Stage Information
Bone marrow sampling is done to assess cellularity, fibrosis, and cytogenetics.
The Philadelphia chromosome (Ph1) is usually more readily apparent in marrow
metaphases than in peripheral blood metaphases; in some cases, it may be
mashed and reverse transcriptase–polymerase chain reaction (RT–PCR) or fluorescent in situ hybridization (FISH) analyses on blood or marrow aspirates may be necessary to demonstrate the 9;22
translocation.
The most common finding on physical examination at diagnosis is
splenomegaly.[1] The spleen may be enormous, filling most of the abdomen and
presenting a significant clinical problem, or the spleen may be only minimally
enlarged. In about 10% of patients, the spleen is neither palpable nor
enlarged on splenic scan.
Histopathologic examination of bone marrow aspirate demonstrates a shift in the
myeloid series to immature forms that increase in number as patients progress
to the blastic phase of the disease. The marrow is hypercellular, and
differential counts of both marrow and blood show a spectrum of mature and
immature granulocytes similar to that found in normal marrow. Increased
numbers of eosinophils or basophils are often present, and sometimes
monocytosis is seen. Increased megakaryocytes are often found in the marrow,
and sometimes fragments of megakaryocytic nuclei are present in the blood,
especially when the platelet count is very high. The percentage of lymphocytes
is reduced in both the marrow and blood in comparison with normal subjects, and
the myeloid/erythroid ratio in the marrow is usually greatly elevated. The
leukocyte alkaline phosphatase enzyme is either absent or markedly reduced in
the neutrophils of patients with chronic myelogenous leukemia (CML).[1]
Transition from the chronic phase to the accelerated phase and later the blastic
phase may occur gradually over a period of 1 year or more, or it may appear
abruptly (blast crisis). The annual rate of progression from chronic phase
to blast crisis is 5% to 10% in the first 2 years and 20% in subsequent
years.[2,3] Signs and symptoms commonly heralding such a change include the following:
- Progressive leukocytosis.
- Thrombocytosis or thrombocytopenia.
- Anemia.
- Increasing and painful splenomegaly or hepatomegaly.
- Fever.
- Bone pain.
- Development of destructive bone lesions.
- Thrombotic or bleeding
complications.
In the accelerated phase, differentiated cells persist,
though they often show increasing morphologic abnormalities, and increasing
anemia and thrombocytopenia and marrow fibrosis are apparent.[1]
Studies have suggested that certain presenting features have prognostic
significance.
The following are predictive of a shorter chronic phase:
- Increased splenomegaly.
- Older age.
- Male gender.
- Elevated serum lactate
dehydrogenase.
- Cytogenetic abnormalities in addition to the Ph1.
- A
higher proportion of marrow or peripheral blood blasts.
- Basophilia.
- Eosinophilia.
- Thrombocytosis.
- Anemia.
Predictive models using multivariate analysis have been derived.[2-7]
Chronic-phase CML
Chronic-phase CML is characterized by bone marrow and cytogenetic findings as described above with
less than 10% blasts and promyelocytes in the peripheral blood and bone marrow.[8]
Accelerated-phase CML
Accelerated-phase CML is characterized by 10% to 19% blasts in either the peripheral blood or bone
marrow.[8]
Blastic-phase CML
Blastic-phase CML is characterized by 20% or more blasts in the peripheral blood or bone marrow.
When 20% or more blasts are present in the face of fever, malaise, and
progressive splenomegaly, the patient has entered blast crisis.[8]
Relapsing CML
Relapsed CML is characterized by any evidence of progression of disease from a stable remission. This may include the following:
- Increasing myeloid or blast cells in the peripheral blood or bone marrow.
- Cytogenetic positivity when previously cytogenetic-negative.
- FISH positivity for BCR/ABL (breakpoint cluster region/Abelson) translocation when previously FISH-negative.
Detection of the BCR/ABL translocation by RT–PCR during prolonged remissions does not constitute relapse on its own. However, exponential drops in quantitative RT–PCR measurements for 3 to 12 months correlates with the degree of cytogenetic response, just as exponential rises may be associated with quantitative RT–PCR measurements that are closely connected with clinical relapse.[9]
References
-
Sawyers CL: Chronic myeloid leukemia. N Engl J Med 340 (17): 1330-40, 1999.
[PUBMED Abstract]
-
Sokal JE, Cox EB, Baccarani M, et al.: Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 63 (4): 789-99, 1984.
[PUBMED Abstract]
-
Sokal JE, Baccarani M, Russo D, et al.: Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 25 (1): 49-61, 1988.
[PUBMED Abstract]
-
Kantarjian HM, Smith TL, McCredie KB, et al.: Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival. Blood 66 (6): 1326-35, 1985.
[PUBMED Abstract]
-
Sacchi S, Kantarjian HM, Smith TL, et al.: Early treatment decisions with interferon-alfa therapy in early chronic-phase chronic myelogenous leukemia. J Clin Oncol 16 (3): 882-9, 1998.
[PUBMED Abstract]
-
Hasford J, Pfirrmann M, Hehlmann R, et al.: A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 90 (11): 850-8, 1998.
[PUBMED Abstract]
-
Kvasnicka HM, Thiele J, Schmitt-Graeff A, et al.: Bone marrow features improve prognostic efficiency in multivariate risk classification of chronic-phase Ph(1+) chronic myelogenous leukemia: a multicenter trial. J Clin Oncol 19 (12): 2994-3009, 2001.
[PUBMED Abstract]
-
Cortes JE, Talpaz M, O'Brien S, et al.: Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal. Cancer 106 (6): 1306-15, 2006.
[PUBMED Abstract]
-
Martinelli G, Iacobucci I, Rosti G, et al.: Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients. Ann Oncol 17 (3): 495-502, 2006.
[PUBMED Abstract]
|