title: Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.
abstract: We analyzed the outcome of 537 adolescents (age 12-18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14). Event-free survival in the same groups was respectively 83%, 64% and 71% (P=0.04). Cumulative incidence of rejection was 8% in matched family donor hematopoietic stem cell transplantation and 9% in transplants post failed front-line immunosuppression (P=0.62). Cumulative incidence of acute graft-versus-host disease was 12% in matched family donor transplants and 18% in transplants post failed immunosuppression (P=0.18). Chronic graft-versus-host disease was higher in matched family donor hematopoietic stem cell transplantation (8%) than in transplants post failed immunosuppressive therapy (20%) (P=0.0009). Cumulative incidence of post-therapy malignancies was 0.7% in matched family donor transplantations, 7% in transplantations post failed immunosuppression and 21% after front-line immunosuppression (P=0.0017). In the whole cohort, under multivariate analysis, the diagnosis to treatment interval of two months or under positively affected overall survival whereas up-front immunosuppression alone (with no subsequent rescue transplants) negatively affected event-free survival. In transplanted patients an interval from diagnosis to treatment of 2 months or under, bone marrow as source of cells and first-line matched family donor transplants provided a significant advantage in overall and event-free survival. Aplastic anemia in adolescents has a very good outcome. If a matched family donor is available, hematopoietic stem cell transplantation using bone marrow cells is the first choice treatment. If such a donor is not available, immunosuppressive treatment may still be an acceptable second choice, also because, in case of failure, hematopoietic stem cell transplantation is a very good rescue option.
authors.affiliation: Clinical and Experimental Hematology Unit. G Gaslini Childrens' Hospital, Genova, Italy carlodufour@ospedale-gaslini.ge.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Pediatric Hemato-Oncology Clinic, University of Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Pillon
authors.affiliation: Basel University Hospital, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.affiliation: Department of Hematology, Hospital St Louis, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Second Division of Hematology, San Martino Hospital, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.affiliation: Pediatric Hemato-Oncology Clinic, University of Padova, Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Franceschetto
authors.affiliation: Pediatric Hemato-Oncology Clinic, University of Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Carraro
authors.affiliation: Second Division of Hematology, San Martino Hospital, Genova, Italy.
authors.forename: Rosi
authors.initials: R
authors.lastname: Oneto
authors.affiliation: Hematology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Italy.
authors.forename: Antonio Maria
authors.initials: AM
authors.lastname: Risitano
authors.affiliation: Department of Hematology, Hospital St Louis, Paris, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Basel University Hospital, Switzerland.
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
authors.affiliation: Basel University Hospital, Switzerland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rovo
authors.affiliation: Pediatric Hematopoietic Stem Cell Transplantation, St Anna Kinderspital, Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.affiliation: Institut for Clinical Transfusion Medicine and Immunogenetics, and Department of Transfusion Medicine University of Ulm, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Hoechsmann
authors.affiliation: Department of Paediatric and Adolescent Haematology and Oncology, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS. Current address: Great Ormond Street Children's Hospital, London UK.
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
authors.affiliation: Department of Haematological Medicine, King's College Hospital/King's College London, UK.
authors.forename: Austin G
authors.initials: AG
authors.lastname: Kulasekararaj
authors.affiliation: Institut for Clinical Transfusion Medicine and Immunogenetics, and Department of Transfusion Medicine University of Ulm, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.affiliation: King Faisal Specialist Hospital & Research Center, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Department of Haematological Medicine, King's College Hospital/King's College London, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Marsh
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy; D016026:Bone Marrow Transplantation; D002648:Child; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000209:etiology; D019538:Health Care Surveys; D019337:Hematologic Neoplasms / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008297:Male; D063868:Patient Outcome Assessment; D011379:Prognosis; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult
references.citation: Haematologica. 2010 Dec;95(12):2119-25
references.pmid: 20851870
references.citation: J Rheumatol. 2002 Sep;29(9):1989-99
references.pmid: 12233897
references.citation: Blood. 2008 Feb 1;111(3):1054-9
references.pmid: 17989314
references.citation: Hematology Am Soc Hematol Educ Program. 2012;2012:292-300
references.pmid: 23233595
references.citation: Blood. 2007 Aug 15;110(4):1397-400
references.pmid: 17475907
references.citation: J Pediatr. 2012 Oct;161(4):652-7.e1
references.pmid: 22578579
references.citation: Blood. 2011 Sep 1;118(9):2618-21
references.pmid: 21677312
references.citation: Haematologica. 2012 May;97(5):710-6
references.pmid: 22180425
references.citation: Haematologica. 2011 May;96(5):771-4
references.pmid: 21273269
references.citation: Pediatr Endocrinol Diabetes Metab. 2011;17(4):173-7
references.pmid: 22248776
references.citation: Pediatr Blood Cancer. 2013 Jun;60(6):893-4
references.pmid: 23193097
references.citation: Blood. 1998 Mar 15;91(6):1959-65
references.pmid: 9490678
references.citation: N Engl J Med. 2011 Aug 4;365(5):430-8
references.pmid: 21812672
references.citation: Blood. 2012 Aug 9;120(6):1185-96
references.pmid: 22517900
references.citation: Br J Haematol. 2009 Oct;147(1):43-70
references.pmid: 19673883
references.citation: Br J Haematol. 1999 Nov;107(2):330-4
references.pmid: 10583220
references.citation: Int J Pediatr Endocrinol. 2011 Nov 18;2011(1):18
references.pmid: 22099887
references.citation: Bone Marrow Transplant. 2013 Feb;48(2):161
references.pmid: 23165496
references.citation: Haematologica. 2014 Apr;99(4):664-71
references.pmid: 24213150
references.citation: Br J Haematol. 2012 May;157(3):339-46
references.pmid: 22372373
references.citation: Eur J Endocrinol. 2012 Sep;167(3):387-92
references.pmid: 22728345
references.citation: PLoS One. 2012;7(2):e32640
references.pmid: 22389717
references.citation: Blood. 2012 Jun 7;119(23):5391-6
references.pmid: 22544699
references.citation: Haematologica. 2012 Aug;97(8):1142-8
references.pmid: 22315497
references.citation: Haematologica. 2007 Jan;92(1):11-8
references.pmid: 17229630
references.citation: N Engl J Med. 1993 Oct 14;329(16):1152-7
references.pmid: 8377778
references.citation: Br J Haematol. 2006 Jun;133(6):622-7
references.pmid: 16704436
references.citation: Blood. 2006 Oct 15;108(8):2509-19
references.pmid: 16778145