Malignant hemopathies

What is the defining feature of multiple myeloma (MM)?

Uncontrolled proliferation of a single clone of plasma cells synthesizing a single class of immunoglobulin, detectable in serum and/or urine.

Which interleukin acts as a growth factor for myeloma cells?

Interleukin-6 (IL-6).

Which interleukin is responsible for the progression of GMSN into MM by activating osteoclasts?

Interleukin-1 (IL-1).

Name two oncogenes involved in the pathogenesis of MM and their roles.

c-myc (stimulates monoclonal Ig synthesis), bcl-2 (inhibits apoptosis).

What is the difference between polyclonal and monoclonal gammopathies?

Polyclonal gammopathies involve multiple immunoglobulin clones; monoclonal gammopathies involve proliferation of a single immunoglobulin clone.

List three subtypes of malignant monoclonal gammopathies.

Classic MM, Smoldering MM, Plasma cell leukemia.

What syndrome is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes?

POEMS syndrome.

What are the most common initial symptoms of MM?

Bone pain or spontaneous fractures, fever, weight loss, recurrent infections, neurological symptoms.

What neurological manifestations can MM cause due to vertebral collapse?

Sciatica, paresis, paraplegia.

What is Bence-Jones proteinuria and how is it detected?

Urinary excretion of a single kappa or lambda light chain, detected by heating urine to 50-60°C and observing precipitation and redissolution.

Which laboratory finding is characteristic of MM on serum protein electrophoresis?

Monoclonal (M) peak.

What type of anemia is commonly seen in MM and what is its cause?

Normocytic normochromic anemia, due to bone marrow infiltration and cytokine-mediated suppression of erythropoiesis.

What radiological findings are typical in MM?

Lytic bone lesions, diffuse osteoporosis, vertebral compression/fractures, rib deformities.

What is the significance of serum beta-2-microglobulin in MM?

It is used for staging and prognosis; higher levels indicate worse prognosis.

What are the major diagnostic criteria for MM?

Plasmocytosis in tissue biopsy, >10% plasma cells in BM smear, monoclonal Ig (IgG >3.5 g%, IgA >2 g%, or light chains >1g/day in urine).

How is MM diagnosis confirmed according to the criteria?

1 major + 1 minor criterion, or 3 minor criteria (including first two minor).

What are the three stages of MM in the Durie-Salmon system?

Stage I: low tumor burden, Stage II: intermediate, Stage III: high tumor burden with advanced bone lesions and high M component.

What is the International Staging System for MM based on?

Serum beta-2-microglobulin and albumin levels.

List three unfavorable prognostic factors in MM.

High beta-2-microglobulin, renal dysfunction (creatinine >2 mg/dL), and plasmablastic morphology.

What is the primary mechanism of action for bortezomib in MM treatment?

Inhibition of the 26S proteasome, disrupting protein degradation and inducing cancer cell death.

What are common side effects of bortezomib?

Peripheral neuropathy.

Name two other proteasome inhibitors besides bortezomib.

Carfilzomib, Ixazomib.

What is the role of monoclonal antibodies in MM treatment? Name one example.

Target plasma cells; example: Daratumumab (Darzalex).

Which immunomodulatory drugs are used in MM?

Thalidomide, Lenalidomide, Pomalidomide.

What supportive treatments are important in MM?

Transfusions, hemodialysis, antibiotics/antivirals, therapy for hypercalcemia (e.g., zoledronic acid).

What is the only potentially curative treatment for MM?

Allogeneic bone marrow transplantation or autotransplantation.

What is the main indication for plasmapheresis in MM?

Severe hyperviscosity syndrome.

What is nonsecretory myeloma?

MM subtype with bone changes but no detectable monoclonal protein in blood or urine.

How does amyloidosis complicate MM, and what are its manifestations?

Causes sensorimotor peripheral neuropathy, carpal tunnel syndrome, and inflammatory joint changes.

What is the main difference in clinical presentation between MM and Waldenstrom macroglobulinemia?

Organomegaly is common in Waldenstrom and rare in MM; kidney disease and lytic lesions are common in MM, rare in Waldenstrom.

What is the defining laboratory feature of Waldenstrom macroglobulinemia?

High level of monoclonal IgM (macroglobulin).

What are the main clinical consequences of IgM paraprotein in Waldenstrom macroglobulinemia?

Hyperviscosity syndrome, cryoglobulinemia, coagulation abnormalities, peripheral neuropathy, amyloidosis.

What is the median survival for Waldenstrom macroglobulinemia?

78 months.

What are the main causes of death in Waldenstrom macroglobulinemia?

Disease progression, infection, heart failure, kidney failure, stroke, gastrointestinal bleeding.

What emergency treatment is indicated for hyperviscosity in Waldenstrom macroglobulinemia?

Plasmapheresis.

Name two mainstays of chemotherapy for Waldenstrom macroglobulinemia.

Alkylating agents, purine nucleoside analogues.

Which monoclonal antibody is used in Waldenstrom macroglobulinemia?

Rituximab.

What kinase inhibitor is used in Waldenstrom macroglobulinemia therapy?

Ibrutinib.

What are the criteria for a complete response in Waldenstrom macroglobulinemia?

Disappearance of monoclonal protein in serum electrophoresis, no histological BM damage, resolution of lymphadenopathy and organomegaly.

What is a minor response in Waldenstrom macroglobulinemia therapy evaluation?

25% reduction in IgM with no new signs or symptoms of active disease.

What is the role of interferon alpha in Waldenstrom macroglobulinemia?

Used as adjunct therapy to control disease progression.

What is the significance of cryoglobulinemia in Waldenstrom macroglobulinemia?

It can cause vascular and immunological complications, including Raynaud phenomenon and vasculitis.

What is the clinical significance of lupus anticoagulant activity in Waldenstrom macroglobulinemia?

It contributes to coagulation abnormalities and increased bleeding risk.

What is the typical infiltration pattern of malignant cells in Waldenstrom macroglobulinemia?

Bone marrow, spleen, lymph nodes, and occasionally other organs like lungs, liver, GI tract, skin, eyes, CNS.

What laboratory abnormality is often seen in MM due to increased bone resorption?

Hypercalcemia.

What are the main complications of MM evolution?

Infectious, renal, neurological, hemorrhagic, bone fractures, cachexia.

What is the main method for monitoring disease progression in MM?

Myelogram, immunoelectrophoresis, C-reactive protein, beta-2-microglobulin, bone radiography.

What is the main difference between solitary plasmacytoma and classic MM?

Solitary plasmacytoma is localized (single lesion), classic MM is systemic with multiple lesions.

What is the significance of increased LDH in MM?

Indicates high tumor burden and poor prognosis.

What is the role of zoledronic acid in MM?

Used to treat hypercalcemia and prevent skeletal complications in patients with osteolysis.