Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study

Abstract

Introduction: We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1).

Methods: We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021.

Results: The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Conclusions: Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Keywords: first allogeneic hematopoietic stem cell transplantation; hematological malignancy; prognosis factor; relapse; second allogeneic hematopoietic stem cell transplant.

Figure 1

HLA-matching pathway. MSD, Matched sibling donor; MUD, matched unrelated donor; HID, haploidentical donor; UCB, unrelated cord blood donor; Auto, autologous.

Figure 2

OS (43.8% [95%CI,39.7-48.0]) (A) and LFS 42.1% [95%CI,38.6-47.8] (B), CIR(30.0%[95%CI,26.4-34.7] (C) and TRM 38.5%[95%CI,34.7-42.3] (D) outcomes following allo-HSCT2 among 199 patients.

Figure 3

OS[score 3(63.3% [95%CI,56.6-70.0]) vs score 2(43.9%[95%CI,36.1-50.5]) vs score 1(24.2% [95%CI,18.4-30.6]6.7%)vs score 0(20.0%[95%CI,8.3-32.0]),P=0.0001)] (A) and LFS[score3(63.8%[95%CI,56.6-70.0]) vs score 2(43.9%[95%CI,36.6-50.5]) vs score 1(18.3%[95%CI,12.3-24.7]) vs score0 (20.0%[95%CI,8.3-32.0]), P=0.0001] (B) CIR [score 3 (5.5%[95%CI,2.4-8.6]) vs score 2(30.0%[95%CI,21.2-38.8]) vs score 1(65.5%[95%CI,54.6-76.4]) vs score0(51.5% [95%CI,30.6-73.3]), P=0.0001] (C) and TRM [score 3(32.9%[95%CI,26.2-39.6]) v score2(35.6%[95%CI,29.6-41.6]) vs score1(40.5%[95%CI,33.9-47.6]) vs score0(55.9%[95%CI,37.1-74.0]), P=0.007] (D) outcomes following allo-HSCT2 among 199 patients, according to prognostic score.