Pitfalls and Successes in Trials in Older Transplant Patients with Hematologic Malignancies

Zhao, Aaron T.; Sung, Anthony D.

doi:10.1007/s11912-022-01194-3

Cited by 3 publications

(2 citation statements)

References 84 publications

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“…With the advances in supportivecare, better donor selection and the development of reduced intensity conditioning (RIC) extended the indications for allogeneic HSCT to wider patients with hematologic malignancies including elderly one with more emphasis on comorbidities than age alone for patient selection [ 13 , 14 ]. Ageing affected humoral immune response both quantitatively and qualitatively, as specificity and class of antibody produced were changed and immunosenescence in individuals generally began at the age over 50 years old [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT

Pan,

Ma,

You

et al. 2024

Immun Ageing

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Background With the development of Hematopoietic Stem Cell Transplantation (HSCT) technology, increasing numbers of elderly patients were undergoing allogeneic HSCT and elderly patients with hematologic malignancies could benefit most from it. Preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) were associated with graft failure in HLA-mismatched allogeneic HSCT and the absence of DSA was the main criterion of selecting the donor. Except for sensitization events such as transfusion, pregnancy or previous transplantation, ageing affects the humoral immune response both quantitatively and qualitatively. To evaluate the prevalence and distribution of anti-HLA and antibodies of MHC class I chain related antigens A (MICA) specificities in different age groups before initial HSCT would provide HLA and MICA specific antibody profiles under the impact of ageing, which could provide meaningful information in the process of selecting suitable HLA-mismatched donors by avoiding preformed DSA. Results There were no significant differences in the distribution of anti-HLA class I, class II and anti-MICA antibodies among the three age groups in this study except that a significant lower negative ratio of anti-HLA class I, class II antibodies and higher positive rate of MICA antibodies with maximum mean fluorescent intensity (MFI) > 5000 in the elderly than in young age group. The distribution of antibody specificities against HLA -A, -B, -C, -DR, -DQ, -DP and MICA antigens in the three age groups were generally consistent. The anti-HLA class I antibody specificities with higher frequencies were A80,A68;B76,B45;Cw17, which were unlikely to become DSA in Chinese. Anti-HLA class II antibody specificities were more likely to become potential DSA than class I.DR7, DR9, DQ7, DQ8 and DQ9 were most likely to become potential DSA. Conclusions The prevalence of anti-HLA and anti-MICA antibodies increased slightly as age increased. While ageing had a small impact on the distribution of antibody specificity frequencies against HLA-A, -B, -C, -DR,-DQ, -DP and MICA antigens in recipients awaiting initial HSCT from East China. The risk of developing preformed DSA was basically consistent in the three age groups and the elderly group might be more favorable in HLA-mismatched HSCT due to higher positive rate of anti-MICA antibody.

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Section: Discussionmentioning

confidence: 99%

The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT

Pan,

Ma,

You

et al. 2024

Immun Ageing

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“…It is well established that the risk of graft-versus-host disease (GVHD) increases with age and the use of a peripheral blood stem cell (PBSC) graft [7][8][9][10][11]. In the last decade, several reports have described that the outcome of older patients undergoing haplo-SCT has improved due to effective prophylaxis strategies for acute or chronic GVHD.…”

Section: Introductionmentioning

confidence: 99%

Reduced-toxicity conditioning regimen with low dose post-transplantation cyclophosphamide and low-dose anti-thymocyte globulin as graft-versus-host disease prophylaxis for haploidentical stem cell transplantation in older patients

Ye,

Wu,

Cao

et al. 2024

Ann Hematol

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Reduced-toxicity conditioning (RIC) regimens are used for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older patients. However, successful outcomes are still hindered by graftversus-host disease (GVHD), treatment-related mortality (TRM) and relapse, especially in the setting of haploidentical donor (HID) hematopoietic cell transplantation (HCT). The aim of this study was to evaluate the effectiveness of a RIC conditioning regimen that included a combination of lower doses of post-transplantation cyclophosphamide (PTCy) (40 mg/kg on day +3) and anti-thymocyte globulin (ATG) (7.5 mg/kg) as GVHD prophylaxis, followed by haplo stem cell transplantation (SCT) in older patients.Method: We retrospectively analyzed 55 patients ≥ 55 years of age with hematologic malignancies treated with udarabine, Cytarabine, busulfan, and low dose cyclophosphamide as the conditioning regimen between January 1, 2019 and November 30, 2023.Results: Neutrophil engraftment was successful in all the patients within 28 days, with 54 (98.2%) patients achieving complete donor chimerism. The cumulative incidence of non-relapse mortality was 0 at 30 days, 7.5% at 100 days and 19% at 1-year. The cumulative incidence of grade II-IV aGVHD was 25% (95%CI,15%−38%), while grade III-IV aGVHD was 9.1% (95%CI,3.3%−19%). The cumulative incidence of extensive cGVHD at 1 year was 3.6% (95%CI,0.66%-11%). The cumulative incidence of relapse (CIR), overall survival (OS) and GVHD-free/relapse-free survival (GRFS) at 1-year were 9.0%, 71.6%, and 67.1%, respectively.Conclusions: These results suggested that a RIC conditioning regimen including a combination of lower PTCy/ATG as GVHD prophylaxis, followed by haplo-SCTmight be a promising option for appropriately selected older patients.

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Reduced-toxicity conditioning regimen with low dose post-transplantation cyclophosphamide and low-dose anti-thymocyte globulin as graft-versus-host disease prophylaxis for haploidentical stem cell transplantation in older patients

Ye,

Wu,

Cao

et al. 2024

Preprint

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Reduced-toxicity conditioning (RIC) regimens are used for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older patients. However, successful outcomes are still hindered by graft-versus-host disease (GVHD), treatment-related mortality (TRM) and relapse, especially in the setting of haploidentical donor (HID) hematopoietic cell transplantation (HCT). The aim of this study was to evaluate the effectiveness of a RIC conditioning regimen that included a combination of lower doses of post-transplantation cyclophosphamide (PTCy) (40 mg/kg on day +3) and anti-thymocyte globulin (ATG) (7.5 mg/kg) as GVHD prophylaxis, followed by haplo stem cell transplantation (SCT) in older patients. Method: We retrospectively analyzed 55 patients ≥ 55 years of age with hematologic malignancies treated with fludarabine, Cytarabine, busulfan, and low dose cyclophosphamide as the conditioning regimen between January 1, 2019 and November 30, 2023. Results: Neutrophil engraftment was successful in all the patients within 28 days, with 54 (98.2%) patients achieving complete donor chimerism. The cumulative incidence of non-relapse mortality was 0 at 30 days, 7.5% at 100 days and 19% at 1-year. The cumulative incidence of grade II-IV aGVHD was 25% (95%CI,15%−38%), while grade III-IV aGVHD was 9.1% (95%CI,3.3%−19%). The cumulative incidence of extensive cGVHD at 1 year was 3.6% (95%CI,0.66%-11%). The cumulative incidence of relapse (CIR), overall survival (OS) and GVHD-free/relapse-free survival (GRFS) at 1-year were 9.0%, 71.6%, and 67.1%, respectively. Conclusions: These results suggested that a RIC conditioning regimen including a combination of lower PTCy/ATG as GVHD prophylaxis, followed by haplo-SCTmight be a promising option for appropriately selected older patients.

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Pitfalls and Successes in Trials in Older Transplant Patients with Hematologic Malignancies

Cited by 3 publications

References 84 publications

The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT

The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT

Reduced-toxicity conditioning regimen with low dose post-transplantation cyclophosphamide and low-dose anti-thymocyte globulin as graft-versus-host disease prophylaxis for haploidentical stem cell transplantation in older patients

Reduced-toxicity conditioning regimen with low dose post-transplantation cyclophosphamide and low-dose anti-thymocyte globulin as graft-versus-host disease prophylaxis for haploidentical stem cell transplantation in older patients

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