Transplant CD34+ Cell Dose Affects Outcomes Following Allogeneic Peripheral Blood Stem Cell Transplantation from a Matched Unrelated Donor.
Authors: Nakamura Ryotaro , Palmer Joycelynne , Rodriguez Roberto , Parker Pablo , Senitzer David , Stein Anthony , Rosenthal Josheph , Wang Sean , Schriber Jeffrey , Forman Stephen J. , Nademanee Auayporn 
Published: October 2019

Abstract
Peripheral blood stem cells (PBSC) have been increasingly used in the matched unrelated donor (MUD) transplant setting, but the impact of CD34 cell dose on outcomes following MUD-PBSC transplant have not been well characterized. Between 8/00-12/04, a total of 181 patients underwent MUD-PBSC transplantation at our institution under IRB-approved protocols. Patient’s age at transplant ranged from 1 to 67 years (median 44). Eighty-two were female and 99 were male. The cohort consisted of 68 patients with AML, 38 with ALL, 18 with CML, 18 with NHL, 17 with MDS, and the remaining 22 with other diagnosis (CLL, MM, MPD, etc.). Of 181 patients, 35 were considered to have low-risk disease (acute leukemias in CR1 or CML-CP). Patients were conditioned with either full-intensity regimen (TBI+Cy or VP16, or BuCy: n=83) or reduced-intensity regimen (fludarabine+melphalan or busulfan: n=98). GVHD prophylaxis consisted of tacrolimus+methotrexate for full-intensity transplants and cyclosporine+mycophenolate+/− methotrexate for reduced-intensity transplants. Median (range) CD34+ cell, lymphocyte (Ly), and mononuclear cell (MNC) doses were 6.7 (0.6–28) x106/kg, 440 (40–2640) x106/kg, and 710 (50–5060) x106/kg respectively. A strong correlation exists between Ly and MNC doses (r2=. 52, p<0.01), but not between CD34+ cell and Ly or MNC doses. The median time to ANC≥500/uL was 16 days (range: 7–52) and platelet≥20k/ul at 20 days (range: 12–98). After a median follow up of 18 months (range: 3–49), 103 patients are alive. The two-year overall survival (OS), disease-free survival (DFS), relapse, and transplant-related mortality (TRM) probabilities were 54%, 46%, 30%, and 31% respectively. Grade II–IV acute GVHD occurred in 64% of patients (grade 3–4: 31%). Chronic GVHD was observed in 64% of evaluable patients. By univariate analysis, a CD34+ cell dose ≥ 4.2x106/kg (the lowest quartile) was associated with significantly lower relapse risk (Hazard Ratio=0.4; p=0.02), and a trend for improved DFS (HR=0.6; p=0.06) and OS (HR=0.64; p=0.08). After adjusting for the patient’s age at transplant, disease risk classification, and conditioning regimen (full-intensity vs. reduced intensity), the impact of CD34+ cell dose (≥ 4.2x106/kg) remained significant for relapse (HR=0.4; p<0.01), DFS (HR=0.6; p=0.05), with a trend for OS (HR=0.6; p=0.07). CD34+ cell dose ≥6.7x106/kg (median) was associated with a trend for reduced relapse risk (HR= 0.5; p=0.06) without impact on DFS, OS, or TRM. A CD34+ cutoff at 9.5 x106/kg (the highest quartile) had no impact on OS, DFS, relapse, or TRM. There was no association between the CD34 cell dose and acute GVHD (grade II–IV or III–IV). In conclusion, within the range of CD34 doses in our study, the CD34+ cell dose ≥ 4.2x106/kg was associated with better transplant outcomes in MUD-PBSC transplants. We observed no adverse effect of receiving CD34+cell dose > 9.5 x106 (the highest quartile) in transplant outcomes including acute GVHD and TRM.