To examine prevalence and changes in symptoms of psychological distress over 1 year after initial cancer diagnosis in adolescent and young adult (AYA) patients with cancer. Sociodemographic and ...clinical predictors of changes in distress were examined.
In this multisite, longitudinal, prospective study of an ethnically diverse sample, 215 patients age 14 to 39 years were assessed for psychological distress within the first 4 months of diagnosis and again 6 and 12 months later. Linear mixed models with random intercept and slope estimated changes in distress, as measured by the Brief Symptom Inventory-18 (BSI-18).
Within the first 4 months of diagnosis, 60 respondents (28%) had BSI-18 scores suggesting caseness for distress. On average, distress symptoms exceeded population norms at the time of diagnosis, dipped at the 6-month follow-up, but increased to a level exceeding population norms at the 12-month follow-up. A statistically significant decline in distress over 1 year was observed; however, the gradient of change was not clinically significant. Multivariate analyses revealed that the reduction in distress over time was primarily a function of being off treatment and involved in school or work. Notably, cancer type or severity was not associated with distress.
Findings emphasize the importance of early psychosocial intervention for distress in AYAs as well as the need to manage treatment-related symptoms and facilitate AYAs' involvement in work or school to the extent possible. Continued research is needed to understand how distress relates to quality of life, functional outcomes, treatment, and symptom burden throughout the continuum of care.
Summary
Pre‐existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non‐Hodgkin lymphoma (NHL). The ...outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS+) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS−). There were significant baseline differences between the cohorts. CNS+ patients were more likely to be younger, have lower performance scores, higher age‐adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression‐free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS+ group with a subset of CNS− patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS+ patients can achieve excellent long‐term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We outline here the essential elements of training for health care professionals who work with adolescent and young adult (AYA) patients with cancer. Research is emerging that a number of cancers ...manifest themselves differently in the AYA population, both in terms of biology and treatment response. In addition, there are a number of issues uniquely experienced by the AYA population that are critical for health care professionals working within AYA oncology (AYAO) to understand. The LIVESTRONG Young Adult Alliance, a Lance Armstrong Foundation program and a result of the Adolescent and Young Adult Oncology Progress Review Group cosponsored by the Lance Armstrong Foundation and the National Cancer Institute, assembled a group of experts representing relevant medical, psychosocial, and advocacy disciplines to create a blueprint for the training and development of health care professionals caring for AYA patients with cancer. The Alliance recommends that all health care professionals working in AYAO receive training that provides expertise in the following three critical areas: AYA-specific medical knowledge; care delivery specific to AYAs relative to pediatric and older adult populations; and competency in application and delivery of AYA-specific practical knowledge. These three areas should form the foundation for curricula and programs designed to train health care professionals caring for AYAO patients.
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic ...therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies. We demonstrate that the combination of TKIs with venetoclax is highly synergistic in vitro, decreasing cell viability and inducing apoptosis in Ph(+)ALL. Furthermore, the multikinase inhibitors dasatinib and ponatinib appear to have the added advantage of inducing Lck/Yes novel tyrosine kinase (LYN)-mediated proapoptotic BCL-2-like protein 11 (BIM) expression and inhibiting up-regulation of antiapoptotic myeloid cell leukemia 1 (MCL-1), thereby potentially overcoming the development of venetoclax resistance. Evaluation of the dasatinib-venetoclax combination for the treatment of primary Ph(+)ALL patient samples in xenografted immunodeficient mice confirmed the tolerability of this drug combination and demonstrated its superior antileukemic efficacy compared to either agent alone. These data suggest that the combination of dasatinib and venetoclax has the potential to improve the treatment of Ph(+)ALL and should be further evaluated for patient care.
Cancer researchers have found midlife couples to have poorer outcomes compared to older couples due to the off-time nature of the illness for them. It is unknown if young couples (aged 18-39), who ...are under-represented in cancer studies and overlooked for supportive programs, are at further risk. This study explored the moderating roles of survivor age and sex on the associations between active engagement and protective buffering and depressive symptoms in couples surviving cancer.
The exploratory study comprised 49 couples (aged 27-58) 1-3 years post-diagnosis. Multilevel modeling was used to explore the moderating roles of survivor age and sex, controlling for interdependent data.
Approximately, 37% of survivors and 27% of partners met clinical criteria for further assessment of depression, with 50% of couples having at least one member meeting the criteria. Survivors and their partners did not significantly differ on depressive symptoms, active engagement, or protective buffering. Male survivors reported significantly higher levels of active engagement by their partners than female survivors and female survivors reported significantly higher levels of protective buffering by their partners than male survivors. We found some evidence to suggest that survivor age and sex may play moderating roles between active engagement and protective buffering and depressive symptoms. Older partners and female survivors appeared to experience more positive effects from engaging in positive dyadic behaviors than younger partners and male survivors.
Findings not only confirm the important role of dyadic behaviors for couples surviving cancer together, but also the important roles of survivor age and sex may play in whether such behaviors are associated with lower levels of depressive symptoms. Future research that examines these complex associations over time and across the adult life span in diverse populations is needed.
Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of ...patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www.clinicaltrials.gov as NCT00224874.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP