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Monoclonal Gammapathies (GM) (Multiple myeloma (Treatment (Supportive…
Monoclonal Gammapathies (GM)
group of diseases reflect conditions in which abnormal proteins (immunoglobulins) are produced by the clone of
plasmocytes
in bone marrow
Classification
Immunoproliferative disorders of uncontrolled proliferation
1) Multiple myeloma (plasmocytoma)
2) Multiple myeloma of bones isolated
3) Multiple myeloma isolated located outsite of the sceteton
4) Plasmocytic leukaemia
5) Waldenström Disease
6) Heavy chain disease
7) Proliferative syndromes with uncompleted immunoglobulin molecule
8) Amyloidosis related with immunocyte discrasia (AL.)
Monoclonal gammapathy of undetermined significance MGUS
Immunolgicaly related diseases with no symptoms of neoplastic disease
Multiple myeloma
malignant neoplastic proliferation of a single plasma cell line that produces monoclonal immunoglobulin (usually of the IgG (55%) or IgA (20%) type). etiology is unclear.
Epidemiology:
•1% of all neoplasms
•14% of haematologic neoplasms
•90% cases after 50th year of age
•common in males and in black Africans but less in Asians.
Symptoms
Early non-characteristic: Recurent infections (Most common cause of death), Bone pain (commonly backache owing to vertebral involvement (60%), Fatigue
Late: Bone fractions (pathological), Renal insufficiency due to (Myeloma nephrosis, Hypercalcemia), Disturbances of consciousness and coma
Patients can be asymptomatic
examinations
CBC – anemia (normocytic normochromic) should be explored
ESR – Above 40 mm if CRP normal
Urine analysis – Proteinuria –test for Bence-Jones protein
X-ray – detect lytic bone lesions
protein examinations
Electrophoresis (serum or urine):
M protein presence
–note to hematologist)
Immunofixation
Free light chains (FLC) - kappa/lambda
Final diagnosis (haematologists)
Bone marrow criteria (cytologic and histopatologic examination): Clonality, Percentage of plasmocytes in bone marrow
Clinical criteria – SLiMCRAB symtoms
S (Sixty) – ≥ 60% plasmocytes in bone marrow
Li (Light chains) – involved/uninvolved light chain ratio > 100
M (MRI) – more than 1focal lesion > 5 mm in MRI
C (Calcium) – hypercalcemia
R (Ren, Renis) – renal failure
A (Anemia) – anaemia
B (Bones) – destructive bone lesions
The presence of at least one of these markers will be considered sufficient for a diagnosis of multiple myeloma
Smoldering multiple myeloma (SMM)
M protein in serum ≥30 g/l and/or clonal plasmocytes in marrow ≥10%
AND
no (SLiMCRAB)
Symptomatic multiple myeloma
Plasmocytes in marrow >10%
AND
Presence of M protein in serum or urine(excluding non secretory myeloma)
AND
Presence of at least one SLiMCRAB marker
M protein class
IgG–50%
IgA–20%
Light chain disease (Bence-Jones myeloma) –20%
IgD, IgE, IgM,
postać biklonalna
< 10%
Treatment
necessary only in symptomatic patients
Supportive therapy
Anaemia should be corrected: blood transfusion (carefully in patients with high protein (M protein) level: hyperviscosity risk & chemotherapy induced macrocytosis), Erythropoietinif hemoglobin below 10 g/dl
Hypercalcaemia, kidney injury and hyperviscosity should be treated
Infection treated with antibiotics. Give flu vaccinations.
Bone pain by
Bisphosphonates: Oral – Bonefos, I.V.– zoledronic acid every 4 weeks (hypokalcemia and osteonecrosis of the jaw risk – dental care before starting)
Analgetic treatment: opioid drugs – transdermal
Pathological fractures may also be prevented by prompt orthopaedic surgery
Specific therapy
based on eligibility for transplantation as a consolidation in first line treatment Patients eligible for transplantation: VTD, VCD, PAD, CTD
V(P) –bortezomib–inhibitor of proteasom
T –thalidomide–lek immunomodulujący
C -cyclophosphamide
A –antracycline
D -dexametason
Patients non eligible for transplantation:
I line: MPT, VMP
M –melphalan
P –prednison
II line: Rd, MPR -R
R –lenalidomide (Revlimid)
Complication of therapy
Proteasome inhibitors –(bortezomib): Polineuropathy, Thrombosis, Gastroentheropathy
Thalidomide: Polineuropathy, Somnolence, Constipation, Thrombosis, Mielosupresion(pancytopenia) -lenalidomide
Steroids: Diabetes
Prognostic factors
Reduced serum albumin, increased serum β2-microglobulin and increased serum lactate dehydrogenase (LDH).
ISS (International Staging System)
Stage 1 – β2M <3.5 mg/L and serum albumin ≥35 g/L
Stage 2 – not stage 1 or 3
Stage 3 – β2M >5.5 mg/L
Durie-Salmone classification (severity assesment)
Stadium I: Hb.10 g/dl, Ca<11 mg/dl, without osteolysis, low rate of M protein
Stadium II: Non I and III features
Hb<8,5 g/dl, Ca>11 mg/dl, osteolytic lesions, high rate of M protein
Monoclonal gammapathy of undetermined significance MGUS
M protein in serum < 30 g/l
Clonal plasmocytes in marrow < 10%
No SLiMCRAB features
All 3 criteria must be fullfil
due to:
◦Idiopathic
◦Concomitant: other neoplastic diseases, chronic infections, connective tissue diseases – rheumatoidal arthritis, thyroid gland diseases)
Common in the elderly
Fewer than 20% develop multiple myeloma
No specific treatment is necessary, just close observation.
Waldenström macroglobulinemia
Neoplastic, clonal proliferation of lymphoplasmocytes in bone marrow with infiltration of lymphnodes, liver and spleen.
Lymphoplasmocytes produced monoclonal protein IgM class.
after 50 year of age
symptoms
Fatigue, Hemorrhages, Lymphadenopathy, hepato-and splenomegaly, Neurological symptoms, hyperviscosity syndrome (IgM pentamers in serum)
diagnosis
Presence of M protein IgM class
Infitration of bone marrow with small lymphopasmocytes
Immunophenotypisation: CD5, CD19, CD20 (+), CD10, CD23 (-), IgM–on cel surface
treatment
Indication for treatment: IgM> 20 g/l & Severe cytopenia
Chemotherapy – Rituximab, Purine analogs, alkylating agents
If serum total protein > 140 g/l -plasmapheresis
Other monoclonal gammapaties
Plasmocytoma – plasma cell tumour in soft tissue, usually without M protein in serum, treatment–radiotherapy
Amyloidosis – aconsequence of abnormal protein (amyloid) deposits in body tissues and organs. Symptoms result from abnormal functioning of the particular organs affected. Diagnosis is made with a biopsy. Treatment options for amyloidosis depend on the type of amyloidosis and involve correcting organ failure.
POEMS –GM with polineuropathy, organomegaly, endocrinopathy and skin lesions
Plasma cell leukemia – transformation of myeloma to agressive, leukemic (rarely de novo leukemia) -usually resistant to traetment