Treatment of Omenn syndrome by bone marrow transplantation☆,☆☆,★,★★
Section snippets
METHODS
Between 1981 and 1989 we performed BMT on six girls and three boys with Omenn syndrome, as defined by early onset of exudative erythroderma, associated with pachyderma and alopecia (n = 8), dermal and epidermal infiltration by activated T cells, failure to thrive (n = 7) (with or without diarrhea), liver and spleen enlargement (n = 8 and n = 6, respectively), lymph node enlargement with T- and B-cell depletion, increased T-cell counts with large numbers of activated T cells (HLA-DR+, CD25+),
RESULTS
Engraftment occurred in four of five recipients of HLA-identical marrow. The failure in patient 1 was probably due to inadequate myeloablation, because only ATG and cyclosphosphamide were used for conditioning. Engraftment occurred in three of four recipients of nonidentical marrow. The failure in patient 8 was associated with marrow aplasia that led to death. Full chimerism was achieved in all but one patient (No. 6). Hematologic reconstitution was unremarkable: all the patients had at least
DISCUSSION
In previous reports seven of 26 patients with Omenn syndrome were cured by BMT.5, 14, 15, 16, 17, 18, 19, 20 Failures were due to a lack of engraftment, metabolic complications, or infections (especially early bacterial infections). In the European registry of BMT for immunodeficiencies, we found a further 10 cases of Omenn syndrome treated with BMT. One patient who received marrow from an HLA-matched sibling died 2 days after BMT of an infection; one recipient of marrow from a matched
Acknowledgements
We are grateful to the medical staff and the nursing staff who cared for our patients.
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Cited by (54)
Hematopoietic stem cell transplantation for primary immune deficiencies
2020, Stiehm's Immune Deficiencies: Inborn Errors of ImmunityPrimary Immunodeficiency Masquerading as Allergic Disease
2015, Immunology and Allergy Clinics of North AmericaCitation Excerpt :Care should be taken to treat underlying infections and screening for opportunistic infections should be initiated before immune suppression, given the underlying SCID phenotype. To date, curative treatment and ultimate resolution requires HSCT.13 Infants with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) usually present with severe diarrhea owing to enteropathy, endocrinopathy usually manifesting as type 1 diabetes mellitus, and dermatitis (eczema, erythroderma).
Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency
2014, Stiehm's Immune DeficienciesDiagnosis and treatment of primary immunodeficiency disease in patients with gastrointestinal symptoms
2011, Clinical ImmunologyCitation Excerpt :Patients with Omenn syndrome have T-cells, but decreased numbers of B cells, and hypomorphic mutations of 1 of the 2 recombination-activating genes, Rag1 or Rag2, or mutations in the Artemis gene [33]. The syndrome presents with erythroderma, hepatosplenomegaly, and lymphadenopathy, often accompanied by recurrent infections, as well as failure to thrive and alopecia [31,32,34]. Omenn syndrome patients also present with intractable diarrhea due to malabsorption or infection with enteric pathogens [35,36].
Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: Entering a new century, do we do better?
2010, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Their outcome is poor, possibly explaining the unexpectedly worse outcome in this younger age group in contradistinction to patients with SCID transplanted at the same age (Fig E3). A separate analysis of the T-lymphocyte deficiency category showed worse outcome for these 3 diagnoses, and the generally poor overall outcome for the T-immunodeficiency group was not skewed by particularly poor results for a specific disease category within the group (see this article's Fig E5 in the Online Repository at www.jacionline.org)—as previously demonstrated in disease-specific series.33,34 Beyond a year, survival improves as well patients with no or minimal organ damage are treated.
Bone marrow transplantation for primary immunodeficiency diseases
2010, Pediatric Clinics of North AmericaCitation Excerpt :OS is inevitably fatal if untreated and HSCT is the only potentially curative option. Initial reports suggested that survival after HSCT was poor for children with OS, mainly as a result of graft failure, infections, and metabolic complications.53,54 More recently, however, survival rates of greater than 80% have been reported with the use of HLA-haploidentical parental and unrelated donor (UD) graft.55,56
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From the Unité d'Immunologie et d'Hématologie and INSERM U429, Hôpital Necker-Enfants Malades, Paris, France, and the Immunodeficiency Pediatric Unit, Institute of Immunology, Moscow, Russia
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Supported by INSERM and a grant from the Association de la Recherche sur le Cancer.
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Reprint requests: Alain Fischer, MD, PhD, INSERM U429, Hôpital Necker-Enfants Malades, 149 rue de Sevres, 75015 Paris, France.
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0022-3476/95/$3.00 + 0 9/20/64386