For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than ...standard treatment.
We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life.
For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04).
For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life.
Internationally, there is limited evidence about the role and impact of nurse practitioners (NPs) in complex malignant hematology (CMH). In one Canadian CMH program, NPs have existed for 20 years but ...not been evaluated. This study aimed to understand stakeholder perceptions of CMH NP role structures, processes, and outcomes and the extent to which the role meets patient and health service needs.
A qualitative descriptive study was conducted, guided by the PEPPA-Plus framework. Purposive sampling was used to recruit stakeholders who participated in focus groups and interviews. Content analysis was used to analyze the data.
Participants included patients (n = 8) and healthcare professionals (n = 27). Themes about structures related to evolution of the CMH Program, model of care, and need for strategic vision. Process themes related to provision of accessible, comprehensive, and holistic care and NP workload. Positive and negative outcomes and lack of outcome measurement were identified.
Structures related to patient and NP characteristics, organizational change, staffing, and how NP work is organized impacts on NP role implementation and outcomes. Organizational structures can be strengthened to improve the model of care and NP role implementation and workload. Value-added NP contributions related to providing comprehensive care with attention to safety and social determinants of health. Research is needed to evaluate NP role outcomes in CMH.
The results can inform role design and organization policies and strategies to promote the recruitment, retention, and optimization of NP roles in CMH settings. Priorities for future research are also identified.
To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM).
Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2 ...intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements.
Twenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty-one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy.
Bortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted.
The International Extranodal Lymphoma Study Group-32 (IELSG32) randomized patients with primary central nervous system lymphoma (PCNSL) for induction treatment with methotrexate-cytarabine, ...methotrexate-cytarabine-rituximab, or methotrexate-cytarabine-thiotepa-rituximab (MATRix) and reported significantly improved complete remission with the MATRix regimen. This study assessed cost-effectiveness among these three induction strategies for PCNSL. A Markov model was developed based on the IELSG32 trial over a 20 year time horizon from the Canadian health care system perspective. Costs for induction, consolidation, inpatient treatment administration, follow-up, adverse events, relapsed disease, and palliative care were included. Methotrexate-cytarabine-rituximab was subject to extended dominance by the other two strategies. The MATRix regimen compared to methotrexate-cytarabine produced 3.05 quality-adjusted life year (QALY) gains at added costs of $75,513, resulting in an incremental cost-effectiveness ratio of $24,758/QALY gained. The MATRix regimen was the optimal strategy in the majority of simulations (98% probability at willingness-to-pay of $50,000/QALY gained) and results appeared robust across sensitivity analyses.
Erythropoiesis-stimulating agents (ESAs) have been used in orthopedic patients to reduce allogeneic blood transfusion (ABT). The purpose of this systematic review of randomized clinical trials is to ...evaluate the efficacy of preoperative administration of ESAs on hemoglobin level at discharge and frequency of ABT in patients undergoing hip or knee surgery. Pooled results of 26 trials with 3560 participants showed that the use of preoperative ESAs reduced ABT in patients undergoing hip or knee surgery RR: 0.48, 95% CI: 0.38 to 0.60, P<0.00001. Hemoglobin mean difference between ESA and control groups was 7.16 (g/L) 95% CI of 4.73 to 9.59, P=0.00001. There was no difference in the risk of developing thromboembolism between ESA and control groups RD: 0, 95 % CI: -1%-2%, P=0.95. ESAs offer an alternative blood conservation method to avoid ABT in patients undergoing hip or knee surgery.
The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing ...gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL. The response rate to SC was 47% in TRIL and 45% in DL (P = .81). Transplantation rates were similar: TRIL 53% and DL 52% (P = 1.0). With a median follow-up of 53 months, 4 year overall survival was 39% for TRIL and 41% for DL (P = .78); 4 year event-free survival (EFS) was 27% for TRIL and 27% for DL (P = .83). Post-ASCT, 4-year EFS was 45% for TRIL and 46% for DL. Histology (TRIL or DL) was not a predictor of any outcome in multivariate models. Patients with relapsed or refractory TRIL and DLBCL have similar outcomes with SC and ASCT; this therapy should be considered the standard of care for patients with TRIL who have received prior systemic chemotherapy. NCIC CTG LY12 is registered at ClinicalTrials.gov as #NCT00078949.
•Patients with relapsed or refractory transformed indolent lymphoma and DLBCL have similar outcomes with salvage therapy and ASCT.•This therapy should be considered the standard of care for previously treated transformed indolent lymphoma.
Many of the newer treatments for adults with newly-diagnosed and relapsed multiple myeloma (MM) are orally administered. Adherence is a challenge, and little is known about strategies to optimize ...adherence.
Forty-seven patients initiating orally-administered anti-myeloma therapy were enrolled and randomized in a pilot study to receive either standard of care teaching or the Multinational Association of Supportive Care in Cancer Oral agent Teaching Tool (MOATT), a structured teaching tool. Adherence was measured electronically with a Medication Event Monitoring System (MEMS) cap. Optimal adherence was defined as an adherence rate of ≥90% over the six months study duration. Patients completed surveys regarding cancer therapy satisfaction and self-efficacy for medication management at one month and six months following the initiation of treatment in both arms.
The mean adherence of patients over six months was 86.9%; 43.9% of the cohort were classified as non-adherent using the 90% threshold of adherence. Mean adherence was similar among standard of care teaching (87.9%) versus the MOATT intervention tool (85.6%) as was cancer therapy satisfaction and self-efficacy for medication management.
In our pilot, the MOATT tool was not found to be feasible or acceptable. There were no preliminary differences noted between standard of care teaching versus the structured MOATT teaching tool with regards to overall adherence rates, cancer therapy satisfaction, or self-efficacy in medication management. Overall adherence rates were suboptimal in our study. Future research should work to identify aspects of educational interventions which are effective, and investigate different strategies which can be used to supplement patient education and potentially optimize medication adherence in patients with MM.
A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. ...Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 × 109 platelets/product) or low-dose (150- < 300 × 109 platelets/product) platelets. The primary outcome (World Health Organization WHO bleeding ≥ grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5.2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49.2% (30/61) in the standard-dose arm and 51.7% (30/58) in the low-dose group (relative risk RR, 1.052; 95% confidence interval CI, 0.737-1.502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on http://www.clinicaltrials.gov as NCT00420914.
To determine the response rate and toxicity of flavopiridol in patients with previously untreated or relapsed mantle-cell lymphoma.
Adult patients with previously untreated or in first or second ...relapse of previously responsive mantle-cell lymphoma were given flavopiridol 50 mg/m2/d by intravenous bolus for 3 consecutive days every 21 days with antidiarrheal prophylaxis. Flavopiridol was continued until disease progression, unacceptable toxicity, or stable disease for four cycles. Disease was reassessed every two cycles.
From 33 registered patients, 30 were eligible after pathology review, 30 were assessable for toxicity, and 28 were assessable for response. A median of four cycles of treatment was administered; 90% of patients received at least 90% of planned dose-intensity. No complete responses were seen; three patients had a partial response (11%), 20 patients had stable disease (71%), and five patients had progressive disease (18%). The median duration of response was 3.3 months (range, 2.8 to 13.2 months). The most common toxicities were diarrhea (97%), fatigue (73%), nausea (47%), and vomiting (27%). At least one nonhematologic grade 3 or 4 toxicity was seen in 14 patients (47%). Hematologic toxicity was modest.
Flavopiridol given as a daily bolus for 3 consecutive days every 3 weeks has modest activity as a single agent for mantle-cell lymphoma. The number of stable and partial responses that was seen indicates that it is biologically active and may delay progression. Future studies in mantle-cell lymphoma should test this agent with other active agents and using different schedules.
The impact of the addition of rituximab to salvage chemotherapy prior to autologous stem cell transplant (ASCT) was evaluated in a retrospective subgroup analysis of NCIC CTG LY.12. Among 414 ...patients who relapsed following R-CHOP, 96 received salvage chemotherapy alone R − cohort; and 318 received rituximab with chemotherapy R + cohort following a protocol amendment. The R−cohort had a higher proportion of patients with PS ≥2 and relapse <1 year after R-CHOP. The response rate (45.6% vs. 25.0%, p = 0.0003), CR/CRu (15.7% vs. 4.2%, p = 0.003) and transplantation rate (51.9% vs. 31.3%, p = 0.0004) was higher in the R + cohort. Event-free (27% vs. 22%, p = 0.0954) and overall survival at four years (43% vs. 31%; p = 0.045) were greater in the R + cohort when the patients with best response SD/PD to R-CHOP were excluded. Addition of rituximab to salvage therapy before ASCT appears to improve the response rate, transplantation rate, and overall survival in patients with CD20+ lymphoma who responded to R-CHOP.
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