Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction

Hirabayashi, Koichi; Kurata, Tadao; Horiuchi, Kazuki; Saito, Shoji; Shigemura, Tomonari; Tanaka, Miyuki; Yanagisawa, Ryu; Matsuda, Kazuyuki; Sakashita, Kazuo; Koike, Kenichi; Nakazawa, Yozo

doi:10.1002/pbc.25819

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…To our knowledge, HLA-loss has not been reported after Haplo-HSCT for lymphoid neoplasms. There is only one report of HLA-loss in acute lymphoblastic leukemia after allo-HSCT, but in this study the relapse occurred after HSCT from related donors with HLA-DRB1 and HLA-DQB1 mismatches (30). The reported lack of HLA-loss relapses after LPS might be due to the difficulty in studying the relapse, because FFPE samples are not always accessible.…”

Section: Discussionmentioning

confidence: 71%

Clinical Utility of the Detection of the Loss of the Mismatched HLA in Relapsed Hematological Patients After Haploidentical Stem Cell Transplantation With High-Dose Cyclophosphamide

et al. 2021

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Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with high-dose cyclophosphamide (PTCy) has resulted in a low incidence of graft-vs.-host disease (GVHD), graft failure, and non-relapse mortality. However, post-transplantation relapse remains a common cause of treatment failure in high-risk patients. Unraveling the mechanisms of relapse is therefore crucial for designing effective relapse treatment strategies. One of these mechanisms is the loss of the mismatched HLA on the recipient's leukemic cells. To study the incidence and clinical relevance of this phenomenon, we analyzed 181 patients treated with Haplo-HSCT with PTCy (2007–2019), of which 37 relapsed patients after transplantation. According to the kit employed for HLA-loss analysis, among 22 relapsed patients, we identified HLA loss at relapse in 6 of the 22 patients (27%) studied. Based on the results obtained, the genomic loss of HLA was more common in females than males (66 vs. 33%) and HLA-loss relapses occurred later than classical relapses (345 vs. 166 days). Moreover, the patients with HLA-loss had a greater presence of active disease at the time of transplantation and had undergone a larger number of treatment lines than the group with classical relapses (66 vs. 43% and 66 vs. 18%, respectively). Four of these relapses were studied retrospectively, while two were studied prospectively, the results of which could be considered for patient management. Additionally, two relapsed patients analyzed retrospectively had myeloid neoplasms. One patient had not undergone any treatment, and three had undergone donor lymphocyte infusions (DLIs) and chemotherapy. All presented severe GVHD and disease progression. In contrast, the two patients studied prospectively had a lymphoid neoplasm and were not treated with DLIs. One of them was treated with chemotherapy but died from disease progression, and the other patient underwent a second Haplo-HSCT from a different donor and is still alive. We can conclude that the detection of HLA-loss at the onset of relapse after Haplo-HSCT with PTCy could help in clinical practice to select appropriate rescue treatment, thereby avoiding the use of DLIs or a second transplantation from the same donor.

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Section: Discussionmentioning

confidence: 71%

Clinical Utility of the Detection of the Loss of the Mismatched HLA in Relapsed Hematological Patients After Haploidentical Stem Cell Transplantation With High-Dose Cyclophosphamide

et al. 2021

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“…Other smaller case reports in adults affected by lymphoid malignancies receiving mismatched HSCT showed a similar incidence of HLA. Notably, HLA loss relapses have been recently reported to occur with similar frequency also after haplo-HSCT employing posttransplant cyclophosphamide (PT-Cy) [3], further demonstrating that HLA loss is an intrinsic relapse mechanism after HSCT [4] and especially when using mismatched donors [5,6]. This finding also suggests that even though PT-Cy can dramatically decrease the risk of severe GvHD after haplo-HSCT, it does not eliminate T-cell alloreactivity against the partially HLA-mismatched leukemia.…”

Section: To the Editormentioning

confidence: 98%

HLA-haplotype loss after TCRαβ/CD19-depleted haploidentical HSCT

Shyr

Zhang

Saini

et al. 2020

Bone Marrow Transplant

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“…Потеря гетерозиготности по генам HLA -проявление геномной нестабильности опухоли, характеризующееся выпадением участка короткого плеча 6-й хромосомы. Среди злокачественных заболеваний крови данный механизм описан при рецидивах острых лейкозов у взрослых и детей после алло-ТГСК [11,18,19]. Потеря донор-специфичного гаплотипа HLA на бластной популяции приводит к необратимой потере экспрессии HLA, невозможности распознавания антигенов опухоли T-клетками и подавлению реакции «трансплантат против лейкемии».…”

Section: обсуждение результатов исследованияunclassified

The prophylaxis of severe hemophilia A with inhibitors in children in the Republic of Belarus: a 12-year experience

Dmitriev,

Volkova,

Aleinikova

et al. 2023

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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The development of inhibitory antibodies against FVIII is the most serious complication associated with the use of FVIII concentrates in hemophilia A patients. There is a need for more research on measures that could reduce the risk of inhibitor formation in previously untreated patients (PUPs) with severe hemophilia A. The purpose of this study was to determine the effectiveness of the prevention of clotting inhibitor development in PUPs (or minimally treated patients) with severe hemophilia A by administering plasma-derived factor VIII concentrate (pdFVIII) at a dose of 25 IU/kg once a week for a year. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Between 2010 and 2022, 56 boys were newly diagnosed with severe hemophilia A. Twenty-one of them received pdFVIII as on-demand treatment to stop bleeding (Group 1). Thirty-five boys received pdFVIII at a dose of 25 IU/kg body weight once a week during the first 50 weeks of treatment for the prevention of inhibitor development (Group 2). The administration of pdFVIII at a dose of 25 IU/kg once a week in the PUPs (or minimally treated patients) contributed to a decrease in the cumulative incidence of inhibitors to 15.9 ± 7.7% (4 out of the 35 patients who had been treated prophylactically) compared with 43.7 ± 11.8% (8 out of the 21 patients who had received hemostatic therapy to stop bleeding) (log-rank test, p = 0.041). Thus, the administration of pdFVIII concentrate at a dose of 25 IU/kg once a week for the first 50 weeks of treatment lead to a decrease (p = 0.009) in the cumulative incidence of inhibitors against the administered coagulation factor VIII to 15.9 ± 7.7%.

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Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction

Cited by 10 publications

References 13 publications

Clinical Utility of the Detection of the Loss of the Mismatched HLA in Relapsed Hematological Patients After Haploidentical Stem Cell Transplantation With High-Dose Cyclophosphamide

Clinical Utility of the Detection of the Loss of the Mismatched HLA in Relapsed Hematological Patients After Haploidentical Stem Cell Transplantation With High-Dose Cyclophosphamide

HLA-haplotype loss after TCRαβ/CD19-depleted haploidentical HSCT

The prophylaxis of severe hemophilia A with inhibitors in children in the Republic of Belarus: a 12-year experience

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