(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. In last part we covered diagnostic advances for AML, ALL, CML, CLL, myeloproliferative neoplasms, and myelodysplastic syndrome.
Ans: Let us continue with other malignancies i.e. myeloma and lymphomas. Most important advances in field of myeloma diagnosis include:
1. Free light chain assay: about 20% of myeloma patients produce only light chains. These patients have all clinical features, but their protein electrophoresis does not show M band. Such patients can now be diagnosed by use of FLC assay. Also, this test is much more sensitive, hence picks up a very small amount of monoclonal protein in blood. Hence now we do not use 24 hour urine collection to concentrate light chains excreted in urine. Also, FLC assay helps in diagnosis of amyloidosis. Since FLC assay is very sensitive, and also has a short half life, it can be used in follow up of all myeloma patients, especially to detect response to treatment earlier.
2. Cytogenetic abnormalities in bone marrow examination – useful for prognostication.
3. PET-CT scan: sometimes used for better staging and more accurate assessment of overall disease status.
4. Practical criteria: Criteria for diagnosis are now more practical, including number of plasma cells required in bone marrow, and definition of organ injury (CRAB – calcium increase, renal involvement, anemia, bone lesions). >10% monoclonal plasma cells and one of CRAB is required to diagnose myeloma. Without CRAB, it would be smoldering or indolent myeloma.
Advances in field of Lymphoma are many, but especially in field of IHC and importance of obtaining excisional node biopsy (or at least a Trucut biopsy).
1. For some lymphomas, molecular/cytogenetic tests are required for diagnosis e.g. Mantle cell lymphoma can be confirmed by presence of cyclin D1 amplification; Burkitt lymphoma by C-Myc amplification; ALK mutation for anaplastic large cell lymphoma…
2. Ki 67 is an IHC marker suggestive of rate of proliferation. It helps in certain treatment decisions, as highly proliferative tumors need to be treated with more frequent or continuous infusion chemotherapy.
3. PET-CT is now essential part of management for many lymphomas, especially Hodgkin, and most cases of DLBCL. This is especially important in early stages where a metabolic CR allows reduction of chemotherapy cycles from 6-8 to 2-4. This is a very useful decision for patients. Lack of response on PET is also one of the strongest predictors of poor long term survival, independent from very established clinical scores like IPI.
4. Differentiating between AC or GC type or gene expression profile have not been validated yet for clinical use.
5. Another important point is to test for hepatitis B in every patient who is likely to start Rituximab. Untreated hepatitis B can flare up to a serious potentially fatal level in some patients treated with Rituximab.
6. Lymphoblastic lymphoma diagnosis must be separated from other lymphomas, as treatment is very different. It is treated like acute lymphocytic leukemia rather than like lymphoma.
7. Double hit lymphomas: diagnosed by IHC i.e. any 2 of three abnormalities present – BCL 2, BCL 6 and MYC. Double hit lymphomas relapse much faster and are considered for upfront transplant i.e. right after 6-8 cycles of chemotherapy.
In next few parts, we will summarize advances in treatment of hematological malignancies, including role of new medicines, and role of transplant.
June 13th, 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