Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Immune-mediated cytopenia in pediatric primary immune deficiency patients following HSCT

Bone Marrow Transplantation volume 52, pages 1571–1574 (2017)Cite this article

Subjects

Immune-mediated cytopenia following hematopoietic stem cell transplantation (HSCT) has been observed in patients with primary immune deficiency (PID), particularly in those patients receiving umbilical cord blood transplants.1, 2, 3, 4, 5 The association with other non-malignant disorders, and concomitant risk factors, is not fully understood.6 We describe a fatal case of immune-mediated hemolytic anemia in a patient with immune deficiency, followed by a single-center analysis of pediatric patients with PID and other non-malignant disorders developing immune cytopenia as a complication of HSCT.

A 9-month-old female presented to our hospital with failure to thrive, diarrhea and history of bacterial urinary tract infection and pneumonia. Her past medical history included an uncomplicated birth at term and no family history of immune deficiency. An immune deficiency work-up was performed and demonstrated hypogammaglobulinemia (IgG 178 mg/dL) and lymphopenia (absolute lymphocyte count <500 cells/μL). Peripheral blood flow cytometry revealed severe deficiency of T (<100 cells/mL) and B lymphocytes (<50 cells/mL) and analysis of both CD4+ and CD8+ T cells demonstrated absence of CD45RA expression. Mitogen testing revealed decreased T-cell proliferation in response to multiple stimulants. Genetic testing was performed, which revealed two heterozygous RAG1 mutations. The first mutation was the previously described R975Q mutation.7 The second mutation was a novel c.908 arginine to cytidine substitution resulting in a histidine substitution for proline at position 303 (P303H), and this mutation is considered to be a disease-causing alteration. Based on these results and her clinical presentation, she was diagnosed with Omenn syndrome, and was referred for HSCT. Omenn syndrome is a form of severe combined immune deficiency (SCID) where T cells (typically an oligoclonal population) are present, and is often termed ‘leaky’ SCID. These patients frequently develop T-cell-mediated erythroderma and diarrhea with infections secondary to barrier breakdown. Omenn syndrome is uniformly fatal without HSCT.8

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Holbro A, Abinun M, Daikeler T . Management of autoimmune diseases after haematopoietic stem cell transplantation. Br J Haematol 2012; 157: 281–290.

    Article  CAS  Google Scholar 

  2. Daikeler T, Labopin M, Ruggeri A, Crotta A, Abinun M, Hussein AA et al. New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation. Blood 2013; 121: 1059–1064.

    Article  CAS  Google Scholar 

  3. Horn B, Viele M, Mentzer W, Mogck N, DeSantes K, Cowan M . Autoimmune hemolytic anemia in patients with SCID after T cell-depleted BM and PBSC transplantation. Bone Marrow Transplant 1999; 24: 1009–1013.

    Article  CAS  Google Scholar 

  4. Drobyski WR, Potluri J, Sauer D, Gottschall JL . Autoimmune hemolytic anemia following T cell-depleted allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 17: 1093–1099.

    CAS  PubMed  Google Scholar 

  5. Ahmed I, Teruya J, Murray-Krezan C, Krance R . The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post-first and post-second hematopoietic stem cell transplant. Pediatr Transpl 2015; 19: 391–398.

    Article  Google Scholar 

  6. O'Brien TA, Eastlund T, Peters C, Neglia JP, Defor T, Ramsay NK et al. Autoimmune haemolytic anaemia complicating haematopoietic cell transplantation in paediatric patients: high incidence and significant mortality in unrelated donor transplants for non-malignant diseases. Br J Haematol 2004; 127: 67–75.

    Article  Google Scholar 

  7. Villa A, Sobacchi C, Notarangelo LD, Bozzi F, Abinun M, Abrahamsen TG et al. V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood 2001; 97: 81–88.

    Article  CAS  Google Scholar 

  8. Villa A, Notarangelo LD, Roifman CM . Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol 2008; 122: 1082–1086.

    Article  CAS  Google Scholar 

  9. Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ et al. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant 2005; 35: 345–352.

    Article  CAS  Google Scholar 

  10. Rowley SD . Hematopoietic stem cell transplantation between red cell incompatible donor-recipient pairs. Bone Marrow Transplant 2001; 28: 315–321.

    Article  CAS  Google Scholar 

  11. Worel N, Greinix HT, Schneider B, Kurz M, Rabitsch W, Knobl P et al. Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems. Transfusion 2000; 40: 543–550.

    Article  CAS  Google Scholar 

  12. Benjamin RJ, Connors JM, McGurk S, Churchill WH, Antin JH . Prolonged erythroid aplasia after major ABO-mismatched transplantation for chronic myelogenous leukemia. Biol Blood Marrow Transplant 1998; 4: 151–156.

    Article  CAS  Google Scholar 

  13. Sanz J, Arriaga F, Montesinos P, Orti G, Lorenzo I, Cantero S et al. Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients. Bone Marrow Transplant 2007; 39: 555–561.

    Article  CAS  Google Scholar 

  14. Page KM, Mendizabal AM, Prasad VK, Martin PL, Parikh S, Wood S et al. Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are increased in very young infants undergoing unrelated donor umbilical cord blood transplantation. Biol Blood Marrow Transplant 2008; 14: 1108–1117.

    Article  Google Scholar 

  15. Sevilla J, Gonzalez-Vicent M, Madero L, Diaz MA . Acute autoimmune hemolytic anemia following unrelated cord blood transplantation as an early manifestation of chronic graft-versus-host disease. Bone Marrow Transplant 2001; 28: 89–92.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Blood and Marrow Transplant Program, University of Alabama at Birmingham, Birmingham, AL, USA

    J H Chewning, H L Haines & F D Goldman

  2. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    I Aban

  3. Children’s Hospital of Alabama, Birmingham, AL, USA

    R Brown

  4. Children’s Hospital of Alabama Pharmacy Department, Birmingham, AL, USA

    H H Buchanan

Authors
  1. J H Chewning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I Aban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H L Haines
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H H Buchanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F D Goldman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J H Chewning.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chewning, J., Aban, I., Haines, H. et al. Immune-mediated cytopenia in pediatric primary immune deficiency patients following HSCT. Bone Marrow Transplant 52, 1571–1574 (2017). https://doi.org/10.1038/bmt.2017.170

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2017.170

Search

Advanced search

Quick links