Feasible diet and circadian interventions reduce in vivo progression of FLT3-ITD-positive acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia. METHODS: The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like 1), in effects of diet timing was studied by overexpression in FLT3-ITD-bearing AML cells. RESULTS: Reduced tumor burden in FLT3-ITD AML-bearing mice was observed with interventions utilizing low-sucrose and/or low-fat diets, or time-restricted feeding (TRF) compared to mice fed normal chow ad libitum. In a tasting study, macronutrient matched low-sucrose and low-fat meals were offered to pediatric acute leukemia patients who largely reported liking the meals. Expression of the circadian protein, BMAL1, was heightened with TRF and the low-sucrose diet. BMAL1 overexpression and treatment with a pharmacological inducer of BMAL1 was cytotoxic to FLT3-ITD AML cells. CONCLUSIONS: Mouse models for FLT3-ITD AML show that diet composition and timing slows progression of FLT3-ITD AML growth in vivo, potentially mediated by BMAL1. These interventions to enhance therapy efficacy show preliminary feasibility, as pediatric leukemia patients responded favorable to preparation of macronutrient matched meals.

Impact of a Genetic Evaluation Initiative to Increase Access to Genetic Services for Adolescent and Young Adults at a Tertiary Cancer Hospital.

Purpose: Adolescents and young adults (AYAs) with cancer are at increased risk for inherited cancer predisposition syndromes. Genetic counseling (GC) is important for accurate risk assessment, diagnosis, and management of inherited cancers. Numerous barriers prevent AYA access to genetic services. This study describes outcomes of a genetic evaluation initiative (GEI) regarding utilization of genetic services among AYAs. Methods: To improve AYA access to GC, the AYA program at UT MD Anderson Cancer Center implemented GEI, a process for identifying and referring eligible patients for GC. We collected retrospective electronic medical record data between July 12, 2018 and July 12, 2019 to capture AYA's clinical characteristics, genetic referral, scheduled appointments, counseling, testing, and results. Results: In total, 516 AYAs were referred to the AYA clinic during the study period with a median age of first cancer diagnosis of 17 years. One hundred sixty-six AYAs were identified who would benefit from genetic evaluation, 57 (34.3%) of whom had previously undergone counseling. One hundred nine patients were recommended for referral to GC, and 64.2% (70/109) were referred by the AYA team. To date, 58.6% (41/70) met with a genetic counselor and 75.6% (31/41) completed genetic testing, which yielded 1 pathogenic, 2 uncertain, and 29 benign results. Conclusion: The GEI resulted in a 72.0% relative increase in the rate of GC utilization and represents a novel approach to increasing AYA patient access to cancer genetic services in this population.

Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma.

Venetoclax is approved for adult patients with chronic lymphocytic leukemia and acute myeloid leukemia. Expanding its use to the pediatric population is currently under investigation, but more robust data are needed. We retrospectively analyzed the safety and efficacy of venetoclax in children/AYA with ALL/LBL. We identified 18 patients (T-cell ALL, n = 7; T-cell LBL, n = 6; B-cell ALL, n = 5) aged 6-22 years. No new venetoclax safety signals were identified; the most common toxicity was myelosuppression. No deaths occurred within 30 days from the start of the therapy. A mean of 2.6 (range 0-8) prior lines of therapy were given. The mean duration of venetoclax was 4.06 months (range 0.2-24.67 months). Complete remission was achieved in 11 (61%) patients. Of the eight patients who remain alive, four are continuing on venetoclax combination therapy, and four proceeded to hematopoietic stem cell transplantation. Three patients who initially achieved CR, later relapsed, and are deceased. Nine patients are deceased, and one patient was lost to follow-up. Overall survival is 9.14 months (range 1.1-33.1), and progression-free survival is 7.34 months (range 0.2-33.1). This is the largest cohort of pediatric/AYA patients who received venetoclax for ALL/LBL. Our data support the consideration of venetoclax-based regimens in pediatric patients with R/R ALL/LBL and its investigation as upfront therapy for T-cell ALL/LBL.

Continuity of care of colorectal cancer survivors at the end of treatment: the oncology-primary care interface.

PURPOSE: This study examines at a population level how colorectal cancer (CRC) survivors evaluate the continuity and quality of their follow-up care after treatment, particularly for those in the care of a primary care provider (PCP). METHODS: A survey was mailed in 2010 to all individuals in Manitoba, Canada diagnosed in 2008/2009 with stage II and III CRC. Respondents were asked to identify the main provider(s) of their follow-up care. Those indicating a PCP completed the Patient Continuity of Care Questionnaire (PCCQ), which assesses continuity of care upon discharge from hospital to community. Quality of life (QOL) on the Functional Assessment of Cancer Therapy--Colorectal (FACT-C) and the Illness Intrusiveness Rating Scale was collected as well as demographic information. Descriptive statistics and regression analyses were utilized. RESULTS: The response rate was 246/360 or 68.3 %. Most participants were Caucasian with a mean age of 70 and 18 months from diagnosis. A single "main provider" of follow-up care was named by 47 %, most frequently a FP or oncologist, but a majority (53 %) indicated multiple providers. Twenty-four combinations of providers were described. The 106 respondents (43.1 %) who named a PCP as a main provider completed the PCCQ and reported high scores on its five subscales. In multivariate analysis, lower FACT-C QOL scores (OR 2.72, CI 1.12-6.57) and male gender (OR 2.82, CI 1.11-7.18) predicted poorer evaluations of continuity of care. Concern was highest regarding sexual function, body image, fatigue, impact on work and recreation, and bowel control, and in those who were younger or with rectal cancer. CONCLUSIONS: The organization of CRC follow-up care between providers is complex and variable, but patients followed by PCPs evaluate their transitions of care after treatment favorably. Specific clinical issues and higher risk groups are identified and may benefit from specific attention from all providers. IMPLICATIONS FOR CANCER SURVIVORS: Most CRC survivors are satisfied when their primary care provider becomes responsible for follow-up care. However, this is less true for those who are having more challenges in recovery. These survivors should ensure that information transfer and support services are identified that will smooth this transition.