Days of Pheresis Needed for Harvesting CD34+ Cells for Autologous Hematopoietic Stem Cell Transplantation Is Associated with Speed of Neutrophil Recovery and the Development of Secondary AML/MDS.

The number of CD34+ cells alone is used to determine the adequacy of mobilized pheresis products for autologous hematopoietic stem cell transplantation. The quantity of CD34+ cells infused predicts the speed of hematopoietic recovery following transplantation. To investigate the extent to which the number of days of pheresis required to collect the minimum number of CD34+ cells (i.e. 2 ×10⁶ cells/kg) might influence the speed of hematopoietic recovery, we analyzed the speed of neutrophil and platelet recovery following autologous transplantation of 496 consecutive individuals transplanted for Hodgkin or non-Hodgkin lymphoma from 1998-2008. All had undergone mobilization using 2g/m² of etoposide and 10μg/kg/day of G-CSF. Recovery for neutrophils was defined as PMN > 500 k/μl and for platelets >20,000 k/μl independent of transfusion. Recursive partitioning analysis (RPA) with a log-rank splitting method was used to identify cutpoints in days of pheresis that predict neutrophil or platelet engraftment. The cutpoints of <5 days vs. ≥ 5 days was identified for both endpoints. Age, gender, race, diagnosis, months from diagnosis to transplant, number of prior chemotherapy regimens, prior radiation therapy, prior monoclonal antibody therapy, preparative regimen, disease status at transplant, CD34+ cell number, and days of pheresis were analyzed as potential prognostic factors for neutrophil and platelet recovery. Multivariable analysis was done with stepwise Cox proportional hazards analysis. In univariable analysis, ≥5 days of pheresis was associated with delayed neutrophil (hazard ratio [HR] 0.54, p<0.001) and platelet engraftment (HR 0.64, p<0.001). In multivariable analysis, ≥ 5 days of pheresis was associated with delayed neutrophil engraftment (HR 0.69, p=0.001), while larger CD34+ dose was associated with more rapid neutrophil engraftment (HR 1.13 per 5 × 10⁶ cells/kg increase, p<0.001). Female gender (HR 1.23, p=0.048), non-Caucasian race (HR 1.46, p=0.030), and larger CD34+ dose (HR 1.15, p<0.001) were associated with faster platelet engraftment; ≥ 5 days of pheresis was not quite significant (HR 0.81, p=0.06). Findings were similar for neutrophil and platelet engraftment when days of pheresis was analyzed as a continuous variable (results not shown). In univariable analysis, ≥ 5 days of pheresis was associated with increased risk of secondary AML/MDS (HR=4.70, p=0.010) while larger CD34+ dose was associated with decreased risk (HR 0.49, p=0.034). Multivariable analysis was precluded by the small number of patients (13) with secondary AML/MDS. In conclusion, our data show that the speed of neutrophil recovery is reduced as the number of days of pheresis required to collect an adequate number of CD34+ cells for transplantation increases. The data also suggest that a prolonged course of pheresis is associated with an increased risk for development of secondary AML/MDS.

No relevant conflicts of interest to declare.