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🌱 來自: Huppert’s Notes
Plasma Cell Disorders🚧 施工中
Plasma Cell Disorders
A framework for plasma cell disorders:
• Spectrum of disease: See Figure 7.6
- Monoclonal gammopathy of uncertain significance (MGUS) (asymptomatic)
- Smoldering multiple myeloma (asymptomatic): <3g/dL M-spike or 10% plasma cells on bone marrow biopsy
- Active multiple myeloma
- Plasma cell leukemia
- Amyloidosis: Some clones make light chains that are amyloidogenic – can occur with any of the four above
Monoclonal gammopathy of undetermined significance (MGUS)
• Pathophysiology: Asymptomatic pre-malignant plasma cell proliferation that typically occurs in elderly patients. See increase in serum protein with M-spike on SPEP, but no other associated symptoms. Fewer than 20% of patients with MGUS develop multiple myeloma (MM), but almost all patients with MM have preceding MGUS.
• Diagnostic criteria:
- Serum monoclonal Ig protein (M-spike) <3 g
FIGURE 7.6: Spectrum of plasma cell dyscrasias.
- Bone marrow clonal plasma cells <10%
- No end organ damage (i.e., no CRAB criteria)
• Work-up:
- CBC, CMP, Mg2+, phosphorus, LDH, total immunoglobulins (IgA, IgG, IgM)
- Serum protein electrophoresis (SPEP) – quantifies a monoclonal abnormal protein (M-spike)
- Immunofixation (IFE) – classifies the abnormal protein
- Serum free light chain (sFLC) – Detects LOW levels of free light chains in serum, so it can pick up lighter proteins. Note: In CKD, increased K:L ratio up to 3 can be normal due to ↓clearance of FLC
- UA, urine spot protein/Cr.
- 24hr UPEP – quantifies urine M protein, UIFE – classifies abnormal protein, urine free light chains (Bence Jones protein)
- Beta-2-microglobulin: Strong prognostic value but non-specific
- Skeletal survey (long bones, skull) to rule out lytic lesions suggesting multiple myeloma. Alternatively, can consider low dose whole body CT scan or MRIs.
• Treatment: None needed, observation. Monitoring depends on risk factors (Ig type, M-spike, light chains).
Multiple myeloma (MM)
• Pathophysiology: Malignant proliferation of a single plasma cell line that makes a monoclonal immunoglobulin – most often large amounts IgG or IgA
• Clinical features: Often patients in 60s with fractures or bone pain
- Diagnostic criteria = SLiM-CRAB
• Sixty percent plasma cells on bone marrow biopsy
• Serum Free Light chain ratio >100
• MRI with >1 focal lesion (plasmacytoma)
• HyperCalcemia (>10.5 mg/dL)
• Renal insufficiency (immunoglobulins precipitate in renal tubules - Bence Jones protein, Cr >2mg/dL without an alternative diagnosis)
• Anemia (Hgb<10 g/dL without an alternative diagnosis)
• Bony disease (“punched out” lytic bone lesions or osteoporosis). Bone pain most common presenting symptom.
- Other clinical features:
• Amyloidosis: Kappa chain accumulation → carpal tunnel syndrome
TABLE 7.4 • R-ISS Staging for Multiple Myeloma: Criteria and Prognosis
• Infection: Lack of immunoglobulin diversity can lead to increased risk of infection
• Diagnosis: Need labs (SPEP, SFLC), imaging (usually PET/CT), and bone marrow biopsy
- Serum monoclonal protein present (M-spike >3g)
- Bone marrow clonal plasma cells >10%
- End organ damage present (i.e., SLiM-CRAB)
- Other common findings:↑ESR, ↑serum protein. Smear: RBC = Rouleaux (“stacks of RBCs” – RBCs stick together due to increased plasma proteins)
• Staging: Revised-International Staging System (R-ISS): Uses Beta-2-microglobulin, albumin, LDH, and chromosomal abnormalities to predict overall and progression-free survival at 5 yr. See Table 7.4.
• Treatment: Typically, chemotherapy followed by autologous stem cell transplant
- Classes of therapy:
• Proteasome inhibitors: Bortezomib, carfilzomib
• Immunomodulatory agents: Lenalidomide
• Monoclonal Antibody: Daratumumab (anti-CD38 targeting MM cells)
- Common regimens:
• Hyper CD (cyclophosphamide + dexamethasone) – commonly used for rapid reduction in patients with a high disease burden
• RVD: lenalidomide (Revlimid), bortezomib (Velcade), dexamethasone
• KRD: carfilzomid (Kyprolis), lenalidomide (Revlimid), dexamethasone
• Daratumumab, lenalidomide, dexamethasone
Waldenström macroglobulinemia
• Pathophysiology: Malignant clonal proliferation of IgM producing plasmacytoid lymphocytes
• Clinical features: Similar to MM, but IgM protein is larger and “stickier,” so it causes more symptoms of hyperviscosity syndrome (up to 30% of patients). Cold cryoglobulinemia in 10% of patients.
• Treatment: Plasmapheresis may be needed to emergently manage hyperviscosity. Treatment usually includes rituximab.
AL amyloidosis
• Pathophysiology: Immunoglobulin light chain amyloid from malignant clonal proliferation of plasma cells (e.g., MM, Waldenström). The proteins deposit in tissues and cause end organ damage.
• Clinical features: Nephrotic syndrome, restrictive cardiomyopathy, neuropathy
• Diagnosis: Biopsy (often fat pad biopsy) to look for deposition of amyloid protein. SPEP will show an M-spike and serum free light chains will show an abnormal sFLC ratio.
• Treatment: Treat underlying plasma cell disorder. Consider autologous stem cell transplant.
title: “PLASMA CELL DISORDERS” date: “2023-02-08” enableToc: false
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🌱來自: Pocket Oncology
PLASMA CELL DISORDERS
MGUS and Multiple Myeloma (MM) Waldenström Macroglobulinemia Amyloidosis