Plasma cell Disorders

S. Sami Kartı, MD, Prof.

Plasma cells

Terminally differentiated cells of B-lymphocyte lineage

Produce antibodies Normal plasma cells are incapable of

dividing

Classification of plasma cell disease

Multiple myeloma Variants Non-secretory myeloma Indolant myeloma Smoldering myeloma Plasma cell leukemia

Classification of plasma cell diseases

Plasmocytoma Solitary plasmocytoma Multiple plasmocytoma

Primary amyloidosis POEMS Syndrome Waldenström’s Macroglobulinemia Heavy Chain Diseases

Multiple Myeloma

Definition

B-cell malignancy characterised by abnormal proliferation of plasma cells able to produce a monoclonal immunoglobulin (M protein)

Incidence

3-9 cases per 100,000 population/y more frequent in elderly modest male predominance

Clinical forms of MM

Multiple myeloma Non-secretory myeloma Smoldering myeloma Plasma cell leukemia

M-protein (paraprotein) Seen in 99% of cases in serum and/or

urine IgG > 50% IgA 20-25% IgE and IgD 1-3% light chain 20%

1% of cases are nonsecretory

Clinical manifestations are related to malignant behavior of plasma cells

and abnormalities produced by M protein

plasma cell proliferation multiple osteolytic bone lesions Hypercalcemia bone marrow suppression ( pancytopenia )

monoclonal M protein decreased level of normal immunoglobulins hyperviscosity

Symptoms

Bone pains Weakness and fatigue Weight loss

Laboratory

ESR > 100 anaemia, thrombocytopenia rouleaux in peripheral blood smears marrow plasmacytosis hyperproteinemia hypercalcemia proteinuria azotemia

Causes of renal failure in MM

Hyperviscosity Hypercalcemia Hyperuricemia Light chain deposition Analgesic nephropathy

Evaluation for a suspected MM

Serum and urine protein electrophoresis

Serum and urine immunofixation and immunglobulin quantitation

Radiographic skeletal survey Bone marrow examination

Protein electrophoresis in a MM patient

Rouloux formation in peripheral smear

Lytic lesions in cranial x-ray

Bone marrow aspiration and biyopsy in a MM patient

Bone marrow aspiration of a MM patient

Immunohistochemistry in MM

Immunohistochemistry in MM

Diagnostic Criteria for Multiple Myeloma

Major criteria I. Plasmacytoma on tissue biopsy II. Bone marrow plasma cell > 30% III. Monoclonal M spike on electrophoresis IgG > 3,5g/dl,

IgA>2g/dl, light chain>1g/dl in 24h urin sample Minor criteria

a. Bone marrow plasma cells 10-30% b. M spike but less than above c. Lytic bone lesions d. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl

Minimum of 1 major and 1 minor or 3 minor criteria including A and B

Staging of Multiple Myeloma

Clinical staging is based on level of haemoglobin, serum

calcium, immunoglobulins and presence or not of lytic bone lesions

correlates with myeloma burden and prognosis

I. Low tumor mass II. Intermediate tumor mass

III. High tumor mass subclassification

A - creatinine < 2mg/dlB - creatinine > 2mg/dl

Poor prognosis factors

Cytogenetical abnormalities of 11 and 13 chromosomes

Beta-2 microglobulin > 2,5 ug/ml

Treatment

Patients <65-70 years Velcade + Deksametazon Thalidomid VAD (Vincristin, Adriamycin, Dexamethasone) high-dose therapy with autologous stem cell

transplantation allogeneic stem cell transplantation

( conventional and „mini”) Patients >65 years

conventional chemotherapy

Treatment

Conventional chemotherapy Velcade + dekasametazon Talidomid VAD (Vincristin, Adriamycin, Dexamethasone) Melphlan + Prednisone M2 ( Vincristine, Melphalan, Cyclophosphamid,

BCNU, Prednisone) Response rate 50-60% patients Long term survival 5-10% patients

Treatment

Autologous transplantation patients < 65-70 years treatment related mortality 10-20% response rate 80% long term survival 40-50%

Treatment

non-myeloablative therapy and allogeneic transplantation

Treatment

Supportive treatment biphosphonates, calcitonin recombinant erythropoietin immunoglobulins plasma exchange radiation therapy

Monoclonal gammopathy of undetermined significance ( MGUS)

M protein presence, stable levels of M protein: IgG<3,5g IgA<2g, ligh chain<1g/day normal immunoglobulins - normal levels marrow plasmacytosis < 5% complete blood count - normal no lytic bone lesions no signs of disease

Monoclonal gammopathy of undetermined significance ( MGUS)

M protein 3% of people > 70 years 15% of people > 90 years 10% of patients with MGUS develop multiple

myeloma

Diagnostic criteria for smoldering myeloma

Same as MGUS except: Serum M-component at myeloma levels Marrow plasmocytosis 10-30%

Plasma cell leukemia

Plasma cell leukemia

>2x109 plasma cells in peripheral blood

Younger age Higher incidence of organomegaly

and lymphadenopathy More extensive bone marrow

infiltration Poor response to chemotherapy

Non-secretory myeloma

1% of multiple myeloma No serum or urine monoclonal protein Must rule out IgD and IgE myeloma

Waldenström’s Macroglobulinemia

Monoclonal protein is IgM No lytic lesions Hyperviscosity (headache, tinnitus,

dizziness, somnelence, etc) Bone marrow aspiration reveals

lymphoplasmocytic cells

Bone marrow aspiration and biopsy in WM

Solitary plasmacytoma

Localized plasma cell tumor Absence of plasma cell infiltrate in

bone marrow biyopsy No evidence of other lytic lesions on

radiographic examination Absence of renal failure, anemia or

hypercalcemia

Osteosclerotic Myeloma(POEMS Syndrome)

Polyneuropathy Organomegaly (hepatomegaly, LAP) Endocrinopathy (hypogonadism, hypoyhtroidism) Monoclonal gammopathy Skin changes (hyperpigmentation)