Key Points• The overall response rate following 4 induction cycles of VTD prior to ASCT is higher than that of 4 cycles of VCD.The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamidedexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P 5 .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P 5 .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT.

Background The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear. Methods We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture. Findings We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% [1.18; 4.26] p = 0.013). Interpretation Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional. Registration As an observational study, this study has not been registered.

In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in patients enrolled in this study. Multivariate analysis showed that ISS stages 2 and 3 and achievement of response less than very good partial response (VGPR) both after induction therapy and after autologous stem cell transplantation were adverse prognostic factors for progression-free survival, the most important one being achievement of response less than VGPR after induction. Progression-free survival was significantly improved with bortezomib-dexamethasone induction therapy in patients with poor-risk cytogenetics and ISS stages 2 and 3 compared with vincristine-adriamycin-dexamethasone. In these 2 groups of patients, achievement of at least VGPR after induction was of major importance. IntroductionHigh-dose therapy with autologous stem cell transplantation (HDT-ASCT) is the standard of care for previously untreated multiple myeloma (MM) patients younger than 65 years of age. 1 Extensive evidence from studies in the transplant setting supports the relationship between achievement of complete response (CR) or very good partial response (VGPR) after transplant with substantially prolonged progression-free survival (PFS) and overall survival in previously untreated MM patients. 2-10 However, with conventional induction regimens the prognostic impact of achieving CR or at least VGPR before ASCT remained controversial, mainly because this situation did not occur frequently enough. 11-14 Nevertheless, the type of response achieved with novel agents as induction before ASCT might have an important prognostic impact. 15 Combinations that use novel agents, including bortezomibbased therapy, are currently evaluated as induction treatment before ASCT, with the objective of increasing the CR or CR plus VGPR rate both before and after ASCT. [16][17][18] In this setting, the recent phase 3 study by the Intergroupe Francophone du Myélome (IFM2005-01; NCT00200681) demonstrated the superiority of bortezomibdexamethasone induction before HDT-ASCT compared with vincristine-adriamycin-dexamethasone (VAD), the previous standard of care. In this trial, bortezomib-dexamethasone resulted in greater postinduction and posttransplant rates of VGPR or greater and a trend toward improved PFS. 19 The purposes of this post-hoc analysis were to assess the prognostic impact of initial characteristics as well as response to therapy in patients enrolled in the IFM 2005-01 study. MethodsPatients and study design IFM 2005-01 study details have been reported previously. 19 In brief, 482 patients aged 65 years or younger with untreated symptomatic MM were randomized to VAD induction (n ϭ 242), either without (arm A1) or with dexamethasone, cyclophosphamide, etoposide, and cis-platinum consolidation (A2), or bortezomib-dexamethasone in...

Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; Po0.0001), with higher viral load (Po0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR) ¼ 5.4, P ¼ 0.02 and OR ¼ 3.5, P ¼ 0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.