Subsets of CD34+ hematopoietic progenitors and platelet recovery after high dose chemotherapy and peripheral blood stem cell transplantation

Abstract

BACKGROUND AND OBJECTIVE: Randomized clinical trials have shown that peripheral blood stem cell transplantations (PBSCT) with appropriate doses of CD34+ cells are associated with rapid, complete and sustained recovery of marrow functions. Nevertheless, in a minority af patients delayed platelet recovery may occur and it remains to be established whether analysis of transplanted CD34+ cell subsets may demonstrate correlation with this phenomenon. We studied a series of 80 consecutive transplanted patients with the aim of evaluating the effect of CD34+ stem cell numbers and, in a subgroup of 32 patients, the effect of the lineage specific subset numbers on time to platelet engraftment (i.e. time to platelet counts higher than 20x10(9)/L for two consecutive days without the need for platelet transfusions). DESIGN AND METHODS: Different clinical and paraclinical factors were examined in a multivariate analysis for effect on platelet engraftment in 80 patients. RESULTS: The number of CD34+ cells/kg infused was the most important factor predicting the time to platelet engraftment. Patients receiving more than 10x10(6) CD34+ cells/kg had prompt platelet engraftment. The majority of the patients (78%) received fewer than 10x10(3) CD34+ cells/kg and 17/62 (27%) of these patients experienced delayed platelet engraftment. In 32 patients receiving fewer than 10x10(6) CD34+ cells/kg we focused on the content of different lineage specific CD34+ subsets in the PBSC products. The most significant correlation was recognized for CD34+/CD61+ megakaryocytic cell number and platelet engraftment. An inverse correlation between the CD34+/CD38Eth subset and platelet engraftment was found, indicating that a high number of CD34+/CD38Eth in the PBSC product might increase the risk for delayed engraftment. These results were further confirmed by the observation that patients who experienced platelet engraftment after day 20 had significantly more CD34+/CD38Eth cells/kg infused than patients with fast engraftment. INTERPRETATION AND CONCLUSIONS: The number of total CD34+ cells/kg infused was the most important factor predicting time to platelet engraftment. CD34+ subset analysis in a subgroup of patients suggests that a high number of uncommitted progenitors may be associated with slower platelet recovery than transplantation with a higher fraction of more committed peripheral blood stem cells.