Transient Myeloproliferative Disorder: Whats Eosinophilia Got to Do With It?

Wade L. Schulz, PhD

1
, Malini B. DeSilva, MD
2
and R. Scott Velders, MD
3

University of Minnesota
1
Medical Scientist Training Program and
2
Departments of Internal Medicine and Pediatrics;
3
Hennepin County Medical Center Pediatrics

References
1. Gamis, A. S., & Smith, F. O. (2012). Transient myeloproliferative disorder in children with Down syndrome: clarity to this enigmatic disorder. British journal of haematology, 159(3), 27787.
2. Ishigaki, H., Miyauchi, J., Yokoe, A., Nakayama, M., et al. (2011). Expression of megakaryocytic and myeloid markers in blasts of transient abnormal myelopoiesis in a stillbirth with Down syndrome: report of histopathological findings of an autopsy case. Human
pathology, 42(1), 1415.
3. Kawase, K., Azuma, E., Ohshita, H., Tanaka, T.,et al. (2012). Risk factors for early death in transient myeloproliferative disorder without phenotypic features of Down syndrome: a case report and literature review. Journal of pediatric hematology/oncology, 34(6),
4759.
4. Moiz, B., & Shafiq, M. (2012). Transient myeloproliferative disorder. Blood, 120(24), 46724672.
5. Seewald, L., Taub, J. W., Maloney, K. W., & McCabe, E. R. B. (2012). Acute leukemias in children with Down syndrome. Molecular genetics and metabolism, 107(1-2), 2530.
6. Shimizu, R., & Yamamoto, M. (2012). Contribution of GATA1 dysfunction to multi-step leukemogenesis. Cancer science, 103(12), 203944.
7. Suda, J., Eguchi, M., Akiyama, Y., Iwama, Y., et al. (1987). Differentiation of blast cells from a Downs syndrome patient with transient myeloproliferative disorder. Blood, 69(2), 50812.
8. Webb, D., Roberts, I., & Vyas, P. (2007). Haematology of Down syndrome. Archives of disease in childhood. Fetal and neonatal edition, 92(6), F5037.
9. Zon, L. I., Yamaguchi, Y., Yee, K., Albee, E. a, Kimura, a, Bennett, J. C., Orkin, S. H., et al. (1993). Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. Blood, 81(12), 323441.





Transient Myeloproliferative Disorder
Occurs in 10% of newborns with Down syndrome
Often asymptomatic and found incidentally
In severe cases, TMD can cause respiratory
distress, cardiovascular compromise, and
liver failure
Peripheral blood characterized by circulating blasts
Case reports have also described basophilia
Typical peripheral blood smear in a patient with
transient myeloproliferative disorder. Note the
predominance of blasts with a deeply basophilic
cytoplasm.
Genetics and Differentiation
Proliferation due to mutation in GATA-1 that
accompanies trisomy 21
No documented cases of eosinophilia
Monocytes, eosinophils, and megakaryocytes derived
from common myeloid progenitor
Recent studies have shown GATA-1 also regulates
eosinophil differentiation

Case Follow Up and Discussion
Patient remained asymptomatic over hospital course
Patients white cell count continued to decrease spontaneously
Discharged on 6
th
day of life with close follow-up by PCP at outside facility
Documented cases of TMD have shown circulating blasts or basophils in the peripheral
blood; however, this case had an unusual presentation. Recent evidence has shown that
the GATA-1 gene product implicated in the development of TMD also controls eosinophil
differentiation. In patients with suspected TMD, the presence of eosinophilia is likely
consistent and may not require additional workup for an infectious cause. While initially
concerning to providers and parents, TMD is normally asymptomatic and spontaneously
resolves, but demands close follow-up due to the increased risk of leukemia.
Initial Presentation
Full-term female infant born to mother of advanced maternal age by C-section
Physical characteristics of Down syndrome, karyotype revealed 47,XX,+21
By 30 hours of life, patient developed hyperbilirubinemia and hepatosplenomegaly which
prompted the need for phototherapy and further evaluation
CBC revealed WBC count of 35.2x10
9
cells/L with 44% eosinophils
Management and Treatment
Majority of cases resolve spontaneously within weeks
Treatment with cytarabine (Ara-C) used for symptomatic cases
Long-term follow-up with CBC every 3-6 months for the first few years of life
due to increased risk of AML (30% of cases by 3 years of age)
American Academy of Pediatrics recommends counseling parents on signs of
leukemia, including easy bruising, petechiae, increased lethargy, and
changes in feeding

Learning Objectives
Understand the presentation of transient myeloproliferative disorder (TMD)
Demonstrate variations in the presentation of TMD
Understand the genetic basis of TMD and cell differentiation
Recognize findings of TMD that require treatment and potential long-term effects of TMD
Peripheral Morphology
Anisopoikilocytosis with evidence of increased red cell regeneration
Moderate absolute eosinophilia with a subset of immature neutrophils
Immature subset lacked nuclear segmentation
Characterized by basophilic and eosinophilic granules
Platelet count normal with rare circulating megakaryocyte nuclei
Hospital Course
Infant was afebrile, but due to a failed hearing screen she was evaluated for
infectious causes of eosinophilia; CMV and toxoplasma found to be negative
WBC count declined to 22.5x10
9
cells/L and eosinophilia resolved by day five of life
Hyperbilirubinemia resolved, thought to be physiologic jaundice of the newborn
Final pathology diagnosis of transient myeloproliferative disorder (TMD)