Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose

Abstract

We report outcomes of 932 recipients of unrelated donor peripheral blood stem cell hematopoietic cell transplantation (URD-PBSC HCT) for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome enrolled on a prospective National Marrow Donor Program trial from 1999 through 2003. Preparative regimens included myeloablative (MA; N = 611), reduced-intensity (RI; N = 160), and nonmyeloablative (NMA; N = 161). For MA recipients, CD34(+) counts greater than 3.8 x 10(6)/kg improved neutrophil and platelet engraftment, whereas improved overall survival (OS) and reduced transplant-related mortality (TRM) were seen for all preparative regimens when CD34(+) cell doses exceeded 4.5 x 10(6)/kg. Higher infused doses of CD34(+) cell dose did not result in increased rates of either acute or chronic graft-versus-host disease (GVHD). Three-year OS and disease-free survival (DFS) of recipients of MA, RI, and NMA approaches were similar (33%, 35%, and 32% OS; 33%, 30%, and 29% DFS, respectively). In summary, recipients of URD-PBSC HCT receiving preparative regimens differing in intensity experienced similar survival. Higher CD34(+) cell doses resulted in more rapid engraftment, less TRM, and better 3-year OS (39% versus 25%, MA, P = .004; 38% versus 21% RI/NMA, P = .004) but did not increase the risk of GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00785525.

Figures

Figure 1

Cumulative incidence of neutrophil and platelet engraftment after MA URD-PBSC transplantation by CD34+ dose. CD34+ cell doses higher than 3.8 × 106/kg recipient weight improved neutrophil and platelet engraftment compared with lower doses (P = .025 for neutrophil engraftment at 25 days; P < .001 for platelet engraftment > 50000/μL at 60 days). ANC indicates neutrophil engraftment; PLT, platelet engraftment; Low, no more than 3.8 × 106 CD34+/kg (n = 107, ANC; n = 106, PLT); High, greater than 3.8 × 106 CD34+/kg (n = 327, ANC; n = 324, PLT).

Figure 2

Cumulative incidence of GVHD after URD-PBSC transplantation by quartile (Q) of CD34+ dose. Higher CD34+ cell doses did not increase the incidence of GVHD. (A) Grades III-IV acute GVHD after MA transplantation (P = .599 at 180 days); (B) grades III-IV acute GVHD after RI/NMA transplantation (P = .305 at 180 days); (C) chronic GVHD after MA transplantation (P = .068 at 2 years); (D) chronic GVHD after RI/NMA transplantation (P = .189 at 2 years). MA: Q1 indicates no greater than 3.8; Q2, 3.8 to 6.2; Q3,6.2 to 9.5; Q4, greater than 9.5; RI/NMA: Q1, no greater than 3.6; Q, 3.6 to 5.9; Q3, 5.9 to 9.4; Q4, greater than 9.4 (× 106 CD34+/kg).

Figure 3

Overall survival after URD-PBSC transplantation by CD34+ dose. CD34+ cell doses higher than 4.5 × 106/kg recipient weight improved overall survival compared with lower doses. However, doses much higher than 4.5 × 106/kg did not further improve the survival rate compared with doses just above 4.5 × 106/kg. (A) Overall survival after MA transplantation (P = .020 at 3 years for Medium vs Low; P = .489 at 3 years for Medium vs High). (B) Overall survival after RI/NMA transplantation (P = .045 at 3 years for Medium vs Low; P = .157 at 3 years for Medium vs High). Low indicates no greater than 4.5 (n = 142, MA; n = 80, RI/NMA); Medium, 4.5 to 9.5 (n = 183, MA; n = 102, RI/NMA); High, greater than 9.5 (n = 110, MA; n = 54, RI/NMA) (× 106 CD34+/kg).

Figure 4

Key outcomes after URD-PBSC transplantation by preparative regimen. (A) Grades III-IV acute GVHD, (B) chronic GVHD, (C) TRM, (D) relapse, (E) overall survival, and (F) primary cause of death. ARDS indicates acute respiratory distress syndrome.