1.
Unique reduced intensity conditioning haploidentical peripheral blood stem cell transplantation protocol for patients with hematological malignancy
Xu, J., Miao, W., Yuan, H., Liu, Y., Chen, G., Wang, H., Aizezi, G., Qu, J., Duan, X., Yang, R., et al
Transplantation and cellular therapy. 2023
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Abstract
Reduced-intensity conditioning haploid hematopoietic stem cell transplantation (RIC-haplo-HSCT) requires more hematopoietic progenitor and stem cells (HPSCs) to promote engraftment and immune reconstitution and needs stronger graft versus leukemia (GVL) effect. Peripheral blood stem cells (PBSCs) offer more advantages compared to bone marrow (BM). However, higher dose non-T cell depleted (non-TCD) in vitro PBSCs may increase the occurrence of severe graft versus host disease (GVHD). This prospective, single-arm clinical research was performed to investigate high-dose non-TCD in vitro PBSCs as graft, Flu/Ara-C/Bu (FAB) as conditioning regimen, adopting rATG to remove T cells in vivo, and enhancing GVHD prophylaxis with IL-2 receptor antagonist in RIC-haplo-HSCT in patients with hematological malignancies aged 50 to 70 years or < 50 years with comorbidities (HCT-CI scores ≥2) classified as intermediate to higher risk. The primary endpoint was day-100 acute GVHD (aGVHD). A total of 47 patients were enrolled; the median age was 52 years (range: 30-68 years), the median follow-up time was 34 months (range: 2-99), and the medium-infused doses of MNC, CD34+ cells, and CD3+ cells were 15.93 × 10(8)/kg, 8.68 × 10(6)/kg and 5.57 × 10(8)/kg, respectively. The cumulative incidence of grade II-IV aGVHD at day-100 was 30.3% (95% CI: 15.9-44.8), while that of grade III-IV aGVHD was 10.2% (95% CI: 0.6-19.8). The two-year cumulative incidence of chronic GVHD (cGVHD) was 34.9% (95% CI: 19.0-50.8). The two-year cumulative incidences of localized and extensive cGVHD were 26.1% (95% CI: 11.80-40.40) and 8.7% (95% CI: 3.26-20.65), respectively. The two-year cumulative incidence of relapse was 17.3% (95% CI: 5.1-29.5). The two-year overall survival and disease-free survival rates were 71.2% (95% CI: 57.9-84.5) and 66.2% (95% CI: 52.1-80.3), respectively. The outcomes showed that the incidence of aGVHD was not high, and the overall efficacy was good. This study demonstrated that this unique RIC-haplo-PBSCT protocol was effective in treating hematological malignancies. Nonetheless, larger prospective multi-center clinical trials and experimental studies should be performed to further confirm our findings.
PICO Summary
Population
Adults with haematological malignancies aged 50 to 70 years or less than 50 years but with intermediate or higher risk comorbidities (HCT-CI scores ≥2), from a single centre in China (n=47)
Intervention
Reduced intensity conditioning haploidentical HSCT: high-dose non-T-cell depleted in vitro peripheral blood stem cells as graft, Flu/Ara-C/Bu (FAB) as conditioning regimen, rabbit antithymocyte globulin (rATG) to remove T cells in vivo, and enhanced GVHD prophylaxis with IL-2 receptor antagonist.
Comparison
None
Outcome
The median age was 52 years (range: 30-68 years), the median follow-up time was 34 months (range: 2-99), and the medium-infused doses of MNC, CD34+ cells, and CD3+ cells were 15.93 × 10(8)/kg, 8.68 × 10(6)/kg and 5.57 × 10(8)/kg, respectively. The cumulative incidence of grade II-IV aGVHD at day-100 was 30.3% (95% CI: 15.9-44.8), while that of grade III-IV aGVHD was 10.2% (95% CI: 0.6-19.8). The two-year cumulative incidence of chronic GVHD (cGVHD) was 34.9% (95% CI: 19.0-50.8). The two-year cumulative incidences of localized and extensive cGVHD were 26.1% (95% CI: 11.80-40.40) and 8.7% (95% CI: 3.26-20.65), respectively. The two-year cumulative incidence of relapse was 17.3% (95% CI: 5.1-29.5). The two-year overall survival and disease-free survival rates were 71.2% (95% CI: 57.9-84.5) and 66.2% (95% CI: 52.1-80.3), respectively.
2.
Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis
Ma, S., Shi, W., Li, Z., Tang, L., Wang, H., Xia, L., Hu, Y.
Journal of Cancer. 2020;11(17):5223-5235
Abstract
Background: Historically, reduced-intensity conditioning (RIC) was recommended to be performed for older patients who were considered ineligible for myeloablative conditioning (MAC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the evidence regarding the optimal conditioning intensity in younger patients with AML or MDS is weak and contradictory. Methods: PubMed, Medline, Embase, and other online sources were searched from the initial period to February 25, 2020. Odds ratios and 95% confidence intervals were calculated to estimate pooling effects. Results: Four randomized controlled trials (RCTs) about conditioning intensity involving 633 patients were included. There were no significant differences of 1/2/4/5 years progression-free survival (PFS) and relapse incidence (RI) between two conditioning intensities. Overall survival (OS) was similar at 1/2/4 years, but patients receiving RIC had a higher OS at 5 years. Additionally, RIC were associated with lower non-relapse mortality, less grade II-IV and grade III-IV acute graft-versus-host disease (GVHD), and lower incidence of chronic GVHD compared with MAC regimens. Subgroup analysis showed similar OS and RI for AML patients, and there was a trend towards lower NRM and grade II-IV aGVHD in RIC group. Available data for MDS indicated that OS, PFS, and RI were comparable. For intermediate-risk patients, there was no evidence that RIC is inferior to MAC. However, for high-risk patients, MAC tends to perform better. Conclusions: Based on the above results, it might be concluded that RIC is a feasible treatment option for adults with AML or MDS younger than 66 years, particularly those with intermediate-risk disease. Future RCTs incorporating of risk stratifications are warranted to guide the optimal decision under certain conditions.