Assessment of Patient-Specific Human Leukocyte Antigen Genomic Loss at Relapse After Antithymocyte Globulin–Based T-Cell–Replete Haploidentical Hematopoietic Stem Cell Transplant

Wu, Huitao; Shi, Jimin; Luo, Yi; Yu, Jian; Lai, Xiaoyu; Liu, Lizhen; Fu, Haidong; Ouyang, Guifang; Xu, Xiao‐Jun; Xiao, Haowen; Huang, He; Zhao, Yanmin

doi:10.1001/jamanetworkopen.2022.6114

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…Crucitti et al and Wang et al suggested that the HLA allele matching degree is an independent risk factor of HLA loss. 7,18 Wu et al reported that the incidence of HLA loss in patients with myeloid leukaemia undergoing haplo-HSCT was up to 54.7% (29/53), 19 and patients treated by HLA mismatched HSCT were more vulnerable to develop HLA loss relapse than those treated by HLA matched HSCT. Those results were in agreement with our findings.…”

Section: Discussionmentioning

confidence: 99%

Risk factors and survival analysis of human leukocyte antigen loss in relapsed acute myeloid leukaemia/myelodysplastic syndrome patients after allogeneic haematopoietic stem cell transplantation

Zhang,

Zhou

et al. 2024

Br J Haematol

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SummaryTo investigate the clinical characteristics and risk factors of specific human leukocyte antigen loss (HLA loss) in relapsed acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) patients after allogeneic haematopoietic stem cell transplantation (allo‐HSCT), and compare the responses of patients with HLA loss relapse with those without HLA loss (non‐HLA loss) to different treatment regimens. Clinical data of traceable patients with AML/MDS after myeloablative allo‐HSCT in our centre between January 2010 and June 2021, who experienced disease relapse after the transplantation, were collected. The patients were divided into the HLA loss relapse group and the non‐HLA loss relapsed group based on HLA loss gene test findings by next‐generation sequencing. The patients' median overall survival (OS) after the relapse were compared, and univariate and multivariate analyses were performed using the Kaplan–Meier survival curve and Cox proportional hazard model to explore the responses to different treatments after relapse. A total of 2359 patients were selected. Retrospective HLA gene loss gene detection was performed for the deoxyribonucleic acid in 179 relapsed patients, including 47 patients in the HLA loss group (27.2%), 126 patients in the non‐HLA loss group (72.8%) and 6 patients were excluded due to a lack of confirmed results. There was no significant statistical difference in the baseline characteristics of patients between the two groups, but as to transplantation‐related characteristics, the donor–recipient relationship and HLA mismatched loci were statistically different between the two groups (both p < 0.001). Multivariate Cox analysis showed that more HLA mismatched loci ≥3 (HR = 3.66; 95% CI: 1.61–8.31; p = 0.002), time (≤6 months) from HSCT to relapse (HR = 7.92; 95% CI: 3.35–18.74; p < 0.001) and donor chimerism (CD3) in bone marrow at relapse (HR = 1.02; 95% CI: 1.00–1.03; p = 0.036) were independent factors affecting HLA loss relapse. The ratio of negative conversion of FLT3‐ITD or CEBPA mutation was significantly lower in patients with post‐transplantation HLA loss relapse than in the non‐HLA loss group (0.0% vs. 45.5%, p = 0.003; 0.0% vs. 80.0%, p = 0.035), with none of the patients with FLT3‐ITD or CEBPA mutation turned negative in the HLA loss group. The number of gene mutations turned negative when relapse in the non‐HLA loss group was remarkably higher than that in the HLA loss group (p = 0.001). Using donor lymphocyte infusion (DLI) could not prolong OS for the HLA loss group (p = 0.42). Nevertheless, second transplantation had a significant positive impact on OS in the HLA loss group (p = 0.017), although only five patients in the HLA loss group underwent second transplantation. However, patients in the non‐HLA loss group using DLI had a relatively longer OS time than those without DLI (p = 0.017). Second transplantation could also prolong OS in the non‐HLA loss group, but the effect was not as significant as in the HLA loss group (p = 0.053). In summary, HLA loss detection is essential for patients with recurrence after transplantation, especially for those with more HLA mismatched loci and non‐sibling donor. Furthermore, the detection of HLA loss has a guiding role in choosing subsequent therapy when relapsed, as secondary transplantation is more suitable than DLI for those with HLA loss.

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Section: Discussionmentioning

confidence: 99%

Risk factors and survival analysis of human leukocyte antigen loss in relapsed acute myeloid leukaemia/myelodysplastic syndrome patients after allogeneic haematopoietic stem cell transplantation

Zhang,

Zhou

et al. 2024

Br J Haematol

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“…As previously described [ 7 ] all patients received either a myeloablative busulfan/cyclophosphamide-based conditioning regimen or a reduced intensity regimen consisting of fludarabine/busulfan. Antithymocyte globulin-Genzyme (ATG-G) or anti-thymocyte globulin Fresenius (ATG-F) was applied as preparation for haplo-HSCT.…”

Section: Methodsmentioning

confidence: 99%

Haploidentical transplants deliver equal outcomes to matched sibling transplants: a propensity score-matched analysis

Zhao

Gao

et al. 2023

J Transl Med

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The success of allogeneic hematopoietic stem cell transplant for hematological malignancies is heavily dependent on the availability of suitable donors. Haploidentical donor (HID) and matched sibling donor (MSD) are two important donor options providing faster and easier sources of stem cells, however, due to confounding factors present in most retrospective studies, the validity of comparing outcomes between these two donor types remains uncertain. We conducted a post-hoc analysis of a prospective clinical trial (trial registration: Chinese Clinical Trial Registry; #ChiCTR-OCH-12002490; registered 22 February 2012; https://www.chictr.org.cn/showproj.aspx?proj=7061) to compare outcomes of HID versus MSD peripheral blood stem cell-derived transplants in patients with hematologic malignancies between 2015 and 2022. All HID-receiving patients had antithymocyte globulin-based conditioning. Propensity score matching was employed to minimize potential confounding factors between the two cohorts. A total of 1060 patients were initially reviewed and then 663 patients were ultimately included in the analysis after propensity score matching. The overall survival, relapse-free survival, non-relapse mortality rate and cumulative incidence of relapse were similar between HID and MSD cohorts. Subgroup analysis revealed that patients with positive measurable residual disease in first complete remission may have better overall survival with an HID transplant. The present demonstrated that haploidentical transplants can provide outcomes comparable to conventional MSD transplants, and HID should be recommended as one of the optimal donor choices for patients with positive measurable residual disease in first complete remission.

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“…Loss of HLA antigens reduces the efficacy of the GVL effect and favors the immune escape of AML cells. In haploidentical HSCT, as there is no incompatible target to stimulate alloreactivity, the GVL effect remains low[ 168 , 169 ]. Wu et al [ 169 ] analyzed nearly 800 cases of AML and ALL that were subjected, following an ATG T cell-replete conditioning regimen, to haploidentical HSCT and delineated that relapse occurred faster in AML patients who experienced loss of HLA antigens vs those who did not (223 d vs 321 d, P = 0.03).…”

Section: Intervention and Treatment Strategies For Post-allo-hsct Rel...mentioning

confidence: 99%

“…In haploidentical HSCT, as there is no incompatible target to stimulate alloreactivity, the GVL effect remains low[ 168 , 169 ]. Wu et al [ 169 ] analyzed nearly 800 cases of AML and ALL that were subjected, following an ATG T cell-replete conditioning regimen, to haploidentical HSCT and delineated that relapse occurred faster in AML patients who experienced loss of HLA antigens vs those who did not (223 d vs 321 d, P = 0.03). The factors linked with HLA loss in AML were aGVHD (odds ratio = 4.84) and body mass index < 18.5 kg/m 2 (odds ratio = 0.10).…”

Section: Intervention and Treatment Strategies For Post-allo-hsct Rel...mentioning

confidence: 99%

“…However, the efficacy of DLI varies greatly for different types of hematological malignancies. Clinical data show that DLI enables most patients with relapsed chronic myeloid leukemia to achieve CR in the early stage of relapse, while the remission rate is lower than 30% for patients with relapsed acute leukemia[ 169 ]. The main side effects of DLI are GVHD and pancytopenia.…”

Section: Intervention and Treatment Strategies For Post-allo-hsct Rel...mentioning

confidence: 99%

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Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

Chen¹,

Li²,

Xu³

et al. 2023

World J Clin Cases

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As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and post-transplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

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Assessment of Patient-Specific Human Leukocyte Antigen Genomic Loss at Relapse After Antithymocyte Globulin–Based T-Cell–Replete Haploidentical Hematopoietic Stem Cell Transplant

Cited by 10 publications

References 34 publications

Risk factors and survival analysis of human leukocyte antigen loss in relapsed acute myeloid leukaemia/myelodysplastic syndrome patients after allogeneic haematopoietic stem cell transplantation

Risk factors and survival analysis of human leukocyte antigen loss in relapsed acute myeloid leukaemia/myelodysplastic syndrome patients after allogeneic haematopoietic stem cell transplantation

Haploidentical transplants deliver equal outcomes to matched sibling transplants: a propensity score-matched analysis

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

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