1
Fifth stage
Medicine
Lec-14
د.خالد نافع
24/4/2016
Multiple Myeloma
Multiple Myeloma
Malignant proliferation of plasma cells.
Normal plasma cell form Ig which contain heavy and light chain
Normal variety of Ig polyclonal & each contain Kappa & Lambda light chain
Myeloma plasma cell : Ig of single heavy and light chain lead to monoclonal
protein (para protein)
In some light chain may be only produced and appear in urine as Bence-
Jones proteinuria.
Incidence : 4 new cases/100,000 peoples/year.
Sex ratio : M:F → 2:1
Age : median age 60-70 years.
Plasma cell myeloma
Variants
Non - secretory myeloma
Indolent myeloma
Smouldering myeloma
Plasma cell leukaemia
Plasmacytoma
- Solitary plasmacytoma of bone
- Extramedullary plasmacytoma
Immunoglobulin deposition diseases
- Primary amyloidosis
- Systemic light and heavy chain deposition disease
Osteosclerotic myeloma (POEMS)
Heavy chain diseases
γHCD
αHCD
µHCD
2
Etiology : Unknown
Classification of MM
Paraprotein
frequency %
IgG
55%
IgA
21%
Light chain only
22%
Other (D, E, non secretory) 2%
The diagnosis of MM requires two of the following :
marrow plasmacytosis.
Serum and/or urinary paraprotein
+
≥ 1 of `` CRAB``
Clinical features
Weight loss ,malaise and fatigue.
Bone pain found in 60% of cases at the back and ribs.
Anorexia , diarrhea, vomiting, constipation, polyuria, polydipsia occur with
hypercalcemia in 30%,
3
Renal impairment due to hypercalcaemia and dehydration present in 50%
Pneumococcal, chest and urinary tract infection due to low
immunoglobulin(Ig) production.
Headache , Confusion, Breathlessness, Visual Disturbance and bleeding can
occur secondary to hyperviscosity (IgA).
5% present with paralysis secondary to spinal cord compression by extra-
dural plasma cell mass.
Carpal-tunnel syndrome, nephrotic syndrome, cardiac failure and
neuropathy secondary to amyloid deposition.
4
Management
Immediate support
• High fluid intake to treat renal impairment and hypercalcaemia
Analgesia for bone pain.
• Bisphosphonates for hypercalcaemia and to delay other skeletal related events .
• Allopurinol to prevent urate nephropathy.
• Plasmapheresis, if necessary, for hyperviscosity
**Chemotherapy with or without HSCT
In older patients, thalidomide combined with the alkylating agent melphalan and
prednisolone has increased the median overall survival to more than 4 years.
In younger, fitter patients, standard treatment includes first-in chemotherapy to maximum
response and then an autologous HSCT
Management cont.
1-BORTEZOMIB(VELCADE) VTD+Z
2- Thalidomide
3-Lenalidomide(Revlimid) VRD+Z
4- Dexamethasone
5-Bisphosphonate (Zoledronate)
Treatment is administered until paraprotein levels have stopped falling. This is
termed‘plateau phase’ and can last for weeks or years.
Radiotherapy; for localised bone pain and for pathological fractures.
It is also useful for the emergency treatment of spinal cord compression complicating
extradural plasmacytomas
Waldenstrӧm macroglobulinaemia
This is a low-grade lymphoplasmacytoid lymphoma associated with an IgM
paraprotein.
Patients classically present with features of hyperviscosity,such as nosebleeds,
bruising, confusion and visual disturbance.
Anaemia, systemic symptoms, splenomegaly or lymphadenopathy
5
Investigation ; have an IgM paraprotein associated with a raised plasma
viscosity. The bone marrow with infiltration of lymphoid cells and prominent
mast cells
TREATMENT
1-Plasmapheresis for anaemia and hyperviscosity.
2- Chlorambucil
3- Fludarabine
4- Rituximab
*Monoclonal gammopathy of uncertain significance (MGUS);
a paraprotein is present in the blood but with no other features of myeloma, Waldenstrӧm
macroglobulinaemia, lymphoma or related disease.
The bone marrow may have increased plasma cells but these usually constitute less than
10% of nucleated cells.
After follow-up of 20 years, only one-quarter of cases will progress to myeloma or a related
disorder (i.e.around 1% per annum)