Effects of Method of Peripheral Blood Hematopoietic Stem Cell Mobilization (G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF) on Engraftment and Sustained Graft Function: Comparison Across Cohorts with Similar CD34+ Cell Dose

Autologous peripheral blood hematopoietic stem cell transplantation (AHSCT) is a key therapeutic modality in the management of multiple myeloma (MM) and lymphomas (Ly). The dose of CD34+ cells/kg in the mobilized peripheral blood product has long been regarded as the main determinant of neutrophil and platelet engraftment after AHSCT. Whether the method of hematopoietic stem cell mobilization, namely G-CSF alone (G), G-CSF + plerixafor (G+P) or cyclophosphamide +G/GM-CSF (Cy+G/GM) independently affects engraftment and graft function is unknown.

We used a database of AHSCT patients with MM or Ly to define 3 groups with different mobilization strategies (G, G+P, Cy+G/GM) but receiving similar CD34+ cell doses. Mobilization strategies had been determined by the standard practice at the time of the transplant (Cy + G/GM) or, more recently, by an algorithm factoring in the target CD34+ cell dose and the peripheral blood CD34+ count after 4 days of G-CSF mobilization (G and G+P). Imbalances in cell doses across the three groups were resolved by eliminating from the analysis patients with extremes of CD34+ doses (without investigator awareness of the engraftment endpoints) so all groups had similar averages and variation in CD34+ doses. The three groups were compared in terms of engraftment of neutrophils (defined as the first of 3 consecutive days with neutrophil count >500/mm³) and platelets (first of 3 consecutive days with platelet count >20,000/mm³ without transfusion). Comparisons of sustained graft function were based on total white blood cell count, absolute neutrophil count, and platelet count on or near day 100 after transplantation. All patients received G-CSF support after transplantation at 10 mcg/kg/day from day 7 until neutrophil engraftment.

The initial database contained 123 (70 MM and 53 Ly) patients undergoing transplantation in the three groups (26 G, 38 G+P and 59 Cy+G/GM). The average (+/− SD) cell doses (×10⁶ CD34+/kg) were 4.56 +/−1.85, 5.3 +/−3.07 and 6.63+/−4.31 in G, G+P and Cy+G/GM respectively. After elimination of patients with extremes of CD34+ dose to correct imbalances, 99 patients remained in the analysis (26 G, 33 G+P and 40 Cy+G/GM), defining three groups with similar average and distribution of cell doses. Average cell doses and endpoints are shown in the table. There were no statistically significant differences in time to neutrophil engraftment across the three groups. Platelet engraftment was significantly slower in G+P (16.2 +/− 8.2 days) than in G (12.7 +/− 3.3) or Cy+GM (11.7 +/− 8.2; ANOVA P=0.03). There were no significant differences on day 100 total white blood cell count, absolute neutrophil count or platelet count among the three groups.

Mobilization with G+P may lead to delayed platelet engraftment independently of CD34+ cell dose. Whether this effect is determined by plerixafor itself or by pre mobilization factors associated with plerixafor use remains to be determined. Day 100 graft function is not affected by mobilization strategy.

No relevant conflicts of interest to declare.