Cancer Treatment Today

Severe combined immunodeficiency (SCID) is a serious, life-threatening condition with high morbidity and mortality. SCID, a group of rare genetic disorders characterized by profound abnormalities in the development and function of the T and B lymphocytes and natural killer cells, was first reported more than 50 years ago. In the past two decades, great advances have been made in the understanding and treatment of SCID. A variety of molecular defects have recently been found to cause SCID, including defects in the gene encoding the common gamma chain (X-linked form), adenosine deaminase deficiency (ADA), interleukin-7 receptor deficiency, janus tyrosine kinase-3 (JAK-3) deficiency and recombinase activating gene (RAG)-1 and RAG-2 deficiency.1,2 The two most common forms of SCID are the X-linked SCID (about 50% of all cases) and those due to an ADA deficiency (about 15-20%). Because the disease is rare, no prospective studies of treatment are possible and it is usually classified in studies with a larger group of inherited immunoeficienceis or genetic syndromes. There are no phase II stuides; only case series and reports.
The first ever successful transplant for SCID was performed in 1968. Over the past several decades, the outcome for SCID as a whole has improved dramatically, and a number of large retrospective registry studies have documented the success in improving overall survival (OS) and immunologic recovery. The improvements are due to a number of different factors, including earlier diagnosis, better pre- and post-HSCT supportive care, improved HLA typing, the availability of compatible donors from unrelated volunteer and cord blood banks, and less toxic chemotherapy regimens to prepare patients for HSCT. Many of the major studies have tended to look at SCID as a whole, and outcomes have been presented for all types of SCID. However, the rapid advances in gene identification technology now allow us to make specific diagnoses.

Hyper IgM syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling and recurrent infections. Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.The way to look at this disease as it being in a spectrum of immunodeficiency disease, for which replacement of the bone marrow from another individual removes immunodeficiency and cures it.

Diaz de Heredia C, Ortega JJ, Diaz MA, Olive T, Badell I, Gonzalez-Vicent M, et al. Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies. Bone Marrow Transplant. 2008 Apr;41(7):627-33.

Allewelt H et al, Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience.Pediatr Blood Cancer. 2015 Dec;62(12):2216-22.

Immunodeficiency Foundation Diagnostic and Clincial Care Guidelines for Primary Immunodeficiency Disease, IDF 2008 chrome-extension://oemmndcbldboiebfnladdacbdfmadadm/http://primaryimmune.org/wp-content/uploads/2011/04/IDF-Diagnostic-Clinical-Care-Guidelines-for-Primary-Immunodeficiency-Diseases-2nd-Edition.pdf

Griffith LM, Cowan MJ, Kohn DB, et al. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol 2008; 122:1087.

Inborn Errors Working Party (IEWP)
UPDATED! EBMT/ESID GUIDELINES FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PI
Home/ Working Parties/ Inborn Errors Working Party (IEWP)/ Resources/ UPDATED! EBMT/ESID GUIDELINES FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PI
Published: Dec 01, 2011

There is sufficient evidence in various reports over these two decades to consider it medically necessary.

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H. Bobby Gaspar, Waseem Qasim, E. Graham Davies, Kanchan Rao, Persis J. Amrolia, Paul Veys, How I treat severe combined immunodeficiency.
Blood 2013 122:3749-3758

Diaz de Heredia C, Ortega JJ, Diaz MA, Olive T, Badell I, Gonzalez-Vicent M, et al. Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies. Bone Marrow Transplant. 2008 Apr;41(7):627-33.

Elhasid R, Rowe JM. Hematopoietic stem cell transplantation in neutrophil disorders: severe congenital neutropenia, leukocyte adhesion deficiency and chronic granulomatous disease. Clin Rev Allergy Immunol. 2010 Feb;38(1):61-7.

Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, et al. Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood. 2009 Apr 23;113(17):4114-24.

Steward and Jarisch Haemopoietic stem cell transplantation for genetic disorders
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