Patterns and organ treatment response of Erdheim-Chester disease with cardiac involvement.

OBJECTIVE: To evaluate the heart response of Erdheim-Chester disease (ECD) through continuous follow-up within our large cohort, for which there is a lack of understanding. METHODS: We conducted a retrospective analysis of clinical data from patients with ECD with cardiac involvement diagnosed at our centre between January 2010 and August 2023. We assessed the heart response by integrating pericardial effusion and metabolic responses. RESULTS: A total of 40 patients were included, with a median age of 51.5 years (range: 29-66) and a BRAFV600E mutation rate of 56%. The most common imaging manifestations observed were pericardial effusion (73%), right atrium (70%) and right atrioventricular sulcus infiltration (58%). Among 21 evaluable patients, 18 (86%) achieved a heart response including 5 (24%) complete response (CR) and 13 (62%) partial response (PR). The CR rate of pericardial effusion response was 33%, while the PR rate was 56%. Regarding the cardiac mass response, 33% of patients showed PR. For cardiac metabolic response, 32% and 53% of patients achieved complete and partial metabolic response, respectively. There was a correlation between pericardial effusion response and cardiac metabolic response (r=0.73 (95% CI 0.12 to 0.83), p<0.001). The median follow-up was 50.2 months (range: 1.0-102.8 months). The estimated 5-year overall survival was 78.9%. The median progression-free survival was 59.4 months (95% CI 26.2 to 92.7 months). Patients who received BRAF inhibitors achieved better heart response (p=0.037) regardless of treatment lines. CONCLUSION: We pioneered the evaluation of heart response of ECD considering both pericardial effusion and cardiac metabolic response within our cohort, revealing a correlation between these two indicators. BRAF inhibitors may improve heart response, regardless of the treatment lines.

Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

BACKGROUND: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. METHODS: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. RESULTS: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89). CONCLUSIONS: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

Validation of the composite organ and hematologic response model for prognostic prediction in a Chinese light chain amyloidosis cohort.

To achieve prompt and comprehensive assessment of treatment, we investigated the feasibility of composite hematologic and organ response (CHOR) model in a Chinese light chain (AL) amyloidosis cohort. Three hundred and eighty-eight newly diagnosed patients were assigned scores of 0-3 for complete response, very good partial response, partial response, no response, or progression at 6 months. Organ response (OR) was scored as follows: 0 - all OR (AOR), 1 - mixed OR (MOR), and 2 - no OR (NOR). Finally, patients were divided into CHOR group 1 (total score 0-3) and group 2 (total score 4-5). The patients who achieved AOR and MOR had similar outcomes, which were much better than those of patients with NOR. Group 1 had significantly better overall survival than group 2 (p< .001). The CHOR model had a significantly higher predictive power of survival than hematologic response and OR. We validated the value of the CHOR model as an early indicator of treatment benefit.

Posttreatment dFLC less than 10 mg/L predicts superior organ response and longer time to next treatment in newly diagnosed light-chain amyloidosis patients treated with bortezomib.

Recently, a difference between involved and uninvolved free light chains (dFLC) less than 10 mg/L after treatment (stringent dFLC response) was reported to be associated with superior survival in light-chain (AL) amyloidosis. We conducted a retrospective study of AL amyloidosis patients treated with bortezomib to investigate the predictive value of a stringent dFLC response. Two hundred and thirty-five patients were included. The cardiac and renal responses were much higher in patients achieving a stringent dFLC response (86.5% versus 42.7% and 75.9% versus 38.2%, p < .001). Patients with a stringent dFLC response had significantly longer overall survival and time to next treatment (TNT). Among the very good partial response (VGPR) patients, the TNT of stringent dFLC responders was superior to those of the remaining VGPR patients (p = .045) and comparable to those of complete response patients. In conclusion, a stringent dFLC response might be added to current response criteria for AL amyloidosis.

Clinical Importance of the Posterior Inferior Cerebellar Artery: A Review of the Literature.

The posterior inferior cerebellar artery (PICA), with its unique anatomical complexity, is of great clinical importance and involved in many diseases including aneurysm, ischemic stroke, neurovascular compression syndrome (NVCS), arteriovenous malformation (AVM), and brain tumor. However, a comprehensive systematic review of the importance of the PICA is currently lacking. In this study, we perform a literature review of PICA by searching all the associated papers in the PUBMED database hoping to provide a better understanding of the artery. The PICA has tortuous and variable course and territory, divided into 5 segments. Various aneurysms involving PICA were not uncommon, of which the treatment is challenging. The PICA infarct typically manifests lateral medullary syndrome (LMS) and is more likely to cause mass effects. The PICA frequently compresses the medulla and the cranial nerves resulting in various neurovascular compression syndromes (NVCS). Arteriovenous malformation (AVM) fed by PICA are associated with aneurysm and dissection which have high risk of rupture and worse outcome. PICA injured by head trauma can cause fatal SAH. VA terminating in PICA probably cause Bow hunter's syndrome (BHS). The PICA supplies many brain tumors and can be used in intracerebellar chemotherapy. The PICA can be exposed and injured during surgeries especially in telovelar approach, and it also plays an important role in bypass surgeries, hinting the surgical importance of PICA. In conclusion, PICA is very important in clinical practice.

Clinical presentation and prognostic analysis of adult patients with Langerhans cell histiocytosis with pulmonary involvement.

BACKGROUND: The study aimed to investigate the clinical features and prognosis factors of adult patients with Langerhans cell histiocytosis (LCH) with pulmonary involvement, especially multisystem (MS) LCH with pulmonary involvement. METHODS: We retrospectively analyzed the demographic materials, clinical features and treatment outcomes of 119 adult LCH patients with pulmonary involvement at our center from January 1990 to November 2019. RESULTS: Among 119 patients, 13 (10.9%) had single-system (SS) LCH, and 106 (89.1%) had MS-LCH with pulmonary involvement. SS-LCH patients had higher smoking rate (84.6% vs 52.8%, P = 0.026) and smoking index (300 vs 200, P = 0.019) than MS-LCH patients. The percentage of respiratory symptoms of SS-LCH patients was higher than MS-LCH patients (84.6% vs 53.8%, P = 0.034). Pulmonary function was impaired in 83.8% of the patients, and DLCO was the parameter most frequently impaired, accounting for 81.1%. The median DLCO was 65.1% predicted. Patients with pneumothorax had significantly worse DLCO (P = 0.022), FEV1 (P = 0.000) and FEV1/FVC (P = 0.000) than those without pneumothorax. During the follow-up, 72.4% of the patients had stable pulmonary function, and 13.8% showed improvements after chemotherapy. The estimated 3-year OS and EFS were 89.7 and 58.3%, respectively. Patients with a baseline FEV1 ≤ 55% predicted had worse OS. A history of pneumothorax indicated worse EFS and cytarabine based therapy predicted better EFS. CONCLUSIONS: An FEV1 ≤ 55% predicted and a history of pneumothorax at diagnosis indicated a poor prognosis. Cytarabine based regimen may arrest the decline in pulmonary function in LCH patients with pulmonary involvement and improve EFS.

Clinical presentation and prognostic analysis of Chinese patients with systemic light chain amyloidosis with liver involvement.

To summarize the clinical characteristics and prognostic factors of Chinese patients with systemic light chain amyloidosis with liver involvement. We retrospectively analyzed the clinical features and natural history data of 102 patients diagnosed with systemic light chain amyloidosis with liver involvement at Peking Union Medical College Hospital between March 2007 and May 2018. More than 95% of patients showed the involvement of other organs. Kidney and heart were the most frequently involved organs, accounting for 71.6% and 68.6% of cases, respectively. Hepatomegaly was the most frequently observed physical sign, accounting for 67.6% of cases. Elevated levels of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were frequently observed, accounting for 85.3% and 88.2% of cases, respectively. A significantly better prognosis was observed in patients with normal total bilirubin levels, as compared with those with elevated levels of total bilirubin. Patients in the normal total bilirubin group showed a significantly better progression-free survival (PFS) (38 months) as compared the elevated total bilirubin group (4 months; P < 0.001). The median overall survival (OS) in the normal total bilirubin group was not reached compared with the elevated total bilirubin group (4 months, P < 0.001). Notably, the early death rate was significantly lower in the normal total bilirubin group as compared to the elevated total bilirubin group (14.5% vs 48.5%, P < 0.001). In conclusion, the elevation of total bilirubin indicated an early death and worse PFS and OS. Early diagnosis is therefore essential, and requires appropriate treatment and intensive care.

Clinical presentation and prognosis of immunoglobulin light-chain amyloidosis with high percentage of bone marrow plasma cells.

OBJECTIVE: To summarize the clinical features and outcomes in Chinese patients with immunoglobulin light-chain (AL) amyloidosis with ≥10% bone marrow plasma cells (BMPCs). METHODS: We retrospectively compared the clinical features and outcomes between patients with ≥10% BMPCs (high-BMPC group; n = 56) and those with <10% BMPCs (low-BMPC group; n = 311). RESULTS: Patients in the high-BMPC group had significantly higher levels of N-terminal pro-brain natriuretic peptide, significantly lower levels of 24 h urine protein, and significantly higher levels of difference between the involved and uninvolved serum free light chains (485.3 versus 121.1 mg/L, P < 0.001). Patients in the high-BMPC group had significantly higher early mortality within 3 months of diagnosis (21.4% versus 10.9%, P = 0.018). In a 3-month landmark analysis, median progression-free survival durations were 17.3 and 34.5 months (P = 0.01), and the median overall survival durations were 24.4 months and not reached in the high- and low-BMPC groups, respectively (P = 0.005). CONCLUSION: Patients with AL amyloidosis and ≥10% BMPCs have higher mortality within 3 months of diagnosis and poorer prognosis compared with patients with <10% BMPCs.