Oligoblastic Myelogenous Leukemia (Refractory Anemia with Excess Blasts)



Oligoblastic Myelogenous Leukemia (Refractory Anemia with Excess Blasts)

Definition and History

In 1963, the term smoldering acute leukemia was introduced to highlight a subset of patients, usually those older than age 50 years, who had a low proportion of leukemic blast cells in marrow (3–20%) and blood (0–7%) and who survived for months or years without specific therapy for leukemia.294–296 The terms “smoldering,” “pauciblastic,” “low-infiltrate,” and “oligoblastic” myelogenous leukemia for this type of process are synonyms. Oligoblastic myelogenous leukemia is called refractory anemia with excess myeloblasts in various classification schemes.2,3 This is a peculiar turn of phrase as these are not excess normal myeloblasts but malignant myeloblasts, which if present in the marrow examination imply an overt malignancy (leukemia not an anemia). When the blast count increases to greater than 19 percent, a diagnosis of AML is made. Chronic myelomonocytic leukemia, another type of oligoblastic subacute leukemia, previously included under the rubric myelodysplasia, is better linked to the subacute and chronic myelogenous leukemias discussed in Chap. 90.

Clinical Findings

Oligoblastic leukemia composes approximately 30 to 50 percent of all cases of myelodysplasia, if one uses a definition of ≥4 percent marrow blasts as a requirement. Most patients are older than age 50 years. Males are affected more often than females by approximately 1.5:1. Reticulocytopenic anemia, granulocytopenia, and/or thrombocytopenia are usually present. Qualitative abnormalities of blood cells usually are overt (see “Laboratory Features” above). Myeloblasts constitute from 5 to 19 percent of nucleated marrow cells by definition, but marrow blasts greater than 2 percent are almost never seen in normal marrows, and a lower threshold would increase the proportion of patients with oligoblastic myelogenous leukemia markedly. Auer rods may be present in blast cells. Dysmorphic changes that occur in abnormal marrow precursor cells are described in “Laboratory Features” above. This syndrome evolves into overt AML in approximately 50 percent of cases. Median survival of patients with oligoblastic leukemia is approximately 12 to 24 months, although occasional long-term survival has been reported.275,297


Treatment of oligoblastic myelogenous leukemia should be individualized. In some cases, no active treatment is required. Periodic evaluation is essential to detect deterioration in well-being or blood cell counts. Most patients require treatment in weeks to months. The response to cytotoxic therapy is poor, and symptomatic therapy with component transfusion and antibiotics, as required, is the preferable management if that approach can sustain a reasonable functional status. If the disease progresses such that cytopenias lead to infection, hemorrhage, or anemia and require inordinate amounts of transfusions or if the disease progresses to AML and the patient is fit, intensive cytotoxic therapy for AML may be warranted (see Chap. 89). If the patient has a poor performance status or has comorbid medical conditions that would lower the tolerance for intensive cytotoxic therapy, attenuation of doses should be considered. Cytarabine combined with anthracycline antibiotics, etoposide, or topotecan has produced remissions in approximately half of a group of selected patients.298–304 Recovery may be slow, and remissions tend to be short, however. Patients with a poor performance status or of advanced age, or who choose not to be treated with combined-agent chemotherapy, can be treated with either low-dose cytarabine or 5-azacytidine or decitabine.264–267 Other agents that have been used include etoposide, hydroxyurea, retinoids, butyrates, and other therapies coupled with transfusion therapy for palliation of the disease. Although some patients have improved, these approaches have been of limited benefit. Patients younger than age 50 years of age with a histocompatible donor should be considered for allogeneic hematopoietic stem cell transplantation.307 Older patients may be considered for nonmyeloablative allogeneic transplantation. Some patients in remission can be considered for intensive therapy and autologous stem cell rescue (see “Hematopoietic Stem Cell Transplantation” below).308

Course and Prognosis

The median survival in published series of patients with oligoblastic leukemia varies from 6 to 36 months, with survival of individual patients ranging from 1 to 160 months. In a very large single series that included refractory anemia, median survival was 15 months.272 Approximately half of the patients died of infection associated with severe neutropenia or dysfunctional neutrophils and monocytes, and approximately 25 percent died of bleeding complications resulting from thrombocytopenia. Approximately 30 percent of cases evolved into AML. Length of survival of patients with oligoblastic leukemia after diagnosis is inversely correlated with a higher risk category of the cytogenetic abnormality, a higher proportion of blast cells in the marrow, the presence of N-RAS mutations, greater severity of the neutropenia and thrombocytopenia, and higher serum level of 2-microglobulin.148,275,309–315

A rare case of spontaneous disappearance of oligoblastic leukemia has been documented.316