Transient myeloproliferative disorder (TMD) is a unique clonal proliferation of megakaryocytic precursors that is clinically indistinguishable from congenital leukemia and is seen almost exclusively in neonates with trisomy 21 (Down syndrome).1 TMD is typically characterized by the presence of leukocytosis and circulating blast cells in the blood of an otherwise healthy-appearing newborn. These blast cells will generally resolve spontaneously by 3–6 months of age without any specific interventions.2 However, approximately 20% of patients will present with severe hydrops, organomegaly, hepatic fibrosis, and other life-threatening complications, with an associated mortality rate approaching 45% at 3 years.3
Because of their clinical heterogeneity, patients with TMD have been classified into 3 distinct groups: high risk, intermediate risk, and low risk4 (Table 94-1). High-risk patients with TMD (20%) include those with severe life-threatening complications, such as cardiorespiratory compromise, hyperleukocytosis (white blood cells [WBCs] > 100 × 103/μL) and liver failure (with attendant cholestasis, ascites, or disseminated intravascular coagulation [DIC]). The intermediate-risk patients (40%) include infants with hepatomegaly and hepatic dysfunction but no acute life-threatening complications. Interestingly, although these patients rarely die from acute TMD-related complications, they still have an overall mortality of 23% at 3 years. In contrast, the low-risk patients (40%) experience an 8% overall mortality at 3 years.
Table 94-1Transient Myeloproliferative Disorder (TMD) Risk Groups |Favorite Table|Download (.pdf) Table 94-1Transient Myeloproliferative Disorder (TMD) Risk Groups
| ||Low-Risk TMD ||Intermediate-Risk TMD ||High-Risk TMD |
|Percentage of TMD ||40 ||40 ||20 |
|Clinical characteristics || |
No hepatomegaly OR hepatomegaly without hepatic dysfunction
No life-threatening complications
Hepatomegaly plus evidence of non-life-threatening hepatic dysfunction (ie, significantly elevated AST, ALT, or bilirubin)
No life-threatening complications
|Cardiorespiratory compromise, edema, pericardial/pleural effusions, hyperleukocytosis, hepatomegaly, life-threatening hepatic dysfunction |
|Therapy ||Observation only ||Strongly consider very-low-dose cytarabine therapy || |
Aggressive supportive care (ie, exchange transfusion or leukopheresis)
Very-low-dose cytarabine therapy
Approximately 10%–20% of newborns with Down syndrome with TMD develop acute myeloid leukemia (AML) within the first 2 years of life.1 This leukemia most commonly takes the form of acute megakaryoblastic leukemia (AMKL) and can be traced to the patient’s original TMD by unique genetic markers (ie, GATA1 mutations).5, 6, and 7
The patient with “classic” TMD is an otherwise healthy-appearing infant with physical characteristics suggestive of trisomy 21 (eg, epicanthal folds, hypotonia, single palmar crease). However, as discussed, patients with higher-risk TMD may present with cardiorespiratory compromise caused by severe hydrops (with concomitant edema, pericardial/pleural effusions, ascites) or marked hepatosplenomegaly. Patients may also present with signs and symptoms of hyperviscosity syndrome secondary to hyperleukocytosis, with attendant thrombotic complications. These symptoms may include respiratory distress, apnea, lethargy, irritability, seizures, or other stroke-like symptoms. More recently, an association with a vesiculopustular rash that typically appears on the ...