Welcome to the seventeenth part of a series on Hemato-oncology.
Question: Dr. Chiragbhai, it was interesting to know about pathophysiology of Chronic Myeloid Leukemia. Can you tell us about its diagnosis and treatment?
Answer: CML is diagnosed by identifying the specific genetic abnormality that we discussed last time, from either bone marrow or blood. Diagnosis can be done using karyotyping (traditional cytogenetics method), FISH (newer more sensitive and rapid method), or PCR (most sensitive method). Generally all three tests are done first time, at least first and last test. Both of these tests are also mandatory for follow up, especially quantitative PCR.
LAP score should no longer be used, as it is neither specific nor sensitive like the above tests. And above noted tests are now widely available in India.
Bone marrow aspiration and trephine biopsy are hypercellular, but not diagnostic, without above noted genetic abnormality. BCR ABL negative myeloproliferative diseases are not diagnosed or treated as CML any longer. That is a different disease.
IRMA i.e. Imatinib Resistance Mutation Assay, is routinely not performed at diagnosis. It is more commonly done at time of sign of disease resistance or loss of control.
Que: What are the treatment options?
Ans: Following broad treatment options exist:
- Antineoplastic therapy – hydroxyurea, busulfan, cytarabine
- Immune modulation agents – interferon alpha or beta
- Hematopoietic Stem Cell Transplant
- Tyrosine kinase inhibitors – imatinib, dasatinib, nilotinib
Que: How do you choose between so many treatment options?
Ans: For vast majority of patients, first option is IMATINIB, the famous targeted therapy. However, field of CML treatment is rapidly changing, and it is better to meet expert hematologist to make treatment decisions.
For example, there are two major studies, recently published, which led to US FDA approval for Dasatinib and Nilotinib also as first line treatment. Both studies showed these drugs to be better than Imatinib in terms of effectiveness, and overall well tolerated. However, there are some important side effects with the newer drugs and the follow up is not as long as with imatinib. Hence, there is a debate about what to choose first.
Imatinib has clearly replaced hydroxyurea, interferon and cytarabine as first line treatment, as it is far superior. It has also replaced Transplant as first line treatment, for almost all patients. Busulfan is rarely used, if other options are available and feasibly by affordability. Imatinib is more expensive compared with hydroxyurea. However, a large number of patients in India are receiving this drug for free or at a markedly reduced cost, for many years, through the efforts of Max Foundation and Novartis, from designated clinics or hospitals. Also, many Indian companies now provide this drug at very low cost. Hence, treatment of CML with hydroxyurea is no longer acceptable, even in India.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 98243 12144, 98988 31496
Diplomate American Board of Oncology and Hematology. Ahmedabad. firstname.lastname@example.org Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com