Older Sibling Donors Remain an Excellent Option: Older Donor Age and Lower CD34 Infused Do Not Adversely Impact Outcomes for Matched Sibling Peripheral Blood Stem Cell (PBSC) Transplantation

Abstract

IntroFor unrelated donor allografts, higher cell doses improve outcomes. Increasingly, older patient age is prompting consideration of older sibling donors. On average, older donors mobilize PBSC less well. We hypothesized that outcomes would be worse after older sibling PBSC allografts as older age adversely impacts PBSC yields.MethodsWe reviewed transplant outcomes from HLA matched or single antigen/allele mismatched siblings harvested between January 2001 and April 2008. Donors underwent uniform PBSC mobilization of G-CSF at 10 mcg/kg/day and apheresis on day 5. We evaluated the influence donor and recipient age as continuous variables. We also explore the allograft dose by CD34 dose infused above the median and the peripheral blood (PB) CD34 on day 5 pre-apheresis (a biologic measure of mobilization capacity of the donor). All diseases and conditioning regimens were included. The majority of patients underwent regimens incorporating campath.ResultsOf the 195 sibling donors who underwent mobilization, 182 pts (93%) were infused with PBSCs from one mobilization attempt. The median donor age was 52 years (range 16-70) and 16.9% were 60 years or older. Median recipient age was 53.2 years. The median CD34 infused was 5.4 x10(6)/kg (range 0.34 to 13.2). The risk of acute II-IV GVHD did not correlate with older donor age (HR = 1.01, P0.49), recipient age (HR = 1.04, 95%CI, 0.99-1.09; P = 0.06), CD34 infused above the median (HR = 1.19, P = 0.12), or higher pre-apheresis PB CD34 (HR = 1.01, P = 0.82). However, only 22 recipients developed aGVHD. Donor age was not associated with relapse free survival (RFS) (HR = 1.06, P = 0.45) or OS (HR = 1.06, P = 0.53). Older recipients, however, had inferior OS (HR = 1.02, P = 0.014) but not RFS (HR = 1.01, P = 0.30). OS was not associated with peak PB pre-apheresis CD34 (P = 0.73) or CD34 infused (P = 0.85). In multivariate analysis of donor age, recipient age, disease status and CD34 infused, higher CD34 infused did not impact OS. While older recipient age demonstrated a strong association with poorer OS (P = .008), older donor age showed a borderline associated with improved OS (PS = .049).ConclusionAfter adjusting for recipient age and disease, lower CD34 infused and older donor age had no detrimental impact on GVHD, relapse, or OS. Absent data showing a benefit of younger unrelated donors, we conclude that medically cleared older sibiling donors should be considered the standard of care when available, at least up to age 70 years. IntroFor unrelated donor allografts, higher cell doses improve outcomes. Increasingly, older patient age is prompting consideration of older sibling donors. On average, older donors mobilize PBSC less well. We hypothesized that outcomes would be worse after older sibling PBSC allografts as older age adversely impacts PBSC yields. For unrelated donor allografts, higher cell doses improve outcomes. Increasingly, older patient age is prompting consideration of older sibling donors. On average, older donors mobilize PBSC less well. We hypothesized that outcomes would be worse after older sibling PBSC allografts as older age adversely impacts PBSC yields. MethodsWe reviewed transplant outcomes from HLA matched or single antigen/allele mismatched siblings harvested between January 2001 and April 2008. Donors underwent uniform PBSC mobilization of G-CSF at 10 mcg/kg/day and apheresis on day 5. We evaluated the influence donor and recipient age as continuous variables. We also explore the allograft dose by CD34 dose infused above the median and the peripheral blood (PB) CD34 on day 5 pre-apheresis (a biologic measure of mobilization capacity of the donor). All diseases and conditioning regimens were included. The majority of patients underwent regimens incorporating campath. We reviewed transplant outcomes from HLA matched or single antigen/allele mismatched siblings harvested between January 2001 and April 2008. Donors underwent uniform PBSC mobilization of G-CSF at 10 mcg/kg/day and apheresis on day 5. We evaluated the influence donor and recipient age as continuous variables. We also explore the allograft dose by CD34 dose infused above the median and the peripheral blood (PB) CD34 on day 5 pre-apheresis (a biologic measure of mobilization capacity of the donor). All diseases and conditioning regimens were included. The majority of patients underwent regimens incorporating campath. ResultsOf the 195 sibling donors who underwent mobilization, 182 pts (93%) were infused with PBSCs from one mobilization attempt. The median donor age was 52 years (range 16-70) and 16.9% were 60 years or older. Median recipient age was 53.2 years. The median CD34 infused was 5.4 x10(6)/kg (range 0.34 to 13.2). The risk of acute II-IV GVHD did not correlate with older donor age (HR = 1.01, P0.49), recipient age (HR = 1.04, 95%CI, 0.99-1.09; P = 0.06), CD34 infused above the median (HR = 1.19, P = 0.12), or higher pre-apheresis PB CD34 (HR = 1.01, P = 0.82). However, only 22 recipients developed aGVHD. Donor age was not associated with relapse free survival (RFS) (HR = 1.06, P = 0.45) or OS (HR = 1.06, P = 0.53). Older recipients, however, had inferior OS (HR = 1.02, P = 0.014) but not RFS (HR = 1.01, P = 0.30). OS was not associated with peak PB pre-apheresis CD34 (P = 0.73) or CD34 infused (P = 0.85). In multivariate analysis of donor age, recipient age, disease status and CD34 infused, higher CD34 infused did not impact OS. While older recipient age demonstrated a strong association with poorer OS (P = .008), older donor age showed a borderline associated with improved OS (PS = .049). Of the 195 sibling donors who underwent mobilization, 182 pts (93%) were infused with PBSCs from one mobilization attempt. The median donor age was 52 years (range 16-70) and 16.9% were 60 years or older. Median recipient age was 53.2 years. The median CD34 infused was 5.4 x10(6)/kg (range 0.34 to 13.2). The risk of acute II-IV GVHD did not correlate with older donor age (HR = 1.01, P0.49), recipient age (HR = 1.04, 95%CI, 0.99-1.09; P = 0.06), CD34 infused above the median (HR = 1.19, P = 0.12), or higher pre-apheresis PB CD34 (HR = 1.01, P = 0.82). However, only 22 recipients developed aGVHD. Donor age was not associated with relapse free survival (RFS) (HR = 1.06, P = 0.45) or OS (HR = 1.06, P = 0.53). Older recipients, however, had inferior OS (HR = 1.02, P = 0.014) but not RFS (HR = 1.01, P = 0.30). OS was not associated with peak PB pre-apheresis CD34 (P = 0.73) or CD34 infused (P = 0.85). In multivariate analysis of donor age, recipient age, disease status and CD34 infused, higher CD34 infused did not impact OS. While older recipient age demonstrated a strong association with poorer OS (P = .008), older donor age showed a borderline associated with improved OS (PS = .049). ConclusionAfter adjusting for recipient age and disease, lower CD34 infused and older donor age had no detrimental impact on GVHD, relapse, or OS. Absent data showing a benefit of younger unrelated donors, we conclude that medically cleared older sibiling donors should be considered the standard of care when available, at least up to age 70 years. After adjusting for recipient age and disease, lower CD34 infused and older donor age had no detrimental impact on GVHD, relapse, or OS. Absent data showing a benefit of younger unrelated donors, we conclude that medically cleared older sibiling donors should be considered the standard of care when available, at least up to age 70 years.