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Cancer Health Center

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Adult Acute Myeloid Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Classification of Adult Acute Myeloid Leukemia


Variant: Acute myeloid leukemia/transient myeloproliferative disorder in Down syndrome

Individuals with Down syndrome (trisomy 21) have an increased disposition to acute leukemia, primarily the myeloid type.[76,77] The primary subtype appears to be acute megakaryoblastic leukemia. In cases in which the leukemia remits spontaneously, the process is referred to as transient myeloproliferative disorder or transient leukemia. Clinical features include presentation in the neonatal period (10% of newborn infants with Down syndrome), marked leukocytosis, blast percentage in the blood greater than 30% to 50%, and extramedullary involvement.

Morphologic and cytochemical features include the following:

  • Blasts with round to slightly irregular nuclei and a moderate amount of basophilic cytoplasm.
  • Coarse azurophilic granules in the cytoplasm that resemble basophil granules.
  • Promegakaryocytes and micromegakaryocytes.
  • Dyserythropoiesis.
  • MPO-negative and SBB-negative blasts.

Immunophenotyping reveals markers that are generally similar to those of other cases of childhood acute megakaryoblastic leukemia.

In addition to trisomy 21, some cases may show other clonal abnormalities, particularly trisomy 8.[77,78] Spontaneous remission occurs within 1 to 3 months in transient cases. Recurrence followed by a second spontaneous remission or persistent disease may occur. Treatment outcomes for pediatric patients with Down syndrome and persistent disease may be better than those for pediatric patients with acute leukemia in the absence of trisomy 21.[75]

Acute basophilic leukemia

Acute basophilic leukemia is an AML that exhibits a primary differentiation to basophils. This acute leukemia is relatively rare, comprising less than 1% of all cases of AML.[57] Clinical features include bone marrow failure, circulating blasts, cutaneous involvement, organomegaly, occasional osseous lytic lesions, and symptoms secondary to hyperhistaminemia.

Morphologic and cytochemical features include the following:

  • Medium-sized blasts with a high nuclear-cytoplasmic ratio and an oval, round, or bilobed nucleus with one or more nucleoli.
  • Moderately basophilic cytoplasm containing a variable number of coarse basophilic granules.
  • Sparse numbers of mature basophils.
  • Dysplastic erythroid features.
  • Blasts with metachromatic positivity, with toluidine blue.
  • Blasts with acid phosphatase positivity.
  • Negative by light microscopy for SBB, MPO, and nonspecific esterase.
  • Hypercellular bone marrow.

Immunophenotypically, the blasts express the myeloid markers CD13 and CD33 and the early hematopoietic markers CD34 and class-II HLA-DR. The differential diagnosis includes: blast crisis of CML, other AML subtypes with basophilia such as AML with maturation (M2) associated with abnormalities of 12p or t(6;9), acute eosinophilic leukemia, and, rarely, a subtype of ALL with prominent coarse granules.[57]

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