Abstract
Myelodysplastic and myeloproliferative disorders are rare in childhood and there is no widely accepted system for their diagnosis and classification. We propose minimal diagnostic criteria and a simple classification scheme which, while based on accepted morphological features and conforming with the recent suggestions of the WHO, allows for the special problems of myelodysplastic diseases in children. The classification recognizes three major diagnostic groups: (1) juvenile myelomonocytic leukemia (JMML), previously named chronic myelomonocytic leukemia (CMML) or juvenile chronic myeloid leukemia (JCML); (2) myeloid leukemia of Down syndrome, a disease with distinct clinical and biological features, encompassing both MDS and AML occurring in Down syndrome; and (3) MDS occurring both de novo and as a complication of previous therapy or pre-existing bone marrow disorder (secondary MDS). The main subtypes of MDS are refractory cytopenia (RC) and refractory anemia with excess of blasts (RAEB). It is suggested retaining the subtype of RAEB-T with 20–30% blasts in the marrow until more data are available. Cytogenetics and serial assessments of the patients are essential adjuncts to morphology both in diagnosis and classification.
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References
Passmore SJ, Hann IM, Stiller CA, Ramani P, Swansbury GJ, Gibbons B, Reeves BR, Chessells JM . Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system. Blood 1995; 85: 1742–1750.
Hasle H, Kerndrup G, Jacobsen BB . Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia 1995; 9: 1569–1572.
Bader-Meunier B, Mielot F, Tchernia G, Buisine J, Delsol G, Duchayne E, Lemerle S, Leverger G, De Lumley L, Manel AM, Nathanson M, Plantaz D, Robert A, Schaison G, Sommelet D, Vilmer E . Myelodysplastic syndrome in childhood: report of 49 patients from a French multicenter study. Br J Haematol 1996; 92: 344–350.
Luna-Fineman S, Shannon KM, Atwater SK, Davis J, Masterson M, Ortega J, Sanders J, Steinherz P, Weinberg V, Lange BJ . Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients. Blood 1999; 93: 459–466.
Hasle H, Wadsworth LD, Massing BG, McBride M, Schultz KR . A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada. Br J Haematol 1999; 106: 1027–1032.
Sasaki H, Manabe A, Kojima S, Tsuchida M, Hayashi Y, Ikuta K, Okamura I, Koike K, Ohara A, Ishii E, Komada Y, Hibi S, Nakahata T . Myelodysplastic syndrome in childhood: a retrospective study of 189 patients in Japan. Leukemia 2001; 15: 1713–1720.
Kramárová E, Stiller CA . The international classification of childhood cancer. Int J Cancer 1996; 68: 759–765.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C . Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C . Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French–American–British Cooperative Group. Ann Intern Med 1985; 103: 620–625.
Greenberg P, Cox C, Le Beau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J . International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.
Jaffe ES, Harris NL, Stein H, Vardiman JW (eds). World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues, IARC Press: Lyon 2001.
Antillon F, Raimondi SC, Fairman J, Liang H, Nagarajan L, Head D, Ribeiro RC . 5q- in a child with refractory anemia with excess blasts: similarities to 5q− syndrome in adults. Cancer Genet Cytogenet 1998; 105: 119–122.
Shikano T, Ishikawa Y, Anakura M . Myelodysplastic syndrome with partial deletion of the long arm of chromosome 5: first report of a case in a child. Acta Paediatr Jpn 1992; 34: 539–542.
Uyttebroeck A, Brock P, De Groote B, Renard M, Dal Cin P, Van Den Berghe H, Casteels Van Daele M . 5q− syndrome in a child. Cancer Genet Cytogenet 1995; 80: 121–123.
Emanuel PD . Myelodysplasia and myeloproliferative disorders in childhood: an update. Br J Haematol 1999; 105: 852–863.
Niemeyer CM, Fenu S, Hasle H, Mann G, Stary J, van Wering ER . Differentiating juvenile myelomonocytic leukemia from infectious disease. Blood 1998; 91: 365–367.
Sieff CA, Chessells JM, Harvey BA, Pickthall VJ, Lawler SD . Monosomy 7 in childhood: a myeloproliferative disorder. Br J Haematol 1981; 49: 235–249.
Niemeyer CM, Aricò M, Basso G, Cantù-Rajnoldi A, Creutzig U, Haas OA, Harbott J, Hasle H, Kerndrup G, Locatelli F, Mann G, Stollmann-Gibbels B, van’t Veer Korthof ET, van Wering ER, Zimmermann M and members of the European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS). Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. Blood 1997; 89: 3534–3543.
Hasle H, Aricò M, Basso G, Biondi A, Cantù-Rajnoldi A, Creutzig U, Fenu S, Fonatsch C, Haas OA, Harbott J, Kardos G, Kerndrup G, Mann G, Niemeyer CM, Ptoszkova H, Ritter J, Slater R, Stary J, Stollmann-Gibbels B, Testi AM, van Wering ER, Zimmermann M . Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. Leukemia 1999; 13: 376–385.
Hasle H, Clemmensen IH, Mikkelsen M . Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet 2000; 355: 165–169.
Zipursky A, Brown E, Christensen H, Sutherland R, Doyle J . Leukemia and/or myeloproliferative syndrome in neonates with Down syndrome. Semin Perinatol 1997; 21: 97–101.
Ravindranath Y, Abella E, Krischer JP, Wiley J, Inoue S, Harris M, Chauvenet A, Alvarado CS, Dubowy R, Ritchey AK, Land V, Steuber CP, Weinstein H . Acute myeloid leukemia (AML) in Down’s syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. Blood 1992; 80: 2210–2214.
Lie SO, Jonmundsson G, Mellander L, Siimes MA, Yssing M, Gustafsson G . A population-based study of 272 children with acute myeloid leukaemia treated on two consecutive protocols with different intensity: best outcome in girls, infants, and children with Down’s syndrome. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Br J Haematol 1996; 94: 82–88.
Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB, Gold S, Sanders J, Neudorf S, Smith FO, Woods WG . Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children’s cancer group studies 2861 and 2891. Blood 1998; 91: 608–615.
Gamis AS, Alonzo TE, Lange B, Woods WG, Smith FO . Acute myelogenous leukemia (AML) in Downs Syndrome (DS) patients: Outcome, toxicities, and prognostic factors from the CCG 2891 trial. Blood 2001; 98: 720a.
Sato A, Imaizumi M, Koizumi Y, Obara Y, Nakai H, Noro T, Saito T, Saisho T, Yoshinari M, Cui Y, Suzuki H, Funato T, Iinuma K . Acute myelogenous leukaemia with t(8;21) translocation of normal cell origin in mosaic Down’s syndrome with isochromosome 21q. Br J Haematol 1997; 96: 614–616.
Mueller BU, Tannenbaum S, Pizzo PA . Bone marrow aspirates and biopsies in children with human immunodeficiency virus infection. J Pediatr Hematol Oncol 1996; 18: 266–271.
Brichard B, Vermylen C, Scheiff JM, Ninane J, Cornu G . Haematological disturbances during long-term valproate therapy. Eur J Pediatr 1994; 153: 378–380.
Yetgin S, Ozen S, Saatci U, Bakkaloglu A, Besbas N, Kirel B . Myelodysplastic features in juvenile rheumatoid arthritis. Am J Hematol 1997; 54: 166–169.
Bader-Meunier B, Rötig A, Mielot F, Lavergne JM, Croisille L, Rustin P, Landrieu P, Dommergues JP, Munnich A, Tchernia G . Refractory anaemia and mitochondrial cytopathy in childhood. Br J Haematol 1994; 87: 381–385.
Fohlmeister I, Fischer R, Mödder B, Rister M, Schaefer HE . Aplastic anemia and the hypocellular myelodysplastic syndrome: histomorphological, diagnostic, and prognostic features. J Clin Pathol 1985; 38: 1218–1224.
Elghetany MT, Hudnall SD, Gardner FH . Peripheral blood picture in primary hypocellular refractory anemia and idiopathic acquired aplastic anemia: an additional tool for differential diagnosis. Haematologica 1997; 82: 21–24.
Baumann I, Führer M, Bender-Götze C, Rogge T, Niemeyer CM . Histopathological features of hypoplastic myelodysplastic syndrome and comparison with severe aplastic anemia in childhood. Leuk Res 1999; 23 (Suppl. 1): S41.
Appelbaum FR, Barrall J, Storb R, Ramberg R, Doney K, Sale GE, Thomas ED . Clonal cytogenetic abnormalities in patients with otherwise typical aplastic anemia. Exp Hematol 1987; 15: 1134–1139.
Mikhailova N, Sessarego M, Fugazza G, Caimo A, De Filippi S, van Lint MT, Bregante S, Valeriani A, Mordini N, Lamparelli T, Gualandi F, Occhini D, Bacigalupo A . Cytogenetic abnormalities in patients with severe aplastic anemia. Haematologica 1996; 81: 418–422.
Alter BP, Scalise A, McCombs J, Najfeld V . Clonal chromosomal abnormalities in Fanconi’s anaemia: what do they really mean?. Br J Haematol 1993; 85: 627–630.
Elghetany MT, Vyas S, Yuoh G . Significance of p53 overexpression in bone marrow biopsies from patients with bone marrow failure: aplastic anemia, hypocellular refractory anemia, and hypercellular refractory anemia. Ann Hematol 1998; 77: 261–264.
Chan GCF, Wang WC, Raimondi SC, Behm FG, Krance RA, Chen G, Freiberg A, Ingram L, Butler D, Head DR . Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count. Leukemia 1997; 11: 206–211.
Head DR . Revised classification of acute myeloid leukemia. Leukemia 1996; 10: 1826–1831.
Woods WG, Barnard DR, Alonzo TA, Buckley JD, Kobrinsky N, Arthur DC, Sanders J, Neudorf S, Gold S, Lange BJ . Prospective Study of 90 Children Requiring Treatment for Juvenile Myelomonocytic Leukemia or Myelodysplastic Syndrome: A Report From the Children’s Cancer Group. J Clin Oncol 2002; 20: 434–440.
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A . The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 1998; 92: 2322–2333.
Webb DKH, Passmore SJ, Hann IM, Harrison G, Wheatley K, Chessells JM . Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990–99. Br J Haematol 2002; 117: 33–39.
Niemeyer CM, Duffner U, Bender-Götze C, Ebell W, Hasle H, Klingebiel T, Kremens B, Nrnberger W, Vossen J, Zecca M, Zintl F, Locatelli F . AML-Type intensive chemotherapy prior to stem cell transplantation (SCT) does not improve survival in children and adolescents with primary myelodysplastic syndromes (MDS). Blood 2000; 96: 521a.
Maarek O, Jonveaux P, Le Coniat M, Derre J, Berger R . Fanconi anemia and bone marrow clonal chromosome abnormalities. Leukemia 1996; 10: 1700–1704.
Hasle H, Baumann I, Bergsträsser E, Fenu S, Kardos G, Kerndrup G, Mann G, Rogge T, Schultz KR, Stary J, Wadsworth LD, van Wering ER, Harbott J, Nöllke P, Niemeyer CM . International prognostic scoring system (IPSS) for childhood MDS and JMML. Blood 2001; 98: 624a.
Mandel K, Dror Y, Poon A, Freedman MH . A practical, comprehensive classification for pediatric myelodysplastic syndromes: the CCC system. J Pediatr Hematol Oncol 2002; 24: 343–352.
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Hasle, H., Niemeyer, C., Chessells, J. et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 17, 277–282 (2003). https://doi.org/10.1038/sj.leu.2402765
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DOI: https://doi.org/10.1038/sj.leu.2402765