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)