Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups

Abstract

Graft-versus-host disease-free relapse-free survival, which is defined as the absence of grade III-IV acute graft-versus-host disease, systemically treated chronic graft-versus-host disease, relapse, and death, is a novel, meaningful composite end point for clinical trials. To characterize risk factors and differences in graft-versus-host disease-free relapse-free survival according to a variety of graft sources, we analyzed 23,302 patients with hematologic malignancy that had a first allogeneic transplantation from 2000 through 2013 using the Japanese national transplant registry database. The 1-year graft-versus-host disease-free relapse-free survival rate was 41% in all patients. The rate was higher after bone marrow transplantation than after peripheral blood stem cell transplantation due to the lower risks of III-IV acute and chronic graft-versus-host disease. The rate was highest after HLA-matched sibling bone marrow transplantation. The rate after single cord blood transplantation was comparable to that after HLA-matched unrelated bone marrow transplantation among patients aged 20 years or under, and was comparable or better than other alternative graft sources among patients aged 21 years or over, due to the low risk of chronic graft-versus-host disease. Other factors associated with better graft-versus-host disease-free relapse-free survival include female patients, antithymocyte globulin prophylaxis (for standard-risk disease), recent years of transplantation, sex combinations other than from a female donor to a male patient, the absence of prior autologous transplantation, myeloablative conditioning, negative cytomegalovirus serostatus, and tacrolimus-based prophylaxis. These results provide important information to guide the choice of graft sources and are benchmarks for future graft-versus-host disease prophylaxis studies.

Figure 1.

Cumulative incidence of individual failure events (defined as the first event). Each area represents recurrent malignancy, death without other failure events, onset of systemically treated chronic graft-versus-host disease (GvHD), and onset of grade III–IV acute GvHD. The white area represents GvHD-free relapse-free survival (GRFS). (A) Patients aged 20 years or under with standard-risk disease, (B) patients aged 20 years or under with high-risk disease, (C) patients aged 21 years or over with standard-risk disease, and (D) patients aged 21 years or over with high-risk disease.

Figure 2.

Proportions of failure events at 12 months. (A) Patients aged 20 years or under with standard-risk disease, (B) patients aged 20 years or under with high-risk disease, (C) patients aged 21 years or over with standard-risk disease, and (D) patients aged 21 years or over with high-risk disease. SIB: sibling; BM: bone marrow; PB: peripheral blood stem cell; UR: unrelated; CB: cord blood; GvHD: graft-versus-host disease.

Figure 3.

Adjusted graft-versus-host disease (GvHD)-free relapse-free survival (GRFS) according to graft sources. (A) Patients aged 20 years or under with standard-risk disease. Results are adjusted for patient sex, use of antithymocyte globulin prophylaxis, and year of transplantation. (B) Patients aged 20 years or under with high-risk disease. Results are adjusted for diagnosis, cytomegalovirus (CMV) serostatus and year of transplantation. (C) Patients aged 21 years or over with standard-risk disease. Results are adjusted for diagnosis, CMV serostatus and year of transplantation. (D) Patients aged 21 years or over with high-risk disease. Results are adjusted for diagnosis, CMV serostatus and year of transplantation, patient sex, prior autologous transplantation, and GvHD prophylaxis. SIB: sibling; PB: peripheral blood stem cell; BM: bone marrow; UR: unrelated; CB: cord blood.