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This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to Y-90-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m(2) every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving Y-90-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare lymphoid malignancies that mostly have poor prognoses with currently available treatments. Upfront consolidation with autologous stem cell transplantation (ASCT) is frequently carried out, but its efficacy has never been investigated in randomized trials. We designed a multicenter, international, retrospective study with the main objective of comparing progression-free survival (PFS) and overall survival (OS) of patients with PTCL who underwent ASCT in complete remission (CR) after first-line chemotherapy with a control group who did not undergo ASCT. From the initial population of 286 registered patients, 174 patients with PTCL other than anaplastic large cell lymphoma, ALK-positive, deemed fit for ASCT at the time of diagnosis, and who were in CR or uncertain CR after induction therapy (CR1) were included in our analysis. 103 patients underwent ASCT, whereas 71 did not, in most cases (n=53) because the physician decided against it. With a median follow-up of 65.5 months, PFS was significantly better in the transplanted patients than in the non-transplanted group: 63% vs. 48% at 5 years (p=0.042). OS was significantly longer for ASCT patients in the subgroup with advanced stage at diagnosis (5-year OS: 70% vs. 50%, p=0.028). In the multivariate analysis, first-line ASCT was associated with significantly prolonged PFS (HR 0.57, 95% CI 0.35-0.93) and OS (HR 0.57, 95% CI 0.33-0.99). In conclusion, our study supports the use of ASCT as a consolidation strategy for patients with PTCL in CR1. These results should be confirmed in a prospective randomized study.

Background: Ten years after their availability, thrombopoietin receptor agonists (TPO-RA) have heralded a paradigm shift in the treatment of immune thrombocytopenia (ITP). This study was aimed to analyze the implementation of current recommendations in the standard practice of adult ITP patients, and how age may influence those changes. Methods: We included 121 adult patients (> 65 years, n = 54; younger individuals, n = 67) who initiated treatment with TPO-RA between January 2012 and December 2014. Results: Patients older than 65 years treated with TPO-RA presented at diagnosis with significantly higher platelet counts, less bleeding, and a more prothrombotic profile than younger ones. The high efficacy rates of TPO-RA, preferentially used during the last decade in non-chronic phases, precluded from further therapies in the majority of ITP patients. Their administration was associated with a sharp decline in the last decade in the use of splenectomy and intravenous immunoglobulin, especially in younger ITP individuals. Conclusion: These results confirm (1) that there is a preferential use of TPO-RAs in elderly ITP patients with fewer bleeding complications but more unfavorable prothrombotic conditions than in younger individuals, and (2) that early use of these agents has been established as an effective therapeutic alternative to other second line therapies.

Obra ressenyada: Carlos SCOLARI, Hacer clic: Hacia una sociosemiótica de las interacciones digitales. Barcelona: Gedisa, 2004.

Les principals cadenes de televisió que emeten a Catalunya van cobrir l'anomenada "crisi de les tanques" de Ceuta i Melilla amb un discurs solidari però alarmista en què la representació dels immigrants va oscil·lar entre la victimització i l'amenaça de perill. Aquest són algunes conclusions que s'extreuen de l'estudi que es presenta en aquest article. La recerca analitza i compara una mostra de vuit dies dels teleinformatius del vespre de diverses televisions per conèixer les prioritats informatives dels mitjans, l'elaboració i l'evolució de la noticia, així com la representació dels actors i del conflicte.

The poor prognosis of refractory or relapsed (R/R) classical Hodgkin's lymphoma (cHL) after autologous stem cell transplantation has improved greatly due to the introduction of brentuximab vedotin and PD-1 inhibitors. However, the duration of response achieved with these novel agents is too short. The information about the management of patients after antiPD-1 therapy failure is very limited in cHL, although chemotherapy alone or combined with PD-1 inhibitors has shown encouraging results. We report three cases of heavily pretreated cHL, refractory to nivolumab monotherapy, successfully rescued with the addition of chemotherapy to nivolumab, as a bridge to allogeneic stem cell transplantation (allo-SCT). All three patients presented poor clinical features such as three to four previous lines including brentuximab vedotin and autologous stem cell transplantation, refractoriness to the last line of therapy previous to nivolumab, and rapid disease progression. Notwithstanding these characteristics and nivolumab failure, they achieved a complete response after the addition of chemotherapy, were consolidated with allo-SCT, and still remain in complete response. There are few studies concerning the combination of PD-1 inhibitors and chemotherapy after nivolumab failure, including one retrospective study and one phase II trial with nivolumab plus bendamustine. Therefore, only few patients are consolidated with allo-SCT. However, there are several ongoing trials investigating new combinations of chemotherapy and PD-1 inhibitors in R/R cHL, as well as in first line. All these data suggest that anti-PD-1 therapy may reprogram the immune system, activating and inhibiting effector and immunosuppressive cells, respectively, leading to overtake of chemorefractoriness. Allo-SCT can increase the immune-related events of patients treated with anti-PD-1 previously, consistent on acute graft-versus-host disease, sinusoidal obstruction syndrome, and noninfectious febrile syndrome. In conclusion, the combination of PD-1 inhibitor and chemotherapy may be a feasible therapy after anti-PD-1 treatment failure as a bridge to allo-SCT.

Liposomal amphotericin B (L-AmB) has been a key cornerstone for the management of invasive fungal infections (IFI) caused by a wide array of molds and yeasts during the last three decades. Multiple studies performed over this period have generated a large body of evidence on its efficacy and safety, becoming the main antifungal agent in the management of IFI in patients with hematologic malignancies in several not mutually exclusive clinical settings. First, L-AmB is the most commonly used antifungal agent in patients undergoing intensive chemotherapy for acute leukemia and high-risk myelodysplastic syndrome, as well as in hematopoietic stem cell transplant recipients. Additionally, due to the administration of newer targeted therapies (such as monoclonal antibodies or small molecule inhibitors), opportunistic mold infections are increasingly being reported in patients with hematologic malignancies usually considered low-risk for IFI. These agents usually have a high drug-drug interaction potential, being triazoles, commonly used for antifungal prophylaxis, included. Finally, patients developing breakthrough IFI because of either subtherapeutic concentrations of antifungal prophylactic drugs in blood or selection of resistant strains, require broad spectrum antifungal therapy, usually with an antifungal of a different class. In both situations, L-AmB remains as the best option for early antifungal therapy.

Febrile neutropenia is a very common complication in patients with hematological malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrugresistant bacteria have become a therapeutic challenge in this high-risk patient population, since inadequate initial empirical treatment can seriously compromise prognosis. However, reducing antimicrobial exposure is one of the most significant cornerstones in the fight against resistance. The objective of these new guidelines is to update recommendations for the initial management of hematological patients who develop febrile neutropenia in this scenario of multidrug resistance. The two participating Societies (the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica [ Spanish Society of Infectious Diseases and Clinical Microbiology] and the Sociedad Espanola de Hematologia y Hemoterapia [ Spanish Society of Haematology and Haemotherapy]), designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on bacterial infections. Other aspects related to opportunistic infections, such as those caused by fungi or other microorganisms, especially in hematopoietic stem cell transplantation, are also touched upon. (C) 2019 Elsevier Espafia, S.L.U. and Sociedad Espafiola de Enfermedades Infecciosas y Microbiologia Mica. All rights reserved.

We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as conditioning for autologous stem-cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3-year progression-free survival (PFS). Sixty patients (median age 55 [28-71] years) were included. All patients (except one who died early) engrafted after a median of 11 (9-72) and 14 (4-53) days to achieve neutrophil and platelet counts of >0.5 x 10(9)/l and >20 x 10(9)/l, respectively. Non-relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow-up of 67 (40-77) months, the estimated 3-year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk [RR], 0.27 [95% confidence interval {CI} [0.12-0.56]) and OS (RR, 0.40 [95% CI 0.17-0.97]) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies.

Monitoring measurable residual disease has been postulated to be a surrogate marker of progression free survival in chronic lymphocytic leukemia patients after treatment with immunochemotherapy regimens. In this study, we have analyzed the outcome of 84 patients at 3 years of follow up after first line treatment with fludarabine, cyclophosphamide and rituximab induction followed by 36 months of rituximab maintenance. Measurable residual disease was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3-years of follow up. Bone marrow measurable residual disease analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36-month of maintenance. Thirty-seven cases (44%) had undetectable bone marrow residual disease prior to maintenance. Interestingly, 29 patients with detectable bone marrow residual disease after induction, had undetectable bone marrow residual disease following maintenance. After a median follow-up of 6.30 years, median overall survival and progression free survival were not reached in patients with either undetectable or detectable bone marrow residual disease, who had achieved a complete response at the time of starting maintenance. Interestingly, univariate analysis showed that after rituximab maintenance overall survival was not affected by IGHV status (mutated vs unmutated overall survival: 85.7% alive at 7.2 years vs 79.6 % alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and bone marrow residual disease after 4 courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete 2 additional courses of rituximab and continue with maintenance for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full 6-cycles induction regimen. These data show that fludarabine, cyclophosphamide and rituximab followed by rituximab maintenance produce high-quality responses with less relapse and improved overall survival compared to historic controls, showing a favorable tolerability. Furthermore, attaining an early undetectable residual disease status could reduce the length of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of bone marrow measurable residual disease after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with chronic lymphocytic leukemia undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies. This trial is registered with EudraCT No.: 2007-002733-36 and ClinicalTrials.gov Identifier: NCT00545714.

IMPORTANCE Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. OBJECTIVE To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. INTERVENTIONS Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n=922) or placebo (n=924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. MAIN OUTCOMES AND MEASURES The primary end point was occurrence of confirmed herpes zoster cases. RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P

Achieving and maintaining high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients {less than or equal to} 65 years old with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with intravenous busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the {greater than or equal to} very good partial response rates were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 10 -6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade {greater than or equal to} 3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade {greater than or equal to} 2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at ClinicalTrials.gov (NCT01916252) and EudraCT (2012-005683-10).