Leukemia research最新文献

Background

Methods

Results

Conclusions

Background

Venous thromboembolism (VTE) causes morbidity and mortality in cancer patients. The association of VTE with known risk factors in chronic lymphocytic leukemia (CLL) is not known.

Objective

To examine risk factors and mortality associated with VTE in White, Black, and Asian CLL patients.

Methods

The United States SEER-Medicare database (2000–2015) was used for CLL patients ≥ 65 years. Logistic regression was used to examine VTE risk factors and Cox proportional regression was used to evaluate the effect of VTE on mortality in White, Black, and Asian CLL patients.

Results

Among 34,075 CLL patients, VTE was diagnosed in 11.6 % of 31,395 White, 14.6 % of 2062 Black and 6.3 % of 618 Asian patients. Risk of having VTE was, OR_a = 1.2 (95 % CI, 1.0–1.4) for Black patients and OR_a = 0.5 (95 % CI, 0.4–0.7) for Asian patients compared to White patients. Anemia and heart failure were associated with VTE in all three racial cohorts and were the only risk factors in Asian patients. Other risk factors in White patients were the same as in the overall population, including hypertension, obesity, COPD, kidney disease, diabetes, hyperlipidemia, myocardial infarction, and chemotherapy. In Black patients, other risk factors were hypertension, and chemotherapy. Mortality was slightly higher with VTE in the overall population and in White patients.

Conclusion

There was difference in VTE risk factors in White, Black, and Asian patients. VTE was marginally associated with mortality in CLL patients. Our findings may help to identify patients at higher risk of VTE in racially diverse CLL populations.

Approximately one-third of patients with myeloid disorders like myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) exhibit inflammatory and autoimmune disorders (IADs). These IADs often include atypical and incomplete forms of common autoimmune conditions, and exhibit resistance to conventional immunosuppressive therapies. There is growing interest in molecular relationships between IADs and MDS/CMML to find potential targeted therapies. Recently, patients with somatic mutations in the UBA1 gene were identified as having VEXAS syndrome. Herein, we present a concise case-series illustrating concurrent elderly-onset inflammatory manifestations and myeloid disorders (MDS, CMML, and idiopathic cytopenia of undetermined significance). These patients manifested inflammatory or autoimmune symptoms, including erythema nodosum, Raynaud's phenomenon, Sjogren syndrome, and refractory pruritus, having onset after 60-years of age. The inflammatory manifestations were largely refractory to traditional immunosuppressive regimens. Remarkably, treatment with a JAK-1 inhibitor, upadacitinib, in two cases yielded marked resolution of inflammatory symptoms, facilitating the gradual tapering of corticosteroids, improvement of hemoglobin levels, and reduction in serum C-reactive protein levels. Upon loss of response to upadacitinib, JAK-2 inhibitor ruxolitinib provided clinical benefit in one of the cases, facilitating further tapering of glucocorticoids. This arena warrants further exploration through prospective studies of larger cohorts to delineate optimal management strategies.

Acute myeloid leukemia (AML) with inv(16) is typically associated with a favourable prognosis. However, up to 40 % of patients will eventually experience disease relapse. Herein, we dissected the genomic and transcriptomic profile of inv(16) AML to identify potential prognostic markers and therapeutic vulnerabilities. Sequencing data from 222 diagnostic samples, including 44 relapse/refractory patients, revealed a median of 1 concomitant additional mutation, cooperating with inv(16) in leukemogenesis. Notably, the mutational landscape at diagnosis did not differ significantly between patients experiencing primary induction failure or relapse when compared to the rest of the cohort, except for an increase in the mutational burden in the relapse/refractory group. RNA-Seq of unpaired diagnostic(n=7) and relapse(n=6) samples allowed the identification of oxidative phosphorylation (OXPHOS) as one of the most significantly downregulated pathways at relapse. Considering that OXPHOS could be targeted by Venetoclax/Azacitidine combination, we explored its biological effects on an inv(16) cell-line ME-1, but there was no additional advantage in terms of cell death over Azacitidine alone. To enhance Venetoclax efficacy, we tested in vitro effects of Metformin as a potential drug able to enhance chemosensitivity of AML cells by inhibiting the mitochondrial transfer. By challenging ME-1 with this combination, we observed a significant synergistic interaction at least similar to that of Venetoclax/Azacitidine. In conclusions, we identified a downregulated expression of oxidative phosphorylation (OXPHOS) at relapse in AML with inv(16), and explored the in vitro effects of metformin as a potential drug to enhance chemosensitivity in this setting.