Page 1128 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1092 Part eight Immunology of Neoplasia

may be helpful in identifying the type of amyloid protein (e.g., due to cardiac or hepatic failure as well as infection. There is,
monoclonal light chain versus other forms of amyloid proteins). however, significant variability in median survival, depending
An alternative to mass spectrometry is to use immunoelectron on the nature, number, and extent of organ involvement. Median
microscopy, if available. 24 survival may range from 4 to 6 months in patients diagnosed
Patients with AL amyloidosis frequently have chromosomal at an advanced stage, to in excess of 5 years in patients with
abnormalities, but there is no single chromosomal change that limited organ involvement. Two key prognostic factors include
is diagnostic of this disease. Chromosomal abnormalities reported the presence and severity of cardiac involvement and the presence
with moderate to high frequency in patients with AL amyloidosis of concurrent myeloma. 26
include t(11;14)(q13;q32), del(13q14), and gain of 1q21. 24
Most patients with AL amyloidosis have little or no intact MONOCLONAL IMMUNOGLOBULIN
monoclonal immunoglobulin, but are characterized by the DEPOSITION DISEASES
presence of monoclonal free light chain. The monoclonal light
chain type is lambda in approximately 70% of cases, kappa in Monoclonal immunoglobulin deposition diseases are a non-
25%, and biclonal in 5%. SPEP demonstrates a localized band amyloid monoclonal immunoglobulin chain deposition disease
or peak in less than 50% of patients with AL amyloidosis. that is caused by a clonal plasma cell proliferative disorder. These
Immunofixation electrophoresis detects a serum or urinary diseases are characterized by the deposition of immunoglobulin
monoclonal protein in nearly 90% of cases of AL amyloidosis. light or heavy chain fragments, leading to organ dysfunction.
When serum and urine immunofixation electrophoresis is There are two types of immunoglobulin deposition diseases:
combined with serum free light chain ratio analysis, a monoclonal heavy chain deposition disease (HCDD) and LCDD. They are
protein can be detected in virtually all cases. 24 differentiated from light chain and heavy chain amyloidosis in
Bone marrow biopsy specimens typically demonstrate a slightly that the light chain fragments do not have the necessary biochemi-
increased percentage of plasma cells that may appear morphologi- cal characteristics to form amyloid fibrils.
cally normal. Less commonly, the bone marrow demonstrates
overt myeloma or lymphoplasmacytic lymphoma. A clonal excess Clinical Presentation
of plasma cells (lambda or kappa) can also be demonstrated HCDD is extremely rare, with 37 cases reported in the literature
by immunoperoxidase staining or flow cytometric analysis of from 1992 to 2011. The majority of patients present with hyper-
24
specimens of involved bone marrow. Diagnostic criteria for tension, progressive renal dysfunction, anemia, and nephrotic
27
AL amyloidosis have been developed by the Mayo Clinic and syndrome with microhematuria. Patients with LCDD usually
the IMWG that require the presence of the four criteria outlined present with renal, cardiac, or hepatic involvement and may have
8
in Table 80.7. Approximately 2–3% of patients with AL amy- underlying MM or a lymphoproliferative disorder. 24
loidosis will not meet the requirement for evidence of a mono-
clonal plasma cell disorder listed. Laboratory Findings
In LCDD, a population of clonal plasma cells produces mono-
Management and Prognosis clonal light chain fragments that are deposited as granules in
Amyloidosis patients meeting the criteria in Table 80.8 are the tissues. The deposits in LCDD are almost always composed
25
considered to be eligible for autologous HSCT. Those eligible of kappa light chains; they are granular, not fibrillar, and do not
for HSCT may be treated with melphalan followed by autologous bind Congo red, thioflavin-T, or serum amyloid P component.
HSCT. Those not eligible for HSCT may be treated with Tissue deposits of fragments of monoclonal light chains are
melphalan/dexamethasone or a bortezomib-based regimen. 25 commonly seen and can occur in a variety of organs, including
AL amyloidosis typically has poor long-term prognosis. Death the kidney, heart, liver, and small intestine. Routine electrophoretic
is typically due to organ dysfunction, with major causes of death techniques may not demonstrate a monoclonal protein in the
serum or urine in some patients, but it may be detectable by
serum free light chain analysis. 26
TABLE 80.7 iMWg Diagnostic Criteria for
the Diagnosis of Light Chain amyloidosis

1. Presence of an amyloid-related systemic syndrome (e.g., renal, TABLE 80.8 eligibility Criteria for
liver, heart, gastrointestinal tract, or peripheral nerve involvement). autologous hSCt in Light Chain
To be included as a diagnostic criterion, the organ damage must be amyloidosis Patients
felt to be related to amyloid deposition and not to another common
disease, such as diabetes or hypertension. 1. Physiological age ≤70
2. Positive amyloid staining by Congo red in any tissue (e.g., fat 2. Troponin T <0.06 ng/mL
aspirate, bone marrow, or organ biopsy) or the presence of amyloid 3. N-terminal pro-brain natriuretic peptide (NT proBNP) <5000 ng/L
fibrils on electron microscopy. 4. Creatinine clearance ≥30 mL/min (unless on chronic stable dialysis)
3. Evidence that the amyloid is light chain–related is established by 5. Eastern Cooperative Oncology Group (ECOG) performance status
direct examination of the amyloid using spectrometry-based ≤2
proteomic analysis or immunoelectron microscopy. 6. New York Heart Association functional status Class I or II
4. Evidence of a monoclonal plasma cell proliferative disorder (e.g., 7. No more than two organs significantly involved (liver, heart, kidney,
presence of a serum or urine M-protein, abnormal serum free light or autonomic nerve)
chain ratio, or clonal plasma cells in the bone marrow). 8. No large pleural effusions
9. No dependency on oxygen therapy
Source: Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV,
et al. International Myeloma Working Group updated criteria for the diagnosis of HSCT, hematopoietic stem cell transplantation.
multiple myeloma. Lancet Oncol 2014;15(12):e538–48. doi: 10.1016/S1470- Source: Gertz MA. How to manage primary amyloidosis. Leukemia. 2012;26(2):191–8.
2045(14)70442-5. PubMed PMID: 25439696. doi: 10.1038/leu.2011.219. PubMed PMID: 21869840.