Multiple Myeloma - Lymphoproliferative Disorders

Lymphoproliferative Disorders

Multiple Myeloma

·        = A neoplastic proliferation of plasma cells, characterised by lytic lesions, bone marrow failure and homogenous serum and urinary globulin elevations

 Epidemiology

·        10% of haemopoietic malignancies

·        12 – 16 new cases in Wellington each year

·        Median age approx. 70 (rare under 40), male > female

·        Remains incurable

·        Association with lead, chemicals, agricultural work and FH of autoimmune disorders

Pathogenesis

·        Monoclonal

·        Arises in lymphoid follicle and disseminates to bone marrow. Plasma cells not seen in blood until terminal stage

·        Stromal cells release IL6 ® acts on osteoclasts to cause lytic lesions ® Crush fractures in spine, nerve compression, diffuse osteoporosis, hypercalcaemia. Treat vertebral fractures with radiotherapy

Presentation

·        Bone pain, pathological fracture

·        Anaemia 

·        Amyloidosis in 10 – 15%: macroglossia, cardiomegaly, peripheral neuropathy. Diagnose with rectal/bone marrow biopsy. Stain with Congo Red 

·        Renal complications:

·        Presents with heavy proteinuria, also chronic renal failure – due to infiltration

o  Light chain nephropathy Þ worse prognosis. Casts of free light chains ® obstruction and are directly nephrotic 

o  Amyloid deposition ® nephrotic syndrome

·        Recurrent bacterial infections 

·        Rarely „Hyper-Viscosity Syndrome‟: due to ­IgM or IgG ® retinal haemorrhage

Lab Findings

·        Normochromic, normocytic anaemia 

·        ¯Platelets in advanced disease

·        ­ESR

·        ­Serum uric acid

·        Bone marrow: ­plasma cells

·        Monoclonal band on electrophoresis

·        Light chains (Bense-Jones Proteins) in urine

·        X-rays: multiple punched-out lytic holes in the bone, no sclerosis

·        Gross: „currant jelly‟ – soft, red lesion

·        Micro: resemble plasma cells but variability in cell shape, prominent nucleoli, multinucleation 

·        Differential: chronic osteomyelitis – but will have granulation tissue with at least a sprinkling of other inflammatory cells

Treatment

·        General treatment:

o  Over 65: Melphalan/prednisone

o  Younger: Vincristine, Adriamycin, Dexamethasone

·        Emergency treatment:

o  Hypercalcaemia: pamidronate – coats bone surface to stop osteoclast reabsorption

o  Anaemia: transfusions

o  Hyperviscosity: plasmapheresis

o  Renal failure: dialysis

Prognosis

·        Median survival 3 years

·        Some develop AML or MDS

·        Transplant (auto) extend survival

·        Allo-transplants may cure a select few

Aside: Causes of Paraproteinaemia

·        Benign monoclonal gammopathy: level < 30 g/L (low cf. MM), no light chains in urine. Other Ig‟s normal (cf. suppressed in MM). 15-20% go onto MM but may take 10 – 20 years 

·        Lymphoma or CLL

·        Multiple myeloma 

·        Waldenstrom‟s Macroglobulinaemia: monoclonal proliferation of B cell lineage (half way between lymphocytes & plasma cell). Slowly progressive lymphoma. Monoclonal IgM paraprotein. Present with big glands/liver/spleen – no bone lesions

Aside: Conditions associated with Monoclonal proteins

·        Associated with uncontrolled proliferation:

o  Multiple myeloma

o  Solitary plasmacytoma

o  Waldenstrom‟s macroglobulinaemia

o  Lymphoma

o  Lymphocytic leukaemia

o  Heavy chain disease

o  Primary amyloidosis

·        Associated with controlled proliferation: 

o  MGUS: difficult to distinguish from malignancy, especially in early stages. Tend towards malignancy if:

§  Serial M band levels are increasing

§  Bone lesions

o   IgG > 30 g/l or IgA > 20 g/l

o   Serum or urine light chains present

o   Normal Igs decreased

o   Marrow plasma cells > 10%

o   Renal failure

o   Hypercalcaemia

o   Anaemia

·        Chronic infections

·        Non-lymphoid malignancy

·        Connective tissue disorders

·        Transient (virus, drug reaction)

·        Peripheral neuropathy

·        Transplants