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Hemato-Oncology-38-Myeloproliferative Neoplasms-General (1)


Question: Dr. Chiragbhai, thank you for explaining in last part about importance of supportive care in NHL treatment, tumor lysis syndrome in particular, and role of new drugs like rasburicase. What is the next hemato-oncological disorder we are planning to discuss?
Ans: Next category is a very interesting one, Myeloproliferative Diseases. These diseases are traditionally not thought of as cancer, not as serious as leukemias, and yet most doctors know that they can transform to leukemia or serious cytopenias.
Better understanding of disease biology has led to understanding that these are in fact clonal disorders i.e. neoplasms, in other words cancers. Many of them have an underlying gene defect that leads to this change from normal to cancer, and in many cases it can now be tested.
WHO classification now calls them MPNs (myeloproliferative neoplasms) rather than MPDs (myeloproliferative disorders) to underscore importance of biology and hence prognosis.
Most clinicians are aware of four diagnoses in this category:
1. CML – chronic myeloid leukemia 2. PMF – primary myelofibrosis. Also known as agnogenic myeloid metaplasia in past, or as chronic idiopathic myelofibrosis. 3. PV – polycythemia vera 4. ET – essential thrombocytosis.
Current classification includes following categories. You will notice that similar disease process is now identified with other cell lines e.g. mast cells, eosinophils, apart from platelets or red cells:
1. Chronic myeloid leukemia 5. Essential thrombocythemia
2. Chronic neutrophilic leukemia 6. Chronic eosinophilic leukemia
3. Polycythemia vera 7. Systemic mastocytosis
4. Primary myelofibrosis 8. MPN, unclassifiable

Que: That is certainly interesting. So there is a disease associated with abnormal proliferation for each cell line red cell (PV), platelets (ET), neutrophil, eosinophil, mast cell, and more.
Ans: However they do share many clinical and laboratory features:
1. Insidious onset
2. Organomegaly is common – hepatomegaly or splenomegaly
3. High metabolic rate – frequently with high uric acid
4. Bone marrow hypercellularity, without significant dysplasia
5. Potential for transformation to acute leukemia OR marrow failure due to fibrosis

One of the most important advances in this field is the identification of specific mutations. When present, they are diagnostic in most cases, however, their absence does not rule out disease. CML is an exception, where BCR-ABL mutation is mandatory for diagnosis. There is no such category now as Ph negative CML. Even if Philadelphia chromosome is negative, BCR-ABL mutation by PCR is a must for CML diagnosis.

1. Polycythemia vera – 90% patients have JAK 2 V617F mutation.
2. PMF, ET – many patients have JAK 2 mutation.
3. Systemic mastocytosis – c-kit mutation is common.
4. Chronic eosinophilic leukemia and other MPNs associated with eosinophilia – one of three types of abnormalities is common – PDGFRA, PDGFRB, FGFR1
Thus, this classification is now moving from clinical and morphological criteria towards more of a molecular abnormality defined criteria.

Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad.