Lymphomas/Leukemias/ Other bone marrow disorders (sorta)

Jeffrey T. Reisert, DO 4 MAR 2010 University of New England Physician Assistant Program

Brief Slide Set

Lymphomas Leukemias Misc./other category

Definitions

Disorder of abnormal white blood cell production  Form of cancer Lymphoma   Localized to lymph nodes Clusters of bumps Leukemia   In the blood “Liquid tumor”

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 90% survive Hodgkin’s RT responsive Doxorubicin+bleomycin+vinblastine+acarbazine (ABVD) B symptoms    Fever Night sweats Weight loss Often incurable T cell lymphomas have HTLV-1 retrovirus association

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 LN status Presence of B symptoms

NH Lymphoma treatment

Aggressive   Goal of cure 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

NH Lymphoma treatment cont.

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

Leukemias-4 broad categories

Acute Chronic Lymphocytic Myeloid ALL AML CLL CML

AML

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

AML-Treatment

Induction chemotherapy  Cytarabine (cytosine arabinoside)+anthracycline +/- etoposide Attempt CR  Increased survival Treat relapses

CML

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

ALL

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

CLL

B cell CLL is MC lymphoid leukemia Prolonged survival likely  Median survival is 10 years Treatment  Chlorambucil PO or  Fludarabine IV or  Both

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)) IgG most common, though also IgA and IgD possible Badness     Involves bone (lytic lesions) and bone marrow Pain common (70% of pts get boney pain) Treatment difficult (chemo) Pain, renal failure, bacterial infections, high calcium, anemia, hypercoagulability etc.

Waldenstr öm’s Macroglobulinemia

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

Myelodysplasia

Ineffective hematopoesis   Dyspoeisis-Abnormal functioning marrow Results in cytopenias Many classification systems    French American British (FAB) Modified by World Health Organization Table 94-5 Requires bone marrow biopsy  Standard bone marrow prep  ?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)

Myelodysplasia- Approach to treatment

Observation?

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

All these

Difficult Need to be staged Some more indolent Some more deadly Currently getting more complicated  Genetic testing  Chemo regimens evolving