How I treat and prevent venous thrombotic complications in patients with lymphoma.

Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug-drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.

Evaluation of awareness about importance of high fever in leukemia and lymphoma patients receiving chemotherapy among healthcare professionals working in pharmacies other than hospital pharmacies: A survey from a Central Anatolian city.

INTRODUCTION: Pharmacy staff are part of the healthcare delivery. In some cases, the patient goes to the pharmacy before the doctor and asks for a medicine suitable for his own complaint. The aim of this study is to evaluate the awareness about the importance of high fever in patients with leukemia and lymphoma receiving chemotherapy among healthcare professionals working in non-hospital pharmacies. MATERIAL AND METHOD: The study is a survey study. 140 pharmacy employees working in non-hospital pharmacies in Ankara Province were included in the study. Volunteer participants were included in the study. Seven questions were asked to the participants. RESULTS: About 47.1% of the participants stated that they would advise patients to go immediately to the nearest hospital's emergency department when they presented to the pharmacy and said that they had high fever. It was stated by 56.5% of the participating pharmacy employees that high fever did not pose the same risk for a leukemia or lymphoma patient receiving chemotherapy as it did for a leukemia or lymphoma patient not receiving chemotherapy. CONCLUSION: In this study, it was found that awareness about importance of high fever in leukemia and lymphoma patients receiving chemotherapy among healthcare professionals working in pharmacies other than hospital pharmacies was not very high. Providing necessary information to the pharmacy personnels and increasing the awareness about importance of high fever in leukemia and lymphoma patients receiving chemotherapy among the non-hospital pharmacy staff might also contribute to the reduction of negativities associated with infections in such patients.

Support for adult survivors of lymphoma: a literature review.

BACKGROUND: After the completion of chemotherapy, survivors of lymphoma are at risk of developing late effects of their cancer treatment, which can negatively impact their quality of life. Despite the recommendations for support after active treatment ceases, there is a recognised risk that survivors' needs may not be met. AIM: To review the existing literature surrounding professional support in survivorship to establish whether people's needs are being met. METHOD: A literature review and thematic analysis of 22 primary research articles. FINDINGS: Specialist support and primary care involvement were identified as the two main themes of professional support. Provider-related barriers and individual differences impact the effectiveness of the available support in survivorship. CONCLUSION: Following guidelines and understanding an individual's personal needs following treatment will help to ensure that survivors receive the right support. Further research with survivors of lymphoma is required to improve outcomes in the future.

Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma.

The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 29 patients with the median of 3 prior treatments were eligible for assessment as per international PCNSL collaborative group criteria. The MTD of POM was 5 mg daily for 21 days every 28 days. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 16; 95% CI, 24.7%, 75.4%) with 5 CR, 1 CRu, and 2 PR. Median PFS was 5.3 months (whole study) and 9 months (for responders). One patient had pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic toxicities included lung infection (12%), sepsis (4%), fatigue (8%), syncope (4%), dyspnea (4%), hypoxia (4%), respiratory failure (8%), and rash (4%). POM/DEX treatment is feasible with significant therapeutic activity against relapsed/refractory PCNSL and PVRL. This trial was registered at www.clinicaltrials.gov as #NCT01722305.

Effects of live music during chemotherapy in lymphoma patients: a randomized, controlled, multi-center trial.

PURPOSE: Chemotherapy is associated with both somatic and psychological side effects. Music might ease these problems. Several randomized controlled trials have investigated the effect of music, but the results are inconclusive. We aimed to examine whether live or pre-recorded music listening decreases anxiety during chemotherapy in newly diagnosed lymphoma patients. METHODS: A total of 143 patients with non-Hodgkin and Hodgkin lymphomas were randomly assigned into three groups receiving either 30 min of patient-preferred live music (n = 47), 30 min of patient-preferred pre-recorded music (n = 47), or standard care (n = 49) during up to five outpatient chemotherapy sessions. The primary endpoint was anxiety measured by the Spielberger's State Anxiety Inventory. Secondary endpoints included blood pressure, pulse rate, nausea and vomiting, serum catecholamine levels pre- and post-intervention to measure arousal levels, and health-related quality of life. The Musical Ability Test was used to link musical ability to the primary endpoint. RESULTS: When adjusting for age, sex, diagnosis, number of sessions, and baseline anxiety, the linear mixed model showed a borderline statistically significant reduction in the primary outcome anxiety in the live music group compared to standard care (7% (95% CI, - 14% to 0%, p = 0.05), while the effect of pre-recorded music was non-significant (5% (95% CI, - 12% to + 3%, p = 0.18). No intervention effects were seen in secondary outcomes. CONCLUSION: Our findings suggest that patient-preferred live music reduces anxiety among patients with malignant lymphomas undergoing chemotherapy. Musical ability among this group of cancer patients seems not to be a determining factor for effect of music intervention.

Outcomes and prognostic factors for relapsed or refractory lymphoma patients in phase I clinical trials.

Background Although safety and prognostic factors for overall survival (OS) have been extensively studied in Phase I clinical trials on patients with solid tumours, data on lymphoma trials are scarce. Here, we investigated safety, outcomes and prognostic factors in relapsed or refractory lymphoma patients included in a series of Phase I trials. Method and patients All consecutive adult patients with recurrent/refractory lymphoma enrolled in 26 Phase I trials at a single cancer centre in France between January 2008 and June 2016 were retrospectively assessed. Results 133 patients (males: 65%) were included in the analysis. The median (range) age was 65 (23-86). Aggressive non-Hodgkin, indolent non-Hodgkin and Hodgkin types accounted for 64%, 25% and 11% of the patients, respectively. The patients had received a median (range) of 3 (1-13) lines of treatment prior to trial entry. The median [95% confidence interval] progression-free survival and OS times were 3.0 [1.8-3.6] and 17.8 [12.7-30.4] months, respectively. High-grade toxicity (grade 3 or higher, according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification) was experienced by 56 of the 133 patients (42%) and was related to the investigational drug in 44 of these cases (79%). No toxicity-related deaths occurred. Dose-limiting toxicity (DLT) was encountered in 11 (9%) of the 116 evaluable patients. High-grade toxicity occurred during the DLT period for 34 of the 56 patients (61%) and after the DLT period in the remaining 22 (39%). The main prognostic factors for poor OS were the histological type (i.e. tumour aggressiveness), an elevated serum LDH level, and a low serum albumin level. Early withdrawal from a trial was correlated with the performance status score, the histological type and the serum LDH level. The overall objective response and disease control rates were 24% and 57%, respectively. Conclusion Performance status, LDH, albumin and histological type (tumour aggressiveness) appear to be the most relevant prognostic factors for enrolling Phase I participants with relapsed or refractory lymphoma. 39% of the patients experienced a first high-grade toxic event after the dose-limiting toxicity period, suggesting that the conventional concept of dose-limiting toxicity (designed for chemotherapy) should be redefined in the era of modern cancer therapies.

Pitfalls of Combining Novel Agents in Lymphoma.

OPINION STATEMENT: As our knowledge of lymphoma and its intricate signaling pathways has grown, so has the development of novel agents. While their mechanisms of action vary considerably, these therapies supplement and in some cases offer alternatives to standard chemotherapy. Initial studies have highlighted tolerable side effects though in the majority of instances limited efficacy when used as monotherapy. Research has focused on combining these novel agents to improve outcomes and perhaps offer refined treatment options. Novel combinations represent new territory, inherently dissimilar to combination chemotherapy with new pitfalls and challenges given their unique mechanisms of action. Though promising, it is crucial to consider the complex interplay that can occur. While there is potential for improved outcomes, there is also the possibility of unexpected toxicities. For this reason, it is critical that novel combinations be carefully considered and tested in clinical trials before widespread use. Thus far, research has shown that combination therapies are successful when not only avoiding overlapping toxicity but also capitalizing on synergy. We believe that more specific targets and an improved understanding of their off-/on-target effects will further successful novel combinations.

Factors and Costs Associated With Delay in Treatment Initiation and Prolonged Length of Stay With Inpatient EPOCH Chemotherapy in Patients With Hematologic Malignancies.

Reducing delays related to inpatient chemotherapy may reduce healthcare costs. Using a national database, we identified patients with lymphoma/leukemia with ≥1 etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy claim and evaluated chemotherapy initiation delay (ID), >1 day from admission. Standard tests/procedures prior to initiation were evaluated. Among 4453 inpatient cycles, 19.7% had ID, odds ratio 2.28 (95% confidence interval: 1.83-2.85) with cycle 1 compared to cycle 2, and mean costs were higher in patients with ID than without ID (p < .0001). Prior to cycle 1, patients were more likely to undergo routine diagnostic procedures compared to subsequent cycles. Efforts to perform routine procedures prior to admission may reduce hospital length of stay and costs.

Paraaortic node recurrence 25 years after removal of epithelial ovarian carcinoma.

In epithelial ovarian carcinoma, very late (more than 20 years) recurrence is an unusual event. In patients experiencing such a recurrence, the effectiveness of platinum/taxane chemotherapy has been questioned. A 54-year old woman presented with paraaortic node swelling that appeared 25 years after treatment of stage I epithelial ovarian carcinoma. She underwent a partial resection of the nodes and histologic examination showed high-grade serous carcinoma. She received paclitaxel and carboplatin chemotherapy and a partial response was initially observed on imaging studies; however, serum cancer antigen125 levels increased thereafter. She received radiation therapy to the paraaortic nodal disease with doses of 45 Gy and achieved a complete response. She was disease-free more than eight years after the detection of recurrence. In conclusion, radiation therapy may be an effective treatment option in patients with very late recurrence of epithelial ovarian carcinoma refractory to platinum/taxane chemotherapy.

Targeting PI3-kinase (PI3K), AKT and mTOR axis in lymphoma.

Targeted therapy represents a transformation in oncology, a field that has relied primarily on non-selective cytotoxic therapies. Phosphatidylinositol 3-kinase (PI3K) is a family of ubiquitous signalling molecules involved in a wide variety of cellular processes and likewise, in a broad selection of human cancers. The discovery that the p110-δ form of PI3K is differentially expressed in normal and malignant lymphocytes has led to the development of specific inhibitors that are currently in clinical trials for lymphoma. Downstream effectors of PI3K, including v-akt murine thymoma viral oncogene homolog 1 (AKT; also termed AKT1) and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) are similarly important in lymphoma, and agents targeting these components of the PI3K-AKT-mTOR axis are also underway, although at earlier stages of development. In this review we examine the role of PI3K-AKT-mTOR in normal and malignant lymphocytes, as well as the preclinical and clinical status of a number of inhibitors of this pathway.

[Fever, atrial fibrillation, and angina pectoris in a 58-year-old man]. / Fieber, Vorhofflimmern und Angina pectoris bei einem 58-jährigen Patienten.

Primary cardiac lymphoma (PCL) respresents a very rare type of cardiac tumour. This report illustrates a case of PCL in an immunocompetent 58-year-old man presenting with atrial fibrillation and febrile syndrome. Comprehensive imaging [computer tomography (CT), cardiac magnetic resonance imaging (cMRI), 3-dimensional transesophageal echocardiography (3D-TEE)] identified a large right atrial tumour, leading to pericardial effusion. Isolated cardiac involvement was confirmed by positron emission tomography (PET)-CT. A diffuse large B-cell lymphoma (DLBCL) was diagnosed based on the results of a TEE-guided biopsy. A normalized PET scan (PETAL study) indicated complete remission following R-CHOP 14 immunochemotherapy. Thus, an interdisciplinary and multimodal approach avoided unnecessary cardiac surgery.

[Three cases of uterine cervix lymphoma. Two of them preceded by erroneous hystology reports, resulting in radical surgery with lymphnode desection. Third case--lethality of a 21 year old patient in the course of chemotherapy].

Three cases of primary uterine cervix lymphomas are presented. Two of the cases were preceded by erroneous histology reports. Subsequent radical surgery and post operative establishment of the correct diagnosis. Case 3--young patient with massive tumor under chemotherapy Lethal outcome in the chemotherapy course as a result of multiple PE, that preceded the planned operative intervention. A literature review of this extremely rare pathology is presented.

Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas.

A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888.

Is primary prophylaxis with granulocyte colony stimulating factor (G-CSF) indicated in the treatment of lymphoma?

Febrile neutropenia (FN) is a common complication of cancer therapy. It can contribute to delays in treatment, increased rates of hospitalization, and severe infections. FN may also hinder completion of intended chemotherapy. Granulocyte colony stimulating factors (G-CSF) lower the rates of FN, infections, and hospitalization. Multiple national and international guidelines advocate the use of G-CSF in primary prophylaxis if the overall risk of FN is >20% (accounting for both patient and treatment-related risks). Lymphoma specific guidelines recommend G-CSF use in similar fashion. However, based on our updated review of published literature, we note that primary prophylaxis (PP) with G-CSF fails to improve overall survival as well as infection-related mortality. Moreover, lymphoma specific cost-effectiveness analyses on the use of PP have shed further doubt on the optimal use of this myeloid growth factor. In this general review, we will discuss whether PP with GCSF has any role in the management of adults with non-Hodgkin lymphoma.

Clinical pharmacy services and research for lymphoma patients at a cancer center.

At the National Cancer Centre Singapore, which is currently the largest ambulatory cancer centre in Singapore, clinical pharmacists have taken upon responsibilities to provide direct pharmaceutical care in the center's lymphoma team since 2006. Given the complexity and intricacies of lymphoma treatments, clinical pharmacists are often positioned to ensure supportive care is optimized among these patients. Besides management of chemotherapy-related and supportive care issues, clinical pharmacists play a pivotal role in guiding cost-effective and safe prescribing. In collaboration with the medical team, they are also involved in conducting practice research in order to optimize the delivery of pharmaceutical care. In this report, the dedicated services and research activities conducted by clinical pharmacists of a lymphoma team will be discussed.

Comparison between rheumatoid arthritis with malignant lymphoma and other malignancies: Analysis of a National Database of Rheumatic Disease in Japan.

BACKGROUND: The background status and the current treatment options of patients with rheumatoid arthritis (RA) who develop malignant lymphoma (ML) and other malignancies are unclear. This study investigated the differences in background factors between ML and other malignancies that occur in RA patients and post-malignancy treatment. METHODS: We identified 935 RA patients with new-onset malignancies among 110,571 person-years registered in the National Database of Rheumatic Disease in Japan from 2012 to 2018. Analysis cohorts 1 and 2 included 597 and 490 patients with available data for 1 year before and after the development of malignancies, respectively. Factors associated with the development of ML were longitudinally evaluated by multiple logistic regression analyses. RESULTS: Of the 935 patients (mean age 70.5, standard deviation 9.9), 15.5% had ML; this was comparable to the rate of lung cancer (14.3%). In cohort 1, methotrexate (MTX), biological disease-modifying anti-rheumatic drugs (bDMARDs), and non-steroidal anti-inflammatory drugs (NSAIDs) were used in 74.4%, 23.4%, and 56.7% of ML and in 56.8%, 25.4%, and 35.3% of other malignancies 1 year before the occurrence of malignancies. Clinical disease activity index (CDAI) and C-reactive protein were similar between the two groups. Multivariable analysis showed that MTX use (odds ratio [OR]: 2.22, 95% CI [confidence interval]: 1.32-3.73, p=0.003) and NSAID use (OR: 2.51, 95% CI: 1.58-3.98, p <0.001) were significantly associated with the development of ML versus other malignancies. However, this association was not observed with bDMARDs. In cohort 2, one year after the development of malignancies, MTX was used in none of ML and 41.8% of patients who developed other malignancies. In both malignancy groups, approximately 15% of patients received bDMARDs and 50% received glucocorticoids. IL-6 inhibitors were preferentially prescribed in patients with ML versus those with other malignancies. At year 1, CDAI remission was achieved in 37.3% and 31.1% of patients in the ML and other malignancy groups, respectively. CONCLUSION: Patients receiving long-term treatment with MTX and NSAIDs may be at a relatively high risk of developing ML. The treatment landscape after developing malignancies differed considerably between patients with ML and other malignancies, and different treatment strategies should be established.