Timely follow-up of a GATA2 deficiency patient allows successful treatment

Mannurita, Sara Ciullini; Vignoli, Marina; Colarusso, Gloria; Tucci, Fábio C.; Veltroni, Marinella; Frenos, Stefano; Tintori, Veronica; Collin, Matthew; Favre, Claudio; Gambineri, Eleonora

doi:10.1016/j.jaci.2016.06.004

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…Moreover, there are limited data in this regard. 10, 13 However, three factors play important roles in the indication and timing of transplant: frequency and severity of infections, secondary organ damage such as pulmonary changes, and myeloid progression of cytopenias and cytogenetic abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Parta

Shah

Baird

et al. 2018

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD.

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Section: Discussionmentioning

confidence: 99%

Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Parta

Shah

Baird

et al. 2018

Biology of Blood and Marrow Transplantation

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“…Ciucilli et al reported a young patient who received a transplant from his matched brother using an ablative regimen 75 . Ramazan et al reported a very young patient with Emberger syndrome and MDS who underwent successful myeloablative HSCT with resolution of MDS 76 .…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Germline GATA2 Mutation and Bone Marrow Failure

McReynolds

Calvo

Holland

2018

Hematology/Oncology Clinics of North America

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GATA2 deficiency is an immunodeficiency and bone marrow failure disorder caused by pathogenic variants in GATA2. It is inherited in an autosomal-dominant pattern or can be due to de novo sporadic germline mutation. Patients commonly have B-cell, dendritic cell, natural killer cell, and monocytopenias, and are predisposed to myelodysplastic syndrome, acute myeloid leukemia, and chronic myelomonocytic leukemia. Patients may suffer from disseminated human papilloma virus and mycobacterial infections, pulmonary alveolar proteinosis, and lymphedema. The bone marrow eventually takes on a characteristic hypocellular myelodysplasia with loss of monocytes and hematogones, megakaryocytes with separated nuclear lobes, micromegakaryocytes, and megakaryocytes with hypolobated nuclei.

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“…Thirty patients were previously reported. 11 , 18-20 Data from 500 sporadic adult AML samples (2018-2022) were extracted from the AML database of Toulouse University Hospital registered at the Commission Nationale de l’Informatique et des Libertés (CNIL, #1778920), and sequenced with the same panel, coverage and sensibility of the technique.…”

Section: Methodsmentioning

confidence: 99%

Somatic genetic alterations predict hematological progression in GATA2 deficiency

et al. 2023

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Germline GATA2 mutations predispose to myeloid malignancies resulting from the progressive acquisition of additional somatic mutations. Here we describe clinical and biological features of 78 GATA2 deficient patients. Hematopoietic stem and progenitor cell phenotypic characterization revealed an exhaustion of myeloid progenitors. Somatic mutations in STAG2, ASXL1 and SETBP1 genes along with cytogenetic abnormalities (monosomy 7, trisomy 8, der(1;7)) occurred frequently in patients with GATA2 germline mutations. Patients were classified into three haematopoietic spectra based on bone marrow cytomorphology. No somatic additional mutations were detected in patients with normal bone marrow (spectrum 0), whereas clonal haematopoiesis mediated by STAG2 mutations was frequent in those with a hypocellular and/or myelodysplastic bone marrow without excess blasts (spectrum 1). Finally, SETBP1, RAS pathway and RUNX1 mutations were predominantly associated with leukemic transformation stage (spectrum 2), highlighting their implications in the transformation process. Specific somatic alterations, potentially providing distinct selective advantages to affected cells, are therefore associated with the clinical/haematological evolution of GATA2 syndrome. Our study not only suggests that somatic genetic profiling will help clinicians for their management of patients, but also clarify the mechanism of leukemogenesis in the context of germline GATA2 mutations.

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Timely follow-up of a GATA2 deficiency patient allows successful treatment

Cited by 8 publications

References 10 publications

Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Germline GATA2 Mutation and Bone Marrow Failure

Somatic genetic alterations predict hematological progression in GATA2 deficiency

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