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.

Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen.

Preclinical models and clinical studies have shown that anti-CD20-based treatment has multifaceted consequences on T-cell immunity. We have performed a prospective study of peripheral T-cell compartment in FL patients, all exhibiting high tumor burden and receiving rituximab-chemotherapy-based regimen (R-CHOP). Before treatment, FL patients harbor low amounts of peripheral naive T cells, but high levels of CD4+ TEM, CD4+ Treg and CD8+ TEMRA subsets and significant amounts of CD38+ HLA-DR+ activated T cells. A portion of these activated/differentiated T cells also expressed PD-1 and/or TIGIT immune checkpoints. Hierarchical clustering of phenotyping data revealed that 5/8 patients with only a partial response to R-CHOP induction therapy or with disease progression segregate into a group exhibiting a highly activated/differentiated T cell profile and a markedly low proportion of naive T cells before treatment. Rituximab-based therapy induced a shift of CD4+ and CD8+ T cells toward a central memory phenotype and of CD8+ T cells to a naive phenotype. In parallel, a decrease in the number of peripheral T cells expressing both PD-1 and TIGIT was detected. These observations suggest that the standard rituximab-based therapy partially reverts the profound alterations observed in T-cell subsets in FL patients, and that blood T-cell phenotyping could provide a better understanding of the mechanisms of rituximab-based treatment.

Prevalence of Endoparasites in Urban Stray Dogs from Brazil Diagnosed with Leishmania, with Potential for Human Zoonoses.

BACKGROUND: In tropical environments, abandoned animals can be an important source for human zoonotic infections, such as human visceral leishmaniasis and other vector-borne diseases. Here, we report the frequency of protozoan and helminth intestinal parasites in stray dogs, which might have an implication for human health in urban Brazilian settings. MATERIAL AND METHODS: We performed necropsies on 93 animals, euthanized due to canine visceral leishmaniasis control program, and examined their intestines looking for the presence of helminths; we determined the parasite load, and the elimination of eggs and cysts of protozoan parasites in fecal samples. Further, we performed serology tests for the detection of specific antibodies against Toxoplasma gondii. RESULTS: Overall, a high prevalence of intestinal parasites with potential for human zoonoses resulted and only 8.6% of examined intestines remained negative. The most prevalent helminths were Ancylostoma caninum and Dipylidium caninum. For nematodes, high worm burdens were detected for A. caninum and Trichuris vulpis. Additionally, we analyzed worm burdens and quantitative stool examinations, but found no significant association between positive serology for Leishmania infection and intestinal parasite burden. Interestingly, serology for T. gondii infection revealed a prevalence of 33.3% and a positive result was significantly associated with a higher A. caninum adult worm recovery (p = 0.0087). CONCLUSION: Our results showed stray dogs living in urban areas are heavily parasitized, which presents a potential risk for humans. Beyond the control of canine visceral leishmaniasis, we propose an improvement of the control program to reduce the risk for other parasitic diseases in dogs and humans.

Radioimmunotherapy-augmented BEAM chemotherapy vs BEAM alone as the high-dose regimen for autologous stem cell transplantation (ASCT) in relapsed follicular lymphoma (FL): a retrospective study of the EBMT Lymphoma Working Party.

Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively. BEAM, Z-BEAM and R-BEAM groups were well balanced for age, time from diagnosis to ASCT and disease status at ASCT. The cumulative incidences of relapse (IR) at 2 years were 34, 34 and 32% for Z-BEAM, R-BEAM and BEAM, respectively. By multivariate analysis, there were no significant differences with Z-BEAM or R-BEAM compared with BEAM for IR, non-relapse mortality, event-free survival or overall survival. With the caveat that the limitations of registry analyses have to be taken into account, this study does not support adding radioimmunotherapy or R to BEAM in ASCT for relapsed FL. However, we cannot rule out the existence a particular subset of patients who could benefit from Z-BEAM conditioning that cannot be identified in our series, and this should be tested in a randomized trial.

HHV-6 reactivation as a cause of fever in autologous hematopoietic stem cell transplant recipients.

OBJECTIVES: We report the biological and clinical impacts possibly associated with HHV-6 reactivation in autologous hematopoietic stem cell transplant (AHSCT) recipients after intensive chemotherapy regimen for lymphoma. METHODS: We retrospectively reviewed clinical, biological, radiological, treatment and outcomes of patients with positive HHV-6 DNA in whole blood following autologous hematopoietic stem cell transplantation. RESULTS: Blood HHV-6 reactivation was reported in 27 (8.5%) patients among 316 AHSCT recipients after high dose therapy for lymphoma. Thirteen (4.1%) patients were symptomatic with fever (100%), diarrhea (61.5%), skin rash (46.1%), and pneumonia (23.1%). Antiviral treatment was administered in 9 (69%) patients and outcome was favorable in all cases. CONCLUSION: Our study suggests a possible pathogenic role of HHV-6 in AHSCT recipients and suggests an impact of antiviral treatments on viral replication and clinical signs resolution.

[Radiotherapy for localized gastric and orbital MALT lymphomas]. / Radiothérapie des lymphomes malins non hodgkiniens localisés de type MALT (gastriques et de la région orbitaire).

Primary gastric and orbital MALT lymphomas are both low grade (indolent) B-cell non-Hodgkin's lymphomas. Traditionally, these tumors are radiosensitive and have a good prognosis. In localized orbital and stages IE-IIE gastric MALT lymphomas without Helicobacter pylori infection or in case of persistent H. pylori infection after eradication therapy, several retrospective studies have shown that radiotherapy was an effective and well-tolerated treatment.

Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT.

Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.