{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:49:19Z","timestamp":1791287359702,"version":"4.1.0"},"reference-count":43,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions. RCC is often hypoplastic and may respond to immunosuppressive therapy. In case of immunosuppressive therapy failure, hypercellular RCC, or RCC with monosomy 7, hematopoietic stem cell transplantation (HSCT) using reduced-intensity conditioning regimens is indicated. Almost all patients with refractory anemia with excess blasts are candidates for HSCT; children age 12 years or older have a higher risk of treatment-related death, and the conditioning regimens should be adjusted accordingly. Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL mutations often regresses spontaneously, and therapy is seldom indicated. Conversely, patients with JMML and neurofibromatosis type 1, somatic PTPN11, KRAS, and most of those with NRAS mutations have a rapidly progressive disease, and early HSCT is indicated. The risk of relapse after HSCT is high, and prophylaxis for graft-versus-host disease and monitoring should be adapted to this risk.<\/jats:p>","DOI":"10.1182\/asheducation-2016.1.598","type":"journal-article","created":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T16:05:27Z","timestamp":1480694727000},"page":"598-604","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":67,"title":["Myelodysplastic and myeloproliferative disorders of childhood"],"prefix":"10.1182","volume":"2016","author":[{"given":"Henrik","family":"Hasle","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"2","key":"2019111703530385500_B1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/sj.leu.2402765","article-title":"A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases","volume":"17","author":"Hasle","year":"2003","journal-title":"Leukemia"},{"key":"2019111703530385500_B2","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow","year":"2008"},{"issue":"4","key":"2019111703530385500_B3","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s12185-016-1965-7","article-title":"The current perspective of low-grade myelodysplastic syndrome in children","volume":"103","author":"Hasegawa","year":"2016","journal-title":"Int J Hematol"},{"issue":"3","key":"2019111703530385500_B4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s12308-015-0256-1","article-title":"Myeloproliferative Neoplasms in Children","volume":"8","author":"Hofmann","year":"2015","journal-title":"J Hematop"},{"issue":"7","key":"2019111703530385500_B5","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1182\/blood-2014-08-550483","article-title":"How I treat juvenile myelomonocytic leukemia","volume":"125","author":"Locatelli","year":"2015","journal-title":"Blood"},{"issue":"16","key":"2019111703530385500_B6","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1182\/blood-2014-03-300319","article-title":"Bedside to bench in juvenile myelomonocytic leukemia: insights into leukemogenesis from a rare pediatric leukemia","volume":"124","author":"Chang","year":"2014","journal-title":"Blood"},{"issue":"2","key":"2019111703530385500_B7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1365-2141.2011.08724.x","article-title":"Advances in the prognostication and management of advanced MDS in children","volume":"154","author":"Hasle","year":"2011","journal-title":"Br J Haematol"},{"issue":"1","key":"2019111703530385500_B8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1365-2559.2011.04156.x","article-title":"Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria","volume":"61","author":"Baumann","year":"2012","journal-title":"Histopathology"},{"issue":"10","key":"2019111703530385500_B9","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/ng.923","article-title":"Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)","volume":"43","author":"Ostergaard","year":"2011","journal-title":"Nat Genet"},{"issue":"2","key":"2019111703530385500_B10","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/bjh.13317","article-title":"Haematopoietic and immune defects associated with GATA2 mutation","volume":"169","author":"Collin","year":"2015","journal-title":"Br J Haematol"},{"issue":"11","key":"2019111703530385500_B11","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1182\/blood-2015-09-669937","article-title":"Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents","volume":"127","author":"Wlodarski","year":"2016","journal-title":"Blood"},{"issue":"12","key":"2019111703530385500_B12","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.bbmt.2014.08.004","article-title":"Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2 deficiency","volume":"20","author":"Grossman","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"issue":"1","key":"2019111703530385500_B13","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1309\/AJCP7W9VMJENZOVG","article-title":"Diagnosis of myelodysplastic syndrome among a cohort of 119 patients with fanconi anemia: morphologic and cytogenetic characteristics","volume":"133","author":"Cioc","year":"2010","journal-title":"Am J Clin Pathol"},{"issue":"2","key":"2019111703530385500_B14","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/j.1365-2141.2010.08216.x","article-title":"Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy","volume":"150","author":"Rosenberg","year":"2010","journal-title":"Br J Haematol"},{"issue":"9","key":"2019111703530385500_B15","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.3324\/haematol.2011.057489","article-title":"Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome","volume":"97","author":"Donadieu","year":"2012","journal-title":"Haematologica"},{"issue":"10","key":"2019111703530385500_B16","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.leukres.2015.07.005","article-title":"TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood","volume":"39","author":"Coutinho","year":"2015","journal-title":"Leuk Res"},{"issue":"11","key":"2019111703530385500_B17","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1182\/blood-2011-12-395087","article-title":"Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML","volume":"119","author":"Hirabayashi","year":"2012","journal-title":"Blood"},{"issue":"2","key":"2019111703530385500_B18","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.leukres.2006.06.013","article-title":"Aberrant methylation in pediatric myelodysplastic syndrome","volume":"31","author":"Vidal","year":"2007","journal-title":"Leuk Res"},{"issue":"19","key":"2019111703530385500_B19","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1182\/blood-2010-04-280313","article-title":"Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome","volume":"116","author":"G\u00f6hring","year":"2010","journal-title":"Blood"},{"issue":"1","key":"2019111703530385500_B20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0165-4608(94)00099-W","article-title":"Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype","volume":"79","author":"Hasle","year":"1995","journal-title":"Cancer Genet Cytogenet"},{"issue":"3","key":"2019111703530385500_B21","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3324\/haematol.10683","article-title":"Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia","volume":"92","author":"Yoshimi","year":"2007","journal-title":"Haematologica"},{"issue":"4","key":"2019111703530385500_B22","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3324\/haematol.2013.095786","article-title":"Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood","volume":"99","author":"Yoshimi","year":"2014","journal-title":"Haematologica"},{"issue":"1","key":"2019111703530385500_B23","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/leu.2013.195","article-title":"The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS","volume":"28","author":"Aalbers","year":"2014","journal-title":"Leukemia"},{"issue":"4","key":"2019111703530385500_B24","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3324\/haematol.2014.105569","article-title":"Immune suppression for childhood acquired aplastic anemia and myelodysplastic syndrome: where next?","volume":"99","author":"Samarasinghe","year":"2014","journal-title":"Haematologica"},{"issue":"4","key":"2019111703530385500_B25","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/sj.bmt.1705730","article-title":"Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood","volume":"40","author":"Strahm","year":"2007","journal-title":"Bone Marrow Transplant"},{"issue":"7","key":"2019111703530385500_B26","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.3324\/haematol.2012.074831","article-title":"A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial","volume":"98","author":"Gore","year":"2013","journal-title":"Haematologica"},{"issue":"6","key":"2019111703530385500_B27","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/bjh.13915","article-title":"Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group","volume":"172","author":"Cseh","year":"2016","journal-title":"Br J Haematol"},{"issue":"3","key":"2019111703530385500_B28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/leu.2010.297","article-title":"Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study","volume":"25","author":"Strahm","year":"2011","journal-title":"Leukemia"},{"issue":"10","key":"2019111703530385500_B29","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1002\/pbc.25121","article-title":"Salvage allogeneic stem cell transplantation in patients with pediatric myelodysplastic syndrome and myeloproliferative neoplasms","volume":"61","author":"Kato","year":"2014","journal-title":"Pediatr Blood Cancer"},{"issue":"4","key":"2019111703530385500_B30","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1046\/j.1365-2141.1999.01645.x","article-title":"A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada","volume":"106","author":"Hasle","year":"1999","journal-title":"Br J Haematol"},{"issue":"10","key":"2019111703530385500_B31","first-page":"3534","article-title":"Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases","volume":"89","author":"Niemeyer","year":"1997","journal-title":"Blood"},{"issue":"5","key":"2019111703530385500_B32","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1097\/MPH.0b013e31819ed260","volume":"31","author":"Karow","year":"2009","journal-title":"J Pediatr Hematol Oncol"},{"issue":"2","key":"2019111703530385500_B33","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.jpeds.2015.04.064","article-title":"Unmistakable Morphology? Infantile Malignant Osteopetrosis Resembling Juvenile Myelomonocytic Leukemia in Infants","volume":"167","author":"Strauss","year":"2015","journal-title":"J Pediatr"},{"key":"2019111703530385500_B34","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ng1156","article-title":"Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia","volume":"34","author":"Tartaglia","year":"2003","journal-title":"Nat Genet"},{"key":"2019111703530385500_B35","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.4161\/cc.5.15.3128","article-title":"Germline mutations in components of the Ras signaling pathway in Noonan syndrome and related disorders","volume":"5","author":"Kratz","year":"2006","journal-title":"Cell Cycle"},{"issue":"11","key":"2019111703530385500_B36","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/ng.3420","article-title":"Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network","volume":"47","author":"Caye","year":"2015","journal-title":"Nat Genet"},{"issue":"9","key":"2019111703530385500_B37","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/ng.641","article-title":"Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia","volume":"42","author":"Niemeyer","year":"2010","journal-title":"Nat Genet"},{"issue":"11","key":"2019111703530385500_B38","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1038\/ng.3400","article-title":"The genomic landscape of juvenile myelomonocytic leukemia","volume":"47","author":"Stieglitz","year":"2015","journal-title":"Nat Genet"},{"issue":"12","key":"2019111703530385500_B39","doi-asserted-by":"crossref","first-page":"e0145394","DOI":"10.1371\/journal.pone.0145394","article-title":"Aberrant DNA Methylation Is Associated with a Poor Outcome in Juvenile Myelomonocytic Leukemia","volume":"10","author":"Sakaguchi","year":"2015","journal-title":"PLoS One"},{"issue":"8","key":"2019111703530385500_B40","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1097\/MPH.0b013e3182055e44","article-title":"Acute respiratory failure in 3 children with juvenile myelomonocytic leukemia","volume":"33","author":"Gustafsson","year":"2011","journal-title":"J Pediatr Hematol Oncol"},{"issue":"14","key":"2019111703530385500_B41","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1182\/blood-2015-01-619734","article-title":"Bridging to transplant with azacitidine in juvenile myelomonocytic leukemia: a retrospective analysis of the EWOG-MDS study group","volume":"125","author":"Cseh","year":"2015","journal-title":"Blood"},{"issue":"1","key":"2019111703530385500_B42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3324\/haematol.2014.109892","article-title":"Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia","volume":"100","author":"Niemeyer","year":"2015","journal-title":"Haematologica"},{"issue":"1","key":"2019111703530385500_B43","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1182\/blood-2004-05-1944","article-title":"Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS\/EBMT trial","volume":"105","author":"Locatelli","year":"2005","journal-title":"Blood"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2016\/1\/598\/1252349\/hem088336.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2016\/1\/598\/1252349\/hem088336.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T23:47:20Z","timestamp":1718927240000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2016\/1\/598\/21157\/Myelodysplastic-and-myeloproliferative-disorders"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,2]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,12,2]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2016.1.598","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,2]]}}}