scholarly journals How I treat high-risk myeloma

Blood ◽  
2015 ◽  
Vol 126 (13) ◽  
pp. 1536-1543 ◽  
Author(s):  
Sagar Lonial ◽  
Lawrence H. Boise ◽  
Jonathan Kaufman
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Treatment Approach ◽  
Potential Treatment ◽  
Future Directions ◽  
New Agents ◽  
The Past ◽  
Term Maintenance ◽  
Term Benefit

Abstract The treatment of patients with myeloma has dramatically changed over the past decade due in part to the development of new agents and myeloma-specific targets. Despite these advancements, a group for whom the long-term benefit remains less clear are patients with genetically or clinically defined high-risk myeloma. In order to successfully treat these patients, it is important to first identify these patients, treat them with aggressive combination therapy, and employ the use of aggressive long-term maintenance therapy. Future directions include the use of new immune-based treatments (antibodies or cellular-based therapies) as well as target-driven approaches. Until these treatment approaches are better defined, this review will provide a potential treatment approach for standard- and high-risk myeloma that can be followed using agents and strategies that are currently available with the goal of improving progression-free and overall survival for these patients today.

scholarly journals Attachment and relationships: Milestones and future directions

2010 ◽  
Vol 27 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Jeffry A. Simpson ◽  
W. Steven Rholes
Keyword(s):  
Health Outcomes ◽  
Attachment Theory ◽  
Adult Attachment ◽  
Future Research ◽  
Future Directions ◽  
The Past

Adult attachment researchers have made important strides during the past 25 years in testing and applying attachment theory to multiple personal and interpersonal domains. We highlight some of the major milestones and then propose several directions for future research. Some of the most important and promising directions include testing additional normative processes implied by attachment theory, developing and testing critical connections between attachment theory and other major interpersonal theories, and identifying pathways between attachment processes and long-term health outcomes.

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

Oligodendroglial tumours

2017 ◽  
Author(s):  
Wolfgang Wick ◽  
Colin Watts ◽  
Minesh P. Mehta
Keyword(s):  
Overall Survival ◽  
Randomized Trials ◽  
Current Standard ◽  
Future Directions ◽  
Imaging Parameters ◽  
Term Evaluation ◽  
Molecular Information ◽  
Translational Studies ◽  
Definition Of

Concepts of diagnosis and treatment of oligodendroglial tumours have changed through clinical and translational studies over recent years. Diagnosis is now based on histopathological and integrated molecular information. The latter includes mutations in isocitrate dehydrogenase and the co-deletion of 1p/19q in the tumour tissue. In parallel, the long-term evaluation of large randomized trials performed in Europe and North America led to the current standard of a more aggressive chemoradiation regimen with procarbazine, CCNU (lomustine), and vincristine to optimize progression-free and overall survival. The future directions are delineated, which are aiming at further definition of prognostic and predictive subgroups, based on clinical, molecular, and imaging parameters, integrating immunotherapeutic concepts, as well as a closer look at patient-centred outcomes in upcoming trials.

Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine and Melphalan (FM) Reduced Intensity Conditioning (RIC) for High-Risk AML/MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 838-838
Author(s):  
B. Oran ◽  
R. Saliba ◽  
S. Giralt ◽  
D. Couriel ◽  
A. Carrasco-Yalan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
High Risk ◽  
Disease Progression ◽  
Disease Status ◽  
Independent Effect ◽  
Donor Type

Abstract RIC with FM has extended the use of HSCT to patients otherwise not eligible for this treatment. Longer follow-up and larger number of patients now allow for more robust evaluation of risk factors and outcomes. Herein are the results of such an evaluation. Patients and Methods: We evaluated outcomes of 112 patients with high-risk AML/MDS treated from August 1996 to December 2003 with FM (fludarabine 100–180 mg/m2 and melphalan 100–180 mg/m2) and unmanipulated HSCT. Eligibility included age >54 yrs. or comorbidity precluding an ablative preparative regimen. Disease status at HSCT was relapsed/refractory (n=43, 38.4%), primary induction failure (n=32, 28.6%), untreated (n=7, 6.3%) or complete remission (CR, n=30, 26.8). Cytogenetic risk was intermediate (n=59, 53%), high (n=47, 42%), low (n=3, 2.5%) or unknown (n=3, 2.5%). Donors were HLA matched related (MRD; n=59) or unrelated (UD; n=53). GVHD prophylaxis was tacrolimus based in all but one patient. Anti-thymocyte-globulin was added in 31 UD HSCT. Stem cell sources were bone marrow (n=56) or peripheral blood (n=57). Median age was 55 (range 22–74). Evaluated were the following variables and their influence on disease progression and overall survival: - age, donor type, duration of first CR, disease status at transplant (categorized as CR, No CR with (NoCR/CB) and without circulating blasts (NoCR/NoCB)), cytogenetics, acute and chronic GVHD (time dependent variables), and blood counts on day 30 (lymphocytes, monocytes and platelets). We used a Cox’s regression analysis. Results: Median time of follow up among survivors (n=43) was 28.4 mo (3.3–88.9). CR rate at day 30 post transplant was 87% (n=97), 8 patients died early and 7 did not respond. 25 (26%) of 97 patients progressed after day 30. All but 3 patients relapsed within the first year post HSCT, and only one relapsed more than 2 years after HSCT. In a landmark analysis, disease status at transplant was the only significant risk factor for progression among these 97 patients (HR of 3.7 for the NoCR/CB group compared to the CR group). 69 of 112 patients died with a median survival of 4.6 mo. Seven deaths (10% of all deaths) were observed more than 2 yrs. after HSCT, due to GVHD (n=3), infection (n=2), relapse (n=1) and unknown causes (n=1). Two-year OS and PFS was 44% and 69% respectively. Disease status at HSCT and grade II-IV aGVHD were the only significant predictors of OS on univariate and multivariate analysis. Blood counts on day 30 were associated with disease status at transplant, donor type and aGVHD. Their independent effect on outcome could not be evaluated given sample size. Conclusion: A significant portion of older patients with high-risk AML/MDS may achieve long-term PFS, but early relapses are the major cause of treatment failure in this context. Prognostic factors for event-free and overall survival Variables Multivariate analysis for disease progression CB=circulating blasts Disease status n Events (n) HR 95% CI p 2-yr PFS CR 30 6 1.0 57% (39–72) NoCR/NoCB 41 7 1.1 0.4–3.2 0.9 46% (30–60) NoCR/CB 26 12 3.7 1.4–9.8 0.001 22% (9–38) Multivariate analysis for overall survival (OS) Disease status HR 95% CI p 2-yr OS CR 30 12 1.0 66% (48–80) NoCR/NoCB 49 29 1.8 0.9–3.5 0.06 40% (26–53) NoCR/CB 34 28 2.8 1.4–3.5 0.002 23% (11–37) gd II-IV aGVHD 2.8 1.8–4.6 <0.001

Intensive Asparaginase Therapy in Young Adult Patients with Acute Lymphoblastic Leukemia: Treatment Patterns and Barriers to Asparaginase Use

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4913-4913
Author(s):  
Leonard S Sender ◽  
Tina Doede ◽  
Megan P. Hall ◽  
Celine Bernard
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Young Adult ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Employment Equity ◽  
Term Survival ◽  
The Past ◽  
Equity Ownership

Abstract Background : Although considerable progress has been made in treating acute lymphoblastic leukemia (ALL) in the pediatric population, with long-term survival exceeding 80%, the prognosis for adolescents, young adult, and adult patients with ALL remains poor, with only 30%-45% of patients achieving long-term survival. Several studies suggest that young adult patients have superior overall survival when treated with intensive "pediatric-inspired" regimens that include the use of asparaginase [Dombret H, et al. Curr Hematol Malig Rep. 2014;9(2):158-164]. Despite these results, many young adult patients with ALL continue to be treated with chemotherapy regimens that include little or no asparaginase. The goal of this study was to assess the views and practices of hematologists and oncologists with respect to asparaginase use in young adult patients with ALL. Methods : This study was conducted between May 14 and June 22, 2015, and consisted of a 10-minute online quantitative survey, with a 10-minute per-patient chart audit component for up to 4 charts provided by participating physicians. The survey targeted physicians treating young adult patients (aged 18-40 years) with ALL. To be included in the final analysis, physicians were required to be board certified with 2-30 years in practice, with ≥75% of their time spent in direct patient care and ≥20% of their time spent in an academic setting (NCCN/NCI or academic/teaching hospital). Inclusion criteria also required that physicians' total ALL patient volume (young adults and adults aged >40 years) was greater than 5 over the past 2 years, that the physician primarily treats adult patients, and has personally managed and treated at least 1 young adult ALL patient in the past 2 years. Results: The study included results reported by a total of 63 practicing physicians for 189 young adult patients with ALL (62% were aged 25-40 years). Sixty percent (114/189) of young adult patients were treated with a protocol that included asparaginase, and only 29% (55/189) on a pediatric-inspired protocol. The most common protocols reported for patients receiving asparaginase included the pediatric-inspired CALGB 10403 (18%, 21/114), as well as regimens with more limited asparaginase use, including augmented hyper-CVAD (29%, 33/114) and CALGB 8811 (12%, 14/114). Overall 40% (75/189) of young adult patients were treated with protocols that did not include asparaginase, most commonly hyper-CVAD (77%, 58/75). Fifty percent (18/36) of responding physicians using hyper-CVAD reported the perception of similar outcomes with nonasparaginase regimens as with asparaginase-intensive regimens. When questioned about the greatest barrier to the use of intensive asparaginase-containing regimens, 88% (7/8) of responding physicians reported safety and tolerability concerns. Conclusion: Only 6 out of 10 patients in the study were treated with an asparaginase-containing regimen; of all patients, less than 1 out of 3 received a pediatric-inspired regimen. Fifty-three percent (60/114) of asparaginase-receiving patients were treated on a regimen that structures asparaginase dosing intermittently between alternating courses. Pediatric-inspired regimens include intensive asparaginase therapy and have consistently shown improvements in overall survival when compared with traditional adult protocols in clinical trials [Dombret H, et al. Curr Hematol Malig Rep. 2014;9(2):158-164]. Support: This study was funded by Jazz Pharmaceuticals. Disclosures Sender: Jazz Pharmaceuticals: Research Funding, Speakers Bureau. Doede:Jazz Pharmaceuticals: Employment, Equity Ownership. Hall:Jazz Pharmaceuticals: Employment, Equity Ownership. Bernard:Jazz Pharmaceuticals: Employment, Equity Ownership.

Adjuvant Chemotherapy in Patients with Osteosarcoma

2011 ◽  
Vol 07 (03) ◽  
pp. 183
Author(s):  
Noah Federman ◽  
William Tap ◽  
◽  
Keyword(s):  
Young Adults ◽  
Adjuvant Chemotherapy ◽  
Malignant Neoplasm ◽  
Chemotherapeutic Agents ◽  
Term Survival ◽  
Future Directions ◽  
The Past ◽  
Metastatic Osteosarcoma ◽  
Improvement In Survival

Osteosarcoma is the most common primary malignant neoplasm of bone in children, adolescents and young adults. Prior to 1970, the outcome for patients with osteosarcoma was dismal, with only 10–20 % of patients achieving long-term survival. The improvement in survival over the past four decades, now approaching 75 %, has largely been due to the addition of adjuvant chemotherapy to surgery. However, for patients that have metastatic osteosarcoma or recurrence of their cancer, the outlook is poor and the prognosis has not improved over the past several decades, despite the advent and use of newer chemotherapeutic agents and combinations. This review will focus on the current chemotherapeutic treatments of localised osteosarcoma, the controversies surrounding adjuvant therapy and future directions and additions to our armamentarium.

scholarly journals Recent advances in the management of renal cell carcinoma

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 391 ◽  
Author(s):  
Ana M. Molina ◽  
David M. Nanus
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Therapeutic Options ◽  
New Agents ◽  
The Past ◽  
Recent Advances

Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival.

scholarly journals Disparities in Cancer-Related Mortality and Long-Term Survival in Adolescent and Young Adults with Hodgkin Lymphoma: A Population-Level Analysis across the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4866-4866
Author(s):  
Justine M. Kahn ◽  
Theresa H.M. Keegan ◽  
Elysia Alvarez ◽  
Lori S Muffly ◽  
Helen Parsons ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Diagnosis ◽  
The United States ◽  
Term Survival ◽  
The Past ◽  
After Cancer ◽  
Year 2000 ◽  
Racial Ethnic ◽  
Cause Specific Survival

Abstract Background: Hodgkin lymphoma (HL) is one of the most common, and one of the most curable cancers in adolescents and young adults (AYAs) (15-39 years). Despite excellent outcomes in the majority of patients, the burden of long-term morbidity and mortality persists. Prior analyses of patients treated for HL before the year 2000 have reported mortality rates as high as 30% by 20 years. Further, this mortality risk has historically differed across different racial and ethnic groups. Over the past decade, cooperative groups have expanded the use of risk-adapted, response-based treatment in an effort to maintain high cure rates, while simultaneously reducing the burden of late effects. We examined long-term survival in AYAs with HL treated after the year 2000. Methods: We used the National Cancer Institute Surveillance, Epidemiology, and End Results registry data for 18 regions in the United States (SEER18) to examine survival in AYAs with a confirmed diagnosis of HL between 2000 and 2015. We obtained overall and cause-specific survival estimates for each year after cancer diagnosis (up to 15 years) for each racial/ethnic group with corresponding 95% confidence intervals. From these yearly survival estimates, we calculated the percentage of deaths not attributed to HL at 10- and 15-years after cancer diagnosis. Results: The final analysis included 16,868 HL patients. Racial/ethnic subgroups included: non-Hispanic white (NHW; 11,016, 65%), Hispanic (2,753, 16%), non-Hispanic black (NHB; 2,131, 13%), and Asian/Pacific Islander (API; 968, 6%) AYAs with HL. Across the full cohort, the 10-year and 15-year overall survival probabilities were 90% (95% confidence interval [95%CI]: 89 - 91) and 87% (95% CI: 86 - 88), respectively. At 10- and 15-years, overall survival was highest for NHWs (10-year: 92%: 15-year: 88%) and APIs (91%; 86%) compared to Hispanics (87%; 85%) and NHBs (82%; 78%). Overall survival, cause-specific survival, and percentage of deaths not attributed to HL by race/ethnicity are presented in the Figure. In the first year after diagnosis, 22% of deaths were due to causes other than primary disease, with the percentage of deaths not attributed to HL higher in NHWs and APIs than Hispanics and NHBs. At most time points after cancer diagnosis, a higher proportion of NHW (vs. NHB, Hispanic and API) patients died from causes other than HL. By 10 years after diagnosis, 25% of NHW patients died due to causes other than HL, vs. 20% in API, 17% in NHB, and 15% in Hispanic patients. By 15 years, 33% of all deaths were not attributed to HL. This was observed most dramatically in the NHW cohort in whom 40% of all deaths were not HL-related, compared to 24% of deaths in the NHB cohort and 26% - 27% of deaths in the Hispanic and API groups. Conclusion: In AYAs diagnosed with HL between 2000 and 2015, NHB patients had worse survival compared with NHW and API patients. The higher probability of survival in NHW patients was accompanied by a consistently higher proportion of non-cancer related death in this cohort both 10- years and 15-years after diagnosis. Studies are needed to evaluate risk factors for both short- and long-term mortality in AYAs, and to examine how these risks differ across racial/ethnic groups. Findings also suggest that despite increasing use of response-adapted therapy over the past two decades, all AYAs with HL remain at risk of death in the decades following therapy, further highlighting the need for long-term follow-up of this at-risk patient population. Figure. Figure. Disclosures Muffly: Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Research Funding.

scholarly journals Permanent Bilateral Carotid Filters for Stroke Prevention in Atrial Fibrillation

2020 ◽  
Vol 22 (11) ◽  
Author(s):  
Tom De Potter ◽  
Ofer Yodfat ◽  
Guy Shinar ◽  
Avraham Neta ◽  
Vivek Y. Reddy ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
High Risk ◽  
Stroke Prevention ◽  
Control Group ◽  
Future Directions ◽  
Mechanical Filter ◽  
Bilateral Carotid ◽  
The Common

Abstract Purpose of Review A novel permanent carotid filter device for percutaneous implantation was developed for the purpose of stroke prevention. In this review, we cover rationale, existing preclinical and clinical data, and potential future directions for research using such a device. Recent Findings The Vine™ filter was assessed for safety in sheep and in 2 observational human studies, the completed CAPTURE 1 (n = 25) and the ongoing CAPTURE 2 (planned n = 100). CAPTURE 1 has shown high procedural and long-term implant safety. A control group was not available for comparison. Summary A mechanical filter for permanent stroke prevention can be implanted bilaterally in the common carotid artery safely and efficiently. A randomized trial is planned for 2021 (n = 3500, INTERCEPT) to demonstrate superiority of a filter + anticoagulation strategy over anticoagulation alone in patients at high risk for ischemic stroke.

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