Lenalidomide maintenance following high-dose therapy and autologous haematopoietic stem cell transplantation in chemo-resistant or high-risk non-Hodgkin lymphoma: A phase I/II study.

Improved maintenance treatments are needed for patients with relapsed/refractory aggressive lymphomas after autologous haematopoietic stem cell transplantation (ASCT). Several studies with lenalidomide have been found to have activity in the treatment of relapsed/refractory aggressive lymphomas. In the present phase I/II, single-arm, open-label study, 59 patients with high-risk relapsed non-Hodgkin lymphoma received pretransplant BEAM chemotherapy and ASCT followed by 12 months of maintenance lenalidomide once daily on Days 1-21 (28-day cycles) beginning at post-transplantation Day 100. The most common histologies were mantle cell lymphoma (56%) and diffuse large B-cell lymphoma (24%). The maximum tolerated dose in the dose-finding part of the study was 15 mg, but cytopenias led to the subsequent adoption of a 10 mg dose in the final study. Sixteen patients (27%) completed 12 cycles of lenalidomide maintenance. The most common reason for discontinuation was adverse events (31%). These were primarily haematologic, and 56% of patients experienced Grade 3-4 events. Two-year PFS rates (95% CIs) were 70% (56%-80%), 45% (19%-68%) and 81% (66%-90%); 2-year OS rates (95% CIs) were 91% (80%-96%), 93% (61%-99%) and 90% (76%-96%) in all patients, patients completing and patients not completing 12-month maintenance respectively. These results do not support the use of lenalidomide maintenance in this setting.

Phase 1 trial of carfilzomib in relapsed/refractory peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma.

PURPOSE: Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS: We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS). RESULTS: Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare. CONCLUSION: Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).

Radiologic Differentiation of Primary CNS Posttransplant Lymphoproliferative Disorder From Brain Metastasis.

OBJECTIVE. Primary CNS posttransplant lymphoproliferative disorder (PTLD) may present as multiple contrast-enhancing intraaxial lesions, often with central necrosis and surrounding edema. This imaging appearance is similar to the pattern seen in brain metastases. The purpose of this study was to find differences in the radiologic features of primary CNS PTLD lesions and brain metastases. MATERIALS AND METHODS. We retrospectively reviewed the radiologic findings of 51 primary CNS PTLD lesions in 10 patients and 156 metastatic brain lesions in 25 patients. Lesion size, multifocality, location, necrosis, hemorrhage, perilesional vasogenic edema, contrast enhancement, and diffusion and perfusion features were evaluated. We used the chi-square test or Fisher exact test when appropriate to compare the findings between primary CNS PTLD lesions and brain metastases. RESULTS. Primary CNS PTLD lesions occur in the deep gray matter and periventricular locations more frequently than brain metastases (p < 0.0001) and are not present at the gray and white matter junctions and vascular border zones as commonly as brain metastases are (p < 0.0001). Primary CNS PTLD tends to have less frequent hemorrhage (p < 0.0001), more restricted diffusion (p = 0.001), and lower perfusion (p = 0.002) than brain metastases. We did not find statistically significant differences between primary CNS PTLD and brain metastases for lesion size, multifocality, necrosis, and perilesional edema. CONCLUSION. The imaging characteristics of primary CNS PTLD overlap considerably with those of brain metastases, but there are significant differences between primary CNS PTLD lesions and brain metastases in lesion location, diffusion and perfusion features, and tendency to hemorrhage.

The Meaning of Self-efficacy for Symptom Management in the Acute Phase of Hematopoietic Stem Cell Transplantation.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an intensive treatment that offers the potential for longer life or cure for some types of cancer. Hematopoietic stem cell transplant is associated with decreased quality of life and functional status and distressing symptoms. Self-efficacy for symptom management (SESM) is a person's belief in his/her ability to implement behaviors to manage these symptoms. Presence of SESM can affect symptom distress, healthcare utilization, and posttransplantation outcomes. OBJECTIVE: The aim of this study was to explore the meaning of SESM in adults during the acute phase of HSCT. METHODS: Interviews were conducted before and at 30 days after transplantation. Descriptive thematic analysis was performed on verbatim interview transcripts. RESULTS: Themes of confidence, being responsible, and caring for mind, body, and spirit were identified, with subthemes of self-confidence, confidence in others, confidence and symptom level, vigilance, self-advocacy, and normalcy. Participants reported having high SESM before transplantation and having much less or no SESM when symptom distress was the most severe. CONCLUSIONS: This is the first study to examine the patient's perspective of self-efficacy in the acute phase of HSCT. This contributes to existing literature on the concept of symptom management and expands nursing knowledge of SESM in patients undergoing HSCT. IMPLICATIONS FOR PRACTICE: Nurses can assess SESM before transplantation and implement interventions to enhance SESM when symptoms are at their most distressing after HSCT. The findings from this study can provide the basis for creating behavioral interventions to enhance self-efficacy for symptom management in HSCT patients.

Self-efficacy for symptom management in the acute phase of hematopoietic stem cell transplant: A pilot study.

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intensive treatment associated with distressing treatment and disease-related symptoms that affect patient outcomes such as functional status and quality of life. Self-efficacy for symptom management (SESM) is a person's belief in their ability to perform behaviors to prevent and relieve symptoms. Presence of SESM can impact symptom distress and functional status. This study describes the changes over time and relationships among SESM, symptom distress, and physical functional status in adults during the acute phase of HSCT. METHODS: Patients (n = 40) completed measures of symptom distress, SESM, and physical function at time points prior to and at days 7, 15 and 30 post-transplant. Clinical outcomes were length of stay and number of readmissions. RESULTS: Symptom distress, physical function, and SESM changed significantly over time. There was a significant negative relationship between symptom distress and physical function and between symptom distress and SESM at all points. The lowest levels of SESM and physical function were at day 7 when symptom distress was highest. Symptom distress was a moderator for the relationship between physical function and SESM at day 15. CONCLUSION: This was the first study to examine SESM in the acute phase of HSCT. Higher SESM was associated with fewer symptoms and increased physical function. Less symptom distress was associated with higher physical function and confidence to manage symptoms. These findings provide the basis for development of patient-centered interventions to enhance SESM when symptoms are at their highest immediately after HSCT.

Primary central nervous system post-transplant lymphoproliferative disorders: the spectrum of imaging appearances and differential.

OBJECTIVE: Central nervous system post-transplant lymphoproliferative disorder (CNS-PTLD) is a rare disease that presents with non-specific signs and symptoms. The purpose of this article is to present the imaging appearances of CNS-PTLD by magnetic resonance imaging. We highlight the differential diagnostic considerations including primary central nervous system lymphoma, glioblastoma, cerebral abscess, and metastatic disease. This is an important topic to review since in daily practice the diagnosis of CNS-PTLD is often not initially considered when present due to its rarity and the lack of radiologists' familiarity with the disease. CONCLUSION: Knowing the unique imaging features of CNS-PTLD narrows the differential diagnosis, facilitates the diagnostic work-up, and optimizes making the diagnosis. Advanced MRI data for CNS PTLD is limited but is promising for helping with narrowing the differential diagnosis.

Self-Efficacy for Management of Symptoms and Symptom Distress in Adults With Cancer: An Integrative Review.

PROBLEM IDENTIFICATION: Self-efficacy for symptom management plays a key role in outcomes, such as quality of life (QOL), functional status, and symptom distress, for adults with cancer. This integrative review identified and assessed evidence regarding self-efficacy for management of symptoms and symptom distress in adults with cancer. LITERATURE SEARCH: The authors performed a search of literature published from 2006-2018, and articles that examined the relationship among self-reported self-efficacy, symptom management, symptom distress or frequency, and severity in adults with cancer were selected for inclusion. DATA EVALUATION: 22 articles met the inclusion criteria. All articles were critically appraised and met standards for methodologic quality. SYNTHESIS: Evidence from this review showed that high self-efficacy was associated with low symptom occurrence and symptom distress and higher general health and QOL. High self-efficacy predicted physical and emotional well-being. Low self-efficacy was associated with higher symptom severity, poorer outcomes, and better overall functioning. IMPLICATIONS FOR RESEARCH: Self-efficacy can be assessed using developed instruments. Presence of a theoretical model and validated instruments to measure self-efficacy for symptom management have set the groundwork for ongoing research.

NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

Solid Organ Transplantation in Patients With a History of Lymphoma.

There is an increasing number of long-term survivors of Hodgkin and non-Hodgkin lymphoma. These people may have a need for subsequent solid organ transplantation, often as a result of late effects of their lymphoma treatment. There is abundant literature demonstrating that patients with a history of lymphoma are appropriate candidates for solid organ transplantation. Long-term survival without relapse and with a functioning graft is possible. Patients with a history of post-transplantation lymphoproliferative disorders and patients who have received a prior hematopoietic stem-cell transplantation may also be candidates. Although high-level supporting evidence is not available, most guidelines recommend a waiting period of 2 to 5 years after lymphoma treatment before patients undergo solid organ transplantation. Each patient with a history of lymphoma requires a multidisciplinary approach and should be evaluated on a case-by-case basis before consideration of solid organ transplantation.

Perceived Self-Efficacy: A Concept Analysis for Symptom Management in Patients With Cancer
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BACKGROUND: Perceived self-efficacy (PSE) for symptom management plays a key role in outcomes for patients with cancer, such as quality of life, functional status, symptom distress, and healthcare use. Definition of the concept is necessary for use in research and to guide the development of interventions to facilitate PSE for symptom management in patients with cancer.
. OBJECTIVES: This analysis will describe the concept of PSE for symptom management in patients with cancer.
. METHODS: A database search was performed for related publications from 2006-2016. Landmark publications published prior to 2006 that informed the concept analysis were included.
. FINDINGS: Greater PSE for symptom management predicts improved performance outcomes, including functional health status, cognitive function, and disease status. Clarification of the concept of PSE for symptom management will accelerate the progress of self-management research and allow for comparison of research data and intervention development.

Rituximab Improves the Outcome of Patients With Grade 3 Follicular Lymphoma Receiving Anthracycline-Based Therapy.

BACKGROUND: The combination of rituximab with chemotherapy has improved the outcome of patients with follicular lymphoma (FL). However, data on Grade 3 FL (FL3) and its subtypes are lacking. The aims of the study were to determine: (1) the clinical features and outcome of patients with FL3 treated with rituximab and anthracycline-based chemotherapy; and (2) the clinical significance of the 3 subtypes of FL3. PATIENTS AND METHODS: Eighty-seven patients with Grade 1/2 FL, 84 with FL3 including 46 FL3A, 17 FL3B, and 21 follicular large cleaved cell (FL3C), and 411 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab and anthracycline-based chemotherapy, and a historical cohort of 167 patients with FL3 who received only anthracycline-based chemotherapy (FL3*) were included in this retrospective study. RESULTS: The FL3 group had a significantly better overall survival (OS) and event-free survival (EFS) compared with those with FL3* or DLBCL. No significant differences in OS were found among the 3 subtypes of FL3. However, patients with FL3B had a shorter EFS than those with FL3A and FL3C. Moreover, patients with FL3B had an outcome similar to those with DLBCL, whereas patients with FL3A and 3C had significantly better outcomes than those with DLBCL. Less than 50% of the patients with FL3B and less than 20% of the patients with FL3A and 3C have relapsed, and relapses were uncommon after 5 years. CONCLUSION: The use of rituximab with anthracycline-based chemotherapy significantly improved the survival of patients with FL3 and should be considered the benchmark by which other therapies for FL3 are evaluated in the future.

NCCN Guidelines Insights: Antiemesis, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.

Hodgkin Lymphoma Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

Venous thromboembolism in patients with hematologic malignancy and thrombocytopenia.

The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000-45,000/µL) versus 165,000/µL (50,000-429,000/µL) in those without (P < 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1-35 days). Therapy during the period of significant thrombocytopenia included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic-dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow-up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21-1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic-dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J. Hematol. 91:E468-E472, 2016. © 2016 Wiley Periodicals, Inc.

Clinicopathologic features, management and outcomes of blastoid variant of mantle cell lymphoma: a Nebraska Lymphoma Study Group Experience.

The objective of this retrospective study (N = 169) was to compare the overall survival (OS) of different subtypes of mantle cell lymphoma (MCL) treated by the Nebraska Lymphoma Study Group between 1984 and 2012. The overall response rate to various therapies including stem cell transplant (SCT) was similar (p = 0.44) between blastoid, diffuse and nodular subtypes. At 5 years, blastoid and diffuse subtypes had worse OS (overall p = 0.005) compared to nodular subtype. In multivariate analysis, the blastoid and diffuse subtypes had similar risk of death (p = 0.14) whereas the nodular subtype had a lower risk compared to blastoid (HR 0.48, 95% CI 0.27-0.87, p = 0.01). The use of SCT was associated with lower risk of death. In univariate analysis, blastoid subtype had better OS with intensive upfront therapy. In conclusion, the OS of blastoid subtype is worse than nodular MCL but may improve with the use of SCT and probably intensive induction therapy.

Combined systemic and ocular chemotherapy for anterior segment metastasis of systemic mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature. FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and fibrin. The AC cells stained positively for CD20. The iris was thickened and coated with lymphoma cells. Iris neovascularization was present. Given extensive systemic and ocular involvement, the patient was given combination chemotherapy with systemic ibrutinib and intravitreal injections of methotrexate and rituximab. The disease response was monitored using multimodal imaging, including anterior segment optical coherence tomography and ultrasound biomicroscopy. Following combination of systemic and intraocular chemotherapy, there was a marked decrease in the ocular tumor load and the systemic disease. CONCLUSIONS: Combination therapy with intravitreal injections of chemotherapeutic agents targeting monoclonal B-cell population and novel systemic agents may help to achieve remission in anterior segment metastasis of aggressive subtypes of NHL such as blastic variant of MCL. Multimodal imaging may assist in the management of these cases.