Gertz, Morie A.

Abstract Cold agglutinin disease is a rare and poorly understood disorder affecting 15% of patients with autoimmune hemolytic anemia. We reviewed the clinical and pathologic features, prognosis, and management in the literature and describe our institutional experience to improve strategies for accurate diagnosis and treatment. Retrospective analysis identified 89 patients from our institution with cold agglutinin disease from 1970 through 2012. Median age at symptom onset was 65 years (range, 41 to 83 years), whereas the median age at diagnosis was 72 years (range, 43 to 91 years). Median survival of all patients was 10.6 years, and 68 patients (76%) were alive 5 years after the diagnosis. The most common symptom was acrocyanosis (n = 39 [44%]), and many had symptoms triggered by cold (n = 35 [39%]) or other factors (n = 20 [22%]). An underlying hematologic disorder was detected in 69 patients (78%). Thirty-six patients (40%) received transfusions during their disease course, and 82% received drug therapy. Rituximab was associated with the longest response duration (median, 24 months) and the lowest proportion of patients needing further treatment (55%). Our institution’s experience and review of the literature confirms that early diagnostic evaluation and treatment improves outcomes in cold agglutinin disease.

Key PointsRadiation is appropriate primary therapy in approximately 25% of cases. Radiation provides long-term remissions in more than 50% of patients.

SummaryIn this review, the key issues that pertain to Waldenström disease are discussed in a concise question‐and‐answer format. Diagnosis, prognosis, and indications for state‐of‐the‐art therapy are updated. Current therapies presented at the 7th International Workshop for Waldenström Macroglobulinaemia are included.

Amyloidosis affecting lymph nodes (LN) may occur in the setting of systemic amyloidosis or as an entity localized to the site of production (peritumoral). Why some LN amyloid remains peritumoral is unknown. We speculated that the composition of amyloid in these two presentations differs. We analyzed the amyloid proteome in LN amyloid samples to identify differences between the systemic and peritumoral subtypes. In immunoglobulin‐derived LN amyloidosis (N = 26), 70% had heavy chain amyloid (AH or mixed AH/AL). True localized LN amyloidosis was rare, with only 2 patients without a monoclonal protein component. Nineteen patients (73%) had typical amyloid syndromes (100% of AL vs 67% of AH/AL, P = 0.02). A trend to improved survival for the AH/AL group in comparison to AL (median 5‐year survival 48 vs. 19 months, P = 0.06) was seen. Mass spectrometric amyloid analysis is a powerful tool for characterizing amyloid and may provide additional prognostic information. Am. J. Hematol. 88:577–580, 2013. © 2013 Wiley Periodicals, Inc.

Disease OverviewImmunoglobulin (Ig) light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of Ig light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma.DiagnosisTissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is of immunoglobulin origin is mandatory.PrognosisN‐terminal pro–brain natriuretic peptide (NT‐proBNP), serum troponin T, and immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months.TherapyAll patients with a visceral amyloid syndrome require therapy to prevent deposition of amyloid in other viscera and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include NT‐proBNP <5,000 ng/mL, troponin T < 0.06 ng/mL, age <70 years, <3 organs involved, and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered melphalan‐dexamethasone. Pomalidomide appears to have activity, as do other combinations of chemotherapy with agents such as cyclophosphamide‐thalidomide (or lenalidomide or bortezomib)‐dexamethasone, bortezomib‐dexamethasone, and melphalan‐prednisone‐lenalidomide.Future ChallengesLate diagnosis remains a major obstacle to initiating effective therapy when organ dysfunction is still recoverable. Recognizing the presenting syndromes is necessary for improving survival. Am. J. Hematol. 88:417–425, 2013. © 2013 Wiley Periodicals, Inc.