(All the articles published in past are available at www.shyamhemoncclinic.com)
Question: Dr. Chiragbhai, thank you very much for helping us summarize this complex topic.
Ans: Let us continue with other aspects. There has been extensive advances in areas of Diagnosis, Prognosis, and Predictive tests (tests which predict if a certain medicine is likely to work or not – something similar to antibiotic sensitivity test). These tests have improved our ability to better diagnose, better follow up and diagnose any relapse at very early stage, and use more targeted approaches, better stratify who is more likely to need transplant and who should not undergo transplant etc. It also includes some good clinical scoring systems.
Que: Yes I have heard of tests like PCR for CML diagnosis. Are you talking about these?
Ans: Yes, that and many more.
1. CML: diagnosis is now done by showing Philadelphia chromosome. In some cases, this is normal but a much more sensitive test PCR is abnormal. Chromosome abnormality detects 1 in 50 abnormal cells, PCR detects one in 100,000 to 10,00,000 cells. There is no category now as Ph negative CML. This highly sensitive test is very helpful in good follow up as well. Early detection of rising PCR helps in change of medicine or decision about transplant in timely manner, before patient is clinically sick. Also, IRMA test helps in detection of resistance to currently available agents, hence better decision making about which drug to use. BCR-ABL is also the target for drug imatinib – hence when this target is present, imatinib works in other diseases as well, for example, in some patients with ALL.
YES, ability to test many of these targets have lead to a very interesting situation, because now many such drugs may work in many varied diseases. For example, presence of c-kit mutation in tumor/malignant cells predicts response to Imatinib. So imatinib which was originally investigated and approved for CML also works in some patients with severe eosinophilia, patients with GIST (one type of gastrointestinal tumor) and others. Therefore, availability of such molecular tests is becoming more and more important.
2. CLL: FISH test for various abnormalities helps in deciding prognosis and resistance to certain drugs. This is important in making choice of medicine. Also, it is important to note that Rai stage 0 patients do not need treatment even if these abnormalities are present.
3. AML: Now it is nearly impossible to manage AML without cytogenetics, and molecular tests like FLT 3. These tests determine type of therapy, including need for transplant. Morphology or categories like M1 M2 etc do not matter in these decisions now. PML RAR alpha is must for diagnosis of APL, as well as very useful for follow up. Multiplex PCR – such panels to look at multiple mutations now allow detection of many molecular abnormalities from one test – they are more sensitive, need less sample, faster and cost effective. Used for ALL, MDS as well.
4. ALL: same as AML – mandatory to check cytogenetics and at least rule out Philadelphia chromosome. MRD (minimal residual disease) detection is very useful new test for deciding prognosis and important treatment decisions. Day 8 response to prednisone – number of blasts in peripheral blood – a simple tests still remains very accurate and useful for prognosis.
5. MPD (myeloproliferative diseases): JAK 2 mutation is now almost mandatory for diagnosis of polycythemia vera, and very useful for diagnosis of myelofibrosis and essential thrombocytosis. Also, it is the target for a new medicine called Ruxolitinib for myelofibrosis.
6. MDS (myelodysplastic syndrome): IPSS, WHO scoring system take into account simple information, but are highly accurate for prognosis and decision making about treatment like transplant as well. FISH is more sensitive than routine cytogenetics for various abnormalities, and is faster as well. Detection of del 5q is very important, as these patients respond extremely well to thalidomide or lenalidomide.
April 14th, 2014.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. 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