Higher CD34 Cell Dose Is Associated with Improved 5-Year Survival after Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies

Abstract

<h3>Introduction</h3> Higher CD34+ cell dose is associated with improved short-term outcomes (e.g., engraftment) but may also be associated with an increased risk of complications after allogeneic hematopoietic stem cell transplantation (alloHCT), including graft-versus-host disease (GVHD). We examined the impact of CD34+ cell dose by actual and ideal body weight (ABW, IBW) on overall survival (OS) and graft-versus-host disease-free, relapse free survival (GRFS) in patients undergoing alloHCT with peripheral blood stem cell (PBSC) graft source. <h3>Methods</h3> We identified 377 adults with hematologic malignancies who received myeloablative or reduced-intensity conditioning alloHCT with matched sibling donor PBSC at the University of Minnesota from 2002-2015. <h3>Results</h3> Patients had a median age of 52 years (range 18-74), were predominantly male (n=237, 63%) and had primarily leukemia (68%) or lymphoma (25%) with an intermediate disease risk index (n=258, 68%). Median CD34+ dose was 6.1 × 10⁶/kg by ABW (quartiles in Table 1) and 7.72 × 10⁶/kg by IBW [QT1 <5.93, QT2 5.93,7.72, QT3 7.72, 10.12, QT4 >10.12]. Patients in higher quartiles were younger at transplant (p <0.02) with younger donors (p <0.01). QT4 donors required fewer collections (median 1, range 1-5, p<0.01). Highest quartile cell dose by ABW was associated with increased OS at both 1 year [HR 0.48 (0.29-0.80), p=0.02] and 5 years [HR 0.56 (0.38-0.83), p=0.01] (Figure 1) and platelet engraftment [HR 1.58 (1.19-2.09), p<0.01] in multivariate analysis. The top 3 quartiles by ABW showed significantly increased ANC engraftment and a trend toward increased GRFS at both 1 and 5 years. There was no association between cell dose and acute or chronic GVHD. Cell dose by IBW was not associated with survival, relapse, engraftment or treatment-related mortality. <h3>Conclusion</h3> The highest quartile of CD34+ cell dose by ABW is associated with superior OS at 5 years and improved engraftment without increased risk of morbidity. These data support further development of novel stem cell mobilization techniques in donors at higher risk for low collection yield. Further studies should evaluate if cell dose has similar prognostic impact in 5-year survival in alternative donor transplant.