Long-term persistent lymphopenia in hematopoietic stem cell donors after donation for donor lymphocyte infusion

Objectives: To analyze the consequences of lymphocyte donations on lymphopoiesis in donors having previously undergone hematopoietic stem cell collection for allogeneic stem cell transplantation.

Methods: Repeated analysis of leukocyte subsets in the peripheral blood of 76 hematopoietic stem cell donors undergoing lymphocyte donation(s) for DLI.

Results: Grade I/II lymphopenia was present in 22 donors (29%) just before first apheresis for lymphocyte collection, demonstrating that former stem cell donation induced prolonged lymphopenia in a subset of donors. The monocytic lineage was not affected. Older age and history of PBSC harvest constituted 2 independent factors of lymphopenia, but had no influence on monocytopenia. The first apheresis induced lymphopenia in 36 donors (47%) and monocytopenia in 23 donors (39%). Lymphopenia before first apheresis and prior history of PBSC harvest were independent factors of apheresis-induced lymphopenia while those factors had no influence on monocytopenia. A time-dependent decrease in lymphocyte counts was observed in donors undergoing repeated aphereses, resulting in persistent and prolonged lymphopenia in 50% of donors. No persistent monocytopenia over time and aphereses was observed. Kaplan-Meier estimate of the risk to develop persistent lymphopenia after multiple aphereses was 21% +/- 6% at 2 months, 38% +/- 8% at 4 months, and 64% +/- 10% at 12 months. After Cox regression analysis, previous PBSC harvest remained the unique factor associated with the risk for persistent lymphopenia.

Conclusions: Monitoring the potential long-term effects of repeated aphereses in hematopoietic stem cell donors appears important. Selecting young bone marrow donors for subsequent DLI significantly reduces the risk for acute and prolonged lymphopenias.