Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.

Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy.

IMPORTANCE: The management of lymphoma diagnosed during pregnancy is controversial and has been guided largely by findings from case reports and small series. OBJECTIVE: To determine maternal and fetal outcomes of women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis studied a cohort of 39 pregnant women diagnosed with HL and NHL (31 HL and 8 NHL) at a single specialized cancer institution between January 1991 and December 2014. MAIN OUTCOMES AND MEASURES: We examined data on disease and treatment characteristics, as well as maternal and fetal complications and outcomes. The Kaplan-Meier method was used to compare progression free survival (PFS) and overall survival (OS) according to receipt of antenatal therapy and other clinical factors. Univariate and multivariate analyses were performed by using Cox proportional hazard regression models to identify potential associations between clinical and treatment factors and survival. RESULTS: The median (range) age of the 39 women in the patient cohort was 28 (19-38) years; 32 women (82%) had stage I or II disease at diagnosis, and 13 had bulky disease. Three women electively terminated the pregnancy to allow immediate systemic therapy; of the remaining 36 women, 24 received antenatal therapy (doxorubicin based combination chemotherapy in 20 of 24 patients), and 12 deferred therapy until after delivery. Four women experienced miscarriage, all of whom had received antenatal systemic therapy and 2 during the first trimester. Delivery occurred at a median (range) of 37 (32-42) weeks and was no different based on receipt of antenatal (median [range], 37 [33-42] weeks) vs postnatal (median [range], 37 [32-42] weeks) therapy (P = .21). No gross fetal malformations or anomalies were detected. At a median (range) follow-up time of 67.9 (8.8-277.5) months since the diagnosis of lymphoma, 5-year rates of PFS and OS were 74.7% and 82.4%, respectively; these rates did not differ according to timing of therapy. On univariate analysis, bulky disease (>10 cm), extranodal nonbone marrow involvement, and poor performance status (Eastern Cooperative Oncology Group score, ≥2) predicted increased risk of disease progression. On multivariate analysis, extranodal nonbone marrow disease and performance status remained significant for both PFS and OS. CONCLUSIONS AND RELEVANCE: Systemic therapy given for lymphoma after the first trimester of pregnancy is likely safe and results in acceptable maternal and fetal outcomes.

Changing Nursing Practice in Survivorship Care With Clinical Decision Tools.

The paradigm shift to include survivorship care as part of the cancer care continuum underscores the critical need for a change in nursing practice. One way to ensure that change in practice is delivered in a safe and efficient manner is through the use of clinical decision tools (CDTs). Such tools can be used to increase relevant knowledge and skills of nurses and patients. Despite the widespread recognition of their value, CDTs to educate providers on cancer survivors' care are limited and, when available, often are not used. Clinical practice algorithms were developed for disease-specific survivorship clinics in a cancer academic center. This article reviews the conceptual framework of the survivorship algorithms, describes the application of the algorithms in multidisciplinary disease-specific survivorship clinics, and discusses the implementation strategies used to promote clinicians' adoption and implementation of the algorithms. At a Glance • The authors found that algorithms can be successfully used as clinical decision tools(CDTs) to deliver survivorship care. • Algorithms and other CDTs are powerful tools to enhance professional practice. • Additional studies are needed to assess their effect on clinical practice and survivor outcomes.

How is flow experienced and by whom? Testing flow among occupations.

The aims of this paper are to test (1) the factorial structure of the frequency of flow experience at work; (2) the flow analysis model in work settings by differentiating the frequency of flow and the frequency of its prerequisites; and (3) whether there are significant differences in the frequency of flow experience depending on the occupation. A retrospective study among 957 employees (474 tile workers and 483 secondary school teachers) using multigroup confirmatory factorial analyses and multiple analyses of variance suggested that on the basis of the flow analysis model in work settings, (1) the frequency of flow experience has a two-factor structure (enjoyment and absorption); (2) the frequency of flow experience at work is produced when both challenge and skills are high and balanced; and (3) secondary school teachers experience flow more frequently than tile workers.

Follicular dendritic cell sarcoma: a report of 14 cases and a review of the literature.

Follicular dendritic cell sarcomas (FDCS) are grouped with the histiocytic and dendritic cell neoplasms. The natural history and response to different treatments have not been well established. The cases of 14 patients with FDCS who were seen at M. D. Anderson between 1995 and 2005 were reviewed. Median patient age was 48 years (range, 25-69 years). Histologically, four cases showed low-grade features, three cases showed low-grade features with focal high-grade features, and five cases showed high-grade features. Tumors were positive for CD21, CD23, and CD35 in 83, 90, and 44% of cases, respectively. Twelve (92%) of 13 tumors were strongly positive for epidermal growth factor receptor. Information on initial treatment was available in 11 patients, which included surgery alone in one patient, surgery and radiation in two, surgery and chemotherapy in one, chemotherapy alone in three, chemotherapy and radiation in one, surgery followed by radiation and chemotherapy in three patients. In eight patients the initial chemotherapy regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone. Complete remission was achieved in 7 (63%) of 11 patients. Ten patients were alive at a median follow up of 22 months, 3 (23%) of 13 had no evidence of disease, and 7 (53%) of 13 patients were alive with disease. Follicular sarcoma is an aggressive neoplasm. Although most of the patients initially responded to treatment, the majority of them (81%) relapsed. A better understanding of the biology of FDCS could guide our efforts in the development of new treatment modalities for this rare disease.

Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center.

PURPOSE: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are currently considered the same entity, but controversy remains over whether CLL and SLL should be treated similarly. We assessed whether characteristics of patients with CLL and SLL differ in ways other than the absolute lymphocyte count (ALC) and evaluated treatment outcomes and prognostic factors. METHODS: We searched the electronic database for patients with CLL or SLL who presented to The University of Texas M.D. Anderson Cancer Center (Houston, TX) between 1985 and 2005. We reviewed patient records to determine presenting characteristics, treatment, and clinical outcomes. Cox models using training and validation sets of patients and resampling methods were used to develop a model predicting survival. RESULTS: Among 2,126 consecutive CLL/SLL patients, 312 (15%) had ALC less than 5 x 10(9)/L. Patients with ALC less than 5 x 10(9)/L had lower rates of cytogenetic abnormalities (P = .0002) and higher rates of CD38-positive results (P = .0002) and had mutated immunoglobulin heavy-chain variable region gene status (P = .034). Rates of response, survival, and failure-free survival (FFS) were not different among ALC groups. Regimens that included rituximab and a nucleoside analog were associated with superior rates of response and FFS compared with other therapies, irrespective of ALC. Deletion 17p or 6q with or without other cytogenetic abnormalities, age at least 60 years, beta2-microglobulin at least 2 mg/L, albumin less than 3.5 g/dL, and creatinine at least 1.6 mg/dL were each found to independently predict shorter survival and formed the basis of a scoring system. CONCLUSION: Patients with CLL or SLL can be treated similarly. A new prognostic score is proposed.