ABSTRACT
Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for posttransplantation maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We, therefore, conducted a phase 2 multicenter study of the anti-PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary end point was progression-free survival (PFS) at 18 months after ASCT. Twenty-one patients were treated in this study and 67% (n = 14) completed 8 cycles of treatment. Among all patients who were evaluable, 13 of 21 were alive and achieved PFS at 18 months after ASCT, meeting the study's primary end point. The estimated 18-month PFS was 83.6% (95% confidence interval [CI], 68-100), and overall survival 94.4% (95% CI, 84-100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab, with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02362997.
Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell, Peripheral , Humans , Disease-Free Survival , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Recurrence, Local/etiology , Transplantation, Autologous , Lymphoma, T-Cell, Peripheral/drug therapy , T-Lymphocytes/pathology , Stem Cell TransplantationABSTRACT
Antibodies targeting PD-1 or 4-1BB achieve objective responses in follicular lymphoma (FL), but only in a minority of patients. We hypothesized that targeting multiple immune receptors could overcome immune resistance and increase response rates in patients with relapsed/refractory FL. We therefore conducted a phase 1b trial testing time-limited therapy with different immunotherapy doublets targeting 4-1BB (utomilumab), OX-40 (ivuxolimab), and PD-L1 (avelumab) in combination with rituximab among patients with relapsed/refractory grade 1-3A FL. Patients were enrolled onto 2 of 3 planned cohorts (cohort 1 - rituximab/utomilumab/avelumab; cohort 2 - rituximab/ivuxolimab/utomilumab). 3+3 dose escalation was followed by dose expansion at the recommended phase 2 dose (RP2D). Twenty-four patients were enrolled (16 in cohort 1 and 9 in cohort 2, with one treated in both cohorts). No patients discontinued treatment due to adverse events and the RP2D was the highest dose level tested in both cohorts. In cohort 1, the objective and complete response rates were 44% and 19%, respectively (50% and 30%, respectively, at RP2D). In cohort 2, no responses were observed. The median progression-free survivals in cohorts 1 and 2 were 6.9 and 3.2 months, respectively. In cohort 1, higher density of PD-1+ tumor-infiltrating T-cells on baseline biopsies and lower density of 4-1BB+ and TIGIT+ T-cells in on-treatment biopsies were associated with response. Abundance of Akkermansia in stool samples was also associated with response. Our results support a possible role for 4-1BB agonist therapy in FL and suggest that features of the tumor microenvironment and stool microbiome may be associated with clinical outcomes (NCT03636503).
Subject(s)
Antineoplastic Agents , Lymphoma, Follicular , Humans , Rituximab , Lymphoma, Follicular/drug therapy , Programmed Cell Death 1 Receptor , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Agents/therapeutic use , Antibodies, Monoclonal/adverse effects , Immunotherapy , Tumor MicroenvironmentABSTRACT
BACKGROUND: Oncologists are often concerned that talking about death with patients may hinder their relationship. However, the views of death held by patients have not been thoroughly investigated. This study aimed to describe the perception of death among patients with advanced cancer receiving early palliative care (EPC) and their caregivers. MATERIAL AND METHODS: Qualitative and quantitative analyses were performed on 2 databases: (a) transcripts of open-ended questionnaires administered to 130 cancer patients receiving EPC with a mean age of 68.4 years and to 115 primary caregivers of patients on EPC with a mean age of 56.8; (b) texts collected from an Italian forum, containing instances of web-mediated interactions between patients and their caregivers. RESULTS: Quantitative analysis shows that: (a) patients and caregivers are not afraid of speaking about death; (b) patients and caregivers on EPC use the word "death" significantly more than patients on standard oncology care (SOC) and their caregivers (Pâ <â .0001). For both participants on EPC and SOC, the adjectives and verbs associated with the word "death" have positive connotations; however, these associations are significantly more frequent for participants on EPC (verbs, Psâ <â .0001; adjectives, Psâ <â .003). Qualitative analysis reveals that these positive connotations refer to an actual, positive experience of the end of life in the EPC group and a wish or a negated event in the SOC group. CONCLUSIONS: EPC interventions, along with proper physician-patient communication, may be associated with an increased acceptance of death in patients with advanced cancer and their caregivers.
Subject(s)
Attitude to Death , Neoplasms , Patients , Aged , Humans , Middle Aged , Caregivers/psychology , Caregivers/statistics & numerical data , Neoplasms/pathology , Neoplasms/therapy , Palliative Care , Patients/psychology , Patients/statistics & numerical data , Physician-Patient RelationsABSTRACT
BACKGROUND: Oncologists' fear of taking away hope from patients when proposing early palliative care (EPC) is a barrier to the implementation of this model. This study explores hope perceptions among bereaved caregivers of onco-hematologic patients who received EPC. MATERIALS AND METHODS: Open-ended questionnaires were administered to 36 primary caregivers of patients who received EPC (26 solid and 10 hematologic cancer patients; mean age: 51.4 years, range age: 20-74), at 2 cancer centers, 2 months to 3 years after a patient death. Definitions of hope in the caregivers' narratives were analyzed through a directed approach to content analysis. Results were complemented with automated lexicographic analysis. RESULTS: Caregivers perceived hope mainly as resilience and as expectations based on what they were told about the patients' clinical conditions. Their hope was bolstered by trusting relationships with the healthcare teams. EPC interventions were recalled as the major support for hope, both during the illness and after the death of the patient. The automated quantitative lexical analysis provided deeper insights into the links between hope, truth, and trust. CONCLUSIONS: Our findings suggest that telling the truth about an incurable onco-hematologic disease and beginning EPC might be the combination of factors triggering hope in the setting of incurable cancer.
Subject(s)
Bereavement , Neoplasms , Oncologists , Adult , Aged , Caregivers , Humans , Middle Aged , Palliative Care , Young AdultABSTRACT
BACKGROUND: Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' "gestalt" assessments. METHODS: Gait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN-based categorizations of oncologists' treatment intensity recommendations, including gait speed. RESULTS: The median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4-0.6 m/s), 34.0 months (0.6-0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6-0.8 m/s: HR, 1.76; 0.4-0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity. CONCLUSION: In older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection.
Subject(s)
Hematologic Neoplasms/therapy , Walking Speed/physiology , Aged , Aged, 80 and over , Female , Hematologic Neoplasms/mortality , Hematologic Neoplasms/physiopathology , Humans , Male , Proportional Hazards ModelsABSTRACT
We undertook a cross-sectional survey of a random sample of thoracic oncologists from the American Society of Clinical Oncology clinical directory to characterize whether prognostic uncertainty has increased and if tolerance of uncertainty is associated with prognostic discussion practices. We also assessed the Physicians' Reactions to Uncertainty Scale and presented a vignette about an incurable patient with uncertain life expectancy. One hundred and ninety-two of 438 surveys (43.8%) were received. Of the respondents, 52.1% agreed "there is more prognostic uncertainty in the management of lung cancer now than 10 years ago," and 37.4% noted difficulty "staying up-to-date." In multivariable analyses, physician-reported anxiety about uncertainty (p = .05) and reluctance to disclose uncertainty (p = .04) were inversely associated with reporting having prognostic discussions with most patients. For the vignette, 92.1% reported they would discuss incurability, but only 76.3% said they would discuss the patient's life expectancy. Our data suggest prognostic uncertainty has increased in thoracic oncology and oncologists' tolerance of uncertainty may affect discussion practices.
Subject(s)
Neoplasms , Oncologists , Attitude of Health Personnel , Cross-Sectional Studies , Humans , Prevalence , Prognosis , Surveys and Questionnaires , UncertaintyABSTRACT
BACKGROUND: Little is known about the underlying mechanisms through which early palliative care (EPC) improves multiple outcomes in patients with cancer and their caregivers. The aim of this study was to qualitatively and quantitatively analyze patients' and caregivers' thoughts and emotional and cognitive perceptions about the disease prior to and during the EPC intervention, and in the end of life, following the exposure to EPC. MATERIALS AND METHODS: Seventy-seven patients with advanced cancer and 48 caregivers from two cancer centers participated in semistructured interviews. Their reports were qualitatively and quantitatively analyzed by the means of the grounded theory and a text-analysis program. RESULTS: Participants reported their past as overwhelmed by unmanaged symptoms, with detrimental physical and psychosocial consequences. The EPC intervention allowed a prompt resolution of symptoms and of their consequences and empowerment, an appreciation of its multidimensional approach, its focus on the person and its environment, and the need for EPC for oncologic populations. Patients reported that conversations with the EPC team increased their acceptance of end of life and their expectation of a painless future. Quantitative analysis revealed higher use of Negative Affects (p < .001) and Biological Processes words (p < .001) when discussing the past; Agency words when discussing the present (p < .001); Positive Affects (p < .001), Optimism (p = .002), and Insight Thinking words (p < .001) when discussing the present and the future; and Anxiety (p = .002) and Sadness words (p = .003) when discussing the future. CONCLUSION: Overall, participants perceived EPC to be beneficial. Our findings suggest that emotional and cognitive processes centered on communication underlie the benefits experienced by participants on EPC. IMPLICATIONS FOR PRACTICE: By qualitative and quantitative analyses of the emotional and cognitive perceptions of cancer patients and their caregivers about their experiences before and during EPC interventions, this study may help physicians/nurses to focus on the disease perception by patients/caregivers and the benefits of EPC, as a standard practice. The analysis of words used by patients/caregivers provides a proxy for their psychological condition and support in tailoring an EPC intervention, based on individual needs. This study highlights that the relationship of the triad EPC team/patients/caregivers may rise as a therapeutic tool, allowing increasing awareness and progressive acceptance of the idea of death.
Subject(s)
Neoplasms , Palliative Care , Advance Directives , Caregivers , Humans , Neoplasms/therapyABSTRACT
Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Hodgkin Disease/drug therapy , Adult , Aged , Consolidation Chemotherapy/methods , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation , Hodgkin Disease/mortality , Hodgkin Disease/surgery , Humans , Male , Middle Aged , Programmed Cell Death 1 Receptor/immunology , Salvage Therapy/methods , Transplantation, AutologousABSTRACT
BACKGROUND: Patients with blood cancers experience high-intensity medical care near the end of life (EOL) and low rates of hospice use; attributes of goals of care (GOC) discussions may partly explain these outcomes. METHODS: By using a retrospective cohort of patients with blood cancer who received care at Dana-Farber Cancer Institute and died in 2014, the authors assessed the potential relationship between timing, location, and the involvement of hematologic oncologists in the first GOC discussion with intensity of care near the EOL and timely hospice use. RESULTS: Among 383 patients, 39.2% had leukemia/myelodysplastic syndromes, 37.1% had lymphoma, and 23.7% had myeloma. Overall, 65.3% of patients had a documented GOC discussion. Of the first discussions, 33.2% occurred >30 days before death, 34.8% occurred in the outpatient setting, and 46.4% included a hematologic oncologist. In multivariable analyses, having the first discussion >30 days before death (odds ratio [OR], 0.37; 95% CI, 0.17-0.81), in the outpatient setting (OR, 0.21; 95% CI, 0.09-0.50), and having a hematologic oncologist present (OR, 0.40; 95% CI, 0.21-0.77) were associated with lower odds of intensive care unit admission ≤30 days before death. The presence of a hematologic oncologist at the first discussion (OR, 3.07; 95% CI, 1.58-5.96) also was associated with earlier hospice use (>3 days before death). CONCLUSIONS: In this large cohort of blood cancer decedents, most initial GOC discussions occurred close to death and in the inpatient setting. When discussions were timely, outpatient, or involved hematologic oncologists, patients were less likely to experience intensive health care use near death and were more likely to enroll in hospice.
Subject(s)
Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Terminal Care , Aged , Female , Hematologic Neoplasms/pathology , Hospices , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Patient Care PlanningABSTRACT
Patients with advanced myeloma experience a high symptom burden particularly near the end of life, making timely hospice use crucial. Little is known about the quality and determinants of end-of-life care for this population, including whether potential increases in hospice use are also accompanied by "late" enrollment (≤ 3 days before death). Using the Surveillance, Epidemiology, and End-Results-Medicare database, we identified patients ≥ 65 years diagnosed with myeloma between 2000 and 2013 who died by December 31, 2013. We assessed prevalence and trends in hospice use, including late enrollment. We also examined six established measures of potentially aggressive medical care at the end of life. Independent predictors of late hospice enrollment and aggressive end-of-life care were assessed using multivariable logistic regression analyses. Of 12,686 myeloma decedents, 48.2% enrolled in hospice. Among the 6111 who enrolled, 17.2% spent ≤ 3 days there. There was a significant trend in increasing hospice use, from 28.5% in 2000 to 56.5% by 2013 (Ptrend <0.001), no significant rise in late enrollment (12.2% in 2000 to 16.3% in 2013, Ptrend =0.19), and a slight decrease in aggressive end-of-life care (59.2% in 2000 to 56.7% in 2013, Ptrend =0.01). Patients who were transfusion-dependent, on dialysis, or survived for less than one year were more likely to enroll late in hospice and experience aggressive medical care at the end of life. Gains in hospice use for myeloma decedents were not accompanied by increases in late enrollment or aggressive medical care. These findings suggest meaningful improvements in end-of-life care for this population.
Subject(s)
Hospice Care/trends , Multiple Myeloma/therapy , Terminal Care/trends , Aged , Aged, 80 and over , Blood Transfusion , Female , Hospice Care/statistics & numerical data , Humans , Male , Medicare , Quality of Health Care , Renal Dialysis , SEER Program , Terminal Care/statistics & numerical data , United StatesABSTRACT
BACKGROUND: Although patients with blood cancers have significantly lower rates of hospice use than those with solid malignancies, data explaining this gap in end-of-life care are sparse. METHODS: In 2015, we conducted a mailed survey of a randomly selected sample of hematologic oncologists in the United States to characterize their perspectives regarding the utility and adequacy of hospice for blood cancer patients, as well as factors that might impact referral patterns. Simultaneous provision of care for patients with solid malignancies was permitted. RESULTS: We received 349 surveys (response rate, 57.3%). The majority of respondents (68.1%) strongly agreed that hospice care is helpful for patients with hematologic cancers; those with practices including greater numbers of solid tumor patients (at least 25%) were more likely to strongly agree (odds ratio, 2.10; 95% confidence interval, 1.26-3.52). Despite high levels of support for hospice in general, 46.0% felt that home hospice is inadequate for their patients' needs (as compared to inpatient hospice with round-the-clock care). Although more than half of the respondents reported that they would be more likely to refer patients to hospice if red cell and/or platelet transfusions were available, those who considered home hospice inadequate were even more likely to report that they would (67.3% vs 55.3% for red cells [P = .03] and 52.9% vs 39.7% for platelets [P = .02]). CONCLUSIONS: These data suggest that although hematologic oncologists value hospice, concerns about the adequacy of services for blood cancer patients limit hospice referrals. To increase hospice enrollment for blood cancer patients, interventions tailoring hospice services to their specific needs are warranted. Cancer 2017;123:3377-84. © 2017 American Cancer Society.
Subject(s)
Cause of Death , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hospice Care/statistics & numerical data , Palliative Care/statistics & numerical data , Surveys and Questionnaires , Adult , Analysis of Variance , Critical Illness/therapy , Female , Health Care Surveys , Hematologic Neoplasms/diagnosis , Humans , Male , Medical Oncology/ethics , Middle Aged , Multivariate Analysis , Practice Patterns, Physicians' , Terminal Care/methods , United StatesABSTRACT
Although hematopoietic cell transplantation (HCT) is the only curative therapy for many advanced hematologic cancers, little is known about the financial hardship experienced by HCT patients nor the association of hardship with patient-reported outcomes. We mailed a 43-item survey to adult patients approximately 180 days after their first autologous or allogeneic HCT at 3 high-volume centers. We assessed decreases in household income; difficulty with HCT-related costs, such as need to relocate or travel; and 2 types of hardship: hardship_1 (reporting 1 or 2 of the following: dissatisfaction with present finances, difficulty meeting monthly bill payments, or not having enough money at the end of the month) and "hardship_2" (reporting all 3). Patient-reported stress was measured with the Perceived Stress Scale-4, and 7-point scales were provided for perceptions of overall quality of life (QOL) and health. In total, 325 of 499 surveys (65.1%) were received. The median days since HCT was 173; 47% underwent an allogeneic HCT, 60% were male, 51% were > 60 years old, and 92% were white. Overall, 46% reported income decline after HCT, 56% reported hardship_1, and 15% reported hardship_2. In multivariable models controlling for income, those reporting difficulty paying for HCT-related costs were more likely to report financial hardship (odds ratio, 6.9; 95% confidence interval, 3.8 to 12.3). Hardship_1 was associated with QOL below the median (odds ratio, 2.9; 95% confidence interval, 1.7 to 4.9), health status below the median (odds ratio, 2.2; 95% confidence interval, 1.3 to 3.6), and stress above the median (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.5). In this sizable cohort of HCT patients, financial hardship was prevalent and associated with worse QOL and higher levels of perceived stress. Interventions to address patient financial hardship-especially those that ameliorate HCT-specific costs-are likely to improve patient-reported outcomes.
Subject(s)
Hematopoietic Stem Cell Transplantation/economics , Patient Reported Outcome Measures , Quality of Life , Aged , Aged, 80 and over , Costs and Cost Analysis , Female , Health Status , Hematopoietic Stem Cell Transplantation/psychology , Humans , Income , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
BACKGROUND: As the population ages, the prevalence of myelodysplastic syndromes (MDS) will increase, and many patients with MDS will require end-of-life (EOL) care. Little is known about the intensity of EOL care received by patients with these malignancies. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database and standard EOL quality measures, we assessed the prevalence and predictors of intensive care unit (ICU) admission in the last 30 days of life, chemotherapy in the last 14 days of life, and hospice enrollment among MDS patients who were 65 years old or older and died between 2006 and 2011. RESULTS: Of 6,955 patients, 28% were admitted to the ICU and 7% received chemotherapy near the EOL, while 49% enrolled in hospice. In multivariable models, patients dependent on red blood cell or platelet transfusions at the EOL were less likely to enroll in hospice (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.61-0.78). Nonwhite patients were less likely to enroll in hospice (OR, 0.77; 95% CI, 0.67-0.89) and more likely to be admitted to the ICU near the EOL (OR, 1.19; 95% CI, 1.03-1.38). Finally, the prevalence of hospice enrollment increased in later years (P < .001). CONCLUSIONS: The intensity of EOL care for patients with MDS varies but is potentially suboptimal with respect to the traditional measure of hospice use. The lower odds of enrollment for transfusion-dependent patients suggest that the current hospice model, which largely disallows transfusions, may not be meeting the palliative needs of this population.
Subject(s)
Cause of Death , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Quality of Health Care , Terminal Care/methods , Age Factors , Aged , Aged, 80 and over , Critical Illness/therapy , Databases, Factual , Female , Hospice Care/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Logistic Models , Male , Multivariate Analysis , Myelodysplastic Syndromes/pathology , Odds Ratio , Patient Care Team/organization & administration , Retrospective Studies , Risk Assessment , SEER Program , Sex Factors , Survival Analysis , United StatesABSTRACT
Little is known about quality of care for patients with myelodysplastic syndromes (MDS), or patient and provider factors that influence quality. We identified Medicare enrollees diagnosed with MDS between 2006 and 2011, and analysed linked claims for performance on two widely-accepted quality measures: diagnostic bone marrow cytogenetic testing (diagnostic quality) and pre-treatment iron assessment for patients receiving an erythropoiesis-stimulating agent (ESA; treatment quality). A total of 4575 patients met the criteria for diagnostic quality measurement, and 3379 for treatment quality measurement. In the diagnostic cohort, 74% had a claim for marrow cytogenetic testing 3 months before to 3 months after diagnosis. In multivariate models, younger age (P < 0·001), treatment at a higher-volume MDS centre (P < 0·001), and claims for pancytopenia (P < 0·001) were all associated with higher levels of testing. A borderline result was observed for diagnostic year, with improvement over time (P = 0·06). In the treatment cohort, 56% had evidence of pre-ESA iron assessment, with higher rates for later years of diagnosis (P < 0·001), higher household income (P = 0·03), and those treated at higher-volume centres (P = 0·01). In this large cohort of patients with MDS, quality of care was suboptimal overall, but worse in several specific subgroups. These data suggest that targeted educational and/or process-focused interventions are warranted.
Subject(s)
Medicare/standards , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/therapy , Quality of Health Care/standards , Aged , Aged, 80 and over , Bone Marrow Examination , Cohort Studies , Cytogenetics , Female , Hematinics , Humans , Iron/analysis , Male , Quality Indicators, Health Care/standards , United StatesABSTRACT
The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.
Subject(s)
Immunoblastic Lymphadenopathy/genetics , Lymphoma, T-Cell/genetics , Mutation , Adult , Aged , Aged, 80 and over , Cohort Studies , DNA Mutational Analysis , Female , Gene Frequency , Humans , Immunoblastic Lymphadenopathy/epidemiology , Lymphoma, T-Cell/epidemiology , Male , Middle AgedABSTRACT
There are no "benign lymphomas", a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH translocations associated with the in situ forms of follicular lymphoma and mantle cell lymphoma, respectively. There are other clonal B-cell proliferations with low risk of progression; these include the pediatric variants of follicular lymphoma and marginal zone lymphoma. Historically, early or incipient forms of T/NK-cell neoplasia also have been identified, such as lymphomatoid papulosis and refractory celiac disease. More recently an indolent form of T-cell lymphoproliferative disease affecting the gastrointestinal tract has been described. Usually, CD8(+), the clonal cells are confined to the mucosa. The clinical course is chronic, but non-progressive. NK-cell enteropathy is a clinically similar condition, composed of cytologically atypical NK-cells that may involve the stomach, small bowel or colon. Breast implant-associated anaplastic large cell lymphoma is a cytologically alarming lesion that is self-limited if confined to the seroma cavity. Atypical lymphoid proliferations that lie at the border of benign and malignant can serve as instructive models of lymphomagenesis. It is also critical that they be correctly diagnosed to avoid unnecessary and potentially harmful therapy.
Subject(s)
B-Lymphocytes/pathology , Lymphoma/diagnosis , T-Lymphocytes/pathology , Antigens, CD/metabolism , Antineoplastic Agents/therapeutic use , B-Lymphocytes/metabolism , Biomarkers/metabolism , Cell Proliferation , Clone Cells , Early Diagnosis , Gene Expression , Humans , Immunophenotyping , Lymphoma/classification , Lymphoma/pathology , Lymphoma/therapy , T-Lymphocytes/metabolism , Translocation, GeneticABSTRACT
Patients with hematologic malignancies experience high rates of depression. These patients are vulnerable to depression throughout the disease trajectory, from diagnosis to survivorship, and at the end of life. In addition to the distressing nature of depression, it has substantial downstream effects including poor quality of life, increased risk of treatment complications, and worse survival. Therefore, systematic screening for depression and integration of robust psychological interventions for affected patients is crucial. Although depression has been historically studied mostly in patients with solid malignancies, research focusing on patients with hematologic malignancies is growing. In this article, we describe what is known about depression in patients with hematologic malignancies, including its assessment, prevalence, risk factors, and implications. We also describe interventions to ameliorate depression in this population. Future research is needed to test effective and scalable interventions to reduce the burden of depression among patients with blood cancers.
Subject(s)
Hematologic Neoplasms , Neoplasms , Humans , Quality of Life , Depression/diagnosis , Depression/epidemiology , Depression/etiology , Hematologic Neoplasms/complications , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , SurvivorshipABSTRACT
OBJECTIVE: This article reports on the results of an analysis of metaphorical language used by patients diagnosed with advanced cancer and their caregivers receiving early palliative care (EPC). METHODS: Data were collected through a pen-and-paper questionnaire on respondents' perceptions of the disease, its treatment and their idea of death, before and after receiving EPC. The data were analysed by identifying all metaphorical uses of language, following the 'metaphor identification procedure' proposed by the Praggjelaz Group. RESULTS: Metaphors were used from a variety of semantic fields. EPC was described using spiritual terms, to indicate that this approach was instrumental in 'restoring life', 'producing hope' and making patients feel 'accompanied'. The most recurrent metaphors were those referring to light and salvation; spatial metaphors were used to describe the treatment and the hospital as a 'safe haven' and 'an oasis of peace'. Patients and caregivers were overall consistent in the aforementioned ways of referring to illness and treatment; caregivers were more likely than patients to use war metaphors, although their use overall was rare. CONCLUSIONS: Our results suggest that EPC is perceived positively by patients and their caregivers and provide insights regarding the manner in which EPC could be presented to patients, caregivers and the public.
ABSTRACT
CONTEXT: Patients with blood cancers have low rates of hospice use. While lack of transfusion access in hospice is posited to substantially contribute to these low rates, little is known about the perspectives of hospice providers regarding transfusion access in hospice. OBJECTIVES: To characterize hospice providers' perspectives regarding care for patients with blood cancers and transfusions in the hospice setting. METHODS: In 2022, we conducted a cross-sectional survey of a sample of hospices in the United States regarding their experience caring for patients with blood cancers, perceived barriers to hospice use, and interventions to increase enrollment. RESULTS: We received 113 completed surveys (response rate = 23.5%). Of the cohort, 2.7% reported that their agency always offers transfusions, 40.7% reported sometimes offering transfusions, and 54.9% reported never offering transfusions. In multivariable analyses, factors associated with offering transfusions included nonprofit ownership (OR 5.93, 95% CI, 2.2-15.2) and daily census >50 patients (OR 3.06, 95% CI, 1.19-7.87). Most respondents (76.6%) identified lack of transfusion access in hospice as a barrier to hospice enrollment for blood cancer patients. The top intervention considered as "very helpful" for increasing enrollment was additional reimbursement for transfusions (72.1%). CONCLUSION: In this national sample of hospices, access to palliative transfusions was severely limited and was considered a significant barrier to hospice use for blood cancer patients. Moreover, hospices felt increased reimbursement for transfusions would be an important intervention. These data suggest that hospice providers are supportive of increasing transfusion access and highlight the critical need for innovative hospice payment models to improve end-of-life care for patients with blood cancers.