Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency

Abstract

Summary:Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention. Keywords: autoimmune thrombocytopenia; BMT; severe combined immunodeficiency Severe combined immunodeficiency (SCID) is a syndrome describing children with profound cellular and humoral immune dysfunction attributable to different causes such as enzyme deficiencies (ADA, PNP), 1,2 T cell defects, defective HLA expression, as well as the more common ␥c deficiency. 3 For these patients, with the exception of ADA deficiency, bone marrow transplantation (BMT) is the therapy of choice. 4,5 The time taken for engraftment of the marrow cells and immune reconstitution varies depending on multiple factors. These include: (a) the use of T cell depleted 6-8 vs unfractionated bone marrow cells; 9,10 (b) pre-transplant conditioning; (c) the presence or absence of graft-versushost disease (GVHD) and its treatment; 11 (d) concomitant infections; and (e) the general status of the patient. 12 During this early post-transplant period, the immune imbalance observed as the donor immune system emerges, modified by the host, results in well described symptom complexes such as GVHD. 11,[13][14][15][16] This underlying immune dysregulation may also result in autoimmune cytopenias. 12,17 We report two cases of severe AITP following a haploidentical, T cell-depleted allogeneic BMT for SCID. Case report Patient AA girl presented with recurrent respiratory infections and persistent diarrhea and was diagnosed with T − B + SCID with normal adenosine deaminase (ADA) and purine nucleophosphorylase (PNP) levels at 3 months of age. Her hematological and immunological profile at presentation were: hemoglobulin (Hb) 11.8 g/dl, white cell count (WCC) 4.6 × 10 9 /l, platelet count (plat) 225 × 10 9 /l, Ig G/A/M of 1.7, Ͻ 0.1, 0.3 g/l, respectively, CD3 Ͻ0.02 (normal 0.9-1.6), CD4 Ͻ0.02 (normal 0.7-1.2), CD8 Ͻ0.02 (0.3-9.7), CD19 1.74 (0.16-0.36) and NK cells 0.39 (0.13-0.35) × 10 9 /l. Response to mitogen was not performed due to the almost absent number of T cells. She underwent a T cell-depleted (soybean lectin sheep E-rosetting), haploidentical BMT without conditioning from her father at 4 months of age. Engraftment was documented on day +21 post-transplant by fluorescent in situ hybridization (FISH) studies for XY cells and the post-transplantation course was complicated by respiratory failure, acute renal failure and graft-versus-host disease (GVHD) involving skin and gastrointestinal tract...

IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H)

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“…The occurrence of ITP in BMT recipients has been reported in several articles, in which GVHD was considered to play a role in the pathogenesis of ITP. 3,4 In the present case, however, there was no sign of GVHD throughout the clinical course. The platelet count drastically decreased 2 weeks after the influenza vaccination, possibly suggesting that the influenza vaccination caused this complication.…”

Correction of Celiac Disease After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia

“…Bone marrow aspiration and biopsy showed increased megakaryocytes consistent with a platelet-destructive process, and the patient was diagnosed with posttransplant idiopathic thrombocytopenic purpura. [9][10][11] She was treated on 1 occasion with anti-D antibody (WinRho; Baxter Healthcare, Deerfield, IL) and on 1 occasion with intravenous Ig, in each case with a good response. She continues to have mild-to-moderate thrombocytopenia but has not been treated further, with her single dose of intravenous Ig having been given 7 months before her most recent serologic studies for CD.…”