Can we modify transplant outcome by improving lymphocyte recovery?

Abstract

In patients with hematologic malignancies, disease relapse and transplant-related mortality (TRM) are the major causes of treatment failure after stem cell transplantation (SCT). Early post-SCT, lymphocyte recovery [defi ned as the absolute lymphocyte count (ALC) at 5 to 30 days post-SCT], a surrogate maker for early immune recovery, is a simple biomarker of outcome after SCT and chemotherapy (1,2). Low ALC is consistently associated with poor outcome after high-dose chemotherapy, autologous (auto-SCT), related and unrelated donor allogeneic stem cell (allo-SCT) transplantation and after cord blood transplantation (CBT) (2 – 7). ALC is a signifi cant, independent prognostic factor for survival after auto-SCT, including acute myeloid leukemia, breast cancer, Hodgkin ’ s lymphoma, non-Hodgkin ’ s lymphoma (NHL) and multiple myeloma, suggesting the possibility of an autologous graft-versus-tumor (GvT) effect similar to the GvT seen in allo-SCT (2,6). Early lymphocyte recovery, its composition and impact on outcome, depends on a variety of factors: the amount and type of prior therapy, disease status pre-SCT, type of transplantation (autologous versus allogeneic versus CBT), T-depletion, graft-versus-host disease (GvHD) prophylaxis, intensity of conditioning regimen (myeloablative versus reduced intensity), mobilization strategies [granulocyte – colony-stimulating factor (G-CSF) versus G-CSF plus high-dose chemotherapy versus G-CSF plus plerixafor] and, most importantly, timing of ALC analysis (2,3,6,8 – 11). In this issue of Cytotherapy , Schmidmaier et al. (1) show ALC (as early as day 5) was predictive for developing neutropenic fever after auto-SCT for multiple myeloma. Day 5 lymphocytes constituted a