Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL.

Key Points• Population-based data show a favorable outcome with upfront autologous stem cell transplantation in PTCL.• The addition of etoposide to CHOP was associated with favorable PFS in patients #60 years with PTCL.Peripheral T-cell lymphomas (PTCLs) are rare lymphomas with mostly poor outcome with current treatment. The addition of etoposide to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and upfront consolidation with autologous stem cell transplantation (auto-SCT) have shown promising results but have never been tested in randomized trials. As a complement to retrospective analyses of clinical trials, we aimed at analyzing prognostic factors and outcome in an unselected, population-based cohort. Through the Swedish Lymphoma Registry, we identified 755 PTCL patients diagnosed during a 10-year period. In addition to International Prognostic Index factors, male gender was associated with an adverse overall survival (OS) (hazard ratio [HR], 1.28; P 5 .011) and progression-free survival (PFS) (HR, 1.26; P 5 .014). In an intention-to-treat analysis in 252 nodal PTCL and enteropathy-associated T-cell lymphoma patients (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma), upfront auto-SCT was associated with a superior OS (HR, 0.58; P 5 .004) and PFS (HR, 0.56; P 5 .002) compared with patients treated without auto-SCT. The addition of etoposide to CHOP resulted in superior PFS in patients £60 years (HR, 0.49; P 5 .008). This study is the largest population-based PTCL cohort reported so far and provides important information on outcome in PTCL outside the setting of clinical trials. (Blood. 2014;124(10):1570-1577

Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ∼97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism-detected copyneutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35-9.878, P = 0.011) and 3.19 (95% confidence interval, 1.06-9.57, P = 0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes.

Follicular lymphoma (FL) is one of the most common types of non-Hodgkin's lymphoma. It is usually diagnosed at an advanced stage, for which many treatment options exist, however, no curative standard therapy has been identified. The outcome is highly variable with a median survival of approximately 10 years. The life expectancy of patients with FL has been extended with the use of rituximab, a monoclonal antibody targeting the CD20 antigen on FL cells, but there remains a group of patients who fail to respond to chemoimmunotherapy and die early of their disease. Transformation of FL to an aggressive histology is an important event with high morbidity and mortality. The Follicular Lymphoma International Prognostic Index has become the clinically useful prognostic tool, but gives only a rough estimate of expected outcome. There is a need for useful biomarkers for prediction of the disease course of single patients to individualize therapy, especially in the new era of chemoimmunotherapy.

The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using

In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

Patients treated for tumors in the hypothalamic-pituitary region or treated with testicular irradiation or with high doses of alkylating agents had severe gonadal and sexual dysfunction. Most of the other patients had good prospects for preserved gonadal and sexual function.

Childhood cancer survivors (CCS) have an increased risk of impaired spermatogenesis, but data regarding the disease- and treatment-related risk factors of azoospermia are scarce. Such information is crucial both for counselling CCS and for selecting patients for testicular tissue cryopreservation. The proportion of azoospermic men in CCS was 18% [95% confidence interval (CI): 12-26], specifically for leukaemias (19%; 95% CI: 5.5-42), Hodgkin's disease (53%; 95% CI: 29-76), non-Hodgkin's lymphoma (11%; 95% CI: 0.28-48) and testicular cancer (11%; 95% CI: 0.28-48). In CCS treated with high doses of alkylating agents, the proportion of azoospermic men was 80% (95% CI: 28-99) and if radiotherapy was used additionally, the proportion was 64% (95% CI: 35-87). In CCS with subnormal Inhibin B levels, the proportion of azoospermic men was 66% (95% CI: 47-81) and for those with elevated follicle-stimulating hormone (FSH) levels, the proportion was 50% (95% CI: 35-67). Among CCS with subnormal testicular volume (≤ 24 mL), azoospermia was found in 61% (95% CI: 39-80) of the cases. Most childhood cancer diagnoses are associated with an increased risk of azoospermia, especially in CCS receiving testicular irradiation, high doses of alkylating drugs and other types of cytotoxic treatment, if combined with irradiation. Inhibin B, FSH and testicular volume can be used as predictors for the risk of azoospermia.