Three years follow-up of Venetoclax in advanced-stage, relapsed or refractory AL amyloidosis with cardiac involvement and t(11;14) with BCL2 expression.

Further line treatment of patients with advanced stage AL amyloidosis with cardiac involvement is challenging. Venetoclax is a promising option, especially in t(11;14) and BCL2 expression.In our multicentre observational study, we report the 3-year follow-up of Venetoclax treatment in 9 patients with advanced, relapsed or refractory AL amyloidosis with t(11;14) and BCL-2 expression in > 50% of plasma cells. At baseline, all patients had been previously treated with daratumumab, all had cardiac involvement with revised Mayo stage III or IV/ European modification of Mayo 2004 IIIA or IIIB (1/9 unclassified due to missing troponin T), 5/9 patients had renal involvement.After a median of 35 months (range 25-49) since the start of Venetoclax, 8/9 patients were still alive (OS 89%). First and best hematological responses were observed after a median of 26 days (11-125) and 106 days (35-659), overall response rate was 100% (7/9 CR, 2/9 VGPR). Where observed, organ response was documented within the first 6 months of therapy, including cardiac (6/9) and renal (3/5) improvements. Venetoclax was discontinued in 6/9 patients after a median of 15 months (11-48) due to toxicity (2/9), disease progression (2/9), fixed treatment duration (1/9), or safety concerns (1/9).In conclusion, Venetoclax induces a rapid and deep hematologic response with consistent improvement in organ function with an acceptable safety profile in patients with pretreated, advanced stage AL amyloidosis with cardiac involvement and BCL2 expression with and potentially without detected t(11:14), which warrants further investigation.

Acquired haemophilia A in southern Switzerland from 2013 to 2019: a case series.

AIMS OF THE STUDY: Acquired haemophilia A is a rare disease with an annual incidence of 1.48 per million. Based on clinical observations, we suspect a higher incidence in southern Switzerland, and aimed at providing local epidemiological data, and clinical information regarding diagnosis, treatment and outcome in our region. METHODS: All adult patients with acquired haemophilia A treated between 2013 and 2019 in our facility were included in the present retrospective analysis. RESULTS: We treated 11 patients with acquired haemophilia A between 2013 and 2019, resulting in an annual incidence of 4.5 per million (95% confidence interval [CI] 0-9.0). Median delay from first symptoms to diagnosis was 4.5 days, and the median age at diagnosis was 79 years (range 23-87). Possible causative conditions were: pregnancy (n = 1), polyarteritis nodosa (n = 1), myelodysplastic syndrome (n = 1), chronic human immunodeficiency virus (HIV) (n = 1), and HIV postexposure prophylaxis (n = 1). In five patients no underlying or associated condition was identified. Median activated partial thromboplastin time (aPTT)) at baseline was 79 seconds (65-117; ref. value <38 sec), and FVIII:C 2.15% (<1-3.75%). A FVIII:C <1% was present in 4/10 patients. Median FVIII-inhibitor titre was 10.3 BU/ml (2.4-75.0 BU/ml). All patients had bleeding symptoms, 5/10 patients had major bleedings, and 7/10 patients were treated with bypassing agents. All patients received corticosteroids; 7/10 patients received immunosuppressive combination therapy. FVIII levels of ≥50% were achieved after a median of 40 days (8-62). One patient had a severe immunosuppressive therapy-related infection. An 87-years-old woman died for reasons not related to acquired haemophilia A or immunosuppressive therapy. CONCLUSIONS: Acquired haemophilia A is a rare disease, but manageable despite the advanced patient age and comorbidities. Its incidence in Southern Switzerland is higher than previously suspected.

Genetics and epigenetics of CLL.

Chronic lymphocytic leukemia (CLL) has a heterogeneous biological behavior, which is highly influenced by its immunogenetic, epigenetic, and genomic properties. The remarkably variable clinical course of the disease has been associated with genetic features such as chromosomal abnormalities, the presence of either high or low numbers of somatic hypermutations (SHM) in the variable region of the immunoglobulin heavy chain locus (IGHV), and somatic mutations of several specific driver genes. Next-generation sequencing (NGS) technologies have provided a comprehensive characterization of the genomic and epigenomic landscape in CLL, elucidating important underlying mechanisms of the disease's biology. The scope of this review is to summarize the most recent discoveries about novel genetic and epigenetic alterations, discussing their impact on clinical outcomes and response to currently available therapy.