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Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.

Achieving major molecular response (MMR) with BCR::ABL1 tyrosine kinase inhibitors (TKIs) is associated with lower chances of progression to advanced phase disease and higher chances of treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML). Failure to achieve this molecular milestone after one year has been highlighted as "suboptimal" or "warning" sign of treatment failure in CML guidelines and recommendations and implied to predict a poor long-term outcome. In this analysis, we report the long-term outcome of 131 patients who did not achieve MMR within the first two years of TKI therapy. Patients who achieved major cytogenetic response (MCyR; roughly equivalent to BCR::ABL1 transcript levels on the International Scale [IS]10%) had good long-term overall survival (OS) (10-year OS of 88%) and CML-related overall survival (CML-OS) (10-year CML-OS of 95%). Achievement of MCyR within the first two years of treatment predicted for better OS (HR=0.43, P=0.03). The value of MMR was even less pronounced among patients aged 60 years or older at diagnosis, in whom mortality was primarily due to comorbidities unrelated to CML (10-year OS of 55% vs 10-year CML-OS of 100%). In conclusion, achievement of MCyR within two years is a reasonable milestone in CML, and these patients can still have good outcomes even when MMR is not achieved. This article is protected by copyright. All rights reserved.

Recurrence of MRD in AML is associated with imminent relapse unless intervened upon. Change in chemotherapy regimen and/or immediate transplant improve outcomes.

The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions’ experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6–21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), IDH1/2 (n = 2), monosomy 5 (n = 1), NUP98 (n = 1) and ASXL1 (n = 1). The majority (86%) received venetoclax with a hypomethylating agent. Grade 3 or 4 adverse events included febrile neutropenia in 37% (n = 16), non-febrile neutropenia in 12% (n = 5), anemia in 14% (n = 6), and thrombocytopenia in 14% (n = 6). Of 40 patients evaluable for response, 10 patients (25%) achieved complete response (CR), 6 patients (15%) achieved CR with incomplete blood count recovery (CRi), and 2 patients (5%) had a partial response, (CR/CRi composite = 40%; ORR = 45%). Eleven (25%) patients received a hematopoietic stem cell transplant following venetoclax combination therapy, and six remain alive (median follow-up time 33.6 months). Median event-free survival and overall survival duration was 3.7 months and 8.7 months, respectively. Our findings suggest that in pediatric patients with AML, venetoclax is well-tolerated, with a safety profile similar to that in adults. More studies are needed to establish an optimal venetoclax-based regimen for the pediatric population.

Background Studies have shown that dementia caregivers are inclined to sacrifice their well-being leaving them susceptible to an increased risk of anxiety, low quality of life, and depression. With the proportion of female caregivers being unusually high, most studies focused exclusively on the burden of care in female caregivers, resulting in a knowledge gap regarding male caregiver burden. This study aimed to assess the difference in the burden of care experienced by male and female caregivers of dementia patients and the association of burden of care with psychological wellbeing according to gender. Methods This was a cross-sectional survey of dementia patients’ caregivers from various locations in Lebanon, administered over the phone using structured questionnaires from February to April 2019. The population consisted of 50 females and 11 males' informal unpaid caregivers above the age of 18 in daily contact with the patient. The sample was conveniently selected and identified through two main non-profit organizations. The patient and the caregiver’s sociodemographic information were recorded. The psychological distress was measured using the General Health Survey Questionnaire (GHQ 12) whereas the burden of care was measured using the Zarit Burden Interview 22 (ZBI 22). Results A large proportion of caregivers reported a severe level of burden (41 %). Only item 17 of the ZBI questionnaire (Feeling of life loss control since relative’s illness) was substantially higher among females. Of the caregivers, 70.5% experienced moderate to severe distress, being significantly higher in females. The sex of caregivers was the only socio-demographic factor significantly associated with the burden of care. Female caregivers who experienced severe burden had significantly higher odds of distress compared to those with no or mild to moderate burden (adjusted OR=15.55). No association among male caregivers.Conclusion This study demonstrated that female caregivers experience a greater burden compared to males when assessed about anger. This could be explained by the different gender roles imposed by the Lebanese society on its members. Caregivers should be part of the holistic treatment of dementia patients since they represent an essential pillar of the informal care provided.

In the era of precision medicine, treatment schemes for advanced Colorectal (CRC) disease include monoclonal antibodies which block the epidermal growth factor receptor (EGFR) implicated in tumor proliferation, invasion, migration and neovascularization. Resistance to these agents has been correlated with activating downstream mutations in KRAS, BRAF and NRAS genes, among others, leading to constitutive activation of the EGFR axis bypassing EGFR blockade. The assessment of tumor RASandBRAFmutational status has thus become standard clinical practice. While multiple investigations reported roughly mutations rates of 40% in KRAS, 7% in NRAS and 5-15 % in BRAF, numbers vary across different populations with limited data specifically from the Middle East.This is a retrospective observational Laboratory information system (LIS) chart review of all the patients with pathologically confirmed colorectal carcinoma (CRC) or metastatic CRC who underwent KRAS, NRAS and/or BRAF mutational analysis testing at the Molecular Diagnostics Laboratory of the American University of Beirut Medical Center (AUBMC) from January 2012 to December 2018, inclusive. Data retrieved included the results of mutation testing performed for KRAS, NRAS and BRAF genes, the age, gender, and tumor location for each patient. Analysis of the mutations was performed using polymerase chain reaction (PCR) hybridization StripAssay® (ViennaLab, Vienna, Austria).130 (47.6%) out of 273 histologically confirmed CRC cases, had positive KRAS mutations, namely in codons 12 (82%), 13 (17%), 146 (1.5%), 117 (0.75%), or 61 (0.75%). Two patients had two concomitant mutations: 12 + 12 (different mutations) and 12 + 146. Of 203 CRC cases tested for NRAS mutations, 16 (7.8%) were found to be positive for a mutation in codon 12 (37.5%), 61 (37.5%), or 13 (12.5%). Two patients had two concomitant mutations: 12 + 13 and 59 + 61. Of 172 CRC cases tested for BRAF mutations, 2 (1.2 %) were positive for the V600E -.This retrospective study is the first to report the frequencies of KRAS, NRAS and BRAF gene mutations in a Lebanese CRC cohort diagnosed and managed at a tertiary care center. The frequencies of the studied somatic gene mutations were similar to previously reported cohorts in other populations however the rate of BRAF mutation was lower in this cohort than expected.