Hemato-Oncology-19-Chronic Myeloid Leukemia Treatment (1)

HEMATO-ONCOLOGY PART-19

Welcome to the ninteenth part of a series on Hemato-oncology.

Question: Dr. Chiragbhai, I am very curious to know more about the Tree and Roots that we started discussing last time. Please tell us how different treatment options work on this CML tree.

Answer: Yes, my favorite Tree of CML.

Hydroxyurea or Busulfan can clear the Tree, but do not affect Roots. Hence, they can control disease for about 3 years, but eventually, genetic abnormality worsens with more mutations, and CML goes into blast crisis (similar to acute leukemia). At that point, even transplant cures only 10% patients. Rest of the treatment options work on Roots to a variable degree, as below.

1. Interferon clears cytogenetics (cytogenetic remission) in about 10-20% patients. Even these 10% patients live about 10 years or more.
2. Allogeneic Stem Cell Transplant clears PCR (known as molecular remission) in about 70% patients. This is the modality providing best results, and with longest data of about 30 years. So, we know for sure that 70% patients can actually be cured. Due to this long term results, proven data, and cost of lifelong Imatinib, TRANSPLANT is still the first choice in many countries, especially for young patients. But transplant procedure has about 10% risk of mortality, and 20% risk of significant morbidity.
3. Imatinib clears cytogenetics in about 80% patients, and PCR in about 30%. Recent medicines like Dasatinib and Nilotinib clear PCR in about 40-50% patients. However, even imatinib is only about 10 years old, and needs lifelong treatment. Hence, we do not know if any patient can actually be cured. Also, majority of patients who stop imatinib have relapse of CML. We also do not know effects of very long term therapy, which is a concern, especially for younger patients. Not all patients tolerate drug well.

So, as you can understand, decision making is complex, and changing. Transplant is the only known curative modality at present, however it has significant early risk and cost. Whereas imatinib has very little early risk, but is probably not curative, requires lifelong treatment and future is unclear.
Good thing is that patients who fail imatinib can still be transplanted and generally with good results. Also, because of PCR, strict monitoring is possible and resistance to imatinib can be detected very early, before overt relapse or blast crisis.
IRMA assay is another test which helps in early decision making, Second line treatment options i.e. Dasatinib or Nilotinib are also available now, but at a very high cost i.e. about 7 lac per year (likely to reduce in future), and to be continued lifelong also. Their long term results and safety are even less clear compared to imatinib. Other new medicines are also in advance stages of clinical trials, and likely to be approved soon, which will add more options for patients and more complexity to decision making as well.

Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 98243 12144, 98988 31496
Diplomate American Board of Oncology and Hematology. Ahmedabad. drchiragashah@gmail.com
Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com