The differential diagnosis of AML with multilineage dysplasia includes acute erythroid-myeloid leukemia and acute myeloblastic leukemia with maturation (FAB classifications M6a and M2). Some cases may overlap two morphologic types.
As evidenced in several Southwest Oncology Group studies, such as SWOG-8600 and NCT00023777, the numerous chromosome abnormalities observed in AML with multilineage dysplasia were similar to those found in MDS and frequently involved gain or loss of major segments of certain chromosomes, predominately chromosomes 5 and/or 7.[45,46,47,48] The probability of achieving a complete remission has been reported to be affected adversely by a diagnosis of AML with multilineage dysplasia.[45,46,47]
Acute Myeloid Leukemias and Myelodysplastic Syndromes, Therapy Related
This category includes AML and MDS that arise secondary to cytotoxic chemotherapy and/or radiation therapy. The therapy-related (or secondary) MDS are included because of their close clinicopathologic relationships to therapy-related AML. Although these therapy-related disorders are distinguished by the specific mutagenic agents involved, a recent study suggests this distinction may be difficult to make because of the frequent overlapping use of multiple potentially mutagenic agents in treating cancer.
Alkylating agent-related acute myeloid leukemia and myelodysplastic syndromes
The alkylating agent/radiation-related acute leukemias and myelodysplastic syndromes typically occur 5 to 6 years following exposure to the mutagenic agent, with a reported range of approximately 10 to 192 months.[49,51] The risk for occurrence is related to both the total cumulative dose of the alkylating agent and the age of the patient. Clinically, the disorder commonly presents initially as an MDS with evidence of bone marrow failure. This stage is followed by dysplastic features in multiple cell lineages with a blast percentage that is usually less than 5%. In the MDS phase, approximately 66% of cases satisfy the criteria for refractory cytopenia with multilineage dysplasia (RCMD), with approximately 33% of these cases exhibiting ringed sideroblasts in excess of 15% (RCMD-RS). (Refer to the PDQ summary on Myelodysplastic Syndromes Treatment for more information.) Another 25% of cases satisfy the criteria for refractory anemia with excess blasts 1 or 2 (RAEB-1; RAEB-2). The MDS phase may evolve to a higher grade MDS or AML. Although a minority of patients may present with acute leukemia, a substantial number of patients succumb to the disorder in the MDS phase.
Common morphologic features include the following:
- Ringed sideroblasts (60% of cases; >15% in 33% of cases).
- Hypercellular bone marrow (50% of cases).
Cases may correspond morphologically to AML with maturation, acute monocytic leukemia, AMML, erythroleukemia, or acute megakaryoblastic leukemia (FAB classifications M2, M5b, M4, M6a, and M7, respectively).
Cytogenetic abnormalities have been observed in more than 90% of cases of therapy-related AML or MDS and commonly include chromosomes 5 and/or 7.[49,52,53] Complex chromosomal abnormalities (≥3 distinct abnormalities) are the most common finding.[50,52,53,54] Therapy-related AML is usually refractory to antileukemia therapy. Median survival after diagnosis of these disorders is approximately 7 to 8 months.[50,52]