OBJECTIVETo evaluate the usage of Mayo staging system in Chinese patients with primary light chain (LC) amyloidosis.

METHODClinical data, treatment and outcome of 162 primary LC amyloidosis patients with Mayo Clinic staging in Peking Union Medical College Hospital from January 2009 to June 2015 were retrospectively analyzed.

RESULTSThe median age of 162 patients with Mayo Clinic 2004 stage was 57 (20-81) y, of them 62.3% were male. The number of patients with stage I to III were 44 (27.2%), 69 (42.6%), and 49 (30.2%), respectively. The median overall survival was not reached, 23 months and 12 months in patients with Mayo Clinic 2004 stage I, II, and III, respectively (P<0.001). Among 128 patients with Mayo Clinic 2012 stage, 48 patients (37.5%), 32 patients (25.0%), 32 patients (25.0%) and 16 patients (12.5%) were staged as Mayo Clinic 2012 stage 1 to 4, and the median OS was not reached, not reached, 13 months and 3 months, respectively (P<0.001).

CONCLUSIONMayo Clinic staging systems had important prognostic value in patients with primary LC amyloidosis.

Adult ; Aged ; Aged, 80 and over ; Amyloidosis ; diagnosis ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

Objective: To evaluate the clinical characteristics and outcomes of very high risk patients with primary immunoglobulin light-chain amyloidosis (pAL) at a single center in China. Method: Clinical data, treatment and outcome of 205 pAL patients in Peking Union Medical College Hospital from January 2009 to February 2016 were retrospectively analyzed. A 'very high risk’ group includes patients with Mayo 2004 stage Ⅲb and Mayo 2012 stage 4. Results: Of 205 patients, 34 (16.6%) were defined as very high risk pAL patients. The median age at diagnosis was 57 (20-84) years, and 22 patients (64.7%) were male. All 34 patients were diagnosed with cardiac involvement, multi-organ involvement was observed in 15 patients (44.1%) , and 27 (81.8%) had New York Heart Association Class Ⅲ or Ⅳ. Median values of serum cTnI, NT-proBNP, and free light chains difference were 0.25 μg/L, 11 733 ng/L, and 403 mg/L, respectively. Eight (24.2%) had more than 10% plasma cell on the bone marrow aspirate. Sixteen (47.1%) patients received bortezomib based chemotherapy and overall hematologic response rate was 58.3%. Median overall survival (OS) was 4 months. The estimated OS at 3, 6, 12, and 24 months was 51.3%, 44.0%, 35.2%, and 29.6%, respectively. Fourteen (41.2%) patients died within 3 months after the diagnosis. The estimated 1-year survival rate for the patients who got hematologic response, without hematologic response, and palliative treatment was 90.9%, 11.1%, and 0, respectively (P<0.001) . Conclusion Patients with very high risk pAL had very poor prognosis and the early death rate remained high. Those patients who obtained hematologic remission would have significantly better outcomes.

Primary light-chain (AL) amyloidosis is a rare and fatal plasma cell disease. In recent years, the treatment of AL amyloidosis has changed from the era of bortezomib to the era of daratumumab immunotherapy. However, for the treatment choice of advanced-staged patients, how to achieve organ responses at the early stage and how to monitor the disease are questions that need to be further explored. The 64th American Society of Hematology Annual Meeting in 2022 has reported advances in the diagnosis and treatment of AL amyloidosis, which are briefly reviewed in this article.

Objective:To investigate the clinical features and outcomes of patients with light-chain (AL) amyloidosis with an ultra-high level of serum free light-chain (FLC) .Methods:Five hundred and ninety-five patients with AL amyloidosis were retrospectively reviewed between January 2009 and January 2020 at Peking Union Medical College Hospital. We analyzed the clinical features and prognosis of patients with ultra-high FLC levels [difference between involved and uninvolved light chains (dFLC) >500 mg/L; n=124] and those without ultra-high FLC levels (dFLC≤500 mg/L; n=471) . Results:Patients with ultra-high FLC presented with more frequent cardiac involvement (82.3% vs 70.1%, P=0.007) , and a higher percentage of patients with 2004 Mayo Ⅲ stage (41.8% vs 33.8%, P=0.029) , but less frequent renal involvement than patients without an ultra-high FLC (59.7% vs 71.8%, P=0.009) . Patients with an ultra-high FLC achieved a lower proportion of hematologic (72.4% vs 82.3%, P=0.048) and cardiac response (37.3% vs 54.7%, P=0.016) and had shorter overall survival (13.0 months vs not reached, P<0.001) and a higher early death rate within 3 months (28.2% vs 11.3%, P<0.001) than those without an ultra-high FLC. Ultra-high FLC independently predicted worse prognosis in patients with AL amyloidosis ( HR=2.279, 95% CI 1.685-3.083, P<0.001) . Conclusions:Patients with an initially ultra-high FLC represented a subgroup with more common cardiac involvement, more advanced cardiac stages, and extremely poor prognosis.

Objective:To explore the clinical characteristics and outcome of patients with type Ⅱ cryoglobulinemia in our center.Methods:Clinical data of 61 patients diagnosed with type Ⅱ cryoglobulinemia in Peking Union Medical College hospital from May 2015 to January 2020 were retrospectively analyzed.Results:A total of 61 patients were enrolled in the study, including 26 (42.6%) males, with a median age of 53 (range 28-79) years. The primary diseases identified were hepatitis C virus infection (21.3%) , hepatitis B virus infection (21.3%) , autoimmune diseases (14.8%) , and hematological tumors (11.5%) . Idiopathic cryoglobulinemia patients accounted for 19 cases (31.1%) . The major symptoms presented were purpura, proteinuria, hematuria, renal failure, fever and arthralgia. The median concentration of cryoglobulin level was 215.9 (22.0-17 075.8) g/L, and the IgM-monoclonal component of cryoglobulin was identified in 54 patients (88.5%) . Rheumatoid factor increased in 93.2% of patients. C3 decreased in 57.6% of patients. C4 decreased in 61.0% of patients. Treatment was initiated in 49 patients (80.3%) , and the total clinical remission rate was 75.5%. The expected 3-year overall survival was 89.3%.Conclusion:Type Ⅱ cryoglobulinemia was a systemic disease with multi-organ involvement. Most type Ⅱ CGs were secondary to hepatitis virus infection. Early diagnosis and proper treatment could bring better outcome.

Objective: To evaluate the response of oral melphalan plus high-dose dexamethasone (MDex) for patients with primary light chain amyloidosis (pAL). Methods: Clinical data, hematological and organ responses, and survival of 76 patients with pAL who had received MDex from January 2009 to July 2017 were retrospectively analyzed. Results: Of 76 patients (47 males and 29 females with the median age of 56 [range, 20-74] years old), 19.70% patients were defined as Mayo 2004 stage 3, involvement of more than or two organs was presented in 65 (85.53%) patients. Among 60 response evaluable patients, overall hematological response was 48.33% with complete response of 20.00% and very good partial response of 20.00%, respectively. The median time to the hematological response was 5 (range, 1-15) months. 36.67% patients achieved organ response. After the median follow up of 23(range, 1-113) months for surviving patients, median progression-free survival (PFS) and overall survival (OS) were 34 and 43 months, respectively. In a three months landmark analysis, the median rates of PFS and OS were 46 and 65 months, respectively. The median OS rates of patients with Mayo 2004 stage 3 and non Mayo 2004 stage 3 were 5 and 65 months (P=0.001), respectively. Conclusions MDex was an effective treatment for patients with early stage pAL, but was not suitable for those with severe cardiac involvement.

Systematic light chain (AL) amyloidosis is the most common forms of amyloidosis, which manifests as multiple organ system involvement, rapid progress, dire prognosis, difficult therapy and high mortality. Many patients may miss the optimal treatment as a result of not being diagnosed timely. Therefore, early diagnosis and assessment of involved extent of AL are clinical focuses. Related clinical studies have demonstrated that nuclear medicine imaging can be non-invasive in detecting amyloid deposits. It can not only early assess the extent and distribution of amyloid deposits in systemic AL amyloidosis, but also offer the indications for risk stratification, treatment response monitoring and prognosis assessment of the patients, especially for positron amyloidosis-specific tracers, which may have great prospects in the future. This review summarizes the application of nuclear medicine imaging in the systematic AL amyloidosis.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

OBJECTIVETo establish a novel method to determine specific type of amyloidosis through laser microdissection and mass spectrometry (LMD/MS) based proteomic analysis.

METHODSThere were 138 formalin-fixed and paraffin-embedded (FFPE) biopsy samples of patients who were diagnosed as systemic amyloidosis used in this study. For each case, a 10 μm section stained with congo-red and positive amyloid deposits were identified under fluorescent light, followed by micro-dissection and mass spectrometry analysis. The amyloidosis subtype was confirmed based on the most abundant amyloid protein.

RESULTSThe tissue types of 138 specimens were as following: subcutaneous abdominal fat accounted for 26%, tongue for 19%, gingiva for 11%, kidney for 9%, intestine for 9%, heart for 6% and others for 20%. Specific types of amyloid were accurately detected in 121 cases, including 106 (87.6%) amyloid light chain (AL) type, 7 (5.8%) amyloid trans-thy-retin (ATTR), 2 (1.7%) amyloidogenic protein A (AA), 2 (1.7%) amyloid heavy chain (AH)/AL+AH, 2 (1.7%) fibrinogen alpha chain (AFib), 1(0.8%) amyloid apolipoprotein A-type II (AApoA-II) and one (0.8%) amyloid lysozyme (ALys). Diagnosis of amyloidosis was excluded in 5 cases. The types of twelve cases were indeterminate by LMD/MS. On the whole, LMD/MS reached 91.3% accuracy rate in amyloid typing. Commonly involved organs (for example, heart, kidney and liver) turned out to be suitable sources of FFPE samples with typing success rate of almost 100%. In contrast, MS analysis was successful in only 83.3% of subcutaneous abdominal fat samples.

CONCLUSIONLMD/MS method provided a more direct technique for accurate typing of amyloidosis in a single procedure.

Amyloid ; Amyloidosis ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Mass Spectrometry ; Proteomics