Chronic Myelogenous Leukemia (CML)

Chronic myelogenous leukemia (CML) is a chronic form of leukemia linked to a particular genetic anomaly in the leukemia cell known as the Philadelphia chromosome (T9 or T22).

Chronic Myelogenous Leukemia Causes:

The production of the anomalous gene occurs due to the displacement of the genetic material ABL from chromosome 9 that occupies the position of the normal part of chromosome 22 located close to a region known as BCR. The resultant fusion gene BCRABL causes the ABL gene to function in anomalous manner leading to the development of leukemia.

Chronic Myelogenous Leukemia Symptoms:

Majority of the patients that have developed CML initially seek medical advice when they developed the following symptoms:

• Weariness
• Low-grade Fever or sweating.
• Feeling fullness in the stomach due to spleen enlargement.

CML occurs in three major phases:

• The ailment mostly originates in the chronic phase when the disease is easily controllable following treatment and the patients are able to subsequently function normally.
• When transplant is not performed, the disease inexorably advances over a span of a few years into the accelerated phase wherein the blood count exhibits precarious levels and patients could develop high fever, bone aches and enlarged spleen that could become increasingly discomforting.
• The blast phase of CML is a type of acute leukemia whose treatment is immensely complicated.

Diagnosis & Tests:

• The general practitioner (GP) would carry out a detailed examination of the patient and carry out a blood test. In case of an irregular test outcome, the patient would be referred to a hospital wherein the haematologists (specialists in treating blood problems), oncologists (specialists in radiotherapy and chemotherapy), pathologists and specialist nurses would provide further advice and guidance.
• The doctors at the hospital would delve into the patient’s history and general health condition. A blood sample would be drawn for checking the amounts of all the varied constituents of the blood or a complete blood count. In case the blood test shows the presence of leukemia cells, then a bone marrow sample would be taken for detecting leukemia and in deciding on the optimal treatment option.
• The bone marrow sample is drawn by the biopsy procedure taken under the influence of local anaesthesia via a syringe from the back section of the hipbone or pelvis to be sent for microscopic analysis for detection of leukemia type, the count of the amount of the immature blood cells or blasts present in the sample. During trephine biopsy the doctor would additionally remove a small-sized core of the bone marrow. The near twenty minutes procedure could feel uncomforting during the time of marrow removal via the syringe for which fast-acting sedative are given for allaying the pain during the test. The bruised and aching feeling experienced subsequent to the test would subside in few days that could be lowered by the use of mild painkillers. A bone marrow biopsy is used in determining if the CML lies in the initial or advanced stage.
• The detection is further corroborated by the occurrence of the Philadelphia chromosome, either using chromosome examination, known as cytogenetics, or using molecular testing for the anomalous BCRABL gene.

Chronic Myelogenous Leukemia Treatment:

Previously, without bone marrow transplantation procedure, the middling survival rate of CML patients would be between 4-6 years. While the disease would show progression in some patients swiftly leading to death, there would be others who could live a decade or more depending on their tolerance levels to particular drugs.

The prognosis of allogeneic transplantation is dependent on a host of factors. For instance, patients in the young age bracket having matching sibling donors and undergo transplants in the preliminary year following their detection have a 70-80% likelihood of improvement.

Chemotherapy

The initial line of treatment employs the use of the chemotherapy drug hydroxyurea for controlling the disease. Hydroxyurea is a mild chemotherapy drug that has lesser side effects. It lowers the white blood cell count, causes shrinkage of the spleen and either allays or eradicates the signs of the disease. Though, the patient’s lasting outcome is not affected by this form of treatment.

Stem Cell Transplantation

The single identified remedial treatment for CML is an allogeneic stem cell transplant, also known as bone marrow transplant. Though it is a complicated and risky procedure, it is generally suggested in the initial year of identification if the patient is fairly healthy, below 60years and has an appropriate stem cell or bone marrow donor.

Allogeneic transplantation when conducted early on during the chronic stage raises the probability of long-lasting survival and healing rate up to 70-80%. In case the transplantation is done after the initial year of detection, then the outcome dips to 50-60%.

The drawback of the transplantation procedure is that treatment-associated death would occur in nearly 15% of the patients in the initial six months. On the other hand, staying put till the disease progresses would also pose problems, as long-standing survival rates tend to plummet to 30% when transplantation is conducted in the accelerated phase, lowering further to 10% or lesser when done in the blast phase.

A viable option for younger patients that did not have a matching sibling donor would be to look for a matching unrelated donor by scanning through the National Marrow Donor Program or NMDP. This form of allogeneic transplant is more complex and risky as compared to the transplant done using a sibling donor. Earlier, the treatment-associated transience of this procedure was 40% with long-standing survival rates between 40-60%. However, innovative and enhanced matching methods could imminently lead to improved results, particularly among the below-35 years young patients transplanted in the initial year of diagnosis.

Those patients with CML that are not entrants for the transplantation procedure, the presently available standard treatment involves the usage of interferon that could be solely administered though it has enhanced functioning when merged with cytarabine(ARA-C). Interferon treatment could lead to better control over blood count known as hematologic remission and could lower the proportion of bone marrow cells that hold the Philadelphia chromosome known as cytogenetic remission. Though it is a non-restorative treatment, interferon in comparison to hydroxyurea has been proven to protract survival rates with CML.

Trial Therapies

The new-fangled trial drug STI-571 intended to have targeted action against the product of the Philadelphia chromosome shows immense potential. It is administered orally and has comparatively lesser side effects. Initial results of using the drug in both the chronic and highly advanced stages of the disease are appearing to be quite reassuring. Though it is known to improbably cure the disease by itself, it is most probable that STI-571 would don crucial role in treating CML. However, presently it is obtainable solely in research studies.

A novel variant of the allogeneic transplantation known as the ‘mini allogenic’ transplant, could make a significant difference on the outcome of CML. This trial procedure has lesser complication and risk factors as compared to a standard transplant. This is ideal for those inapt entrants for standard transplant due to the age aspect or overall health condition. Though initial outcome are quite positive, a wait-&-watch approach would need to be adopted to decipher whether the long-term outcome would be as fruitful as with the standard transplants.

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