A 75-year-old man experienced a 10-month history of progressive exertional dyspnea, profound fatigue, bilateral lower limb edema, and a 5 kg unintentional weight loss. He had been previously diagnosed at another hospital with hypertrophic cardiomyopathy complicated by heart failure, type 2 diabetes mellitus, hypothyroidism, and hypoproteinemia. Despite diuretics and supportive care after the first hospitalization, symptoms recurred and worsened. Past medical history included one year of diabetes and hypothyroidism, a 30-year smoking history, and no known family history of hematologic disease or cardiomyopathy.
On readmission the patient was hypotensive (90/60 mmHg) and demonstrated severe pitting edema of both lower extremities. Laboratory evaluation showed heavy proteinuria (4.10 g/24 h) and markedly elevated cardiac biomarkers: cardiac troponin T (cTnT) 238.4 pg/mL (reference <14 pg/mL) and NT-proBNP 13,971 pg/mL (reference <125 pg/mL). Initial electrocardiography revealed first-degree atrioventricular block, low limb-lead voltage, and poor R-wave progression. Transthoracic echocardiography documented concentric left ventricular hypertrophy (interventricular septum [IVS] 24 mm; left ventricular posterior wall [LVPW] 14 mm), biatrial enlargement, a granular myocardial appearance, pericardial effusion, and impaired diastolic function. Chest, abdominal, and pelvic computed tomography identified mediastinal and inguinal lymphadenopathy, bilateral pleural effusions, ascites, and subcutaneous abdominal wall edema.
The combination of ventricular hypertrophy on echocardiography with low ECG voltage and significant proteinuria prompted investigation for a plasma cell dyscrasia and possible amyloidosis.
Serum immunofixation electrophoresis demonstrated an abnormal monoclonal band in the λ lane consistent with a monoclonal λ free light chain (FLC). Urine testing (Bence Jones protein) was positive for a monoclonal λ FLC. Congo red staining of abdominal fat pad biopsy was positive for amyloid deposits. Proteomic analysis of the biopsy confirmed the amyloid as AL-λ; although fibrinogen α-chain was abundant, its ratio indicated blood contamination rather than amyloid composition.
Bone marrow smear showed hypercellularity with approximately 4% plasma cells, some exhibiting mild atypia. Flow cytometry identified a clonal plasma cell population (CD38++, CD138+, CD19-, CD56-, CD117-, CD200-) with intracellular λ FLC restriction. Electromyography and nerve conduction studies established a predominantly sensory peripheral neuropathy. Serum vascular endothelial growth factor (VEGF) was markedly elevated at 729.89 pg/mL (normal <142.2 pg/mL). Radiographic skeletal surveys revealed no sclerotic bone lesions.
The patient met diagnostic criteria for AL amyloidosis: (1) organ involvement manifest as cardiac dysfunction and significant proteinuria, (2) histologic confirmation with Congo red–positive amyloid deposits and proteomic subtyping showing AL-λ, and (3) evidence of a monoclonal plasma cell disorder with serum/urine monoclonal λ FLC and light-chain–restricted bone marrow plasma cells.
Concurrently, the patient met diagnostic elements for POEMS syndrome: mandatory criteria of polyneuropathy and a monoclonal plasma cell proliferative disorder (λ type), plus major/minor features including marked elevation of VEGF, extravascular volume overload (anasarca, pleural effusion, ascites), mediastinal/inguinal lymphadenopathy (organomegaly/lymphadenopathy), and endocrinopathies (hypothyroidism and diabetes mellitus). Taken together, these findings supported the rare coexistence of cardiac AL amyloidosis and POEMS syndrome in a single patient.
Rapid eradication of the pathogenic plasma cell clone is the principal therapeutic strategy for both AL amyloidosis and POEMS syndrome. Given the patient’s advanced age and significant cardiac involvement, autologous stem cell transplantation (ASCT) was not pursued. The treating team initiated combination chemotherapy with the BCD regimen: monthly cycles with bortezomib 2.0 mg on days 1, 8, 15, and 22; cyclophosphamide 350 mg on the same schedule; and dexamethasone 20 mg on days 1, 8, 15, and 22. Concomitant medications included levothyroxine and antidiuretic/diuretic therapy; acarbose was stopped after glycemic control normalized. Supportive care included gastric protection and antiemetics.
This regimen was chosen as a non‑ASCT option to achieve a hematologic response and, secondarily, organ responses in the heart and kidneys.
After two cycles of BCD therapy, serum and urine immunofixation no longer detected M-protein or abnormal monoclonal bands; urine Bence Jones protein became negative. Serum VEGF normalized following the second cycle. Bone marrow flow cytometry after cycle two showed plasma cells reduced to 1.7% with normalization of immunophenotype. Clinically, symptoms including chest tightness and peripheral edema improved gradually. Serial cardiac biomarkers and NT-proBNP declined progressively, and cardiac enzymes returned to normal ranges.
By completion of 12 cycles, electrocardiographic low-voltage changes in limb leads had resolved and echocardiography showed a reduction in IVS and LVPW thickness. Table data in the original report document progressive declines in NT-proBNP and improvements in wall thickness across cycles. The patient received no further therapy and remained free of clinical heart failure symptoms during a 5‑year follow-up period.
Cardiac involvement is the major prognostic determinant in AL amyloidosis, where misfolded immunoglobulin light chains deposit in myocardium and exert direct cardiotoxic effects. These mechanisms include stress kinase activation, lysosomal dysfunction, impaired autophagy, reactive oxygen species generation, disrupted calcium handling, mitochondrial dysfunction, and myocyte death, culminating in restrictive cardiomyopathy, increased stiffness, and conduction abnormalities. Typical cardiac AL features include markedly elevated NT-proBNP and troponin, low-voltage ECG despite ventricular hypertrophy by imaging, granular myocardial texture, pericardial effusion, biatrial enlargement, and diastolic dysfunction.
By contrast, cardiac manifestations are uncommon in POEMS syndrome, though reported features can include pericardial effusion, ventricular hypertrophy, and biventricular dysfunction, potentially mediated by VEGF-driven microvascular permeability and interstitial edema or by endocrine effects. In this case, overlapping mechanisms from both disorders likely contributed to the patient’s refractory heart failure presentation.
Therapeutic selection must account for organ dysfunction and treatment tolerance. ASCT remains an option for selected AL patients, but eligibility criteria (including physiologic age, performance status, blood pressure, troponin levels, renal function, and NYHA class) limit its use in those with severe cardiac disease. For ASCT-ineligible patients, regimens such as BCD with or without daratumumab are recommended; in this patient BCD alone achieved rapid hematologic remission and organ improvement.
This case illustrates the rare coexistence of AL-λ amyloidosis and POEMS syndrome presenting predominantly as refractory heart failure. Comprehensive evaluation—including tissue biopsy with Congo red staining and proteomic typing, serum and urine immunofixation, bone marrow studies, electrophysiologic testing, and VEGF measurement—was essential to establish both diagnoses. In this patient, 12 cycles of the BCD regimen produced rapid hematologic remission, normalization of VEGF, improvement in cardiac biomarkers and imaging, and prolonged clinical stability over five years. The report underscores that uncommon disease overlap can produce diagnostic and therapeutic complexity and that thorough etiologic assessment is critical to guide individualized treatment.