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Myelofibrosis and Myeloid Metaplasia (MF)
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- Mechanism : hypercellularity leads to fibrosis (osteosclerosis)
- Diagnosis : cytogenic studies / bone marrow biopsy to r/o acute myelofibrosis and myelodysplastic syndrome
Myelofibrosis and Myeloid Metaplasia (MF)clonal myeloproliferation with reactive myelofibrosis / may be associated with various leukemias / myeloid metaplasia = extramedullary hematopoeisis / may or may not be associated with myelofibrosis Presentation: splenomegaly, progressive anemia, constitutional symptoms / infection, bleeding are main problems Labs: abnormal RBC morphology in marrow aspirate Survival: 3-6 yrs from time of diagnosis / 10% develop aggressive acute leukemia Treatment: bone marrow transplant offers only definitive chance of cure (chemotherapy does not really help although thalidomide and IFN are being studied 1/07) / symptomatic splenomegaly may require splenectomy but this can worsen the extramedullary hematopoeisis and cause rebound hepatomegaly / hydroxyurea may reduce organomegaly / thalidomide under investigation (2006) Agnogenic Myeloid Metaplasia (myelofibrosis with myeloid metaplasia) [NEJM] 1.5 per 100,000 / usually over 40 yrs (avg. 65) / rare form may occur in children (usu. Down’s) / idiopathic myelofibrosis / also includes that associated with PRV and essential thrombocythemia Mechanism: hypercellularity leads to fibrosis (osteosclerosis)Findings: HSM, normocytic anemia / myelopthisis, which means leukoerythroblasts (immature granulocytes and nucleated red cells) and teardrop RBCs (dacrocytes) and can also occur with CA mets, plasma cell dyscrasias, myelodysplastic syndrome, CML, lymphomaDiagnosis: cytogenic studies / bone marrow biopsy to r/o acute myelofibrosis and myelodysplastic syndromeProgression: risk of transformation to AML is 2%/yr / 20% terminate as AML / ?does G-CSF hasten transformation to AML Plasma cell dyscrasias Benign Monoclonal Gammopathy (MGUS) [NEJM] very common (1% > 50 yrs, 10% > 75 yrs) Usually > 50 yrs, median age 70 yrs, blacks > whites, men > women Primary monoclonal: IgG (70%), IgM (20%), IgA (10%) Secondary causes: chronic liver disease (esp. due to hepatitis C virus), rheumatologic diseases, CML, chronic neutrophilic leukemia, lichen myxedematosus, pyoderma gangrenosum. Presentation: often asymptomatic (diagnosed incidentally) or may cause neuro (usu. symmetric, distal, IgM instead of IgG), cardiac disease (transient or chronic) or other symptoms of paraproteinemias Labs: level of M component relatively small (< 3g), many normal immunoglobulins present, light chains > 1g/24 hrs is significant (should consider bone marrow biopsy; can have light chain disease with normal serum monoclonal component; if normal hemoglobin, creatinine, calcium may still be able to avoid) [table] Note: 10-30% have falsely decreased HDL due to paraproteins binding to HDL in assay (also occurs with bilirubin, phosphate, LDL, glucose) Risk for progression (to MM, WM, amyloidosis, etc): 1% per year (16% lifetime; median lifetime survival only 2 yrs shorter than age-matched controls) [table] higher g/dL protein (M component > 3g/dL is MM) IgM or IgA higher plasma cells in bone marrow (> 5% is bad; > 10% is MM) higher free light chain ratio (normal .26 to 1.65) presence of Bence-Jones proteinuria, renal failure, lytic bone lesions, ↑ M-fraction or ↑ plasma cells Treatment: none other than follow up // measure SPEP, UPEP, other labs 1 x year // every 4 months if “smoldering” MGUS is seen Multiple Myeloma (Plasma Cell Myeloma) Presentation: bone pain (hurts with movement), slowly progressive renal failure (see below), Raynaud’s (cryoglobulins) / overlap with amyloidosis / non-neoplastic plasmacytosis is common in AIDS Diagnosis: >10% plasma cells in bone marrow [pic] + monoclonal spike (75%) in serum [SPEP] (levels often > 3000) or light chains (25%) in urine [UPEP] or lytic lesions on plain films (or MRI, but bone scan does not show lesions) Labs: anemia (normochromic, normocytic; 80%), thrombocytopenia (10%), leucopenia, low anion gap from positively charged immunoglobulins / purely lytic malignant bone lesions do not raise alk. phos. Complications: majority have punched-out, lytic lesions (compression fractures, hypercalcemia) / spinal cord compression in 5% from local mass (try radiation) Immunologic compromise: lack of useful IgG (increased infection from S. pneumo, S. aureus, H. flu, etc.), WBC dysfunction Renal: Bence-Jones proteins (light chains): deposition, tubular toxicity / tubular casts with “foreign body” reaction [prevention with lots of hydration] Fanconi’s hypercalcemia (15-20%): vasoconstriction + deposition of Ca-salts in tubules amyloidosis (10-15%): deposition nephrotic syndrome hyperuricemia: deposition/tubular damage (treat with allopurinol) hyperviscosity: vascular occlusion (5%) cryoglobulinemia (type I): can cause glomerulopathy (rarely) dehydration: prerenal failure pyelonephritis: also an important cause of renal failure CNS: neuropathy secondary to amyloidosis Platelets: M protein or amyloid coats platelets causing prolonged bleeding time (can sometimes have paradoxical hypercoagulability) Note: ?pneumococcal/H influenza vaccine useful? Treatment: Chemotherapy: steroids, thalidomide, alkylating agents, bortezomib (new) followed by autologous hematopoeitic-cell transplant is standard of care in patients < 65 yrs / few patients remain disease free beyond 10 yrs Opiates Bisphosphonates Control of tumor bulk Allogeneic stem cell transplantation / transplant-related mortality 30-60% but only option for long-term cure / different protocols evolving 1/07 Non-secretory myeloma (<1%): diagnose with bone marrow biopsy Solitary plasmacytoma of bone – uncommon Local collection of plasma cells without marrow plasmacytosis / M component usually absent (presence suggests dissemination) / responsive to local radiation therapy (good long-term prognosis) Extramedullary plasmacytoma most common in sub-epithelial, upper airways / 35% disseminate (likely to have M component) Waldenstrom’s Macroglobulinemia monoclonal IgM gammopathy / 10x less common than multiple myeloma / mean age 63 yrs Presentation: hepatomegaly (20%), splenomegaly (15%), lymphadenopathy (15%), fatigue (from anemia) Manifestations: Hyperviscosity (50%; when serum viscosity > 4 CP): headache, blurred vision, dizziness, neuropsychiatric symptoms, hemorrhage (including retinal hemorrhage, subarachnoid hemorrhage) / may see sausage shaped vessels (from venous congestion) / rouleaux formation Bleeding diathesis: cryoglobulins et al interfere with platelet function may cause purpura Anemia: normochromic, normocytic / DO NOT transfuse, because the blood volume may already be too high, and this will make it worse leading to high-output heart failure Tumor infiltration – bone marrow, lymph, spleen / lytic bone lesions ( < 20%) Peripheral neuropathy: IgM attacks myelin components creating picture similar picture to Guillain-Barré (distal, symmetrical, legs > arms) / also from associated amyloidosis / cranial nerve palsies, mononeuropathy, mononeuritis multiplex from infiltration, hyperviscosity or bleeding diathesis Cryoglobulins (7-20%): undergo reversible precipitation at cold temperatures (grossly visible in blood stain) / can cause vasculitis (WM, along with lymphocytic lymphoma, is one of the few lymphoproliferative disorders that not uncommonly causes vasculitis Download 3.95 Mb. 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