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10.1016/j.jaci.2015.04.027

http://scihub22266oqcxt.onion/10.1016/j.jaci.2015.04.027
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C4641002!4641002!26055221
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suck abstract from ncbi


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pmid26055221      J+Allergy+Clin+Immunol 2015 ; 136 (5): 1178-85
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  • Radiation-Sensitive Severe Combined Immunodeficiency: The arguments for and against conditioning prior to hematopoietic cell transplantation ? What to do? #MMPMID26055221
  • Cowan M; Gennery A
  • J Allergy Clin Immunol 2015[Nov]; 136 (5): 1178-85 PMID26055221show ga
  • Defects in DCLRE1C, PRKDC, LIG4, NHEJ1, and NBS1, involving the non-homologous end joining (NHEJ) DNA repair pathway, result in radiation-sensitive severe combined immunodeficiency (RS-SCID). Results of hematopoietic cell transplantation for RS-SCID suggest that minimizing exposure to alkylating agents and ionizing radiation is important for optimizing survival and minimizing late effects. However, use of pre-conditioning with alkylating agents is associated with a greater likelihood of full T and B cell reconstitution compared to no conditioning or immunosuppression alone. A reduced intensity regimen using fludarabine and low dose cyclophosphamide may be effective for patients with LIG4, NHEJ1 and NBS1 defects although more data are needed to confirm these findings and characterize late effects. For patients with mutations in DCLRE1C (Artemis-deficient SCID), there is no optimal approach that uses standard dose alkylating agents without significant late effects. Until non-chemotherapy agents, e.g., anti-CD45 or anti-CD117 become available, options include minimizing exposure to alkylators, e.g., single agent low dose targeted Busulfan or achieving T cell reconstitution followed several years later with a conditioning regimen to restore B cell immunity. Gene therapy for these disorders will eventually remove the issues of rejection and GvHD. Prospective multi- center studies are needed to evaluate these approaches in this rare but highly vulnerable patient population.
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