1. Lymphomas/Leukemias/ Other bone marrow disorders (sorta) Jeffrey T. Reisert, DO 4 MAR 2010 University of New England Physician Assistant Program

2. Brief Slide Set LymphomasLeukemias Misc./other category

3. Definitions Disorder of abnormal white blood cell production Form of cancer Form of cancerLymphoma Localized to lymph nodes Localized to lymph nodes Clusters of bumps Clusters of bumpsLeukemia In the blood In the blood “Liquid tumor” “Liquid tumor”

4. Lymphoma Hodgkin’s vs...... non-Hodgkin’s Reed Sternberg cell (large cell with bilobed nucleus…owl’s eye appearance) is key microscopic feature in Hodgkin’s lymphoma Reed Sternberg cell (large cell with bilobed nucleus…owl’s eye appearance) is key microscopic feature in Hodgkin’s lymphoma 90% survive Hodgkin’s 90% survive Hodgkin’s RT responsive Doxorubicin+bleomycin+vinblastine+acarbazine (ABVD) B symptoms Fever Fever Night sweats Night sweats Weight loss Weight loss Often incurable T cell lymphomas have HTLV-1 retrovirus association

5. NH lymphomas Classified broadly into aggressive and indolent Includes low grade small cell lymphomas, mantle cell lymphomas arising from the mantle zone of the follicle, and mucosal associated lymphoma (MALT) associated with H. pylori 6 classification systems exist Ann Arbor most common Ann Arbor most common LN status Presence of B symptoms

6. NH Lymphoma treatment Aggressive Goal of cure Goal of cure Multiple meds (many combos) or BM transplant Multiple meds (many combos) or BM transplant Most common is CHOP (Cytoxan+adriamycin+vincristine+prednisone) May add Rituxan (Anti CD 20, against a cell surface AB) RT Indolent-next slide

7. NH Lymphoma treatment cont. Indolent Slower growing Slower growing Quality of life (watchful waiting?) Quality of life (watchful waiting?) Chemo may not alter survival Chemo may not alter survival Treat when symptoms, bulky disease Treat when symptoms, bulky disease Drugs include alkylators, vinca alkaloids, anthracyclines, nucleoside analogues (Fludara), and targeted therapies (Rituxan) Drugs include alkylators, vinca alkaloids, anthracyclines, nucleoside analogues (Fludara), and targeted therapies (Rituxan)

8. Leukemias-4 broad categories AcuteChronic LymphocyticALLCLL MyeloidAMLCML

9. AML >20% myeloblasts WBC’s elevated Usually >15K Usually >15K Non-specific s/s Fatigue, weak Fatigue, weak Pain, fever Pain, fever Enlarged LN’s, or hepatosplenomegaly Enlarged LN’s, or hepatosplenomegalyProgostics Old, worse Old, worse Treatment-next slide

10. AML-Treatment Induction chemotherapy Cytarabine (cytosine arabinoside)+anthracycline +/- etoposide Cytarabine (cytosine arabinoside)+anthracycline +/- etoposide Attempt CR Increased survival Increased survival Treat relapses

11. CML Often have chromosome 9, 22 translocation T (9,22) T (9,22) Seen in 90-95% of pts Seen in 90-95% of pts MC is Philadelphia chromosome MC is Philadelphia chromosomes/s Usually insidious onset Usually insidious onset Hepatosplenomegaly Hepatosplenomegaly Elevated WBC with <5% blasts Elevated WBC with <5% blastsTreatment Cured with allogeneic BM transplant (Family or matched donor with 5-6 MCH Ag match) Cured with allogeneic BM transplant (Family or matched donor with 5-6 MCH Ag match) Imatinide (oral chemo that inhibits ATP binding inducing apoptosis) Imatinide (oral chemo that inhibits ATP binding inducing apoptosis)

12. ALL B cell AL is MC CA in children May have Philadelphia chromosome

13. CLL B cell CLL is MC lymphoid leukemia Prolonged survival likely Median survival is 10 years Median survival is 10 yearsTreatment Chlorambucil PO or Chlorambucil PO or Fludarabine IV or Fludarabine IV or Both Both

14. Plasma cell disorders Chiefly “multiple myeloma” Abnormal clonal proliferation of a plasma cell (B lymphocyte) usually seen in aging Produces M protein (light chains), abnormal spike on protein electrophoresis (blood and urine (Bence Jones proteins)) Produces M protein (light chains), abnormal spike on protein electrophoresis (blood and urine (Bence Jones proteins)) IgG most common, though also IgA and IgD possible IgG most common, though also IgA and IgD possibleBadness Involves bone (lytic lesions) and bone marrow Involves bone (lytic lesions) and bone marrow Pain common (70% of pts get boney pain) Pain common (70% of pts get boney pain) Treatment difficult (chemo) Treatment difficult (chemo) Pain, renal failure, bacterial infections, high calcium, anemia, hypercoagulability etc. Pain, renal failure, bacterial infections, high calcium, anemia, hypercoagulability etc.

15. Waldenström’s Macroglobulinemia IgM secreting clone of lymphoplamacytoid cells Also in aging Features Hyperviscosity Hyperviscosity Enlarged LN’s and spleen Enlarged LN’s and spleen Like Multiple Myeloma Less bone pain Less bone pain Less hypercalcemia Less hypercalcemia

16. Myelodysplasia Ineffective hematopoesis Dyspoeisis-Abnormal functioning marrow Dyspoeisis-Abnormal functioning marrow Results in cytopenias Results in cytopenias Many classification systems French American British (FAB) French American British (FAB) Modified by World Health Organization Modified by World Health Organization Table 94-5 Table 94-5 Requires bone marrow biopsy Standard bone marrow prep Standard bone marrow prep ?Philadelphia chromosome (CML and ALL) ?Philadelphia chromosome (CML and ALL) The first reproducible chromosome abnormality in human malignancy. 9, 22 translocation allows ABL oncogene to be close to BRC (breakpoint cluster region) Gene product leads to independent cell growth Gleevec blocks the response to this (A new form of chemo, now available for CML)

17. Myelodysplasia- Approach to treatment Observation?Support Drugs may help Thalidomide Thalidomide Azacitine (Vidazza®) Azacitine (Vidazza®) Others (Dacagoen, ARA-C, Angiogenesis inhibitors such as Avastin® (used for colon CA), other growth factors Others (Dacagoen, ARA-C, Angiogenesis inhibitors such as Avastin® (used for colon CA), other growth factorsTransfusion Bone marrow transplant in younger pts (<65) Treat aggressively if conversion to leukemia

18. All these Difficult Need to be staged Some more indolent Some more deadly Currently getting more complicated Genetic testing Genetic testing Chemo regimens evolving Chemo regimens evolving