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      Unmanipulated haploidentical hematopoietic stem cell transplantation for pediatric de novo acute megakaryoblastic leukemia without Down syndrome in China: A single-center study

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          Abstract

          Background

          AMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Several researchers have regarded pediatric AMKL without DS as high-risk or at least intermediate-risk AML and proposed that upfront allogenic hematopoietic stem cell transplantation (HSCT) in first complete remission might improve long-term survival.

          Patients and method

          We conducted a retrospective study with twenty-five pediatric (< 14 years old) AMKL patients without DS who underwent haploidentical HSCT in the Peking University Institute of Hematology, Peking University People’s Hospital from July 2016 to July 2021. The diagnostic criteria of AMKL without DS were adapted from the FAB and WHO: ≥ 20% blasts in the bone marrow, and those blasts expressed at least one or more of the platelet glycoproteins: CD41, CD61, or CD42. AMKL with DS and therapy related AML was excluded. Children without a suitable closely HLA-matched related or unrelated donor (donors with more than nine out of 10 matching HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci), were eligible to receive haploidentical HSCT. Definition was adapted from international cooperation group. All statistical tests were conducted with SPSS v.24 and R v.3.6.3.

          Results

          The 2-year OS was 54.5 ± 10.3%, and the EFS was 50.9 ± 10.2% in pediatric AMKL without DS undergoing haplo-HSCT. Statistically significantly better EFS was observed in patients with trisomy 19 than in patients without trisomy 19 (80 ± 12.6% and 33.3 ± 12.2%, respectively, P = 0.045), and OS was better in patients with trisomy 19 but with no statistical significance (P = 0.114). MRD negative pre-HSCT patients showed a better OS and EFS than those who were positive (P < 0.001 and P = 0.003, respectively). Eleven patients relapsed post HSCT. The median time to relapse post HSCT was 2.1 months (range: 1.0–14.4 months). The 2-year cumulative incidence of relapse (CIR) was 46.1 ± 11.6%. One patient developed bronchiolitis obliterans and respiratory failure and died at d + 98 post HSCT.

          Conclusion

          AMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Trisomy 19 and MRD negative pre-HSCT might contribute to a better EFS and OS. Our TRM was low, haplo-HSCT might be an option for high-risk AMKL without DS.

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          Most cited references41

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          The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

          The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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            Proposals for the Classification of the Acute Leukaemias French-American-British (FAB) Co-operative Group

            A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.
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              Chronic graft-versus-host syndrome in man

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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                16 February 2023
                2023
                : 13
                : 1116205
                Affiliations
                [1] 1 Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University , Shenzhen, China
                [2] 2 Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking-Tsinghua Center for Life Science, Research Unit of Key Technique for Diagnosis and Treatment of Hematologic Malignancies, National Clinical Research Center for Hematologic Disease, Peking University People’s Hospital, Peking University Institute of Hematology , Beijing, China
                Author notes

                Edited by: Martin Maiers, National Marrow Donor Program, United States

                Reviewed by: Donglin Yang, Chinese Academy of Medical Sciences and Peking Union Medical College, China; Marco Cerrano, University Hospital of the City of Health and Science of Turin, Italy

                *Correspondence: Yifei Cheng, chengyifei182@ 123456sina.com ; Xiaojun Huang, huangxiaojun@ 123456bjmu.edu.cn

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Hematologic Malignancies, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2023.1116205
                9978202
                36874138
                bb98592e-5c92-4446-85a6-e98b191fb794
                Copyright © 2023 Huang, Hu, Suo, Bai, Cheng, Wang, Zhang, Liu, Sun, Xu, Kong, Yan and Huang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 December 2022
                : 03 February 2023
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 41, Pages: 10, Words: 4766
                Funding
                This work was supported by Sanming Project of Medicine in Shenzhen (SZSM202011004); Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20220530144604011);Clinical Funding of the Seventh Affiliated Hospital, Sun Yat-sen University (ZSQYLCKYJJ202024); Foundation of CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-034).
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                haploidentical,hematopoietic stem cell transplantation,pediatric,acute megakaryoblastic leukemia,de novo

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