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Clinical Trial
. 2011 Dec 22;118(26):6752-9; quiz 6996.
doi: 10.1182/blood-2011-04-350017. Epub 2011 Aug 17.

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

Alan S Gamis  1 , Todd A Alonzo, Robert B Gerbing, Joanne M Hilden, April D Sorrell, Mukta Sharma, Thomas W Loew, Robert J Arceci, Dorothy Barnard, John Doyle, Gita Massey, John Perentesis, Yaddanapudi Ravindranath, Jeffrey Taub, Franklin O Smith
Affiliations
Clinical Trial

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

Alan S Gamis et al. Blood. .

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.

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Figures

Figure 1
Figure 1
Time to TMD resolution from diagnosis for all patients enrolled.
Figure 2
Figure 2
OS and EFS from study entry for all TMD patients.
Figure 3
Figure 3
OS and mEFS (Mod EFS) from study entry comparing observation to intervention patients. Deaths that are not TMD related are competing events in modified EFS (1 − cumulative incidence).
Figure 4
Figure 4
OS and modified EFS (mEFS) based on diagnostic hepatomegaly and WBC values. (A) Diagnostic hepatomegaly. (B) WBC values. These illustrate the univariate impact upon OS and modified EFS of these 2 risk factors.
Figure 5
Figure 5
OS and modified EFS (Mod EFS) for the 3 risk groups of TMD patients. This illustrates that the intermediate risk group, that is, those with hepatomegaly alone, had minimal TMD-related problems but did have significant mortality from other causes.
Figure 6
Figure 6
Impact of TMD resolution upon later risk of developing AML. This illustrates that those children whose resolution of their TMD exceeded the median resolution time were at greater risk of later developing AML.
See this image and copyright information in PMC

Comment in

  • Enigmatic variation.
    Roberts I, Vyas P. Roberts I, et al. Blood. 2011 Dec 22;118(26):6723-4. doi: 10.1182/blood-2011-09-376145. Blood. 2011. PMID: 22194390 No abstract available.

References

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