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Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia

GATA-binding protein 2 (GATA2) is a transcription factor responsible for the regulation of blood cell proliferation, differentiation, and maintenance in hematopoietic stem cells. Here, we describe successful bone marrow transplantation in a carrier of a novel GATA2 pathogenic variant who was diagnos...

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Autores principales: Heropolitańska-Pliszka, Edyta, Piątosa, Barbara, Szmydki-Baran, Anna, Kuczborska, Karolina, Miarka-Walczyk, Karolina, Pastorczak, Agata, Młynarski, Wojciech, Sędek, Łukasz, Szczepański, Tomasz, Ussowicz, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378963/
https://www.ncbi.nlm.nih.gov/pubmed/35983050
http://dx.doi.org/10.3389/fimmu.2022.928529
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author Heropolitańska-Pliszka, Edyta
Piątosa, Barbara
Szmydki-Baran, Anna
Kuczborska, Karolina
Miarka-Walczyk, Karolina
Pastorczak, Agata
Młynarski, Wojciech
Sędek, Łukasz
Szczepański, Tomasz
Ussowicz, Marek
author_facet Heropolitańska-Pliszka, Edyta
Piątosa, Barbara
Szmydki-Baran, Anna
Kuczborska, Karolina
Miarka-Walczyk, Karolina
Pastorczak, Agata
Młynarski, Wojciech
Sędek, Łukasz
Szczepański, Tomasz
Ussowicz, Marek
author_sort Heropolitańska-Pliszka, Edyta
collection PubMed
description GATA-binding protein 2 (GATA2) is a transcription factor responsible for the regulation of blood cell proliferation, differentiation, and maintenance in hematopoietic stem cells. Here, we describe successful bone marrow transplantation in a carrier of a novel GATA2 pathogenic variant who was diagnosed with immunodeficiency a few years after completion of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. At the age of 4 years, the patient was diagnosed with and treated for BCP-ALL. Antileukemic therapy was complicated by pulmonary cryptococcosis. Two years after completion of the maintenance therapy, the child was consulted by an immunologist because of recurrent respiratory tract infections and an episode of sepsis. Flow cytometry revealed deep monocytopenia, lymphopenia, absence of B lymphocytes, considerably reduced NK cells, poor thymic T lymphocyte production, minor defects in T cell maturation, and absence of TCRγδ+ T cells. The presence of the likely pathogenic, heterozygous missense variant within exon 5 of GATA2 (NM_032638.5: c.1047T>G, Cys349Trp) was identified in the proband and confirmed in the father of the patient, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor due to myelodysplastic syndrome with excess blasts at the age of 22 years. An allogeneic hematopoietic stem cell transplantation with a reduced toxicity conditioning protocol was performed using a matched sibling donor. Pre-transplant conditioning included fludarabine (5 × 30 mg/m2), treosulfan (3 × 14 g/m2), and thiotepa (10 mg/kg). Complete donor chimerism was achieved on post-transplant day 17. During the 12 months of the posttransplant observation period, she remained free from symptoms of acute or chronic graft-versus-host disease, and immunosuppressive treatment was therefore stopped. This is the second reported case of BCP-ALL in a patient with GATA2 deficiency, and the first successfully treated with a reduced-toxicity conditioning HSCT protocol. The co-occurrence of lymphoid malignancies and primary immunodeficiencies points to the role of genetic counseling and family screening for possible cancer predisposition syndromes prior to the selection of related HSCT donors.
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spelling pubmed-93789632022-08-17 Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia Heropolitańska-Pliszka, Edyta Piątosa, Barbara Szmydki-Baran, Anna Kuczborska, Karolina Miarka-Walczyk, Karolina Pastorczak, Agata Młynarski, Wojciech Sędek, Łukasz Szczepański, Tomasz Ussowicz, Marek Front Immunol Immunology GATA-binding protein 2 (GATA2) is a transcription factor responsible for the regulation of blood cell proliferation, differentiation, and maintenance in hematopoietic stem cells. Here, we describe successful bone marrow transplantation in a carrier of a novel GATA2 pathogenic variant who was diagnosed with immunodeficiency a few years after completion of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. At the age of 4 years, the patient was diagnosed with and treated for BCP-ALL. Antileukemic therapy was complicated by pulmonary cryptococcosis. Two years after completion of the maintenance therapy, the child was consulted by an immunologist because of recurrent respiratory tract infections and an episode of sepsis. Flow cytometry revealed deep monocytopenia, lymphopenia, absence of B lymphocytes, considerably reduced NK cells, poor thymic T lymphocyte production, minor defects in T cell maturation, and absence of TCRγδ+ T cells. The presence of the likely pathogenic, heterozygous missense variant within exon 5 of GATA2 (NM_032638.5: c.1047T>G, Cys349Trp) was identified in the proband and confirmed in the father of the patient, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor due to myelodysplastic syndrome with excess blasts at the age of 22 years. An allogeneic hematopoietic stem cell transplantation with a reduced toxicity conditioning protocol was performed using a matched sibling donor. Pre-transplant conditioning included fludarabine (5 × 30 mg/m2), treosulfan (3 × 14 g/m2), and thiotepa (10 mg/kg). Complete donor chimerism was achieved on post-transplant day 17. During the 12 months of the posttransplant observation period, she remained free from symptoms of acute or chronic graft-versus-host disease, and immunosuppressive treatment was therefore stopped. This is the second reported case of BCP-ALL in a patient with GATA2 deficiency, and the first successfully treated with a reduced-toxicity conditioning HSCT protocol. The co-occurrence of lymphoid malignancies and primary immunodeficiencies points to the role of genetic counseling and family screening for possible cancer predisposition syndromes prior to the selection of related HSCT donors. Frontiers Media S.A. 2022-08-02 /pmc/articles/PMC9378963/ /pubmed/35983050 http://dx.doi.org/10.3389/fimmu.2022.928529 Text en Copyright © 2022 Heropolitańska-Pliszka, Piątosa, Szmydki-Baran, Kuczborska, Miarka-Walczyk, Pastorczak, Młynarski, Sędek, Szczepański and Ussowicz https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Heropolitańska-Pliszka, Edyta
Piątosa, Barbara
Szmydki-Baran, Anna
Kuczborska, Karolina
Miarka-Walczyk, Karolina
Pastorczak, Agata
Młynarski, Wojciech
Sędek, Łukasz
Szczepański, Tomasz
Ussowicz, Marek
Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia
title Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia
title_full Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia
title_fullStr Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia
title_full_unstemmed Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia
title_short Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia
title_sort case report: successful allogeneic stem cell transplantation in a child with novel gata2 defect associated b-cell acute lymphoblastic leukemia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378963/
https://www.ncbi.nlm.nih.gov/pubmed/35983050
http://dx.doi.org/10.3389/fimmu.2022.928529
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