UNASSIGNED: AL amyloidosis can involve the gastrointestinal (GI) tract in a sporadic manner, affecting certain anatomical areas while sparing others.
UNASSIGNED: Our patient with AL amyloidosis and confirmed colonic involvement was found to have new odynophagia, GI bleeding, and imaging findings that might suggest AL amyloidosis. However, negative pathology results from esophageal biopsies suggested the patient\'s new ulcerations were more likely a side effect of her autologous stem cell transplant (SCT) and chemotherapy meant to target amyloidosis, as opposed to an effect of amyloid infiltration itself.
UNASSIGNED: GI involvement of amyloidosis requires a high degree of clinical suspicion and should be considered in patients with systemic diseases affecting the kidney, heart, and GI tract; however, when satisfactory biopsies obtained from endoscopy results are negative, other causes should be considered.

To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis.
Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies.
Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT.
OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.
Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL.
Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas.
De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO.
El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

暂无摘要。

BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue, with cardiac involvement being very frequent (61%). Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes. Despite the administration of immunotherapeutic agents, in particular bortezomib and daratumumab, which have improved the outcomes of AL amyloidosis, anti-plasma cell therapy remains suboptimal for some patients.
METHODS: We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy. He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen. The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion, in which flow cytometry analysis showed abnormal plasma cells. After two cycles of this regimen, the pleural effusion was controlled effectively with no recurrence.
CONCLUSIONS: This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.

BACKGROUND: Multiple myeloma (MM) can be accompanied by amyloidosis, which occurs in a small number of patients and is characterized by deposition of light chains in the joints, leading to multiple myeloma-associated amyloid arthropathy (MAA). As a rare complication of MM, clinical manifestations of MAA are often similar to those of rheumatoid arthritis, and the two are easily confused.
METHODS: In recent years, our center treated two patients of MM with amyloid arthropathy as the first manifestation, both of whom presented with polyarthritis. After treatment for MM, both patients achieved complete remission. However, subsequently, the two patients underwent hip arthroplasty for femoral neck fractures. Congo red staining and immunofluorescence of the joint tissues confirmed MAA after surgery. Eventually, one of the patients died of MM recurrence, while the other survived.
CONCLUSIONS: MAA should be regarded as an initial symptom of MM and should be taken seriously.

Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis.
To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis.
There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis.
For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.

BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a rare disease. Treatment is challenging, justified in part by systemic compromise and limited scientific evidence.
OBJECTIVE: Develop evidencebased recommendations that allow adequate treatment of patients with amyloidosis AL.
METHODS: A list of PICO format questions focused on the effectiveness and safety of amyloidosis AL treatment was generated. PubMed, Cochrane and Epistemonikos were searched. The levels of evidence and grades of recommendation were based on the GRADE system.
RESULTS: 11 recommendations were generated. In selected patients with amyloidosis AL, autologous hematopoietic stem cell transplantation (ASCT) is recommended after induction with bortezomibbased regimens and conditioning with melphalan, since it could deepen the hematological and organ response, its durability and improve survival. In patients not eligible for ASCT, first-line treatment with bortezomib-based regimens is recommended, since it is likely to achieve a higher rate of hematological and organ response and improve survival. In patients with a contraindication or inaccessibility to bortezomib, treatment with alkylating agents and corticosteroids is recommended, since they are likely to achieve haematological and organ response and improve survival.
CONCLUSIONS: These treatment recommendations are based on the available evidence and the experience of the panel of experts, in a scenario of limited available resources, according to developing countries.
Introducción: La amiloidosis por cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuente. El tratamiento implica un desafío, justificado en parte por el compromiso sistémico y la evidencia científica escasa. Objetivos: Elaborar recomendaciones basadas en la evidencia que permitan realizar un adecuado tratamiento de pacientes con amiloidosis AL. Métodos: Se generó un listado de preguntas con formato PICO centradas en la efectividad y seguridad del tratamiento de la amiloidosis AL. Se realizó la búsqueda en PubMed, Cochrane y Epistemonikos. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE. Resultados: Se generaron 11 recomendaciones. En pacientes con amiloidosis AL seleccionados, se recomienda el trasplante autólogo de células progenitoras hematopoyéticas (TCPH) posterior a una inducción con esquemas basados en bortezomib y el acondicionamiento con melfalán, ya que podría profundizar la respuesta hematológica, de órgano, su durabilidad y mejorar la supervivencia. En pacientes no elegibles para TCPH, se recomienda el tratamiento de primera línea con esquemas basados en bortezomib, dado que es probable que logre mayor tasa de respuesta hematológica, de órgano y mejore la supervivencia. En pacientes con contraindicación o inaccesibilidad al bortezomib, se recomienda el tratamiento con agentes alquilantes y corticoides, dado que es probable que logren la respuesta hematológica, de órgano y mejoren la supervivencia. Discusión: Estas recomendaciones de tratamiento se basan en la evidencia disponible y la experiencia del panel de expertos, en un escenario de recursos disponibles limitados, acorde a los países en vías de desarrollo.

Amyloidosis is caused by the extracellular deposition of fibrils composed of low molecular weight protein subunits. Its two main types are amyloid light chain (AL) amyloidosis and amyloid A (AA) amyloidosis (previously referred to as secondary amyloidosis). Clinical manifestations are dependent upon location, type, and amount of deposit. We report a case of a 72-year-old female who presented to the emergency department for evaluation of cough, fatigue, and shortness of breath. Physical examination was notable for decreased breath sounds bilaterally over the lower lung fields. Computed tomography (CT) of the chest showed a large lobulated right pleural effusion and atelectasis. Two liters of milky, white pleural fluid was removed via thoracocentesis, and pleural fluid analysis was consistent with chylothorax. Over the next 10-day period, there was a reaccumulation of the pleural fluid, which required a pleural catheter placement. The patient underwent video-assisted thoracoscopic surgery with pleural and pericardial tissue biopsy that was consistent with kappa or lambda AL amyloid. Unfortunately, her respiratory status subsequently declined, requiring mechanical ventilation, and eventually leading to cardiac arrest. Cardiac amyloidosis can rarely cause chylous ascites and chylothorax. The absence of electrocardiographic findings of left ventricular hypertrophy combined with apparent left ventricular hypertrophy on echocardiography is strongly suggestive of infiltrative cardiomyopathy such as cardiac amyloidosis. In these cases, cardiac amyloidosis should be considered in the differential diagnosis of chylothorax.

Before 2021, the combination of bortezomib, cyclophosphamide, and dexamethasone (VCd) was one of the most used upfront therapy for systemic immunoglobulin light chain (AL) amyloidosis. Recently, daratumumab in combination with VCd resulted in improved outcomes compared to VCd. However, it\'s still unclear the role of cyclophosphamide in this combination.
We conducted this retrospective single-institutional study to compare the outcomes of upfront bortezomib and dexamethasone with or without cyclophosphamide (VD vs. VCd).
Of 136 total patients, 62 received VD and 74 received VCd. The median age was 64 and the median number of organs involved was 2. Hematologic response was achieved among 73.4% patients in the VD arm and 85.9% in the VCd arm at 3 months (P = .15). Best organ response was not different between 2 arms (34.1% vs. 52.9% for VD and VCd arms, respectively; P = .28). After a median follow-up of 24.4 months, 2-year OS for VD and VCd arm was 70.6% and 84.6% respectively. The median overall survival was 70 months for VD arm and not reached for VCd arm (P = .30). There was no statistically significant difference in median time to next therapy (9.3 vs. 13.5 months for VD and VCd arms, respectively. P = .99).
the addition of cyclophosphamide to VD was not associated with improved outcomes of patients with AL amyloidosis in this retrospective study.

Amyloidosis is a progressive infiltrative disease instigated by the extracellular deposition of amyloid fibrils in various organs such as the heart, kidney, and peripheral nerves. Cardiac amyloid deposits cause restrictive cardiomyopathy, leading to a poor prognosis in systemic amyloidosis. The most common etiologies of cardiac amyloidosis (CA) are immunoglobulin light chain deposits (AL-CA) and misfolded transthyretin deposits (ATTR-CA). In recent years, many developments have been accomplished in the field of diagnosis and treatment of CA. At present, ATTR-CA can be noninvasively diagnosed if the following two conditions are fulfilled in the setting of typical echocardiographic/cardiac MRI findings: (1) grade 2 or 3 myocardial uptake in bone scintigraphy confirmed by SPECT and (2) absence of monoclonal protein confirmed by serum-free light chain assay, and serum/urine protein electrophoresis with immunofixation test. Effective therapies are evolving in both types of CA (tafamidis for ATTR-CA and immunologic treatments for AL-CA). Thus, early suspicion and prompt diagnosis are crucial for achieving better outcomes. In this review, we have summarized the role of multimodal imaging (e.g., echocardiography, cardiac MRI, and bone scintigraphy) and biomarkers (e.g., troponin, BNP) in the diagnosis, risk stratification, and treatment monitoring of CA.