Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Hematology 3
Plasma cell disorders
Def.: B-cell neoplasms than arise from a differentiated clone of
immunoglobulin-secreting cells and produce a monoclonal immunoglobulin (or
part of an immunoglobulin).
Monoclonal immunoglobulin of the class:
IgM – Waldenström’s macroglobulinemia
IgG, IgA, IgD, IgE – multiple myeloma
monoclonal gammopathy of unknown significance (formerly benign monoclonal
gammopathy)
Multiple myeloma
- presence of monoclonal immunoglobulin or light chains in the serum and
urine plus bone destruction caused by focal plasma cell tumors
(plasmocytomas)
Clin: a patient > 50 years, bone pain, mild anemia, and an elevated
sedimentation rate
The patient may have hypercalcemia and renal disease – “light chain
nephropathy”
initial bone radiography may be normal or may demonstrate only osteoporosis
but widespread lytic lesions are typical
Bence Jones protein = free κ or λ light chains may be excreted in the urine
~ 20% of patients do not have a serum M protein but have free light chains
detectable in urine and serum - “light chain disease”
~ 1% of patients have “nonsecretory” myeloma
Clinical syndromes of multiple myeloma
I.
Due to marrow involvement with plasma cells
- anemia
- hypercalcemia
- osteoporosis and osteolytic lesions
- osteosclerosis (POEMS syndrome)
- extraosseous plasmocytomas
II.
Due to abnormal protein
- hyperviscosity (rare)
- amyloidosis
- effective hypogammaglobulinemia (from hypercatabolism)
III. Due to excretion of Bence Jones protein
renal failure (hypercalcemia and amyloid may play role)
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Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
POEMS – Polyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changes
Dg: bone marrow aspiration; however, distribution of tumor in bone marrow is
nonhomogeneous → myeloma cannot be ruled out by normal findings.
Normally, plasma cells make up < 5% of bone marrow cells; more than 10 –
20% plasma cells are required to make a bone marrow diagnosis of multiple
myeloma.
Prognosis: poor prognosis (a median survival of < 2 years) is associated with a
high tumor cell burden, as reflected by anemia, decreased renal function,
hypercalcemia, extensive bony involvement, and large monoclonal protein
peaks. Without these poor prognostic criteria, a median survival may be ~ 5
years.
Th:
- cautious exercise to retard bone resorption
- bone lesions may require local radiation therapy to prevent a pathologic
fracture
- adequate hydration and avoidance of i.v. dye injection to prevent renal
failure
- administration of pneumococcal vaccine and early detection and treatment of
infection
- i.v. gammaglobulin to correct the profound hypogammaglobulinemia
- chemotherapy: alkylating agents, nitrosoureas, anthracycline antibiotics, and
corticosteroids. Alkeran and prednisone or bischlorethylnitrosourea,
cyclophosphamide and prednisone are often used first. VAD (vincristine,
adriamycine, and dexamethasone) is often employed in advancing or
refractory disease. Clinical remission is associated with a decrease of < 1 log
of tumor cells (e.g., 1012 to 1011). Eradication of all tumor cells and cure are
not attainable with current therapy. Bone marrow transplantation combined
with intensive chemotherapy may be successful in young patients.
Waldenström’s macroglobulinemia
Def: clonal disease of IgM – secreting plasmacytoid lymphocytes. Older people
are affected.
Sy: - are due to anemia and the hyperviscosity syndrome: elevated IgM →
nosebleeds, retinal hemorrhages, mental confusion, and congestive heart failure.
Some patients may manifest cryoglobulinemia - blue (cyanotic) fingers, toes,
nose, and earlobes on exposure to cold. Foot and leg ulcers with gangrene may
develop. Bone pain and hypercalcemia rarely occur.
Th: directed at relief of symptoms: hyperviscosity – plasmapheresis;
chemotherapy with alkylating agents (chlorambucil, cyclophosphamide) does
not alter the natural history of the disease but 2-chlorodesoxyadenosine has
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Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
beneficial effect. The median survival is about 3 years but some patients may
live more than 10 years with indolent disease.
Primary amyloidosis
Def: pathologic tissue deposition of monoclonal light chains → abnormal
cardiac, hepatic, gastrointestinal, neurologic, or renal functions.
Complications: congestive heart failure, hemorrhage, nephrotic syndrome,
peripheral neuropathy. Treatment is supportive.
The Anemias of reduced production
1% of red cells must be renewed each day.
The causes of anemia due to decreased production
I.
Normal MCV (82 – 96 fl)
A. Stem cell disorders
1. Myeloaplastic
2. Myelodysplastic
3. Acute leukemia
4. Drug effect or toxicity
B. Lack of erythropoetin
1. Renal failure
2. Antibodies to erythropoietin
3. Abnormal hemoglobin with reduced oxygen affinity
C. Erythropoietic suppression
1. Anemia secondary to chronic disease
2. Anemia due to virus, particularly parvovirus
3. Specific immune inhibition (pure red cell aplasia)
II.
Increased MCV (> 98 fl)
A. Vitamin deficiency
1. Folic acid
2. Vitamin B12
B. Myelodysplasia
III. Decreased MCV (< 82 fl)
A. Iron-deficient hematopoiesis
1. Iron deficiency
2. Poor iron reutilisation
B. Deficient heme synthesis
1. Congenital lack of ALA synthase
2. Secondary to toxin exposure
3. Myelodysplastic (refractory anemia with ringed sideroblasts)
C. Defective globin synthesis
1. Thalassemia
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Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Increased MCV
reticulocytes contain more water than mature cells → their MCV is
greater
Vitamin deficiencies
Both folic acid and vitamin B12 are necessary for the production of
DNA → in their absence the nucleus of the cell cannot undergo mitosis
normally
Clin: megaloblastic anemia due to deficiency of folate or B12
Malnutrition and/or alcohol ingestion → suggestive of folate
deficiency
surgical removal of the stomach or terminal ileum
neurologic symptoms in vitamin B12 deficiency: loss of
proprioception and perception of vibration in the lower extremities,
loss of sense of smell, unusual cerebral symptoms, and even dementia
a sore tongue
frequently, white cells, platelets, or both are diminished in number
neutrophils may have more than the usual number of lobes
(hypersegmentation)
the reticulocyte count is low
bone marrow: megaloblastosis
ineffective erythropoiesis: bone marrow has erythroid hypercellularity
Dg: serum levels of the vitamins
anti-IF and anti-parietal cell antibodies
Th: replacement (reticulocyte count increases)
Thrombocytopenia
Causes of thrombocytopenia
Mechanism
Examples
decreased or ineffective
drugs (ethanol, anticonvulsants)
platelet production
infections
vitamin B 12 deficiency
radiation or systemic chemotherapy
increased platelet
drug-induced thrombocytopenia
destruction
autoimmune thrombocytopenia
consumptive thrombocytopenia
abnormal distribution
splenic sequestration
intravascular dilution
massive transfusion
Thrombocytosis
def: an increase in platelet count above 450000/μl
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Seminars for the 5th year
summer term
Prof. MUDr. Jiří Horák
Secondary thrombocytosis
results from increased platelet production in response to hemorrhage,
hemolysis, infections, or malignancy
successful treatment of the underlying disorder usually results in a
return of the platelet count to normal levels
Primary (essential) thrombocytosis
is a myeloproliferative disorder arising from neoplastic transformation
of a pluripotent stem cell.
Elevated platelet count, splenomegaly, platelet dysfunction, an
increased risk of hemorrhagic as well as thromboembolic events.
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