Sirolimus is effective in relapsed/refractory autoimmune cytopenias: Results of a prospective multi-Institutional trial

Blood

Volumn 127, Issue 1, 2016, Pages 17-28

  Bride, Karen L ^a,b   Vincent, Tiffaney ^a,b   Smith Whitley, Kim ^a,b   Lambert, Michele P ^a,b   Bleesing, Jack J ^c   Seif, Alix E ^a,b   Manno, Catherine S ^d   Casper, James ^e   Grupp, Stephan A ^a,b   Teachey, David T ^a,b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^d NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

Improving autoimmune cytopenias in highly refractory patients; Monotherapy is a safe and effective steroid Sparing agent; Sirolimus; Sirolimus is particularly active in alps and should be an early therapy option for patients who require chronic therapy

Indexed keywords

CORTICOSTEROID; GRANULOCYTE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN G; MERCAPTOPURINE; METHOTREXATE; MYCOPHENOLATE MOFETIL; PYRIMETHAMINE; RAPAMYCIN; RITUXIMAB; IMMUNOSUPPRESSIVE AGENT;

ACNE; ADOLESCENT; ADULT; AUTOIMMUNE DISEASE; AUTOIMMUNE HEMOLYTIC ANEMIA; CHILD; CLINICAL ARTICLE; COMMON VARIABLE IMMUNODEFICIENCY; CORTICOSTEROID THERAPY; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; FEMALE; GASTROESOPHAGEAL REFLUX; HEADACHE; HUMAN; HYPERTENSION; LYMPHOCYTE SUBPOPULATION; LYMPHOPROLIFERATIVE DISEASE; MALE; MONOTHERAPY; MUCOSA INFLAMMATION; MULTICENTER STUDY; OPEN STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; REFRACTORY AUTOIMMUNE CYTOPENIA; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; TREATMENT DURATION; TREATMENT RESPONSE; AUTOIMMUNE DISEASES; CANCER STAGING; CLINICAL TRIAL; DRUG EFFECTS; DRUG RESISTANCE; FOLLOW UP; HEMATOLOGIC DISEASES; INFANT; MORTALITY; PATHOLOGY; PRESCHOOL CHILD; PROGNOSIS; SALVAGE THERAPY; SURVIVAL RATE; TISSUE DISTRIBUTION; TUMOR RECURRENCE; YOUNG ADULT;

ADOLESCENT; ADULT; AUTOIMMUNE DISEASES; CHILD; CHILD, PRESCHOOL; DRUG RESISTANCE, NEOPLASM; FEMALE; FOLLOW-UP STUDIES; HEMATOLOGIC DISEASES; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFANT; MALE; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; PROGNOSIS; PROSPECTIVE STUDIES; SALVAGE THERAPY; SIROLIMUS; SURVIVAL RATE; TISSUE DISTRIBUTION; YOUNG ADULT;

EID: 84955448536     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2015-07-657981     Document Type: Review

References (17)

1. Teachey DT, Lambert MP. Diagnosis and management of autoimmune cytopenias in childhood. Pediatr Clin North Am. 2013;60(6): 1489-1511.
2. Seidel MG. Autoimmune and other cytopenias in primary immuno deficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood. 2014;124(15):2337-2344.
3. Teachey DT. Autoimmune lymphoproliferative syndrome: new approaches to diagnosis and management. Clin Adv Hematol Oncol. 2011;9(3): 233-235.
4. Teachey DT. New advances in the diagnosis and treatment of autoimmune lymphoproliferative syndrome. Curr Opin Pediatr. 2012;24(1):1-8.
5. Teachey DT, Greiner R, Seif A, et al. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 2009;145(1):101-106.
6. Teachey DT, Obzut DA, Axsom K, et al. Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS). Blood. 2006;108(6): 1965-1971.
7. Teachey DT, Seif AE, Grupp SA. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS). Br J Haematol. 2010;148(2):205-216.
8. Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011; 118(22):5741-5751.
9. Dowdell KC, Niemela JE, Price S, et al. Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. Blood. 2010; 115(25):5164-5169.
10. Price S, Shaw PA, Seitz A, et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014;123(13):1989-1999.
11. Oliveira JB, Bleesing JJ, Dianzani U, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010;116(14):e35-e40.
12. Tarbox JA, Keppel MP, Topcagic N, et al. Elevated double negative T cells in pediatric autoimm.
13. Barrett D, Brown VI, Grupp SA, Teachey DT. Targeting the PI3K/AKT/mTOR signaling axis in children with hematologic malignancies. Paediatr Drugs. 2012;14(5):299-316.
14. Miano M, Scalzone M, Perri K, et al. Mycophenolate mofetil and sirolimus as second or further line treatment in children with chronic refractory primitive or secondary autoimmune cytopenias: A single centre experience [published online ahead of print June 8, 2015]. Br J Haematol. doi:10.1111/bjh.13533.
15. Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science. 2014;345(6204):1623-1627.
16. Lucas CL, Kuehn HS, Zhao F, et al. Dominantactivating germline mutations in the gene encoding the PI(3)K catalytic subunit p110d result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88-97.
17. Rao VK. Approaches to managing autoimmune cytopenias in novel immunological disorders with genetic underpinnings like autoimmune lymphoproliferative syndrome. Front Pediatr. 2015;3:65.