1067344
Beschreibung
Mindmap von LewisLewis, aktualisiert more than 1 year ago
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Erstellt von LewisLewis
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Multiple myeloma and amyloidosis
- Multiple myeloma
- Part of mature B cell neoplasm
- Neoplastic proliferation of a single clone of plasma
cells producing monoclonal immunoglobulin
- Bone marrow disease
- The most common plasma cellular disorder
- Median age of diagnosis is 66 yrs
- Etiology
- Mostly unknown
- Several evidences show genetic predisposition
- Exposure to toxins and some pesticides
- Persistence of antigens that may stimulate the plasma cells
- Association observed with rheumatoid arthritis
- Association observed with rheumatoid arthritis
- Mostly unknown
- Evolution
- Multistep disease
- MGUS
- Physiological status, not generally occurring in youngster
- 10-15% probability to develop a multiple myeloma
- Physiological status, not generally occurring in youngster
- Smoldering myeloma
- From here other (oncogene) mutations are needed to reach full blown myeloma
- From here other (oncogene) mutations are needed to reach full blown myeloma
- Myeloma
- Extra-medullary myeloma
- MGUS
- We may have hyperdiploidy, deletion of chromosome 13
- Multistep disease
- Inhibitory activity of the myeloma
cells on other B cells and plasma cells
- Complications
- Osteoporosis, lytic lesions and
pathologic fractures of the bone
- Interaction with osteoclasts leads to osteoclastogenesis,
osteoclast activation and bone reabsorption
- Hypercalcemia
- Interaction with osteoclasts leads to osteoclastogenesis,
osteoclast activation and bone reabsorption
- Osteoporosis, lytic lesions and
pathologic fractures of the bone
- Pathogenesis
- Bone marrow infiltrate
- myeloma cells proliferate there
- myeloma cells proliferate there
- Characteristics coming from the secreted molecules
- Excess production and secretion of light chains
- Cytokines
- Basis of bone reabsorption
- Basis of bone reabsorption
- Excess production and secretion of light chains
- Bone marrow infiltrate
- Clinical presentation
- Bone destruction, bone pain (70, 80%)
- Anemia 70%)
- Hypercalcemia (30, 40%)
- Interstitial nephropathy
- Interstitial nephropathy
- Renal involvement
- Caused by hypovolemia and hypercalcemia,
with the associated interstitial nephropathy
- Caused by hypovolemia and hypercalcemia,
with the associated interstitial nephropathy
- Infections due to hypogammaglobulinemia
- Bleeding due to platelet dysfunction
- Hyperviscosity of blood (10%)
- Neurological symptoms in CNS
- Bone destruction, bone pain (70, 80%)
- Diagnosis
- Major criteria for diagnosis are:
- Plasmacytoma in BM biopsy
- Bone marrow plasma cells >30%
- Serum monoclonal Ig (>3g/dL)
- Plasmacytoma in BM biopsy
- Minor criteria
- BM plasma cells 10 – 30%
- Serum monoclonal Ig>3g/dL
- Osteolytic lesions
- Hypogammaglobulinemia
- BM plasma cells 10 – 30%
- ISS international staging system
- Stage I
- beta2 microglobulin >3.5 mg/L
and serum albumin ≥3.5 g/dL
- beta2 microglobulin >3.5 mg/L
and serum albumin ≥3.5 g/dL
- Stage II
- no I, no III
- no I, no III
- Stage III
- beta2 microglobulin ≥5.5 mg/L
- beta2 microglobulin ≥5.5 mg/L
- Stage I
- Also look at serum creatinine and
azotemia to see how kidneys are working
- Bone marrow aspirate and biopsy
- Protein elecrophoresis ("a orecchie d'asino")
- Plasma cells > 10-30%
- Fibrosis
- Protein elecrophoresis ("a orecchie d'asino")
- Immunofixation
- Used to diagnose and to monitor the serum of the
patient and see how it is responding to therapy
- Used to diagnose and to monitor the serum of the
patient and see how it is responding to therapy
- Major criteria for diagnosis are:
- Prognostic factors
- Performance status
- Serum albumin
- Serum creatinine
- Platelet counts
- Age
- Beta2 microglobulin
- Serum calcium
- Hb
- Cytogenetic
- Performance status
- Therapy
- No curative treatment
- Possibly the only curative approach is
allogenic stem cell transplantation
- In asymptomatic stage I, we wait and watch
- In stage II-III and symptomatic
stage I, we need to treat the patient
- CT or tandem autologous transplantation
- CT or tandem autologous transplantation
- Classical chemotherapeutic compounds
- Melphalan
- Vincristine
- Melphalan
- Antiangiogenic drugs
- Thalidomide
- Lenalidomide
- Thalidomide
- Protease inhibitors
- Bortezomib
- Bortezomib
- No curative treatment
- Typical adhesion factors
- CD138 and CD38
- Involved in many symptoms, like bone involvement
- CD138 and CD38
- Part of mature B cell neoplasm
- Amyloidosis
- AL amyloidosis
- Diagnosis
- Differential diagnosis
- Senile systemic amyloidosis
- Amyloidosis reactive to chronic inflammation
- Hereditary amyloidosis
- Always consider the possibility of coexistence
of MGUS with a non-AL amyloidosis!
- Senile systemic amyloidosis
- Gold standard is the mass-spectrum based proteomics
- For early diagnosis you need red flags
- Increased levels of cardiac biomarkers (NT-proBNP)
- Urinary albumin >300 mg/g
- Progressive length-dependent
small-fiber peripheral sensory neuropathy
- Increased levels of cardiac biomarkers (NT-proBNP)
- If you find the following symptoms it is too late
- Restrictive cardiac hypertrophy, low ECG voltage
- Hepatomegaly or alkaline phosphatase elevation
- Orthostatic hypotension, autonomic neuropathy
- Macroglossia and periorbital purpura
- Restrictive cardiac hypertrophy, low ECG voltage
- It involves 5 steps
- Having strong clinical suspicion
- Proving systemic amyloid deposition
- Typing the deposits
- Assessing the monoclonal disease
- Defining the extent of systemic damage
- Having strong clinical suspicion
- Always perform tissue biopsy (abdominal fat)
- Differential diagnosis
- Therapy
- Chemotherapy +/- ASCT
- Melphalan
- Melphalan
- IMiDs (immunomodulatory drugs)
- Thalidomide
- Lenalidomide
- Pomalidomide
- Thalidomide
- Proteasome inhibitors (Bortezomib)
- New drugs
- Carfilzomib, Ixazomib
- Diflunisal, Tafamidis
- Carfilzomib, Ixazomib
- 2 goals
- Reduce supply of amyloidogenic
monoclonal light chain rapidly
- Restore organ function
- Reduce supply of amyloidogenic
monoclonal light chain rapidly
- Chemotherapy +/- ASCT
- Clinical presentation
- Cardiac involvement
- When the heart is involved the
prognosis of the patient is low
- Exams
- ECG
- Echocardiography
- Cardiac magnetic resonance
- Positive cardiac biomarkers
- ECG
- When the heart is involved the
prognosis of the patient is low
- Organs most frequently involved
- Kidney (74%)
- Heart (60%)
- Liver (27%)
- Nervous system (18%)
- Spleen
- Soft tissues and capillaries (15%)
- Macroglossia (14%) is pathognomonic
- Submandibular swelling (15%)
- Periorbital purpura (11%)
- Kidney (74%)
- Cardiac involvement
- Pathogenesis
- Preferential tissue tropism (some for the heart, some for the kidneys, etc.)
- Preferential tissue tropism (some for the heart, some for the kidneys, etc.)
- Supportive care
- Diuretics
- Mainstay of edema therapy
- But
- Lower the filling pressure, possibly leading
to syncope and reduced blood flow
- Lower the filling pressure, possibly leading
to syncope and reduced blood flow
- Mainstay of edema therapy
- Prophylactic use of amiodarone
- Useful to reduce the risk of sudden death
- Useful to reduce the risk of sudden death
- Diuretics
- Age-dependent pathology
- Caused by a small, indolent but dangerous, plasma
cell clone, which produces amyloidogenic light chain
- The plasma cell clone synthesizes an excess of misfiled free light chain
(LC) secreted in the absence of the heavy chain, then it aggregates
- Formation of oligomers
that are per se pathogenic
- Formation of oligomers
that are per se pathogenic
- The plasma cell clone synthesizes an excess of misfiled free light chain
(LC) secreted in the absence of the heavy chain, then it aggregates
- Diagnosis
- Localized forms
- Alzhiemer's disease
- Creutzfeldt-Jacob disease
- Alzhiemer's disease
- Systemic forms
- AL amyloidosis
- ATTR amyloidosis
- AL amyloidosis
- Insoluble, toxic protein aggregates deposited
in tissues in b-sheet fibrillar protein
- Can be hereditary or acquired
- AL amyloidosis
Medienanhänge
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