Impact of clinical factors and allograft leukocyte content on post-transplant lymphopenia, monocytopenia, and survival in patients undergoing allogeneic peripheral blood haematopoietic cell transplant.

Mary D Thoma,Tanya J Huneke,Jennifer Glejf,Luis F Porrata,Laura F Newell,Shernan G Holtan,Nicci D Johnson,Lori J Decook,Eapen Jacob,Mark R Litzow,Rekha Chandran,Mrinal M Patnaik,William J Hogan

doi:10.1186/2052-1839-14-14

Abstract

BackgroundWe have previously shown that lymphopenia and monocytopenia at 2–3 months post-allogeneic haematopoietic cell transplant (HCT) is associated with poor survival in recipients of both myeloablative and reduced intensity conditioning regimens. It is not known whether the graft leukocyte content has a role in early lymphocyte and monocyte recovery following allogeneic T-cell replete peripheral blood HCT.MethodsHaematologic recovery data, including absolute lymphocyte and monocyte counts (ALC and AMC, respectively) at day +15, +30, +60, and +100, and outcomes data were pooled from two prior independent cohorts, and parameters were correlated with leukocyte graft content in those individuals receiving peripheral blood progenitor cell grafts. 216 consecutive patients from 2001–2010 were included in the analysis.ResultsNeither infused allograft lymphocyte, monocyte, granulocyte, nor CD34+ cell number per kilogram recipient body weight correlated with haematologic recovery parameters or overall survival in this cohort. Prognostic factors for overall survival based on multivariate analysis were as expected from the results of the previous independent cohorts and included severity of chronic GVHD (p < 0.001), development of post-transplant relapse (p = 0.001), day +60 AMC > 0.3 x 109 cells/L (p = 0.0015), and day +100 ALC > 0.3 x 109 cells/L (p < 0.001). Low monocyte and lymphocyte counts at the day +60 and day +100 time points were significantly associated with acute GVHD and/or CMV viraemia.ConclusionsThis study suggests that graft cell count does not influence post-transplant monocyte and lymphocyte recovery following T-cell replete allogeneic peripheral blood HCT. Post-transplant complications such as acute GVHD and/or CMV viraemia negatively influenced monocyte and lymphocyte recovery, and hence the survival. Further studies aimed at understanding the mechanisms behind sustained lymphopenia and monocytopenia post-transplant are needed.

Highlights

We have previously shown that lymphopenia and monocytopenia at 2–3 months post-allogeneic haematopoietic cell transplant (HCT) is associated with poor survival in recipients of both myeloablative and reduced intensity conditioning regimens
The objective of this study was to determine whether the leukocyte content of the T-cell replete peripheral blood haematopoietic cell allograft is responsible at least in part for post-transplant Absolute lymphocyte count (ALC) and Absolute monocyte count (AMC) recovery in the first 100 days post-HCT, or whether the secondary cytopenias predominantly reflect the detrimental impact of transplant complications on graft function and immune reconstitution
Median overall survival for the entire cohort was 26.6 months. 109 patients died at the time of analysis, and the median follow up for surviving patients was 50.1 months. 68 patients (31%) in this cohort died from non-relapse complications, and 41 patients (19%) died from relapse

Summary

Introduction

We have previously shown that lymphopenia and monocytopenia at 2–3 months post-allogeneic haematopoietic cell transplant (HCT) is associated with poor survival in recipients of both myeloablative and reduced intensity conditioning regimens. It is not known whether the graft leukocyte content has a role in early lymphocyte and monocyte recovery following allogeneic T-cell replete peripheral blood HCT. The objective of this study was to determine whether the leukocyte content of the T-cell replete peripheral blood haematopoietic cell allograft is responsible at least in part for post-transplant ALC and AMC recovery in the first 100 days post-HCT, or whether the secondary cytopenias predominantly reflect the detrimental impact of transplant complications on graft function and immune reconstitution. Clarification of the role of infused graft monocytes in controlling acute graft versus host disease (GVHD) could lead to modification of apheresis strategies or other opportunities for allograft engineering to reduce transplant complications

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