High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia

Abstract

We evaluated 190 children with very high-risk leukemia, who underwent allogeneic hematopoietic cell transplantation in 2 sequential treatment eras, to determine whether those treated with contemporary protocols had a high risk of relapse or toxic death, and whether non-HLA-identical transplantations yielded poor outcomes. For the recent cohorts, the 5-year overall survival rates were 65% for the 37 patients with acute lymphoblastic leukemia and 74% for the 46 with acute myeloid leukemia; these rates compared favorably with those of earlier cohorts (28%, n = 57; and 34%, n = 50, respectively). Improvement in the recent cohorts was observed regardless of donor type (sibling, 70% vs 24%; unrelated, 61% vs 37%; and haploidentical, 88% vs 19%), attributable to less infection (hazard ratio [HR] = 0.12; P = .005), regimen-related toxicity (HR = 0.25; P = .002), and leukemia-related death (HR = 0.40; P = .01). Survival probability was dependent on leukemia status (first remission vs more advanced disease; HR = 0.63; P = .03) or minimal residual disease (positive vs negative; HR = 2.10; P = .01) at the time of transplantation. We concluded that transplantation has improved over time and should be considered for all children with very high-risk leukemia, regardless of matched donor availability.

Figure 1

Survival of patients after HCT stratified by disease category and treatment era. (A) Overall survival of ALL patients in earlier cohort Total Therapy 13/Total Therapy 14 versus recent cohort Total Therapy 15 (top panel), and of AML patients in earlier cohort AML97 versus recent cohort AML02 (bottom panel). (B) Leukemia-free survival of patients whose leukemia was in remission at the time of HCT.

Figure 2

Outcomes after HCT stratified by donor type. (A) Overall survival of patients in the earlier cohorts (left panel) and the recent cohorts (right panel) after receiving HCT from a sibling donor, unrelated donor, or HLA haploidentical donor. (B) Cumulative incidence of cause-specific death among patients stratified by the 3 donor types, including death related to GVHD, infection, transplantation-regimen toxicity, and leukemia relapse.