Transplanted CD34+ Cell Dose Is Associated with Long-Term Platelet Count Following Autologous Hematopoietic Stem Cell Transplant in Patients with Non-Hodgkin’s Lymphoma and Multiple Myeloma.
Authors: Stiff Patrick J. , Micallef Ivana NM , Nademanee Auayporn P. , Stadtmauer Edward A. , Maziarz Richard Thomas , Bolwell Brian J. , Bridger Gary , Calandra Gary , Angell Jennifer , DiPersio John F. 
Published: April 2020

Introduction: The impact of transplanted CD34+ cell dose on clinical outcomes remains controversial. The purpose of this study was to examine the relationship between CD34+ cell dose transplanted and platelet, neutrophil, and lymphocyte counts at 100 days, 6, and 12 months following autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM).

Methods: Data were obtained from two phase 3 clinical studies that compared the safety and efficacy of plerixafor and G-CSF with placebo and G-CSF in mobilization of hematopoietic blood stem cells for autologous transplantation in NHL patients and in MM patients. The details of the study designs and preliminary safety and efficacy outcomes have been reported (DiPersio, ASH 2007). The following data were obtained from the two clinical study databases: number of CD34+ cells transplanted (first transplant only) as determined by a central laboratory, absolute neutrophil, platelet, red blood cell, and lymphocyte counts at 100 days, 6, and 12 months post-transplant. The proportions of patients who had platelet ≥150 x 109/L or neutrophil ≥2.5 x 109/L or lymphocyte ≥0.5 x 109/L at 100 days, 6, and 12 months were compared among these transplanted CD34+ cell dose categories regardless of mobilization treatment: 2–4 x 106 cells/kg, &gt;4–6 x 106 cells/ kg, and &gt; 6 x 106 cells/kg. Two separate analyses were performed, one for NHL patients and one for MM patients.

Results: For the NHL study, 135/150 (90.0%) patients in the plerixafor group underwent transplantation after initial mobilization compared with 82/148 (55.4%) patients in the placebo group, p&lt;0.001. The mean number of CD34+ cells transplanted was 6.06 ± 2.98 x 106 (median 5.41, range 1.79–17.6) for the plerixafor-treated patients and 4.09 ± 1.56 x 106 (median 3.85, range 1.98–8.7) for the placebo-treated patients, p&lt;0.001. For the MM study, 142/148 (95.9%) patients in the plerixafor group and 136/154 (88.3%) patients in the placebo group underwent transplantation. The mean number of CD34+ cells transplanted was 5.84 ± 2.64 x 106 (median 5.34, range 1.9 to 16.7) for the plerixafor-treated patients and 4.37 ± 2.01 x 106 (median 3.98, range 1.8 to 16.9) CD34+ cells/kg for the placebo- treated patients. A significant linear trend with increasing proportion of patients with platelet count ≥150 x 109/L with increasing transplanted cell dose categories was observed at 100 days, 6, and 12 months for NHL patients and at 100 days for MM patients (Table 1). There were no apparent significant relationships between transplanted cell dose categories and other hematopoietic parameters.

Table 1: Analysis of percentage of patients reaching a platelet count of ≥ 150 x 109/L by transplanted cell dose categories

Transplant Cell Dose (CD34+ cells/kg) 2–4 x 106 ≥ 4–6 x 106 ≥ 6 x 106 P value* NHL Patients N=76 N=75 N=66 100 days 28 (48.3%) 42 (66.7%) 45 (81.8%) &lt;0.001 6 months 31 (56.4%) 36 (66.7%) 42 (76.4%) 0.026 12 months 18 (56.3%) 21 (80.8%) 24 (82.8%) 0.020 MM Patients N=75 N=82 N=64 100 days 41 (68.3%) 57 (90.5%) 47 (88.7%) 0.004 6 months 48 (78.7%) 61 (89.7%) 51 (87.9%) 0.147 12 months 25 (73.5%) 33 (82.5%) 26 (81.3%) 0.435

For all transplanted cell dose categories, the proportions of patients are based on the number of patients with available data at each time point.*p-value for testing linear trend using Mantel-Haenszel Chi-square test

Conclusions: Results from these ad hoc analyses confirm previous reports that transplanted cell dose may be associated with better long-term platelet recovery. Due to the small sample size in each transplanted cell dose category and the nature of ad hoc analyses, further studies are warranted to determine if the introduction of plerixafor will allow the mobilization and transplantation of higher quantity of CD34+ cells, which may positively influence long-term hematopoietic recovery.