Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia

Abstract

There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis. A total of 44 patients, of whom 28 had acute myeloid leukemia (AML), 13 had acute lymphocytic leukemia (ALL), and 3 had mixed phenotype leukemia (MPL), were enrolled in this study. With a median follow-up of 19 months, the estimated 2-year overall survival (OS) and progression free survival (PFS) were 34.3% (95% CI, 17.9-51.4%) and 33.6% (95% CI, 18.0-50.1%), respectively. The estimated 2-year incidence rates of relapse and non-relapse mortality (NRM) were 43.8% (95% CI 26.4-60.0%) and 19.6% (95% CI 9.1-32.9%), respectively. The estimated 100-day cumulative incidence of acute graft versus host disease (aGvHD) was 43.6% (95% CI 28.7-57.5%), and the 1-year cumulative incidence of chronic GvHD (cGvHD) was 45.5% (95% CI 30.5-59.3%). Compared with the previous studies, the multivariate analysis in this study additionally identified that female donors and cGvHD were associated with lower relapse and better PFS and OS. Male recipients, age younger than 10 years, a diagnosis of ALL, and the intermediate-adverse cytogenetic risk group were associated with increased relapse. On the contrary, extramedullary disease (EMD) and aGvHD were only linked to worse PFS. These data suggested that although only one-third of the patients would obtain PFS over 2 years, salvaged allo-HSCT is still the most reliable and best therapeutic strategy for refractory pediatric acute leukemia. If probable, choosing a female donor, better management of aGvHD, and induction of cGvHD promotes patient survival.

Keywords: acute leukemia; hematopoietic stem cell transplantation; pediatric; primary refractory; relapsed refractory.

Figure 1. Engraftment of neutrophil and platelet

One patients failed to achieve neutrophil and platelet engraftment and another 4 experienced failure of platelet engraftment till 56 days after transplantation.

Figure 2. Cumulative incidence of acute and chronic GvHD

(A) The estimated 100-day cumulative incidence of aGvHD was 43.6% (95% CI 28.7-57.5%). (B) 1-year cumulative incidence of cGvHD was 45.5% (95% CI 30.5–59.3%).

Figure 3. Cumulative incidence of relapse and NRM

The estimated 2-year incidence of relapse and NRM was 43.8% (95% CI 26.4–60.0%) and 19.6% (95% CI 9.1–32.9%), respectively.

Figure 4. OS and PFS of the entire cohort

The estimated 2-year OS (A) and PFS (B) was 34.3% (95% CI 17.9–51.4%) and 33.6% (95% CI 18.0–50.1%), respectively.

Figure 5. OS and PFS stratified by diagnosis

The estimated 2-year OS for AML, ALL and MPL was 49.5% (95% CI 26.3–69.2%), 15.2% (95% CI 0.9–46.7%) and 0.0% (95% CI 0.0-0.0%) respectively (A) and 2-year PFS for AML, ALL and MPL was 46.7% (95% CI 24.8-66.0%), 16.3% (95% CI 1.1–48.1%) and 0.0% (95% CI 0.0–0.0%), respectively (B).

Figure 6. PFS stratified by risk group, disease status, aGvHD and cGvHD

Univariate analysis by Log-Rank test and Kaplan-Meier survival curve for PFS stratified by risk group (A), disease status at transplantation (B), acute GvHD (C) and chronic GvHD (D), respectively.

Figure 7. Design of conditioning regimens