dose in survival, 14,24 and manipulating the stem Lymphocyte count in transplanted HL patients T Seshadri et al cell product to affect immune reconstitution may be an avenue to improve survival in patients undergoing AHCT. There are several caveats to this study; it is exploratory by design with several variables analyzed and it is a retrospective analysis.…”