Page 1565 - Hematology_ Basic Principles and Practice ( PDFDrive )

1392 Part VII Hematologic Malignancies

and/or surgical intervention is warranted. Peripheral neuropathy is predisposition to infectious complication. Prompt diagnosis of infec-
another common manifestation observed in almost one-third of the tious complications and quick institution of therapy, or preferably
newly diagnosed patients if analyzed using sophisticated and sensitive initial prophylactic measures, prevents major complications.
methods. Peripheral neuropathy also can develop as a result of use of
a number of therapeutic agents, such as thalidomide, bortezomib,
and vincristine. Moreover, POEMS syndrome (polyneuropathy, Coagulation Disorders
organomegaly, endocrinopathy, monoclonal gammopathy, and skin
changes) includes a prominent sensory neuropathy associated with Both bone marrow suppression with cytopenias and coagulation
sclerotic myeloma. Paraneoplastic central nervous system (CNS) abnormalities are observed in myeloma. Myeloma might be associ-
manifestations have been reported occasionally in myeloma and are ated with both bleeding problems and thrombotic events. The coagu-
considered to be related to clonal immunoglobulin targeting various lation abnormalities are related to high levels of a paraprotein that
CNS cells and/or structure. The polyneuropathy in myeloma is due interferes with the normal coagulation pathways as well as platelet
to multiple factors, including amyloid deposits, infiltrative processes dysfunction caused by either decreased numbers and/or function.
with other protein deposits, metabolic causes related to hypercalcemia The coagulation abnormalities include an acquired deficiency of
and/or hyperviscosity, immune processes, or cytokines effects. IgM- factor VIII. A hypercoaluable state is observed in 15% of patients
related neuropathy is well described in which a myelin-associated with IgG myeloma and one-third of patients with IgA myeloma, and
globulin (MAG) has been described in 50% of the patients. Presence it is related to hyperviscosity, acquired activated protein C resistance,
of MAG provides diagnostic clues as well as a parameter to follow lupus-like anticoagulants with thromboembolic complications,
therapy. Traditionally, meningeal involvement has been described acquired deficiency of protein S, and a therapy-related hypercoaluable
very rarely in myeloma; however, with prolonged survival with novel state associated specifically with immunomodulatory agents such as
agents, it is being seen more frequently. This type of complication is thalidomide and lenalidomide. In the absence of prophylactic mea-
usually observed with high-risk disease. Finally, intracranial plasma- sures, such immunomodulatory agents have been reported to cause
cytomas involving brain parenchyma, either from the skull or from deep vein thrombosis (DVT) in 10% to 20% of patients, in whom
the skull base, has been reported in advanced cases. the thrombotic risk increases with associated use of dexamethasone,
other chemotherapeutic agents, and/or previous history of DVT or
immobility.
Hyperviscosity Thrombocytosis is more frequently associated with myeloma than
thrombocytopenia, driven mainly by the high levels of IL-6, which
Hyperviscosity is less frequent in myeloma than in Waldenström drives growth and maturation of megakaryocytes. Rarely, extensive
macroglobulinemia, where higher-molecular-weight IgM molecules bone marrow infiltration by myeloma cells, and more commonly
frequently cause an increase in viscosity. In general, hyperviscosity in repeated cycles of chemotherapy, leads to thrombocytopenia during
IgG myeloma is extremely uncommon. For hyperviscosity to develop, the advanced stages of the disease.
generally an IgG more than 10 g/dL, IgA more than 7 g/dL, and IgM
more than 5 g/dL are required to cause symptomatology. Occasion-
ally, certain physicochemical characteristics of immunoglobulin may Amyloidosis
lead to self-aggregating properties and induce viscosity even at a lower
level. This has been reported with IgG3, which is more frequently Monoclonal proteins, specifically light chains, can be deposited in
associated with hyperviscosity than various other IgG myelomas. The various organs as an insoluble fibrillar protein, amyloid, affecting
commonly observed symptoms are related to circulatory decline of organ dysfunction (see Chapter 88). Around 20% of patients with
vital organ function, leading to complaints of headache, visual light-chain (AL) amyloidosis also have a concurrent diagnosis of MM,
symptoms, shortness of breath, bleeding complications such as and all patients with AL amyloid have clonal light-chain production.
nosebleeds, and eventually mental status changes. The confirmation Although clinically overt amyloidosis is observed less frequently in
of viscosity can be obtained by measuring viscosity, which may exceed MM, intense investigation to identify amyloid deposits using fat pad
4.0 centipoise (cP); however, symptoms at lower levels of viscosity biopsies, concurrent staining of bone marrow with Sudan black, and
have been observed. Therapy is instituted more on the basis of obtaining rectal biopsies can identify some level of amyloid deposit
symptomatology than on absolute measured levels of viscosity and in almost one-third of patients. Patients with amyloid deposits can
requires prompt institution of plasmapheresis with quick resolution present with a number of features primarily related to organ damage,
of symptoms. including renal and cardiac dysfunction and symptoms suggesting
carpal tunnel syndrome. Classic presentations of advance amyloid
include cutaneous fragility around the eyelids, with raccoon eyes and
Infections macroglossia. Patients with advanced amyloid with myeloma have a
poor overall outcome; however, therapeutic intervention
Infection is one of the most important causes of morbidity and a currently remains the same in patients with myeloma with
common cause of mortality in myeloma. Owing to compromised amyloidosis.
T- and B-cell function, patients with myeloma are at a significant high
risk of developing recurrent bacterial as well as viral and fungal infec-
tions. As described earlier, various factors lead to inability of patients LABORATORY MANIFESTATIONS
18
with myeloma to mount a humoral immune response. The patients
are susceptible to polysaccharide-encapsulated organisms as well as Investigations to Detect Clonality
enteric gram-negative bacilli. Further susceptibility to infections
also stems from a number of therapeutic interventions, especially Protein Electrophoresis
corticosteroids. For example, fungal infection, most commonly oral
thrush, is observed following high-dose dexamethasone-based therapy, Serum protein electrophoresis is performed to quantitate the mono-
19
whereas herpes zoster viral infection is observed frequently following clonal proteins present in myeloma (Table 86.5). In 70% of the
bortezomib-based therapy. In both cases, prophylactic antibiotics patients, the monoclonal protein is IgG; in 20%, it is IgA; and in
or antivirals are indicated. A number of cases of therapy-induced 5% to 10% of patients, it is light chains only. Less than 1% patients
activation of Mycobacterium tuberculosis in developing countries have have a monoclonal protein that is IgD, IgE, or IgM or truly a non-
been reported. The risk of infection is highest during the first 2 secretory myeloma. The identification of the exact type of paraprotein
months of initiation of therapy, when both myeloma-related immu- in both serum and urine requires immunofixation (Fig. 86.5). This
nosuppression and therapy-related immunosuppression increase the should be performed at the time of initial diagnosis, and it needs to