Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971

• Published in: Blood Vol. 118; no. 26; pp. 6752 - 6759
• Main Authors: Gamis, Alan S., Alonzo, Todd A., Gerbing, Robert B., Hilden, Joanne M., Sorrell, April D., Sharma, Mukta, Loew, Thomas W., Arceci, Robert J., Barnard, Dorothy, Doyle, John, Massey, Gita, Perentesis, John, Ravindranath, Yaddanapudi, Taub, Jeffrey, Smith, Franklin O.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 22.12.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Acute Disease; Antimetabolites, Antineoplastic - therapeutic use; Biological and medical sciences; Chromosome aberrations; Clinical Trials and Observations; CME article; Cytarabine - therapeutic use; Disease Progression; Down Syndrome - complications; Female; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Leukemia, Megakaryoblastic, Acute - complications; Leukemia, Megakaryoblastic, Acute - diagnosis; Leukemia, Megakaryoblastic, Acute - drug therapy; Leukemia, Myeloid - diagnosis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical genetics; Medical sciences; Myeloid Neoplasia; Myeloproliferative Disorders - complications; Myeloproliferative Disorders - diagnosis; Myeloproliferative Disorders - drug therapy; Prognosis; Prospective Studies; Time Factors; Treatment Outcome; Chromosomal aberration; Human; Trisomy; Hematology; Chromosome G21; Aneuploidy; Hemopathy; Down syndrome; Malignant tumor; Transitory; Myeloproliferative syndrome; Cancerology; Newborn; Diagnosis; Child; Natural history; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-04-350017

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.