title: Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971.
abstract: Transient myeloproliferative disorder (TMD), restricted to newborns with trisomy 21, is a megakaryocytic leukemia that although lethal in some is distinguished by its spontaneous resolution. Later development of acute myeloid leukemia (AML) occurs in some. Prospective enrollment (n = 135) elucidated the natural history in Down syndrome (DS) patients diagnosed with TMD via the use of uniform monitoring and intervention guidelines. Prevalent at diagnosis were leukocytosis, peripheral blast exceeding marrow blast percentage, and hepatomegaly. Among those with life-threatening symptoms, most (n = 29/38; 76%) received intervention therapy until symptoms abated and then were monitored similarly. Organomegaly with cardiopulmonary compromise most frequently led to intervention (43%). Death occurred in 21% but only 10% were attributable to TMD (intervention vs observation patients: 13/14 vs 1/15 because of TMD). Among those solely observed, peripheral blasts and all other TMD symptoms cleared at a median of 36 and 49 days from diagnosis, respectively. On the basis of the diagnostic clinical findings of hepatomegaly with or without life-threatening symptoms, 3 groups were identified with differing survival: low risk with neither finding (38%), intermediate risk with hepatomegaly alone (40%), and high risk with both (21%; overall survival: 92% ± 8%, 77% ± 12%, and 51% ± 19%, respectively; P ≤ .001). Among all, AML subsequently occurred in 16% at a median of 441 days (range, 118-1085 days). The trial is registered at http://www.clinicaltrials.gov as NCT00003593.
authors.affiliation: Children's Mercy Hospital & Clinics, Kansas City, MO 64108, USA. agamis@cmh.edu
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Hilden
authors.forename: April D
authors.initials: AD
authors.lastname: Sorrell
authors.forename: Mukta
authors.initials: M
authors.lastname: Sharma
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Loew
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Dorothy
authors.initials: D
authors.lastname: Barnard
authors.forename: John
authors.initials: J
authors.lastname: Doyle
authors.forename: Gita
authors.initials: G
authors.lastname: Massey
authors.forename: John
authors.initials: J
authors.lastname: Perentesis
authors.forename: Yaddanapudi
authors.initials: Y
authors.lastname: Ravindranath
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Taub
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
mesh_terms: D000208:Acute Disease; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use*; D018450:Disease Progression; D004314:Down Syndrome / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D007947:Leukemia, Megakaryoblastic, Acute / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D007951:Leukemia, Myeloid / Q000175:diagnosis; D008297:Male; D009196:Myeloproliferative Disorders / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine