Delayed Neutrophil Engraftment Associated with Early CD 8 Polyclonal Lymphocyte Recovery Post Autologous Stem Cell Transplant for Multiple Myeloma

Delayed engraftment following high-dose chemotherapy and autologous peripheral stem cell transplantation is a rare event. Here, we report two cases of delayed engraftment following autologous peripheral blood stem cell transplant (PBSCT) for Multiple Myeloma (MM) associated with early recovery of polyclonal lymphocytes and response to steroids. Both of our patients were 51 years old at time of transplant and women. The preparative regimen consisted of Melphalan 200mg/m2 prior to stem cell infusion; the stem cell doses were between 2.5 and 2.8 million per kilogram. Per protocol, each received growth factor beginning at day 5 post-transplant. Both patients demonstrated a relative increase in their peripheral blood lymphocyte count without neutrophil recovery by day 15 in one patient and day 25 post-transplant in the other. Peripheral blood for flow cytometry was negative for lymphoproliferative disorder or recurrence of their disease. However, it was noted that their CD4:CD8 ratio was 1:6.5 and1:6.3 with marked increase in CD8 lymphoctyes. This expansion of CD8+ cells has been implicated in autoimmune cytopenias in patients with autoimmune diseases and was thought to be the cause of cytopenias in our patients. Given the delay in neutrophil recovery, prednisone 1mg/kg was started for concerns that the predominantly CD 8 polyclonal lymphocytes were responsible for suppressing hematopoiesis. Within 48-72 hours of starting steroids, the peripheral blood lymphocytes decreased significantly, and both patients demonstrated neutrophil engraftment followed by platelet engraftment in the subsequent two-week period. Delayed engraftment following autologous PBSCT is uncommon. Viral infection is a common etiology, and rarely, lymphoproliferative processes like large granular lymphocytes (LGL) have been reported post high-dose therapy and autologous PBSCT for MM. In our patients, no viral cause was found and there was no clonal lymphocyte population. In conclusion, this is the first report of post autologous PBSCT delayed engraftment in association with a predominantly CD 8 polyclonal lymphocyte population. This process was readily reversible with corticosteroid therapy and did not necessitate re-transplantation.