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The replacement of bleomycin with the immune drug conjugate brentuximab vedotin in the first-line chemotherapy regimen for advanced Hodgkin’s lymphoma prolonged both progression-free and overall survival.

As the survival of patients with mantle cell lymphoma (MCL) continues to improve, patients are increasingly being treated with multiple regimens. However, outcome after each line remains poorly characterized in the modern era. To address this knowledge gap, we retrospectively studied 404 consecutive MCL patients who were managed between 2000 and 2014 at Memorial Sloan Kettering Cancer Center. Histologic diagnosis was centrally confirmed, and patients were followed longitudinally from diagnosis throughout their disease course. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan–Meier method. The median OS and PFS after first-line treatment were 9.7 and 4.0 years, respectively. After second-line therapy, the median OS and PFS were 41.1 and 14.0 months, third line were 25.2 and 6.5 months, and fourth line were 14.4 and 5.0 months. In patients less than 65 years, stem cell transplant (SCT)-based frontline regimens were associated with improved PFS compared with non-SCT regimens (median PFS: 86.2 versus 40.0 months; P < 0.01), with a trend toward longer OS (median OS: 165.0 versus 120.0 months; P = 0.06). Early treatment failure after first-line regimens was associated with worse OS (5.9 versus 2.5 years; P < 0.01). Our study should facilitate establishing proper endpoints for future clinical trials using novel treatment approaches.

Malignant lymphomas are a heterogeneous group of diseases whose treatment and prognosis depend on accurate staging and evaluation of histologic features. The conventional imaging procedure is CT; however, nuclear medicine imaging has also had a prominent role. Single-photon imaging with 67Ga-citrate has been widely used for lymphomas. PET with 18F-FDG has gained a role in the staging and follow-up of lymphomas, largely replacing gallium as the nuclear medicine study of choice. 18F-FDG PET has proved useful in the staging and follow-up of Hodgkin's disease and non-Hodgkin's lymphoma (especially more aggressive types), and the widespread use of PET/CT has also increased the sensitivity and specificity. Its usefulness for the staging of slow-growing lymphomas has not been established. After the basics of staging and classification of lymphomas have been outlined, this article will review the role of 18F-FDG PET in the management of patients with lymphoma. PET tracers other than (18)F-FDG, such as positron-emitting isotopes of gallium and the cellular proliferation marker 18F-3'-deoxy-3'-fluorothymidine, will be discussed and future directions for PET in lymphoma proposed.

Extensive radiation therapy was the first therapeutic advance in the treatment of early-stage Hodgkin's lymphoma. More recently, less extensive radiation therapy in combination with chemotherapy has resulted in the lowest reported rates of early relapse. The HD10 trial (ClinicalTrials.gov number, NCT00265018) of the German Hodgkin Study Group showed that among patients with very favorable stage I or II Hodgkin's lymphoma, the outcome in those who received only two cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus involved-field radiation therapy in reduced doses was similar to the outcome in those who received four cycles of chemotherapy and involved-field . . .

Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.

The purpose of this study was to evaluate the economic burden of frontline failure (FLF) among classical Hodgkin lymphoma (HL) patients during and after treatment. The population consisted of adult HL patients identified from January 2010 through September 2015 without any other primary cancer prior to HL diagnosis, who also had a frontline (FL) regimen indicative of curative intent. Patients were characterized as FLF (those who restart, switch to any chemotherapy; had a hematopoietic stem cell transplant; or newly initiated radiation therapy [RT] after discontinuing FL) or non-FLF (those not considered as FLF). Direct health care utilization and expenditures were measured over both fixed and variable length follow-up periods and during FL therapy. There were 77 FLF and 602 non-FLF patients who met the final inclusion criteria. FLF and non-FLF patients were demographically similar with mean age 38.5 years and 47.5% females. Average per patient per month (PPPM) costs were significantly higher for FLF patients during all follow-up (US$20,266 vs US$7,772, <0.05). Annual total expenditures were significantly higher among FLF patients (US$198,388) vs non-FLF patients (US$37,549). FLF (vs non-FLF) patients had a significantly shorter duration of FL therapy (116 vs 131 days, =0.024) and higher total PPPM expenditures during FL (US$29,040 vs US$16,369, <0.05). Annual cost varied by failure type with those who failed due to restart incurring the highest cost (US$269,189) and those who switched incurring the lowest cost (US$46,951). FLF patients had a significantly greater utilization in every health care resource category during follow-up. FLF (vs non-FLF) patients utilized substantially more health care resources and incurred a substantially higher economic burden. Over 5 years, FLF patients with at least two lines of treatment were projected to incur US$535,846 of health care costs. Further research is needed to determine optimal treatment that could reduce the risk of progression, need for treatment after FL, and enhance long-term clinical and economic outcomes.

We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma). Median number of GAs per case was 6, with 97% of patients harboring at least one alteration. Recurrent GAs were detected in genes with established roles in DLBCL pathogenesis (e.g. MYD88, CREBBP, CD79B, EZH2), as well as notable differences compared to prior studies such as inactivating mutations in TET2 (5%). Less common GAs identified potential targets for approved or investigational therapies, including BRAF, CD274 (PD-L1), IDH2, and JAK1/2. TP53 mutations were more frequently observed in relapsed/refractory DLBCL, and predicted for lack of response to first-line chemotherapy, identifying a subset of patients that could be prioritized for novel therapies. Overall, 90% (n = 169) of the patients harbored a GA which could be explored for therapeutic intervention, with 54% (n = 107) harboring more than one putative target.

In a large randomized trial that compares regimens in which brentuximab vedotin replaced bleomycin, the group receiving the brentuximab had a 4.9 percentage-point improvement in modified progression-free survival, less pulmonary toxicity, and more myelotoxicity and neurotoxicity.

The human immunodeficiency virus (HIV) increases the risk of aggressive B-cell lymphoma, 1 , 2 which often presents at an advanced stage and frequently involves extranodal sites, such as the central nervous system and bone marrow. 3 – 7 In HIV-infected patients, the rate of complete response to the treatment of lymphoma with combination chemotherapy is approximately 50 percent, and the median survival is only five to six months. 4 – 6 , 8 Factors that favor longer survival include a higher number of CD4+ lymphocytes, 4 , 9 the absence of a prior diagnosis indicating progression to the acquired immunodeficiency syndrome (AIDS), 4 , 9 a Karnofsky performance score of . . .