Nonlinear rise in Greenland runoff in response to post-industrial Arctic warming.

The Greenland ice sheet (GrIS) is a growing contributor to global sea-level rise1, with recent ice mass loss dominated by surface meltwater runoff2,3. Satellite observations reveal positive trends in GrIS surface melt extent4, but melt variability, intensity and runoff remain uncertain before the satellite era. Here we present the first continuous, multi-century and observationally constrained record of GrIS surface melt intensity and runoff, revealing that the magnitude of recent GrIS melting is exceptional over at least the last 350 years. We develop this record through stratigraphic analysis of central west Greenland ice cores, and demonstrate that measurements of refrozen melt layers in percolation zone ice cores can be used to quantifiably, and reproducibly, reconstruct past melt rates. We show significant (P < 0.01) and spatially extensive correlations between these ice-core-derived melt records and modelled melt rates5,6 and satellite-derived melt duration4 across Greenland more broadly, enabling the reconstruction of past ice-sheet-scale surface melt intensity and runoff. We find that the initiation of increases in GrIS melting closely follow the onset of industrial-era Arctic warming in the mid-1800s, but that the magnitude of GrIS melting has only recently emerged beyond the range of natural variability. Owing to a nonlinear response of surface melting to increasing summer air temperatures, continued atmospheric warming will lead to rapid increases in GrIS runoff and sea-level contributions.

Tandem versus single haematopoietic stem cell transplant and BV maintenance in relapsed/refractory Hodgkin lymphoma: A matched cohort analysis from the LYSA.

Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high-risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV-naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV-exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.

Species limits and diversification of the Dendropsophus rubicundulus subgroup (Anura, Hylidae) in Neotropical savannas.

Understanding the processes that generate and maintain biodiversity at and below the species level is a central goal of evolutionary biology. Here we explore the spatial and temporal drivers of diversification of the treefrog subgroup Dendropsophus rubicundulus, a subgroup of the D. microcephalus species group, over periods of pronounced geological and climatic changes in the Neotropical savannas that they inhabit. This subgroup currently comprises 11 recognized species distributed across the Brazilian and Bolivian savannas, but the taxonomy has been in a state of flux, necessitating reexamination. Using newly generated single nucleotide polymorphism (SNP) data from restriction-site associated DNA sequencing (RADseq) and mitochondrial 16S sequence data for ∼150 specimens, we inferred phylogenetic relationships, tested species limits using a model-based approach, and estimated divergence times to gain insights into the geographic and climatic events that affected the diversification of this subgroup. Our results recognized at least nine species: D. anataliasiasi, D. araguaya, D. cerradensis, D. elianeae, D. jimi, D. rubicundulus, D. tritaeniatus, D. rozenmani, and D. sanborni. Although we did not collect SNP data for the latter two species, they are likely distinct based on mitochondrial data. In addition, we found genetic structure within the widespread species D. rubicundulus, which comprises three allopatric lineages connected by gene flow upon secondary contact. We also found evidence of population structure and perhaps undescribed diversity in D. elianeae, which warrants further study. The D. rubicundulus subgroup is estimated to have originated in the Late Miocene (∼5.45 million years ago), with diversification continuing through the Pliocene and Early Pleistocene, followed by the most recent divergence of D. rubicundulus lineages in the Middle Pleistocene. The epeirogenic uplift followed by erosion and denudation of the central Brazilian plateau throughout the Pliocene and Pleistocene, in combination with the increasing frequency and amplitude of climatic fluctuations during the Pleistocene, was important for generating and structuring diversity at or below the species level in the D. rubicundulus subgroup.

Linking Predator Responses to Alkaloid Variability in Poison Frogs.

Many chemically-defended/aposematic species rely on diet for sequestering the toxins with which they defend themselves. This dietary acquisition can lead to variable chemical defenses across space, as the community composition of chemical sources is likely to vary across the range of (an aposematic) species. We characterized the alkaloid content of two populations of the Dyeing Poison Frog (Dendrobates tinctorius) in northeastern French Guiana. Additionally, we conducted unpalatability experiments with naive predators, Blue Tits (Cyanistes caeruleus), using whole-skin secretion cocktails to assess how a model predator would respond to the defense of individuals from each population. While there was some overlap between the two D. tinctorius populations in terms of alkaloid content, our analysis revealed that these two populations are markedly distinct in terms of overall alkaloid profiles. Predator responses to skin secretions differed between the populations. We identified 15 candidate alkaloids (including three previously undescribed) in seven classes that are correlated with predator response in one frog population. We describe alkaloid profile differences between populations for D. tinctorius and provide a novel method for assessing unpalatability of skin secretions and identifying which toxins may contribute to the predator response. In one population, our results suggest 15 alkaloids that are implicated in predator aversive response. This method is the first step in identifying the causal link between alkaloids and behavioral responses of predators, and thus makes sense of how varying alkaloid combinations are capable of eliciting consistent behavioral responses, and eventually driving evolutionary change in aposematic characters (or characteristics).

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life.

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree-species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets.[AIC; Amphibia; Batrachia; Phylogeny; gene tree-species tree discordance; genomics; information theory.].

Weak warning signals can persist in the absence of gene flow.

Aposematic organisms couple conspicuous warning signals with a secondary defense to deter predators from attacking. Novel signals of aposematic prey are expected to be selected against due to positive frequency-dependent selection. How, then, can novel phenotypes persist after they arise, and why do so many aposematic species exhibit intrapopulation signal variability? Using a polytypic poison frog (Dendrobates tinctorius), we explored the forces of selection on variable aposematic signals using 2 phenotypically distinct (white, yellow) populations. Contrary to expectations, local phenotype was not always better protected compared to novel phenotypes in either population; in the white population, the novel phenotype evoked greater avoidance in natural predators. Despite having a lower quantity of alkaloids, the skin extracts from yellow frogs provoked higher aversive reactions by birds than white frogs in the laboratory, although both populations differed from controls. Similarly, predators learned to avoid the yellow signal faster than the white signal, and generalized their learned avoidance of yellow but not white. We propose that signals that are easily learned and broadly generalized can protect rare, novel signals, and weak warning signals (i.e., signals with poor efficacy and/or poor defense) can persist when gene flow among populations, as in this case, is limited. This provides a mechanism for the persistence of intrapopulation aposematic variation, a likely precursor to polytypism and driver of speciation.

Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma.

INTRODUCTION: Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. METHODS: We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. RESULTS: Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. CONCLUSION: In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.

Image-guided lymph node core-needle biopsy predicts survival in mycosis fungoides and Sézary syndrome.

BACKGROUND: The prognosis of Sézary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated. OBJECTIVES: To determine the prognostic value of LN CNB in MF/SS. METHODS: A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus. RESULTS: We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26-not reached) vs. 14 months (range 5-30), respectively (P < 0·001). In univariate analyses, an age > 75 years, LN short-axis diameter > 15 mm, N3 stage, presence of large-cell transformation, TOX > 60%, PD1 > 25%, Ki67 > 30%, KIR3DL2 > 15%, CD30 > 10% and TCF > 25% were identified as adverse prognostic factors. In multivariate analyses, only an age > 75 years and Ki67 index > 30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis. CONCLUSIONS: CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis.

Ambulatory high-dose methotrexate administration as central nervous system prophylaxis in patients with aggressive lymphoma.

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.

Steep Glacier Bed Knickpoints Mitigate Inland Thinning in Greenland.

Greenland's outlet glaciers have been a leading source of mass loss and accompanying sea-level rise from the Greenland Ice Sheet (GrIS) over the last 25 years. The dynamic component of outlet glacier mass loss depends on both the ice flux through the terminus and the inland extent of glacier thinning, initiated at the ice-ocean interface. Here, we find limits to the inland spread of thinning that initiates at glacier termini for 141 ocean-terminating outlet glaciers around the GrIS. Inland diffusion of thinning is limited by steep reaches of bed topography that we call "knickpoints." We show that knickpoints exist beneath the majority of outlet glaciers but they are less steep in regions of gentle bed topography, giving glaciers in gentle bed topography the potential to contribute to ongoing and future mass loss from the GrIS by allowing the diffusion of thinning far into the ice sheet interior.

Is Niagara Falls a barrier to gene flow in riverine fishes? A test using genome-wide SNP data from seven native species.

Since the early Holocene, fish population genetics in the Laurentian Great Lakes have been shaped by the dual influences of habitat structure and post-glacial dispersal. Riverscape genetics theory predicts that longitudinal habitat corridors and unidirectional downstream water-flow drive the downstream accumulation of genetic diversity, whereas post-glacial dispersal theory predicts that fish genetic diversity should decrease with increasing distance from glacial refugia. This study examines populations of seven native fish species codistributed above and below the 58 m high Niagara Falls - a hypothesized barrier to gene flow in aquatic species. A better understanding of Niagara Falls' role as a barrier to gene flow and dispersal is needed to identify drivers of Great Lakes genetic diversity and guide strategies to limit exotic species invasions. We used genome-wide SNPs and coalescent models to test whether populations are: (a) genetically distinct, consistent with the Niagara Falls barrier hypothesis; (b) more genetically diverse upstream, consistent with post-glacial expansion theory, or downstream, consistent with the riverscape habitat theory; and (c) have migrated either upstream or downstream past Niagara Falls. We found that genetic diversity is consistently greater below Niagara Falls and the falls are an effective barrier to migration, but two species have probably dispersed upstream past the falls after glacial retreat yet before opening of the Welland Canal. Models restricting migration to after opening of the Welland Canal were generally rejected. These results help explain how river habitat features affect aquatic species' genetic diversity and highlight the need to better understand post-glacial dispersal pathways.

Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation.

STUDY QUESTION: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? SUMMARY ANSWER: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. STUDY DESIGN, SIZE, DURATION: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). MAIN RESULTS AND ROLE OF CHANCE: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. LIMITATIONS, REASONS FOR CAUTION: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. TRIAL REGISTRATION NUMBER: NCT02184806.

Dramatic response to brentuximab vedotin in refractory nontransformed CD30- mycosis fungoides allowing allogeneic stem cell transplant and long-term complete remission.

The erythrodermic ulcerated form of mycosis fungoides (MF) is exceptional, and treatment of refractory cases is challenging. Brentuximab vedotin (BV) is a monoclonal antibody combined with monomethyl auristatin E, recently approved for the treatment of refractory CD30+ cutaneous T-cell lymphoma. We report a case of refractory MF in a 56-year-old man with a long history of large-plaque parapsoriasis, as revealed by psoriasiform erythroderma, treated initially with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) polychemotherapy, inducing a 2-year complete response. After relapse, interferon and gemcitabine were unsuccessful. Finally, treatment with BV was decided upon, despite the absence of CD30 expression. After three infusions of BV 1·8 mg kg-1 , we achieved a complete and stable response, allowing an allogeneic stem cell transplant. The patient is still in complete remission, 19 months after the graft. This case illustrates the possibility of using BV in refractory CD30- MF as a salvage therapy.

A cytochrome P450 CYP71 enzyme expressed in Sorghum bicolor root hair cells participates in the biosynthesis of the benzoquinone allelochemical sorgoleone.

Sorgoleone, a major component of the hydrophobic root exudates of Sorghum spp., is probably responsible for many of the allelopathic properties attributed to members of this genus. Much of the biosynthetic pathway for this compound has been elucidated, with the exception of the enzyme responsible for the catalysis of the addition of two hydroxyl groups to the resorcinol ring. A library prepared from isolated Sorghum bicolor root hair cells was first mined for P450-like sequences, which were then analyzed by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to identify those preferentially expressed in root hairs. Full-length open reading frames for each candidate were generated, and then analyzed biochemically using both a yeast expression system and transient expression in Nicotiana benthamiana leaves. RNA interference (RNAi)-mediated repression in transgenic S. bicolor was used to confirm the roles of these candidates in the biosynthesis of sorgoleone in planta. A P450 enzyme, designated CYP71AM1, was found to be capable of catalyzing the formation of dihydrosorgoleone using 5-pentadecatrienyl resorcinol-3-methyl ether as substrate, as determined by gas chromatography-mass spectroscopy (GC-MS). RNAi-mediated repression of CYP71AM1 in S. bicolor resulted in decreased sorgoleone contents in multiple independent transformant events. Our results strongly suggest that CYP71AM1 participates in the biosynthetic pathway of the allelochemical sorgoleone.

Malaria burden and anti-malarial drug efficacy in Owando, northern Congo.

BACKGROUND: In the Republic of Congo, previous epidemiological studies have only been conducted in the south of the country where it is most accessible. Nationally representative data on the efficacy of new anti-malarial tools are lacking in the country. As an initial step to close the gap, clinical efficacy of two artemisinin-based combinations, artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL), was assessed in Owando, a city in equatorial flooded forest in northern Republic of Congo. METHODS: Under 12 years old febrile children attending public health facilities were screened for malaria parasites using lactate dehydrogenase (LDH)-based rapid diagnostic test (RDT) for malaria and microscopic examination of thick blood films. Patients with at least 1,000 asexual Plasmodium falciparum parasites/µl of blood were clinically examined, included after informed consent, and followed up for 28 days, according to the 2009 World Health Organization protocol. Patients were randomly assigned to co-formulated ASAQ (Coarsucam(®)) or AL (Coartem(®)) treatment groups. Plasmodium falciparum recrudescent isolates were compared to pre-treatment isolates by polymerase chain reaction (PCR) using msp1, msp2, and glurp genes to distinguish between re-infection and recrudescence. RESULTS: Between November 2012 and February 2013, 857 under 12 years old febrile children were screened, of whom 198 (23.1%) had positive RDT and 167 (19.5%) positive thick films. ASAQ and AL efficacies were 92.7 and 94.2% before PCR correction, respectively. After genotyping, the overall efficacy was 100% for ASAQ and 98.0% for AL. CONCLUSION: The data reported here represent partially the burden of malaria in 0-11 years old febrile children examined in public health centres of Owando city and serve as reference for further studies. Both artemisinin-based combinations were highly efficacious in patients under 12 years old with acute uncomplicated malaria. ASAQ was associated with more adverse events, which may reduce compliance in unsupervised treatment. TRIAL REGISTRATION: ACTRN12612000940875.

ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial.

BACKGROUND: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. PATIENTS AND METHODS: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥ baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. RESULTS: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P = 0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). CONCLUSION: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP.