Conceptual design of the AGATA 1π array at GANIL Clément, E.; Michelagnoli, C.; de France, G. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
05/2017, Letnik:
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Journal Article
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The Advanced GAmma Tracking Array (AGATA) has been installed at the GANIL facility, Caen-France. This set-up exploits the stable and radioactive heavy-ions beams delivered by the cyclotron ...accelerator complex of GANIL. Additionally, it benefits from a large palette of ancillary detectors and spectrometers to address in-beam γ-ray spectroscopy of exotic nuclei. The set-up has been designed to couple AGATA with a magnetic spectrometer, charged-particle and neutron detectors, scintillators for the detection of high-energy γ rays and other devices such as a plunger to measure nuclear lifetimes. In this paper, the design and the mechanical characteristics of the set-up are described. Based on simulations, expected performances of the AGATA 1π array are presented.
Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. ...Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT.
Renal dysfunction is a common complication of plasma cell myeloma (PCM) that may be severe enough to necessitate hemodialysis. Although high-dose chemotherapy and hematopoietic cell transplant (HCT) ...appears superior to conventional chemotherapy in likelihood of achieving CR and is associated with improvement in and, at times, reversal of renal dysfunction, many patients remain dialysis-dependent presenting the challenge of renal transplantation in this population. We reviewed the published literature and summarize the outcomes on dual organ (HCT and renal allograft) transplantation in patients with PCM and dialysis-dependent renal failure. In a literature review of 14 reports, 26 of 166 dialysis-dependent patients became dialysis-independent. Our review includes a very heterogenous patient population but suggests that HCT and renal allograft may be feasible in a subset of PCM patients with dialysis-dependent renal failure. Although there is a concern for renal allograft rejection upon withdrawal of immunosuppression, data suggest that resumption of antirejection therapy leads to stable renal function. Bortezomib potentially can be used as maintenance treatment in patients who have not achieved a CR while preventing renal allograft rejection. The literature that describes dual transplants has included patients with long-term follow-up (>7 years in some patients). It is possible, however, that there may be publication bias with only favorable results being reported. More research is necessary to further delineate the subset of PCM patients most likely to benefit from renal transplant. A special registry for data collection for long-term follow-up may be useful to improve future patient survival.
The introduction of the tyrosine kinase inhibitors (TKI) into the treatment of patients with Ph or BCR-ABL1-positive acute lymphoblastic leukemia has revolutionized the treatment of this poor ...prognosis acute leukemia. The combination of TKI with chemotherapy has improved response rates and allowed more patients to proceed to allogeneic hematopoietic cell transplant (alloHCT). Older patients have excellent responses to TKI and corticosteroids or in combination with minimal chemotherapy. This raises the question as to whether patients require full-intensity chemotherapy with TKI to achieve molecular remissions. The pediatricians have proposed that cure is achievable without alloHCT in children. These results have suggested that many patients may not require traditional chemotherapy in addition to TKI to achieve remission, and that patients who achieve a negative minimal residual disease state may not require alloHCT. The data in support of these questions is presented here and a suggested future clinical trial design based on these data is proposed.
We describe the long-term outcomes of autologous hematopoietic cell transplantation (HCT) for 315 AML patients in first or second complete remission (CR). All patients were in continuous CR for ≥2 ...years after HCT. Patients were predominantly transplanted in CR1 (78%) and had good or intermediate cytogenetic risk disease (74%). Median follow-up of survivors was 106 (range, 24-192) months. Overall survival at 10 years after HCT was 94% (95% confidence intervals, 89-97%) and 80% (67-91%) for patients receiving HCT in CR1 and CR2, respectively. The cumulative incidence of relapse at 10 years after HCT was 6% (3-10%) and 10% (3-20%) and that of nonrelapse mortality was 5% (2-9%) and 11% (4-21%), respectively. On multivariate analysis, HCT in CR2 (vs CR1), older age at transplantation and poor cytogenetic risk disease were independent predictors of late mortality and adverse disease-free survival. The use of growth factors to promote engraftment after HCT was the only risk factor for relapse. Relative mortality of these 2-year survivors was comparable to that of age-, race- and gender-matched normal population. Patients who receive autologous HCT for AML in CR1 or CR2 and remain in remission for ≥2 years have very favorable long-term survival. Their mortality rates are similar to that of the general population.
To assess the impact of spleen status on engraftment, and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients ...from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil engraftment (NE) and platelet engraftment (PE) were 15 vs 18 days and 22 vs 24 days for the SP and NS groups, respectively (P<0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds ratio of days +14 and +21 NE and day +28 PE were 3.26, 2.25 and 1.28 for SP, and 0.56, 0.55, and 0.82 for SM groups compared to NS (P<0.001), respectively. Among patients with SM, use of peripheral blood grafts improved NE at day +21, and CD34+ cell dose >5.7 × 10(6)/kg improved PE at day+28. After adjusting variables by Cox regression, the incidence of GVHD and OS were not different among groups. SM is associated with delayed engraftment, whereas SP prior to HCT facilitates early engraftment without having an impact on survival.
Background
Although rituximab‐based high‐dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto‐HCT), data ...supporting the benefits are not available. Herein, we report the impact of rituximab‐based conditioning on auto‐HCT outcomes in patients who have DLBCL.
Methods
Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto‐HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab‐containing chemoimmunotherapy and had chemosensitive disease pre‐HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS).
Results
The study cohort was divided into 2 groups: BEAM (n = 667) and R‐BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS (P = .83) or progression‐free survival (PFS) (P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse (P = .15) or nonrelapse mortality (P = .12) was observed. Variables independently associated with lower OS included older age at auto‐HCT (P < .001), absence of CR at auto‐HCT (P < .001) and early chemoimmunotherapy failure (P < .001). Older age (P < .0002) and non‐CR pre‐HCT (P < .0001) were also associated with inferior PFS. There was no significant difference in early infectious complications between the 2 cohorts.
Conclusion
In this large registry analysis of DLBCL patients undergoing auto‐HCT, the addition of rituximab to the BEAM conditioning regimen had no impact on transplantation outcomes. Older age, absence of CR pre auto‐HCT, and early chemoimmunotherapy failure were associated with inferior survival.
Using Center for International Blood and Marrow Transplant Research registry data, we demonstrate that in diffuse large B cell lymphoma patients undergoing autologous hematopoietic cell transplantation, the addition of rituximab to the BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen has no impact on survival outcomes after transplantation.
The optimal post-remission treatment for acute myeloid leukemia in first complete remission remains uncertain. Previous comparisons of autologous versus allogeneic hematopoietic cell transplantation ...noted higher relapse, but lower treatment-related mortality though using bone marrow grafts, with treatment-related mortality of 12-20%. Recognizing lower treatment-related mortality using autologous peripheral blood grafts, in an analysis of registry data from the Center for International Blood and Transplant Research, we compared treatment-related mortality, relapse, leukemia-free survival, and overall survival for patients with acute myeloid leukemia in first complete remission (median ages 36-44, range 19-60) receiving myeloablative HLA-matched sibling donor grafts (bone marrow, n=475 or peripheral blood, n=428) versus autologous peripheral blood (n=230). The 5-year cumulative incidence of treatment-related mortality was 19% (95% confidence interval, 16-23%), 20% (17-24%) and 8% (5-12%) for allogeneic bone marrow, allogeneic peripheral blood and autologous peripheral blood stem cell transplant recipients, respectively. The corresponding figures for 5-year cumulative incidence of relapse were 20% (17-24%), 26% (21-30%) and 45% (38-52%), respectively. At 5 years, leukemia-free survival and overall survival rates were similar: allogeneic bone marrow 61% (56-65%) and 64% (59-68%); allogeneic peripheral blood 54% (49-59%) and 59% (54-64%); autologous peripheral blood 47% (40-54%) and 54% (47-60%); P=0.13 and P=0.19, respectively. In multivariate analysis the incidence of treatment-related mortality was lower after autologous peripheral blood transplantation than after allogeneic bone marrow/peripheral blood transplants relative risk 0.37 (0.20-0.69); P=0.001, but treatment failure (death or relapse) after autologous peripheral blood was significantly more likely relative risk 1.32 (1.06-1.64); P=0.011. The 5-year overall survival, however, was similar in patients who received autologous peripheral blood (n=230) relative risk 1.23 (0.98-1.55); P=0.071 or allogeneic bone marrow/peripheral blood (n=903). In the absence of an HLA-matched sibling donor, autologous peripheral blood may provide acceptable alternative post-remission therapy for patients with acute myeloid leukemia in first complete remission.
Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of ...clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5- and 10-year PFS rates are ~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.
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