Familial cases of myelodysplastic syndromes are rare, but are immensely valuable for the investigation of the molecular pathogenesis of myelodysplasia in general. The best-characterized familial myelodysplastic syndrome is that of familial platelet disorder with propensity to myeloid malignancy, caused by heterozygous germline RUNX1 mutations. Recently, there has been an increase in the number of reported cases, allowing for better understanding of the incidence, clinical features, and pathogenesis of this disorder. These recent cases have highlighted the clinical variability of the disorder and confirmed that many patients lack a bleeding and/or thrombocytopenia history. Additionally, several cases of T-acute lymphoblastic leukemia have now been reported, confirming a risk of lymphoid leukemia in patients with inherited RUNX1 mutations. Furthermore, an increased awareness of clinicians has helped detect a number of additional families affected by inherited myelodysplastic syndromes, resulting in the identification of novel causative mechanisms of disease, such as RUNX1 deficiency resulting from constitutional microdeletions of 21q22 and myelodysplasia-associated with telomerase deficiency. Awareness of predisposition to myelodysplastic syndromes and acute myeloid leukemia in families may be of critical importance in the management of younger patients with myelodysplasia in whom allogeneic hematopoietic stem cell transplantation is considered. Such families should be investigated for inherited deficiencies of RUNX1 and/or telomerase to prevent the use of an affected sibling as a donor for transplantation. Here we provide an update on familial platelet disorder in addition to a review of other known familial myelodysplastic syndromes.

While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in RUNX1 or CEBPA. Recently, novel germline mutations in GATA2 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type RUNX1 and CEBPA, for GATA2 mutations. Screening for other recurrent mutations was also performed. A GATA2 p.Thr354Met mutation was observed in a pedigree in which 2 first-degree cousins developed high-risk myelodys-plastic syndrome with monosomy 7. They were also observed to have acquired identical somatic ASXL1 mutations and both died despite stem cell transplantation. These findings confirm that germline GATA2 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia, and that monosomy 7 and ASXL1 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy in these families.

Mantle cell lymphoma (MCL) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (R/R) disease have a very poor prognosis. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has proven to be an effective agent for patients with R/R MCL. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with R/R MCL are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with R/R MCL.

BPDCN is a rare disorder derived from precursor plasmacytoid dendritic cells that is classified among the Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms.[1] BPDCN is characterized by ...

Chronic lymphocytic leukemia (cll) is the most common adult leukemia in North America. In 2018, the first unified national guideline in Canada was developed for the front-line treatment of cll that helped guide treatment across the country. As an update in 2022, a group of clinical experts from across Canada came together to provide input and guidance that included new and innovative treatments and approaches that will continue to provide health care professionals with clear guidance on the first-line management of cll. Recommendations were provided in consensus based on available evidence for the first-line treatment of cll.