Purpose-To investigate the molecular mechanism underlying intrinsic resistance to Experimental Design-Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after Conclusions-Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML.
HHS Public AccessAuthor manuscript Clin Cancer Res. Author manuscript; available in PMC 2017 September 01.
This Phase I study of clofarabine with etoposide and cyclophosphamide for children with relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities and the recommended phase 2 doses (RP2Ds). All three drugs were administered for five consecutive days in induction and four consecutive days in consolidation, for a maximum of eight cycles. A total of 25 patients (20 ALL and 5 AML) were enrolled in five cohorts. An MTD was not reached. The RP2Ds of clofarabine, cyclophosphamide and etoposide were 40, 440 and 100 mg/m 2 /day, respectively. Complete remission (CR) was achieved in 10 patients (ALL: nine; AML: one), and CR without platelet recovery in six patients (ALL: two; AML: four) for an overall response rate of 64% (ALL: 55%; AML: 100%). Of the 16 responders, 9 patients proceeded to hematopoietic stem cell transplantation. In conclusion, the combination of clofarabine, etoposide and cyclophosphamide was well tolerated and effective in pediatric patients with relapsed/refractory leukemia. Of note, the phase II portion of the trial was amended after the occurrence of unexpected hepatotoxicity. The ongoing phase II study will evaluate the efficacy and safety of this regimen in ALL patients.
Purpose
Adolescent and young adult (AYA) cancer survivors experience barriers to utilizing healthcare, but the determinants of cancer-related medical care of AYAs has not been fully explored.
Methods
We studied factors associated with medical care utilization among 465 AYA cancer survivors in the AYA Health Outcomes and Patient Experience Study (AYA HOPE), a cohort of 15 to 39 year-olds recently diagnosed with germ cell cancer, lymphoma, sarcoma, or acute lymphocytic leukemia. Descriptive statistics and multivariate logistic regression methods were used.
Results
Most AYA cancer survivors (95%), who were 15–35 months post diagnosis, received medical care in the past 12 months and 17% were undergoing cancer treatment. In multivariate analyses, compared with AYAs with no cancer-related medical visits in the previous year, AYAs receiving cancer-related care were more likely to currently have health insurance (odds ratio (OR) = 4.9; 95% confidence interval (CI): 1.7–13.8) or have had health insurance in the past year (OR= 4.0; 95% CI: 0.99–16.3). Cancer recurrence, lacking employment and negative changes in self-reported general health were associated with ongoing cancer treatment versus other cancer-related medical care. 11% of all AYAs and 25% of AYAs who did not receive medical care in the past 12-months lost health insurance between the initial and follow-up surveys.
Conclusion
AYA cancer survivors with health insurance were much more likely to receive cancer-related medical care than those without insurance.
Implications for Cancer Survivors
Despite the need for post-treatment medical care, lacking health insurance is a barrier to receiving any medical care among AYAs.
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