Western Pennsylvania Cancer Institute
Western Pennsylvania Cancer Institute
Shammo J.M.,Rush University Medical Center |
Foran J.M.,University of Alabama at Birmingham |
Houk A.,Aplastic Anemia and MDS International Foundation |
Epstein J.,Imedex LLC |
And 5 more authors.
Cancer Control | Year: 2011
Background: Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematologic malignancies, with an incidence rate of 3.4 cases per 100,000 in the United States. MDS affects patients predominantly over 60 years of age. As these syndromes are not well understood by many medical practitioner, patients with MDS may be underrecognized or underdiagnosed. The availability of new MDS treatment options further establishes the need to more closely assess gaps in clinical practice and underscores the necessity to develop educational activities to address those gaps. Methods: A multidisciplinary panel was convened to examine current educational needs and gaps. A group consensus approach incorporating a modified nominal group technique was utilized to prioritize and review needs identified in the pre-meeting survey and to evaluate data provided by panelists prior to the meeting. Results: The panel identified and prioritized seven educational areas of need: (1) MDS disease awareness, (2) diagnosis, (3) classification and risk stratification, (4) treatment issues, (5) referral to stem cell transplantation or new treatment protocols, (6) clinical monitoring and toxicity management, and (7) translation of new data into patient care. Conclusions: In-depth knowledge is critical to the timely diagnosis and optimal care of MDS patients. A number of key educational needs exist. Educational programs should be practical in orientation to integrate data into practice, and they should be tailored for the intended audience. In addition, an effective educational program must be easily applied by participants.
Wang M.,University of Houston |
Popplewell L.L.,City of Hope National Medical Center |
Collins R.H.,University of Texas Southwestern Medical Center |
Winter J.N.,Northwestern University |
And 15 more authors.
British Journal of Haematology | Year: 2014
The multicentre, open-label, two-stage, single-arm, phase 2, PILLAR (PIvotaL Lymphoma triAls of RAD001)-1 study (NCT00702052) assessed the efficacy and safety of everolimus 10 mg/d in adults with confirmed mantle cell lymphoma (MCL) refractory to or intolerant of bortezomib who received ≥1 other antineoplastic agent, either separately or in combination with bortezomib. Primary endpoint was overall response rate (ORR) per investigator review according to the response criteria for malignant lymphoma. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Fifty-eight patients were enrolled from August 2008-January 2011. Five partial responses were observed (ORR 8·6%; 90% confidence interval [CI] 3·5-17·3%); the study did not meet the prespecified objective of ≥8 objective responses among 57 patients. Median PFS and OS were 4·4 months (95% CI 3·5-6·1) and 16·9 months (95% CI 14·4-29·9), respectively. Grade 3/4 non-haematological toxicities occurred in 70·7% of patients. Based on laboratory values, grade 3/4 thrombocytopenia, neutropenia and anaemia occurred in 13·8%, 13·8% and 8·6% of patients, respectively. Everolimus demonstrated modest activity and acceptable tolerability in heavily pretreated patients with MCL refractory to or intolerant of bortezomib. Future studies evaluating everolimus in a less refractory population or in combination with other targeted therapies in refractory MCL are warranted. © 2014 John Wiley & Sons Ltd.
Fitoussi O.,Service dOnco Hematologie |
Haioun C.,Unite Hemopathies Lymphoides |
Haioun C.,University Paris Est Creteil |
Thieblemont C.,Hospital Saint Louis |
And 8 more authors.
European Journal of Cancer | Year: 2013
This multicentre, single-arm, open-label phase 2 trial investigated the efficacy and safety of lenalidomide monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). Methods Patients received oral lenalidomide 25 mg once daily on days 1-21 of each 28-day cycle for a maximum of 24 months, until disease progression or development of unacceptable adverse events (AEs). The primary end-point was efficacy; safety was evaluated as a secondary end-point. This study was registered with ClinicalTrials.gov, number NCT00655668. Findings A total of 54 patients with PTCL were treated. The overall response rate was 22% (12 of 54), including complete response (CR) or unconfirmed CR (CRu) in 11% of patients; 31% of patients with angioimmunoblastic T-cell lymphoma (AITL) responded (CR/CRu in 15% of patients). The median progression-free survival and median response duration were 2.5 and 3.6 months, respectively, in the intent-to-treat population, and 4.6 and 3.5 months, respectively, in patients with AITL. Thrombocytopenia and neutropenia were the most common grade 3 or 4 haematological AEs, in 11 (20%) and 8 (15%) patients, respectively. Overall, 19 patients (35%) experienced at least 1 AE leading to study dose interruption or reduction (commonly neutropenia or thrombocytopenia). Serious AEs were observed in 54% of patients and 12 patients died during the study; lymphoma progression (n = 6); and acute respiratory distress syndrome, dyspnea, lung infiltration, neutropenic sepsis, pneumonia and cerebral ischaemia (n = 1 each). Interpretation Lenalidomide exhibited single-agent activity in heavily pretreated patients with PTCL, particularly in patients with AITL. Future development is warranted in specific histologies, such as AITL, and in combination with chemotherapy or other agents considered active in PTCL. Funding Celgene Corporation. © 2013 Elsevier Ltd. All rights reserved.
PubMed | University of Bern, Mayo Medical School, Medical College of Wisconsin, Cleveland Clinic and 5 more.
Type: Journal Article | Journal: Cancer | Year: 2015
Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.
PubMed | University of Florida, University of Oklahoma, Nationwide Childrens Hospital, University of North Carolina at Chapel Hill and 25 more.
Type: Journal Article | Journal: Bone marrow transplantation | Year: 2016
Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a Center for International Blood and Marrow Transplant Research study evaluating the incidence, timing, prophylaxis agents, risk factors and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs controls (P=0.0004). After controlling for significant variables, the proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs matched controls (P<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes.
Bashey A.,University of California at San Diego |
Bashey A.,Blood and Marrow Transplant Program at Northside Hospital |
Owzar K.,Duke University |
Johnson J.L.,Duke University |
And 11 more authors.
Biology of Blood and Marrow Transplantation | Year: 2011
We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic HCT (allo-HCT) using a reduced-intensity conditioning regimen of fludarabine 150 mg/m2 plus intravenous busulfan 6.4 mg/kg. Both matched sibling (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD donors received more intensive graft-versus-host disease (GVHD) prophylaxis, including rabbit antithymocyte globulin (ATG) 10 mg/kg, mycophenolate mofetil, and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9-5.8), treatment-related mortality (TRM) at 6 months and 2 years was 8% and 23%, respectively. Neither TRM nor the rates of acute GVHD (aGVHD) were different in those with sibling or MUD donors. Donor CD3 cell chimerism >90% at day +30 was achieved more often in patients with MUD than with matched sibling donors, 70% versus 23% (P < .0001). Median event-free suvival was higher in patients who achieved early full donor chimerism (14.2 versus 8 months, P = .0395). Allo-HCT using this reduced-intensity conditioning regimen can be performed with low TRM in patients who have received a prior AHCT. Efforts to improve early donor CD3 chimerism may improve event-free survival. © 2011 American Society for Blood and Marrow Transplantation.
Goldberg S.L.,John Theurer Cancer Center at Hackensack University Medical Center |
Fenaux P.,University of Paris 13 |
Craig M.D.,West Virginia University |
Gyan E.,CNRS Genetics, Immunotherapy, Chemistry & Cancer Laboratory |
And 8 more authors.
Leukemia Research Reports | Year: 2015
Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50. mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence. © 2014 The Authors.
PubMed | Hopital Maisonneuve Rosemont, University of Washington, University of California at Los Angeles, CNRS Genetics, Immunotherapy, Chemistry & Cancer Laboratory and 6 more.
Type: Journal Article | Journal: Leukemia research reports | Year: 2014
Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.
Dhelaria R.K.,Baystate Medical Center |
Dhelaria R.K.,Tufts University |
Friderici J.,Baystate Medical Center |
Wu K.,Baystate Medical Center |
And 7 more authors.
European Journal of Internal Medicine | Year: 2012
Background: Smoking is a major cause of morbidity in lower socioeconomic groups. In randomized trials, varenicline improves long term quit rates, but effectiveness in a clinic setting is unknown. Methods: We conducted a retrospective cohort study of adults who received a prescription for varenicline or nicotine replacement therapy (NRT) at two inner city health centers in 2008-9. Primary outcome was smoking status at 52 weeks. Secondary outcomes included follow up visits, behavioral counseling, and side effects. Multivariable Poisson regression was used to compare quit rates with varenicline and NRT adjusted for covariates. Key results: A total of 371 patients received a prescription for varenicline (46%) or NRT (54%). The mean age was 43 years, 58% were female, 44% white, 29% African American and 12% Hispanic. Mental illness, alcohol and drug abuse were common. Within one year, 247 (67%) had follow-up, and 26 (10.5%) maintained abstinence through week 52, 10.2% with varenicline and 10.8% with NRT (p = 1.0). Loss to follow-up was 37% for varenicline, 31% for NRT (p = 0.20). Including lost patients as smokers, the adjusted quit rates for varenicline and NRT were similar (6.5% vs. 7.6%, p = 0.69). Only 69/371 (19%) received behavioral counseling. Counseled patients were more likely to maintain abstinence (13% vs. 7.8%, p = 0.04). Side effects were more common with varenicline than NRT (6.5% vs. 2.5%, p = 0.07). Conclusion: In an inner city clinic, abstinence rates were lower than those in clinical trials and did not differ between varenicline and NRT. © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.