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Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)

Atypical Chronic Myelogenous Leukemia

Disease Overview

Atypical chronic myelogenous leukemia (aCML) is a leukemic disorder that exhibits both myelodysplastic and myeloproliferative features at the time of diagnosis.

Atypical CML is characterized pathologically by the following:[1]

  • Peripheral blood leukocytosis with increased numbers of mature and immature neutrophils.
  • Prominent dysgranulopoiesis.
  • No Philadelphia chromosome or BCR/ABL fusion gene.
  • Neutrophil precursors (e.g., promyelocytes, myelocytes, and metamyelocytes) accounting for more than 10% of white blood cells.
  • Minimal absolute basophilia with basophils accounting for less than 2% of white blood cells.
  • Absolute monocytosis with monocytes typically account for less than 10% of white blood cells.
  • Hypercellular bone marrow with granulocytic proliferation and granulocytic dysplasia.
  • Fewer than 20% blasts in the blood or bone marrow.
  • Thrombocytopenia.

Clinical features of aCML include the following:[1-4]

  • Anemia. (Refer to the PDQ summary on Fatigue for more information on anemia.)
  • Thrombocytopenia.
  • Splenomegaly (in 75% of cases).

Although cytogenetic abnormalities are found in as many as 80% of the patients with aCML, none is specific.[1-3,5] No Philadelphia chromosome or BCR/ABL fusion gene exists.

The exact incidence of aCML is unknown. The median age at the time of diagnosis of this rare leukemic disorder has been reported to be in the seventh or eighth decade of life.[1-3]

Morphologically, aCML is characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to chronic myelogenous leukemia, but cytogenetically it lacks a Philadelphia chromosome or BCR/ABL fusion gene.[1] The white blood cell count in the peripheral blood is variable. Median values range from 35 × 109/L to 96 × 109/L, and some patients may have white blood cell counts greater than 300 × 109/L.[1-3,5] Blasts in the peripheral blood typically account for less than 5% of the white blood cells. Immature neutrophils usually total 10% to 20% or more.[1] The percentage of monocytes is rarely more than 10%. Minimal basophilia may be present.[1-3,5] Nuclear abnormalities, such as acquired Pelger-Huët anomaly, may be seen in the neutrophils. Moderate anemia (often showing changes indicative of dyserythropoiesis) and thrombocytopenia are common.[1-4] Bone marrow findings include the following: [1-3,5]

  • Granulocytic hypercellularity.
  • Blast count less than 20%.
  • Dysgranulopoiesis
  • Megakaryocytic dysplasia.
  • Erythroid precursors accounting for more than 30% of marrow cells with dyserythropoiesis present (in some cases).

The median survival times for aCML are reported to be less than 20 months, and thrombocytopenia and marked anemia are poor prognostic factors.[1,2] Atypical CML evolves to acute leukemia in approximately 25% to 40% of patients.[1,3] In the remainder, fatal complications include resistant leukocytosis, anemia, thrombocytopenia, hepatosplenomegaly, cerebral bleeding associated with thrombocytopenia, and infection.[3,4]

Treatment Overview

The optimal treatment of aCML is uncertain because of the rare incidence of this chronic leukemic disorder. Treatment with hydroxyurea may lead to short-lived partial remissions of 2- to 4-months' duration.[4] Atypical CML, appears to respond poorly to treatment with interferon-alpha.[4]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with atypical chronic myeloid leukemia, BCR-ABL1 negative. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

  1. Orazi A, Germing U: The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia 22 (7): 1308-19, 2008. [PUBMED Abstract]
  2. Hernández JM, del Cañizo MC, Cuneo A, et al.: Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia. Ann Oncol 11 (4): 441-4, 2000. [PUBMED Abstract]
  3. Costello R, Sainty D, Lafage-Pochitaloff M, et al.: Clinical and biological aspects of Philadelphia-negative/BCR-negative chronic myeloid leukemia. Leuk Lymphoma 25 (3-4): 225-32, 1997. [PUBMED Abstract]
  4. Kurzrock R, Bueso-Ramos CE, Kantarjian H, et al.: BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol 19 (11): 2915-26, 2001. [PUBMED Abstract]
  5. Bennett JM, Catovsky D, Daniel MT, et al.: The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol 87 (4): 746-54, 1994. [PUBMED Abstract]
  • Updated: December 4, 2014