Chronic myelogenous leukemia

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}} Chronic myelogenous leukemia (or CML) is a form of chronic leukemiacharacterised by increased production of myeloid cells in the bone marrow. It is a type of myeloproliferative diseaseassociated with a characteristic chromosomal translocationtermed the Philadelphia chromosome. It is traditionally treated with chemotherapy, interferonand bone marrow transplantation, although a specific inhibitor (imatinib mesylate) has radically changed the management.

Signs and symptoms

Patients are often asymptomatic at diagnosis, presenting incidentally with an elevated white blood counton a routine laboratory test. Symptoms may include: malaise, low gradefever, increased susceptibility to infections, anemiaand thrombocytopeniawith resultant bruising(although an increased plateletcount, thrombocytosis, may be a feature). Splenomegalymay also be seen.

The disease may remain dormant for years, but a proportion proceed to accelerated phase (in which the diseases progresses rapidly) or overt blast crisis, which has the symptoms and risks of acute myelogenous leukemia(AML).

Diagnosis

CML is often suspected on the basis on the full blood count, which shows increased granulocytesof all types (including basophils). When the index of suspicion is high, a bone marrow biopsyis required to distinguish CML from other diseases that feature the same symptoms.

Ultimately, CML is diagnosed by detecting the Philadelphia chromosome(a translocation between the 9th and 22nd chromosomeleading to an aberrant proteinthat drives cell division). This translocation leads to bcr-abl fusion and activation of protein tyrosine kinase cascade.

Disease activity can be determined on the basis of the bone marrowexamination, cytogeneticsand by quantitative PCR.

Pathophysiology

CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocationnamed Philadelphia chromosome, in 1960. The fusion of two geneson chromosomes 9 and 22, termed abl and bcr respectively, leads to a proteinthat propels mitosisand causes genomic instability(leading to further mutations).

CML progresses to accelerated phase, and then blast crisis, when additional genetic abnormalities speed up the rate at which new malignant cells are produced in the bone marrow. A second Philadelphia chromosome may appear, as well as deletions of (parts of) chromosomes.

Epidemiology

CML occurs in all age groups, but most commonly in the middle-aged and elderly. Its annual incidence is about 1 per million.

Treatment

Chronic phase

Chronic phase CML is treated with imatinib(marketed as Gleevec or Glivec; previously known as STI-571). In the past, hydroxyurea, alkylating agents(e.g. cytarabine), interferon alfa 2band steroidswere used, but this has been replaced by imatinib. Imatinib is a new agent which specifically targets the abnormality caused by the Philadelphia chromosome. It is better tolerated and more effective than previous therapies. Bone marrow transplantswere also used as initial treatment for CML before imatiniband can be curative. In patients who fail to achieve a cytogenetic remission with imatinib or who relapse while on imatinib, a bone marrow transplantshould be considered.

Various combinations of the different treatment modalities are being explored, such as interferon and imatinib together.

In 2005, Bocchia et al reported favourable results of vaccinationwith the bcr-abl p210 fusion protein in patients with stable disease, with GM-CSFas an adjuvant.

Three new drugs dasatinib (BMS-354825), ceflatonin (homoharringtonine) and AMN 107 are currently in active clinical trials in patients with chronic myeloid leukemia (CML) who have developed resistance to imatinib. [1][2]

Blast crisis

Blast crisis carries all the symptoms and characteristics of acute myelogenous leukemia, and has a very high mortalityrate. This stage can most effectively be treated by a bone marrow transplantafter high-dose chemotherapy. In young patients in the accelerated phase, a transplant may also be an option. However the likelihood of replapse after a bone marrow transplant is higher in patients in blast crisis or in the accelerated phase as compared to patients in the chronic phase.

Prognosis

The prognosis of CML depends on a number of different parameters. Two different scoring systems are in use: one by Sokal et al (1984) and one by Hasford et al (1998).

References

• Bocchia M, Gentili S, Abruzzese E, Fanelli A, Iuliano F, Tabilio A, Amabile M, Forconi F, Gozzetti A, Raspadori D, Amadori S, Lauria F. Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet2005;365:657-62.
• Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in good risk chronic granulocytic leukemia. Blood 1984;63:789-799. PMID 6584184.
• Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, Alimena G, Steegmann JL, Ansari H. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 1998;90:850-858. PMID 9625174.

External links

For more information, see:

• Myeloproliferative Disease Support List
• Blood & Marrow Transplant Information Network
• MPD-NET Frequently Asked Questions About Chronic Myelogenous Leukemia
• Association of Cancer Online Resource (ACOR) Leukemia Links

fr:Leucémie myéloïde chronique sv:Kronisk myeloisk leukemi

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Chronic+myelogenous+leukemia Wikipedia article Chronic myelogenous leukemia.