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Successful reduced intensity hematopoietic cell transplant in a patient with deficiency of adenosine deaminase 2

Bone Marrow Transplantation volume 52, pages 1575–1576 (2017)Cite this article

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Deficiency of adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disease characterized initially as a triad of autoinflammation, mild immunodeficiency, most evident in B-cells, and vasculopathy.1, 2 ADA2 is a secreted protein encoded by the CECR1 gene and expressed primarily in myeloid cells; it is thought to catalyze the conversion of extracellular adenosine to inosine.3 The clinical severity of the initial DADA2 patients ranged from limited cutaneous to severe multi-systemic polyarteritis nodosa associated with recurrent strokes and injury to other organs. However, a wider spectrum of phenotypes was subsequently described including bone marrow (BM) failure and immunodeficiency, justifying the consideration of hematopoietic cell transplant (HCT) in this disease.4 We report the first patient to undergo a successful HCT for DADA2 using reduced intensity conditioning.

Our patient presented at 3 years of age with anemia (Hb 6.1 g/dL) and reticulocytopenia (0.2%). The complete blood count (CBC) was otherwise normal. BM aspirate and biopsy demonstrated marked erythroid hypoplasia with normal cellularity and unremarkable myelopoiesis and megakaryopoiesis. Coombs test was negative as was testing for parvovirus, EBV, CMV and mycoplasma. He was diagnosed with pure red cell aplasia (PRCA). IVIg was given for presumed parvovirus-associated PRCA as parvovirus DNA PCR from the BM was not available at the time, with no response. Subsequently our patient was started on high-dose steroids, as first-line immunosuppressive therapy for PRCA, with no benefit. He became transfusion independent for 6 months after starting Cyclosporine A. However, anemia returned (Hb 6.1 g/dL) and he subsequently became transfusion dependent. Findings on a repeat BM aspirate and biopsy were similar to the first evaluation, but also showed decreased granulopoiesis. A trial of mycophenolate mofetil followed by Sirolimus failed to improve his anemia. IgG, IgE, IgA were normal, but IgM was decreased (<6 mg/dL), measured prior to any IVIg treatment. An immunodeficiency profile showed elevated percentage of CD3+CD4+ cells, decreased absolute number and percentage of B-cells, and slightly decreased absolute NK cells (details of the patient presentation is reported by Hashem et al.4). Other clinical manifestations included mild hepatosplenomegaly discovered at 3 years of age, recurrent fevers since age of 2 years (five episodes per year), alopecia areata, immune thrombocytopenia diagnosed at 2 years of age and resolved at 3 years, progressive neutropenia, recurrent oral aphthous ulcers, strabismus, eczema, intermittent urticaria (no skin biopsy was done) and recurrent sino-nasal and ear infections.

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Authors and Affiliations

  1. Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, Nationwide Children’s Hospital, Columbus, OH, USA

    H Hashem

  2. Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA

    A Vatsayan, A Gupta, K Nagle & J Dalal

  3. Department of Medicine and Biochemistry, Duke University Medical Center, Durham, NC, USA

    M Hershfield

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  1. H Hashem
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  2. A Vatsayan
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  3. A Gupta
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  4. K Nagle
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  5. M Hershfield
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  6. J Dalal
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Correspondence to H Hashem.

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Hashem, H., Vatsayan, A., Gupta, A. et al. Successful reduced intensity hematopoietic cell transplant in a patient with deficiency of adenosine deaminase 2. Bone Marrow Transplant 52, 1575–1576 (2017). https://doi.org/10.1038/bmt.2017.173

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