AML

PATH: mutations in tx factors (txlocations) -> failure of differentiation. >20% blasts, AUER RODS, delicate nuclear chromatin, nucleoli, fine azurophilic granules.  Express myeloid antigens, positive for myeloperoxidase.  Can be primary or secondary to myelodysplastic, chemo, radiation

Clin: Pancytopenia - anemia, neutropenia, thrombocytopenia - less prominent splenomegaly than ALL,CN abnormalities, leukemia cutis, DIC. TX: chemo or txplant (for secondary).

Demo: Older adults

Prognostic: Bad - up to 50% w/good karyotype, but low as 15%. Pts>60yo -> palliation (not cure)

ALL 

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: >20% blasts, hyperdiploidy, chromosomal xlocation (worse prog), few nucleoli+condensed chromatin+scant cytoplasm w/o granules,

Clin: Fast course, usually primary, can involve testis or CNS tx w/daunorubicin, vincristine, dexamethasone, L-asparaginase. Post-remission: mtx + 6-MP. CNS PROPHYLAXIS REQ'D

Demo: Kids!

Prognostic: hyperdiploid favorable, >80% peds, 50% adults, >90% remission

Same as AML, but treat w/All-trans Retinoic Acid

CML

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: BCR-Abl! 100%cellular marrow (vs. 50% nl), increased WBC-neutros w/inc. blasts - full range of maturation on peripheral blood smear, alkaline phosphatase absent

Clin: extreme Splenic enlargement, high platelet/basophil counts, change in phase - b sx (fever, wt loss, chills), elevated b12,hyperuricemia TX: imatinib, cure w/allo-sct,

Demo: adults 25-60yo

Prognostic: chronic phase 4-6 years -> accelerated phase -> blast phase (3-6 months)

Polycythemia Vera

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: panmyelosis, increase rbc mass->congestion+infarction, JAK-2 mutation, abnormal platelets

Clin: increase in RBCs, flame hemorrhages, pruritus, eventual bone marrow failure, lots o/clotting (or platelet failure)->budd/chiari syndrome+heart attack+stroke

Demo: older folk

Prognostic: median survival: 10 years, after which "spent phase" -> bone marrow failue, shift of hematopoiesis to the spleen

Chronic Idiopathic Myelofibrosis

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: tear drop red cells, nucleated erythroid precursers, markedly enlarged spleen, marrow hypocellular and fibrotic, 50%JAk2 

Clin: leukemic -> fibrotic phase(anemia, thrombocytopenia),infection+thrombotic+ hemorrhagic episodes, tx - symptomatic (aspirin for platelets, etc), allo-SCT in younger pts

Demo: older pts

Prognostic: 4-5yr survival

Myelodysplastic Syndromes

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: chromosomal DELETIONS, hypercellular bone marrow, cell lines show morphologic dysplasia+elevated blasts (5<x<20%)

Clin: present w/macrocytic normochromic hypoproliferative anemia,cytopenias(~pancytopenias), phagocytic incompetence -->infxn, bleeding (mucocutaneous), B-sx (fevers, night sweats, wt loss) TX: cure-allo-sct, supportive care w/abx + RBCs, G-CSF or G-MCSF,some pts->lenalidomide, other chemo

Demo: Older 50-70

Prognostic: some->AML, 9-29 months survival

CLL

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: usually B cell w/CD5+,no chromosomal xlocations, hypercellular marrow w/mature lymphocytes,proliferation centers, smudge cells (fragile cells)

Clin: hypogammaglobulinemia->infxn, autoimmune hemolysis, TTP, diffuse lymph node enlargement+palpable spleen,lymphocytosis>5,000 tx: observation

Demo: elderly males, most common adult leukemia

Prognostic: 10 yrs, can ->non-hodgkin's lymphoma (Richter's txformation)

Multiple Myeloma

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH:IL-1 secretion-->multifocal destructive bone lesions, neoplastic plasma cells,chromosomal xlocations, IgG, IgA hypersecretion

Clin: bone pain+anemia+renal insuff., hypercalcemia possible, low levels of normal Ig/high monoclonal Ig, >30% plasma cells in marrow, tx ASCT - reduces bone pain, narcotic use.  biphosphonates improve skeletal fxn

Demo: Elderly

Prognostic: 5 yr survival

Hodgkin's Disease

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH: Reed-Steinberg Cell "Owl's Eye Inclusion" - binucleate morphology in a background of normal inflamm. cells, from B-cells,do produce non-productive "IgH", EBV may contribute

Clin: Starts in one lymph node then progresses continuously, excisional biopsy necessary, can obstruct viscera, cause wasting, B-sx, immuno-incompetence TX: ABVD Chemo

Demo: Young & Old Adults (bimodal)

Prognostic: Ann-arbor staging system, I-IV, 75% cure w/<2 bad factors, 55% cure >3

Non-Hodgkins Lymphoma

PATH(morph+pathogenesis): Clin: Demo: Prognostic:

PATH:Balanced chromosomal xlocations (oncogene gets next to Ig gene), Large cell vs. intermediate vs. small,

Clin: high grade - intense chemo + CNS prophylaxis, intermediate grade: R-CHOP, R=rituximab (anti-B ab), Indolent:Not curable w/chemo,slow growth, blood autoimmunity, tx=nothing

Demo:

Prognostic: Depends on stage - high grade = 60% cure,