Key PointsVRD was effective and well tolerated before ASCT; 33.4% complete response/28.8% minimal residual disease–negative after 6 induction cycles. Responses deepened with VRD throughout induction and over the course of treatment with few discontinuations due to toxicity.

Summary:We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P Ͻ 0.001) and a dose of CD34 + cells infused below 6 × 10 6 /kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an Following conventional allogeneic hematopoietic stem cell transplantation (HSCT) all patients experience a period of profound neutropenia and immunodeficiency that are significantly responsible for the serious infectious complications that ensue post transplant. Standard conditioning regimens for HSCT involve high-dose chemoradiotherapy given in doses that are myeloablative or at least severely myelotoxic. However, over the past years several groups of investigators have developed reduced-intensity conditioning (RIC) or non-myeloablative regimens, which lead to engraftment of donor lymphoid and hematopoietic stem cells without the extrahematologic toxicities of traditional myeloablative transplants. [1][2][3][4][5][6][7] This reduced extrahematologic toxicity may lead to a reduction in infectious complications post transplant, since disruption of the gastrointestinal mucosa and/or damage to other key organs is a significant triggering mechanism of many of the infections that occur post transplant. 8,9 On the other hand, graft-versus-host disease (GVHD) and its treatment has a profound negative impact on immune reconstitution following HSCT, 10 and the impact of RIC regimens on the risk of acute and chronic GVHD is currently uncertain. The potential benefit on the ri...

Summary. High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m 2 melphalan (MEL200), 127 patients with 140 mg/m 2 melphalan plus total body irradiation (MEL140 1 TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m 2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P 0´003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26±68] compared with 43% (CI 31±54) for MEL140 1 TBI and 37% (CI: 18±56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 1 TBI groups respectively. These differences were non-significant (P 0´2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 1 TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P 0´01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.Keywords: myeloma, conditioning regimen, autotransplant, survival, registry.Despite the advantages of autologous stem cell transplantation (ASCT) over conventional chemotherapy (Attal et al, 1996;Barlogie et al, 1997), the results of high-dose chemoradiotherapy in multiple myeloma (MM) are still unsatisfactory with a 6-year event free survival (EFS) of only 24% (Harousseau et al, 1995). Apparently, none of the different conditioning regimens shows a clear benefit over any other. In order to improve these results, efforts have focused on three areas: (i) optimizing the timing of ASCT (Harousseau et al,

Summary. Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m 2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55% [95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P ¼ 0AE00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.

Background: ENKTL account for more than 20% of the peripheral T-cell lymphoma in Asia. Patients with r/r ENKTL have a poor prognosis after failing an L-asparaginase based regimen, and the median overall survival is less than 6 months. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance, and recent studies of PD-1 antibodies in pts with r/r ENKTL have demonstrated potential efficacy. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has a safety profile consistent with other approved PD-1 antibodies and was approved for r/r classical Hodgkin lymphoma in China in 2018. Aims: This multicenter, single-arm, phase 2 study aims to validate the efficacy and safety of sintilimab monotherapy in patients with r/r EN-KTL in China. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate based on LUGANO 2014 criteria. Data cut-off date for this analysis was Feb 2, 2019. Results: From Aug 31, 2017 to Feb 7, 2018, a total of 28 patients were enrolled: 60.7% male and the median age was 37 (range: 19~65) yr. Sixty-eight percent of patients were stage IV and 89.3% were ECOG PS  1. All patients had failed an L-asparaginase based regimen, the median lines of previous therapy were 3 (range: 1~13), 78.6% patients received prior radiotherapy and 7.1% had failed HSCT. Median duration of therapy was 14.04 (range: 1.4~17.3) months and 19 patients are still receiving sintilimab. Sixty-eight percent (19/28, 95%CI: 47.6%~84.1%) of patients achieved response (CR+PR), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. The 1-year OS rate was 82.1% and the median OS has not been reached. Most TRAEs were G1~2 (67.9%) and no patients discontinued treatment due to AEs. The most common TRAE was decreased lymphocyte count (46.4%) and 84.6% were grade 1~2. SAEs occurred in 21.4% of patients and none were related to sintilimab. No patients died from AEs. Summary/Conclusion: Sintilimab is effective and well tolerated in r/r ENKTL and could be a promising treatment option for these patients. Early disease progression observed by PET scan in this study could be pseudo-progression as it did not correlate with poor outcome, which warrants further investigation. NCT03228836