Disease morbidities 1; Polyneuropathy, Bing Neel, AmyloidBing Neel Syndrome . What is...
Transcript of Disease morbidities 1; Polyneuropathy, Bing Neel, AmyloidBing Neel Syndrome . What is...
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International Waldentrom’s Patient Meeting
9 oct 2016, Amsterdam
Disease morbidities 1; Polyneuropathy, Bing Neel, Amyloid
Monique Minnema, internist-hematologist
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Waldenstrom Macroglobulinemia
Cancer cells : - B lymfocytes - Plasmacells - Represented as % in reports
Blood;
- “wrong protein ” = M protein/paraprotein - Represented in gr/L
Healthy bone
marrow is
”factory” of
blood cells
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Besides bone marrow the cancer cell can be
present in other places of the body
Spleen, 15-30%
Lymphe nodes ;
15-30%
Brain + Spinal fluid
≈ 1%; Bing Neel Syndrome
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• Complaint difficult to recognise and very diverse – Mood disorder, psychic differences
– Diminished strength arm or leg
– Cranial nerve loss
– Neuropathy
– Balance disorder
– Dizziness
– Pain neck, back, legs
– Memory loss
• Bing Neel Syndrome can arise while bone marrow
disease and M proteine is stable.
Bing Neel syndrome
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Operation for brain
biopsy
Bing Neel Syndrome ; Diagnosis
MRI scan of brain and spine
Lumbar puncture
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• Presence of too many
lymphocytes?
• Different lymphocytes in
morphology?
• Clonal cells ?
– Flow cytometry
– Molecular MYD88L265P
mutation present ?
Bing Neel Syndrome; Spinal fluid
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• Can be treated, several possibities
• Recovery of complaints is possible
• Milestones in IWWM9?
– First international guideline published
– Recognition of BNS improved
– Discussion of several treatment options
– Possibility for clinical study created
Bing Neel Syndrome
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What is Polyneuropathy?
Sensory Neuropathy
-tingling
-change in temperature
-pain
-lack of coordination
-feeling of tight sock/glove
Motorial Neuropathy
-weak muscles, paralyis
-painfull cramps
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• IgM paraprotein reacts with part of nerve cell, such as
myelin (anti-MAG antibody); Inflammation and complaints
• 25-30% has neuropathy at diagnosis
• IgM related disease ; MGUS with neuropathy
• Other causes ;
– Amyloidosis
– Cryoglobulinaemia
– POEMS syndrome
Neuropathy in Waldenström’s
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anti-MAG antibodies in
myelin leaflet ; complaints!
Not everybody has anti
MAG antibodies
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• Bortezomib
• Vincristin
• Anti-CD20 antibodies can sometimes
increase PN
• Waldenström patients more sensitive to
CIPN
CIPN: Chemotherapy induced neuropathy
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• Treatment of the disease itself
– Do not use therapy with increased risk of CIPN
• Chance on positive result; 50%
• Nerve cells divide very slowly
• Pain medication
• IgM MGUS related neuropathy; monotherapy
Rituximab/anti CD20 therapy
Treatment of Waldenström related PN
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• Not possible
• Complaints can be reversible after stopping therapy
• Important to stop in time with anti WM therapy
• Pain medication in PN:
– Amytriptylline
– Neurontin
– Lyrica
• Be cautious: Vitamin B6 can induce PN! (> 200 mg/daily)
Treatment of CIPN
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• Multidisciplinary guideline prepared for evaluation
and treatment of the different types of PN, related
to IgM diseases and Waldenstrom
• New medication (ie BTK inhibitors, oral proteasome
inhibitors)
– effect on PN improvement unknown
– Do not induce CIPN
Polyneuropathy; IMMW9
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• Amyloid is formed from abnormal M protein
• Insoluble fibres in organs, detoriation of organs;
complaints start.
• 6% of AL amyloidosis caused by IgM M proteins due to
Waldenström or IgM-MGUS
• 94% caused by MGUS/Multiple Myeloma (IgG of IgA
M-protein)
Amyloidosis; disease caused by protein accumulation as insoluble fibres
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• Polyneuropathy
• Fatigue
• Worse kidney function
• Proteinurie
• Thickening Cardiac wall
• Enlarged lymphenodes
• Bleeding
• Enlarged liver
• Diarrhea
Symptoms
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How are amyloid fibres formed
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Dominant organ at diagnosis AL amyloidosis %
patients
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Non-IgM
IgM
Lymphoproliferative disease – 52%
‘Plasma cell’ – 6%
Normal bone marrow – 14%
Unknown – 28%
Lymphoproliferative disease
Waldenstrom – 74%
NHL-ns – 25%
Follicular, CLL – 1%
“underlying” disease
Plasma cell dyscrasia
Median ~ 7-9% plasma cell infiltration
15% have Multiple Myeloma
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New staging system for IgM AL amyloidosis
Factors:
• NT-proBNP >332
• Trop-T >0.03 ug/L
• Liver involvement
• Neuropathy ; autonomous
Stage I – 0 (90 m) Stage II– 1 (32m) Stage III - 2 or more (16m)
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• Goal ; M protein as low as possible
– CR / VGPR
• Vulnarable patients
– Bortezomib
– Fludarabine
– Autologous stem cell transplantion
• New ; anti amyloid antibodies
Treatment
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Waldenström workshop