Lymphomas/Leukemias/Lymphomas/Leukemias/Other bone marrow Other bone marrow

disorders (sorta)disorders (sorta)Jeffrey T. Reisert, DOJeffrey T. Reisert, DO4 MAR 20104 MAR 2010University of New EnglandUniversity of New EnglandPhysician Assistant ProgramPhysician Assistant Program

Brief Slide SetBrief Slide Set

LymphomasLymphomas

LeukemiasLeukemias

Misc./other categoryMisc./other category

DefinitionsDefinitions

Disorder of abnormal white blood cell Disorder of abnormal white blood cell productionproduction Form of cancerForm of cancer

LymphomaLymphoma Localized to lymph nodesLocalized to lymph nodes Clusters of bumpsClusters of bumps

LeukemiaLeukemia In the bloodIn the blood ““Liquid tumor”Liquid tumor”

LymphomaLymphoma

Hodgkin’s vs...... non-Hodgkin’sHodgkin’s vs...... non-Hodgkin’s Reed Sternberg cell (large cell with bilobed nucleus…owl’s eye Reed Sternberg cell (large cell with bilobed nucleus…owl’s eye

appearance) is key microscopic feature in Hodgkin’s lymphomaappearance) is key microscopic feature in Hodgkin’s lymphoma 90% survive Hodgkin’s 90% survive Hodgkin’s

RT responsiveRT responsiveDoxorubicin+bleomycin+vinblastine+acarbazine (ABVD)Doxorubicin+bleomycin+vinblastine+acarbazine (ABVD)

B symptomsB symptoms FeverFever Night sweatsNight sweats Weight lossWeight loss

Often incurableOften incurableT cell lymphomas have HTLV-1 retrovirus associationT cell lymphomas have HTLV-1 retrovirus association

NH lymphomasNH lymphomas

Classified broadly into aggressive and indolentClassified broadly into aggressive and indolent

Includes Includes low grade small celllow grade small cell lymphomas, lymphomas, mantle cellmantle cell lymphomas arising from the mantle lymphomas arising from the mantle zone of the follicle, and zone of the follicle, and mucosal associated mucosal associated lymphoma (MALT)lymphoma (MALT) associated with associated with H. pyloriH. pylori

6 classification systems exist6 classification systems exist Ann Arbor most commonAnn Arbor most common

LN statusLN status

Presence of B symptomsPresence of B symptoms

NH Lymphoma treatmentNH Lymphoma treatment

AggressiveAggressive Goal of cureGoal of cure Multiple meds (many combos) or BM transplantMultiple meds (many combos) or BM transplant

Most common is CHOP Most common is CHOP (Cytoxan+adriamycin+vincristine+prednisone)(Cytoxan+adriamycin+vincristine+prednisone)

May add Rituxan (Anti CD 20, against a cell surface AB)May add Rituxan (Anti CD 20, against a cell surface AB)

RTRT

Indolent-next slideIndolent-next slide

NH Lymphoma treatment cont.NH Lymphoma treatment cont.

IndolentIndolent Slower growingSlower growing Quality of life (watchful waiting?)Quality of life (watchful waiting?) Chemo may not alter survivalChemo may not alter survival Treat when symptoms, bulky diseaseTreat when symptoms, bulky disease Drugs include alkylators, vinca alkaloids, Drugs include alkylators, vinca alkaloids,

anthracyclines, nucleoside analogues anthracyclines, nucleoside analogues (Fludara), and targeted therapies (Rituxan)(Fludara), and targeted therapies (Rituxan)

Leukemias-4 broad categoriesLeukemias-4 broad categories

Acute Chronic

Lymphocytic ALL CLL

Myeloid AML CML

AMLAML

>20% myeloblasts>20% myeloblastsWBC’s elevatedWBC’s elevated Usually >15KUsually >15K

Non-specific s/sNon-specific s/s Fatigue, weakFatigue, weak Pain, feverPain, fever Enlarged LN’s, or hepatosplenomegalyEnlarged LN’s, or hepatosplenomegaly

ProgosticsProgostics Old, worseOld, worse

Treatment-next slideTreatment-next slide

AML-TreatmentAML-Treatment

Induction chemotherapyInduction chemotherapy Cytarabine (cytosine arabinoside)Cytarabine (cytosine arabinoside)

+anthracycline +/- etoposide+anthracycline +/- etoposide

Attempt CRAttempt CR Increased survivalIncreased survival

Treat relapsesTreat relapses

CMLCML

Often have chromosome 9, 22 translocationOften have chromosome 9, 22 translocation T (9,22)T (9,22) Seen in 90-95% of ptsSeen in 90-95% of pts MC is Philadelphia chromosomeMC is Philadelphia chromosome

s/ss/s Usually insidious onsetUsually insidious onset HepatosplenomegalyHepatosplenomegaly Elevated WBC with <5% blastsElevated WBC with <5% blasts

TreatmentTreatment Cured with allogeneic BM transplant (Family or matched donor Cured with allogeneic BM transplant (Family or matched donor

with 5-6 MCH Ag match)with 5-6 MCH Ag match) Imatinide (oral chemo that inhibits ATP binding inducing Imatinide (oral chemo that inhibits ATP binding inducing

apoptosis)apoptosis)

ALLALL

B cell AL is MC CA in childrenB cell AL is MC CA in children

May have Philadelphia chromosomeMay have Philadelphia chromosome

CLLCLL

B cell CLL is MC lymphoid leukemiaB cell CLL is MC lymphoid leukemia

Prolonged survival likelyProlonged survival likely Median survival is 10 yearsMedian survival is 10 years

TreatmentTreatment Chlorambucil PO orChlorambucil PO or Fludarabine IV or Fludarabine IV or BothBoth

Plasma cell disordersPlasma cell disorders

Chiefly “multiple myeloma”Chiefly “multiple myeloma”Abnormal clonal proliferation of a plasma cell (B Abnormal clonal proliferation of a plasma cell (B lymphocyte) usually seen in aginglymphocyte) usually seen in aging

Produces M protein (light chains), abnormal spike on protein Produces M protein (light chains), abnormal spike on protein electrophoresis (blood and urine (Bence Jones proteins))electrophoresis (blood and urine (Bence Jones proteins))

IgG most common, though also IgA and IgD possibleIgG most common, though also IgA and IgD possible

BadnessBadness Involves bone (lytic lesions) and bone marrowInvolves 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, Pain, renal failure, bacterial infections, high calcium, anemia,

hypercoagulability etc.hypercoagulability etc.

WaldenstrWaldenströöm’s Macroglobulinemiam’s Macroglobulinemia

IgM secreting clone of lymphoplamacytoid IgM secreting clone of lymphoplamacytoid cellscellsAlso in agingAlso in agingFeaturesFeatures HyperviscosityHyperviscosity Enlarged LN’s and spleenEnlarged LN’s and spleen

Like Multiple MyelomaLike Multiple Myeloma Less bone painLess bone pain Less hypercalcemiaLess hypercalcemia

MyelodysplasiaMyelodysplasiaIneffective hematopoesisIneffective hematopoesis

Dyspoeisis-Abnormal functioning marrowDyspoeisis-Abnormal functioning marrow Results in cytopeniasResults in cytopenias

Many classification systemsMany classification systems French American British (FAB)French American British (FAB) Modified by World Health OrganizationModified by World Health Organization Table 94-5Table 94-5

Requires bone marrow biopsyRequires bone marrow biopsy Standard bone marrow prepStandard bone marrow prep ?Philadelphia chromosome (CML and ALL)?Philadelphia chromosome (CML and ALL)

The first reproducible chromosome abnormality in human malignancy.The first reproducible chromosome abnormality in human malignancy.9, 22 translocation allows ABL oncogene to be close to BRC (breakpoint cluster region)9, 22 translocation allows ABL oncogene to be close to BRC (breakpoint cluster region)Gene product leads to independent cell growthGene product leads to independent cell growthGleevec blocks the response to this (A new form of chemo, now available for CML)Gleevec blocks the response to this (A new form of chemo, now available for CML)

Myelodysplasia- Approach to Myelodysplasia- Approach to treatmenttreatment

Observation?Observation?SupportSupportDrugs may helpDrugs may help

ThalidomideThalidomide Azacitine (VidazzaAzacitine (Vidazza®®)) Others (Dacagoen, ARA-C, Angiogenesis inhibitors such as Others (Dacagoen, ARA-C, Angiogenesis inhibitors such as

AvastinAvastin®® (used for colon CA), other growth factors (used for colon CA), other growth factors

TransfusionTransfusionBone marrow transplant in younger pts (<65)Bone marrow transplant in younger pts (<65)Treat aggressively if conversion to leukemiaTreat aggressively if conversion to leukemia

All theseAll these

DifficultDifficult

Need to be stagedNeed to be staged

Some more indolentSome more indolent

Some more deadlySome more deadly

Currently getting more complicatedCurrently getting more complicated Genetic testingGenetic testing Chemo regimens evolvingChemo regimens evolving