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Hemo Malignancies


Pathophysiologic Basis for Myeloproliferative Disorders Acquired clonal abnormalities of the hematopoietic stem cell; May see changes in all stem cell lines (erythroid, myeloid, & pt cells); poss specific chromosomal changes
True increase in RBC mass Primary P. vera
Relative increase in RBC mass Secondary P. vera
Conditions causing secondary P. vera Hypoxia (COPD, heart disease, smoking), renal disease, ACS, dehydration, high altitude, blood doping
P. vera: incidence/prevalence 60 to 70 yrs (mean age at dx: 65 yrs; rare in pt <40); M/F = 1.2 to 1
P. vera S/S Problems related to hyperviscocity & hypervolemia; pruritis (esp after hot showers/baths), thromboses, dyspnea, HA, visual disturbance, tinnitus; LUQ pain, easy bleeding
Hallmark of P. vera = Erythrocytosis
P. vera H & H M: >18.5 ; F: >16.5 (often HCT is > 60%)
P. vera mgmt Therapeutic phlebotomy (goal Hct <45 % M, <43% F). Myelosuppression PRN. Hydroxyurea (watch WBC/PLT). Anagrelide if thrombocytosis. Aspirin 81mg. Antihistamine for pruritis. Allopurinol PRN.
P. vera survival prognosis Median if treated: 11-15 year; untreated = 18 months.
Causes of Reactive (Secondary) Thrombocytosis Severe hemorrhage; splenectomy; neoplasms; chronic inflame dz; post acute infxn; B12 def; meds (vincristine, epi); ETOH
Causes of Reactive (Secondary) Thrombocytosis Severe hemorrhage; splenectomy; neoplasms; chronic inflame dz; post acute infxn; B12 def; meds (vincristine, epi); ETOH
Thrombocytosis S/S Median 50-60 yrs (but all ages); rare in kids; slight female predominance; 1/3 of pts asymptomatic at dx; 2/3 of pts vasomotor s/s (HA, dizziness, visual changes) or complications from thrombosis/bleeding
Thrombocytosis findings Splenomegaly (>25% ); hepatomegaly (20%); leukocytosis, erythrocytosis, mild anemia; occ immature precursor cells and/or large plts; BM bx: increased number of megakaryocytes, else normal
Thrombocytosis Mgmt ASA to prevent thrombosis; Cytoreductive tx (hydroxyurea, anagrelide); Plt pheresis if severe bleed; BM bx for Philadelphia chr.
Thrombocytosis Prognosis 10 y survival = 64-80% ; 1-5% evolve into AML, 10-15% evolve into myelofibrosis
Disorder in which bone marrow is replaced with scar tissue, leading to anemia Myelofibrosis
Myelofibrosis findings Fibrosis on BM; splenomegaly; giant plts; teardrop poikilocytosis
Myelofibrosis peak incidence & survival 50-70 yrs old; median survival is 2-5 yr from onset; occurs in 10 to 30% of pts w/P. vera
Cause of Myelofibrosis Unknown
Increased bone marrow production of megakaryocytes leads to increased peripheral platelet count Myelofibrosis
Myelofibrosis S/S Early: asymptomatic; later: malaise; wt loss; splenomegaly/splenic infarction; hepatomegaly in 50% of pts
Myelofibrosis findings BM aspirate = dry tap; anemia generally increases over time; normochromic-normocytic & mild poik; NRBCs
Myelofibrosis mgmt No tx to reverse/ctrl underlying pathology; tx supportive; mgmt of complications; (Procrit, Aranesp); pRBC & plt txn; Thalidomide & Revlimid? ; allogeneic BM txplt for younger pt? ; Median survival 5 yrs
Acquired clonal disorders of the hematopoietic stem cell MDS
______ cytopenias affect one or more cell lines (RBC, WBC, and/or PLTs) MDS
Dz occurs when blood cells do not develop into mature cells, but rather stay in an immature stage within the BM MDS
Some chromosomal abnormalities (5q – loss of part of the long arm of chromosome 5); “pre-leukemia” MDS
MDS: risk factors include exposure to: Benzene, radiation, chemotx agents (esp alkylating agents & anthracyclines)
MDS pts Average age ≥ 60 years; pts often asymptomatic; If S/S: fatigue, bleeding, recurrent infxn, fever, splenomegaly, pallor
MDS Labs 85% of pts anemic; 50% neutropenia; 30% thrombocytopenia
MDS CBC Normal or low RBC, WBC, PLTS; Blasts in BM <20%; Pelger-Huet cells (bi-lobed neutrophils)
MDS: >20% blasts in BM indicates: Transition into acute leukemia
Blasts in BM <20%; Pelger-Huet cells (bi-lobed neutrophils) seen in: MDS
MDS BM shows: Hypercellular marrow with delayed/abnormal maturation ( 5q- chromosomal abnormality, ring sideroblasts)
MDS Mgmt Monitor closely (lest transformation); Cytokine and transfusion support; chemotherapy (Thalidomide, Lenolidimide for 5q- syndrome, Azacitadine); Allogeneic BM txplt only curative therapy (most pts too old)
MDS: Allogeneic BM txplt may cure ?? % of pts 30-50%, for pts <60 y.o.
Cornerstone for tx of MDS Supportive care
MDS prognosis Ultimately fatal disease; Infections or bleeding common causes of death
Risk of transformation to leukemia depends on: Percentage of blasts in BM
Etiology of multiple myeloma Etiology unknown. May be associated with pesticides, paper production, leather tanning, exposure to radiation from nukes
Replacement of normal bone marrow by plasma cells leads to bone marrow failure Multiple myeloma
Lytic lesions predisposing patients to bone pain, pathologic fractures, and hypercalcemia Multiple myeloma
Multiple myeloma S/S Fatigue/Anemia; Bone pain (from lytic lesions: back and ribs); Recurrent infxn; Sp cord compression; Unexplained fractures; Kidney failure; Hyperviscosity syndrome
Multiple myeloma findings Anemia; Rouleaux; M-spike on SPEP; Bence-Jones proteins in Urine; Hypercalcemia from bony dz; Renal failure from light chain excretion
Multiple myeloma classic triad: Plasmacytosis (BM bx w/plasma cells > 5%); Bone lytic lesions (on bone survey ); M-protein in serum and/or urine
Important to differentiate btw multiple myeloma and: MGUS (monoclonal gammopathy of unknown significance)
Thalidomide may be part of tx for: Myelofibrosis, MDS, multiple myeloma
Multiple myeloma mgmt Chemo; Local radiation (pain ctrl); Autologous BMT / SCT for LT survival (mortality rate of 40-50%); hypercalcemia tx (bisphosphonates)
Multiple myeloma Prognosis: Median survival w/ transplant = 7 yrs; Median survival with chemo: 3 yrs
MGUS prevalence Present in 1% all adults, 3% over 70yr; Progresses to multiple myeloma 25% of cases
What MGUS looks like Usually, pts have monoclonal IgG spike <2.5g/dL, M-spike remains stable
Malignancy of B lymphocytes Waldenstrom’s Macroglobulinemia
Waldenstrom Macroglobulinemia causes overproduction of: Monoclonal macroglobulin (IgM antibody)
Waldenstrom Sx/Sx Fatigue; hyperviscosity syndrome (nausea, vertigo, visual disturbances, mucosal or GI bleeding); wt loss, HA, cold hypersensitivity, peripheral neuropathy, hepatomegaly, splenomegaly, engorged retinal veins
Fatigue, cold hypersensitivity, peripheral neuropathy, engorged retinal veins may indicate: Waldenstrom Macroglobulinemia
Hallmark of Waldenstrom: Monoclonal IgM spike in SPEP
Waldenstrom Macroglobulinemia Findings Anemia ; Plasmacytic lymphocytes on BM bx; Serum viscosity 1.4 to 1.8 x that of water; Bone radiographs normal
Waldenstrom is differentiated from MGUS by: Presence of bone marrow infiltration
Waldenstrom Macroglobulinemia mgmt If asymptomatic, follow expectantly; Plasmapheresis for hyperviscosity syndrome; Fludarabine & Rituximab prefered to alkylating agent tx; BM txpt? ; Median survival 3-5 yrs
Oncologic emergencies Febrile Neutropenia; SVC Syndrome (superior vena cava syndrome); Tumor Lysis Syndrome; Hypercalcemia; Cord compression (myelomas)
Only curative tx for MDS Allogeneic BMT
Type of HL that accounts for 80% of HL cases Nodular sclerosing HL
Giant plts & teardrop poik Myelofibrosis
Lytic lesions multi myeloma
Serum viscosity 1.4-1.8 xH2O visc Waldenstrom’s
Preleukemia MDS
Immunoproferative diseases Waldenström; Multiple Myeloma; MGUS
Anagrelide may be used for: P vera; thrombocytosis
Cytoreductive therapies include: Anagrelide, hydroxyurea
Post-showering pruritis, plethora, dyspnea, HA, visual disturbance, tinnitus, HTN, splenomegaly, engorged retinal veins, thromboses, high H&H Polycythemia vera
5-20% of P vera cases evolve into this over 20 years myelofibrosis or acute leukemia
"Spent phase" in P vera = 15% of P vera patients: HSM, anemia, circulating immature WBCs, high WBC. BM: myelofibrosis. Tx supportive. Median survival 2 years. May -> to AML.
3 big causes of secondary erythrocytosis 1 Reactive 2/2 hypoxia (altitude, pulmo dz, smoking, cyanotic heart dz). 2 Pathologic (renal cell ca, renal dz, uterine fibroid, hepatoma, cerebellar hemangioma, high androgen levels). 3 Relative 2/2 decreased plasma volume (diuretics)
Hemochromatosis mgmt Phlebotomy (goal mild anemia, low ferritin, transferring saturation <30%). +/- chelating agents (dereroxamine IM). Avoid alcohol or vitamin C.
Created by: Abarnard
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