DIANA PARAMITA
Multistep molecular pathogenesis of MM
Germinal Intra- Extra-
MM
Center MGUS medullary medullary
Cell Line
B cell MM MM
Primary Ig translocations
cyclin D1 or D3
FGFR3 & MMSET
c-maf
others
Karyotypic instability
13q deletion
Somatic mutations
N-ras, K-ras, FGFR3
Secondary Ig translocations
c-myc
others
Lymphoproliferative Disorders Commonly
Associated with a Monoclonal
Gammopathy
Definition:
B-cell malignancy characterised by abnormal
proliferation of plasma cells able to produce a monoclonal
immunoglobulin ( M protein )
Incidence:
3 - 9 cases per 100000 population / year
more frequent in elderly
modest male predominance
Malignant Plasma Cells
Myeloma cells produce substances that attack
bone --producing-> pain, fractures, hypercalcemia!
Diagnostic Criteria for Multiple
Myeloma
u Major criteria
I. Bone marrow plasmacytosis > 30%
II. Histologic diagnosis of plasmacytoma
III. Serum paraprotein IgG > 30 g/L or IgA > 20 g/L
u Minor criteria
a. Bone marrow plasmacytosis 10-30%
b. Serum paraprotein less than major criteria
c. Osteolytic lesion
d. Hypogammaglobulinemia
Symptomatic Myeloma
1. Clonal plasma cells >10% on BM biopsy
2. Monoclonal protein in serum or urine
3. Evidence of end organ damage
Hypercalcemia
Renal insufficiency
Anemia (Hb <10 g/dL)
Bone lesions (lytic lesions or osteoporosis)
Infection
Amyloidosis
Hyperviscocity syndrome
DIAGNOSTIC CRITERIA
(International Myeloma Working Group 2003)
Symptomatic Myeloma
1. Clonal plasma cells >10% on BM biopsy
2. Monoclonal protein in serum or urine
3. Evidence of end organ damage
Hypercalcemia
Renal insufficiency
Anemia (Hb <10 g/dL)
Bone lesions (lytic lesions or osteoporosis)
Infection
Amyloidosis
Hyperviscocity syndrome
DIAGNOSTIC CRITERIA
(International Myeloma Working Group 2003)
Symptomatic Myeloma
1. Clonal plasma cells >10% on BM biopsy
2. Monoclonal protein in serum or urine
3. Evidence of end organ damage
Hypercalcemia
Renal insufficiency
Anemia (Hb <10 g/dL)
Bone lesions (lytic lesions or osteoporosis)
Infection
Amyloidosis
Hyperviscocity syndrome
Pemeriksaan laboratorium
untuk diagnostik (MM working group 2008)
Darah lengkap dengan hitung jenis
Morfologi darah tepi
Urine lengkap (termasuk silinder) dengan skrining
protein Bence Jones
Bila pasien anemi :
Kadar besi serum
TIBC
Feritin
Reticulocyte index
Pemeriksaan laboratorium
untuk diagnostik (MM working group
2008)
Kimia:
Kalsium
LDH
Kreatinin
Elektroforesis protein serum dan urine 24 jam, imunofiksasi serum dan
urine 24 jam
Imunoglobulin kuantitatif (nephelometry):
Ig G, Ig A
Aspirasi sumsum tulang:
Morfologi
Immunophenotyping
Sitogenetik, FISH
Beta-2 microglobulin
Pemeriksaan laboratorium untuk
diagnostik pada keadaan tertentu
C-reactive protein
Serum free light chain assay (belum dapat
dilakukan)
Viskositas serum
Melfalan + Prednison
Radioterapi (Kontrol lokal)
Progresif
Stable disease Indikasi VAD
Remisi sebagian
Kontraindikasi
Progresif
(Remisi sempurna) Stable disease
Remisi sebagian
Maintenance
MP (Intron) (Remisi sempurna) CHOP
Progresif
Stable disease
Remisi sebagian
Progresive kemoterapi
PBSC Rescue
Therapeutics response
Respons sitologi aspirat BMP:
Remisi komplit:
Hitung sel plasma < 5% selama 3 bulan
berturut-turut
Remisi partial:
Respons hitung sel plasma > 50%
Remisi minimal:
Respons hitung sel plasma 25-50%
D Sel plasma
Respons = X 100%
Sel plasma praterapi
VCMP-VACP alternate protocol
every 3 weekly
VCMP Dosis day
Vinkristin 2 mg in 50 mL NS iv drip 30 1
Cyclofosfamid 500 mg/m2 in 100 mL NS iv drip 60 1
Melphalan 6 mg/m2/hari/oral 1-5
Prednison 100 mg/day/oral 1-5