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The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529-0.832) and progression free survival (RR 0.708 (0.577-0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270-0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597-0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.
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Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Adulto , Criança , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Recidiva , Suíça , Condicionamento Pré-Transplante , Transplante Homólogo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory multiple myeloma (RRMM), leading to unprecedented responses in this patient population. Idecabtagene vicleucel (ide-cel) has been recently approved for treatment of triple-class exposed RRMM. We report real-life experiences with the commercial use of ide-cel in RRMM patients. METHODS: We performed a retrospective analysis of the first 16 triple-class exposed RRMM patients treated with ide-cel at a single academic center. We assessed toxicities, response to treatment, CAR T expansion and soluble BCMA (sBCMA) levels. RESULTS: We identified 16 consecutive RRMM patients treated with ide-cel between 06-10/2022. Median age was 69 years, 6 (38%) patients had high-risk cytogenetics, 3 (19%) R-ISS stage III, and 5 (31%) extramedullary disease. Median number of previous treatment lines was 6 (3-12). Manufacturing success rate was 88% (6% required second lymphapheresis, 6% received an out-of-specification product). At 3 months, the overall response rate (ORR) was 69% (44% sCR, 6% CR, 19% VGPR). Cytokine release syndrome (CRS) occurred in 15 (94%) patients (88% G1, 6% G2), immune effector-cell associated neurotoxicity syndrome (ICANS) in 1 (6% G1), febrile neutropenia in 11 (69%), and infections in 5 (31%). Prolonged hematologic toxicity occurred in 4/16 (25%) patients. Other non-hematological toxicities were elevated hepatic enzymes (38%), colitis (6%, G3) and DIC (6%, G2). Responses were more frequent in patients with higher CAR T expansion (100% vs 38%), and lack of decrease or plateau of sBCMA levels was typically observed in non-responders. CONCLUSIONS: We report one of the first cohorts of RRMM treated with commercial ide-cel. The ORR was 69% and safety profile was manageable, but prolonged hematologic toxicity still represents a major challenge. Responses correlated with in vivo CAR T cell expansion, underlining the need of further research to optimize CAR T expansion.
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Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Idoso , Imunoterapia Adotiva/efeitos adversos , Mieloma Múltiplo/terapia , Estudos RetrospectivosRESUMO
Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.
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Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to investigate the correlation between CAR T-cell persistence in the peripheral blood (PB) at 6 months, assessed by droplet digital PCR (ddPCR), with CAR T-cell treatment outcome. 92 patients with r/r B-cell lymphomas were treated with CD19-targeting CAR T-cell therapies at our institution between 01/2019-08/2022. Six months post-treatment, 15 (16%) patients had no detectable circulating CAR-T constructs by ddPCR. Patients with CAR T-cell persistence had a significantly higher CAR T-cell peak (5432 vs. 620 copies/ug cfDNA, p = 0.0096), as well as higher incidence of immune effector cell-associated neurotoxicity syndrome (37% vs. 7%, p = 0.0182). After a median follow-up of 8.5 months, 31 (34%) patients relapsed. Lymphoma relapses were less frequent among patients with CAR T-cell persistence (29% vs. 60%, p = 0.0336), and CAR T-cell persistence in the PB at 6 months was associated with longer progression-free survival (PFS) (HR 2.79, 95% CI: 1.09-7.11, p = 0.0319). Moreover, we observed a trend towards improved overall survival (OS) (HR 1.99, 95% CI: 0.68-5.82, p = 0.2092) for these patients. In our cohort of 92 B-cell lymphomas, CAR T-cell persistence at 6 months was associated with lower relapse rates and longer PFS. Moreover, our data confirm that 4-1BB-CAR T-cells have a longer persistence as compared to CD-28-based CAR T-cells.
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Linfoma de Células B , Linfócitos T , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/etiologia , Linfoma de Células B/terapia , Linfoma de Células B/etiologia , Imunoterapia Adotiva/efeitos adversosRESUMO
INTRODUCTION: A small number of retrospective studies suggest AIHA to be associated with an increased risk to suffer from thromboembolic events. However, based on these studies it remains unclear whether the complement activation per is a risk factor to develop thromboembolic events in AIHA patients. The aim of this retrospective study is to investigate the incidence of thromboembolic events and the relation to complement activation in a cohort of AIHA patients. PATIENTS AND METHODS: We included 77 patients in this study with a positive DAT and hemolytic parameters or with AIHA diagnosis based on the medical report. The included patients were screened for thromboembolic events (TEE) and have been stratified in groups with and without complement activation based on the positivity for complement in the DAT. RESULTS: Of the 77 included patients, 51 (66%) had warm AIHA, 13 (17%) cold-AIHA, 5 (7%) mixed AIHA, and 8 (10%) atypical AIHA, respectively. Primary and secondary AIHA was diagnosed in 44% and 56%, respectively. Twenty patients (26%) suffered from TEE. The majority (80%) of these patients suffered from warm AIHA and 10% from cold-AIHA. Hemolysis parameters did not differ in patients with and without TEE. There was no correlation with complement activation as evidenced by a positivity for complement in the monospecific DAT with the occurrence of TEE. CONCLUSION: AIHA is associated with an increased risk of TEE. Based on these results prophylactic anticoagulation might be considered as soon as the diagnosis of AIHA is confirmed.
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Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/diagnóstico , Autoimunidade , Biomarcadores , Proteínas do Sistema Complemento/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suíça/epidemiologia , Tromboembolia/diagnósticoRESUMO
BACKGROUND: Imetelstat, a 13-mer oligonucleotide that is covalently modified with lipid extensions, competitively inhibits telomerase enzymatic activity. It has been shown to inhibit megakaryocytic proliferation in vitro in cells obtained from patients with essential thrombocythemia. In this phase 2 study, we investigated whether imetelstat could elicit hematologic and molecular responses in patients with essential thrombocythemia who had not had a response to or who had had unacceptable side effects from prior therapies. METHODS: A total of 18 patients in two sequential cohorts received an initial dose of 7.5 or 9.4 mg of imetelstat per kilogram of body weight intravenously once a week until attainment of a platelet count of approximately 250,000 to 300,000 per cubic millimeter. The primary end point was the best hematologic response. RESULTS: Imetelstat induced hematologic responses in all 18 patients, and 16 patients (89%) had a complete hematologic response. At the time of the primary analysis, 10 patients were still receiving treatment, with a median follow-up of 17 months (range, 7 to 32 [ongoing]). Molecular responses were seen in 7 of 8 patients who were positive for the JAK2 V617F mutation (88%; 95% confidence interval, 47 to 100). CALR and MPL mutant allele burdens were also reduced by 15 to 66%. The most common adverse events during treatment were mild to moderate in severity; neutropenia of grade 3 or higher occurred in 4 of the 18 patients (22%) and anemia, headache, and syncope of grade 3 or higher each occurred in 2 patients (11%). All the patients had at least one abnormal liver-function value; all persistent elevations were grade 1 or 2 in severity. CONCLUSIONS: Rapid and durable hematologic and molecular responses were observed in patients with essential thrombocythemia who received imetelstat. (Funded by Geron; ClinicalTrials.gov number, NCT01243073.).
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Indóis/administração & dosagem , Niacinamida/análogos & derivados , Telomerase/antagonistas & inibidores , Trombocitemia Essencial/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Humanos , Indóis/efeitos adversos , Infusões Intravenosas , Janus Quinase 2/genética , Fígado/enzimologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Mutação , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Oligonucleotídeos , Projetos Piloto , Trombocitemia Essencial/genéticaAssuntos
Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Mieloma Múltiplo , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Humanos , Mieloma Múltiplo/terapia , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Transplante Autólogo , Fator Estimulador de Colônias de Granulócitos , BenzilaminasRESUMO
Besides 5-azacytidine (azacitidine, Vidaza®), 5-aza-2'-deoxycytidine (decitabine, Dacogen®) is the most widely used inhibitor of DNA methylation, which triggers demethylation leading to consecutive reactivation of epigenetically silenced tumor suppressor genes in vitro and in vivo. Although antileukemic activity of decitabine is known for almost 40 years, its therapeutic potential in hematologic malignancies has only recently led to its approval in higher-risk MDS patients and as first-line treatment in AML patients>65 years who are not candidates for intensive chemotherapy. Several clinical trials showed promising activity of low-dose decitabine also in CML and hemoglobinopathies, whereas its efficacy in solid tumors is very limited. Clinical responses appear to be exerted both by epigenetic alterations and by induction of cell-cycle arrest and/or apoptosis. Recent and ongoing clinical trials investigate new dosing schedules, routes of administration, and combination of decitabine with other agents, including histone deacetylase inhibitors.
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Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Animais , Azacitidina/uso terapêutico , Metilases de Modificação do DNA/antagonistas & inibidores , Decitabina , HumanosRESUMO
Gemtuzumab ozogamicin (GO), a CD33-targeting antibody drug conjugate, previously showed longer relapse-free survival when combined with induction chemotherapy in patients with favorable-risk acute myeloid leukemia (AML). In this patient population, characterized by lower relapse risk as compared to other ELN risk groups, autologous stem cell transplantation (ASCT) can be used as consolidation strategy. However, there are limited data on the impact of GO on the peripheral blood stem cell (PBSC) mobilization potential. We therefore retrospectively analyzed data from 54 AML patients with favorable-risk AML treated with (n = 17) or without (n = 37) GO during induction treatment. We observed no significant differences in the PBSC mobilization rate between patients treated with vs. without GO. The mobilization success in a first attempt directly following cycle 2 was 65% vs. 70% (p = 0.92); and the mobilization success in a subsequent second attempt after hematologic recovery and repeated stimulation procedure was 24% vs. 19% (p = 0.56). No significant impact on treatment outcome in terms of EFS (p = 0.31) or OS (p = 0.99) was observed. Thus, our results suggest that the addition of GO to induction regimens does not negatively impact PBSC mobilization in favorable-risk AML patients. To our best knowledge, this is the first study comparing the stem cell mobilization potential in favorable-risk AML patients treated with vs. without GO.
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Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.
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(1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients' basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29-2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19-2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit.
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CD19-directed chimeric antigen receptor (CAR)-T cell therapy has become a standard treatment for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). While the benefits of CAR-T cell treatment are clear in the general patient population, there remains a relative scarcity of real-world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR-T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR-T infusion (<70 vs. ≥70 years). Subsequently, descriptive and survival analyses, including propensity score matching, were performed to compare outcomes between both age groups. We identified 109 pts aged <70 and 63 pts aged ≥70 years. Overall response rates for both age groups were comparable (77.7% vs. 78.3%; p = 0.63). With a median follow-up of 8.3 months, median progression-free survival was 10.2 months (95% confidence interval [CI]: 6.5-21.8) and 11.1 months (95% CI: 4.9-NR) (p = 0.93) for both cohorts. Median overall survival reached 21.8 months (95% CI: 11.8-NR) and 34.4 months (95% CI: 10.1-NR) (p = 0.97), respectively. No significant differences in the incidence of cytokine release syndrome (p = 0.53) or grade ≥3 neurotoxicity (p = 0.56) were observed. Relapse and nonrelapse mortality were not significantly different between both groups. Our findings provide additional support that CAR-T cell therapy is feasible and effective in patients with r/r DLBCL aged 70 years or older, demonstrating outcomes comparable to those observed in younger patients. CAR-T cell therapy should be not withheld for elderly patients with r/r DLBCL.
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Chimeric antigen receptor (CAR)-T cell therapy is effective in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) with response rates of 63-84% and complete response observed in 43-54%. Common germline variants of the target antigen CD19 may elicit different responses to CAR-T cell therapy. The CD19 gene single nucleotide polymorphism rs2904880 encoding leucine or valine at amino acid position 174 of the CD19 antigen was prevalent in 51% of the studied DLBCL patients. In a retrospective comparative analysis of clinical outcome, there were significant differences in CD19 L174 versus V174 carriers: the median time of progression-free survival was 22 vs. 6 months (p = 0.06), overall survival was 37 vs. 8 months (p = 0.11), complete response rates were 51% vs. 30% (p = 0.05), and refractory disease rates were 14% vs. 32% (p = 0.04). The single nucleotide polymorphism in CD19 was shown to influence the treatment outcome in FMC63-anti-CD19-CAR-T cell therapy, and the CD19 minor allele L174 predicted a favorable treatment outcome.
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(1) Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard consolidation strategy for patients with newly diagnosed multiple myeloma (MM) and for a subset of patients with relapsed/refractory disease. For stem cell mobilization, G-CSF alone or in combination with chemotherapy mobilizing agents and/or plerixafor are commonly used. Ixazomib is an oral proteasome inhibitor with less neurotoxic potential, which previously showed the ability to mobilize stem cells in preclinical studies. (2) Methods: Prospective single-center phase 1 study assessing the efficacy and safety of stem cell mobilization with ixazomib and G-CSF in patients with newly diagnosed or relapsed/refractory MM undergoing HDCT and ASCT. Primary endpoint was percentage of patients achieving a yield of at least 6.0 × 106/kg CD34+ cells within the first apheresis. G-CSF (filgrastim) 10 µg/kg/day was administered subcutaneously (s.c.) from day 1 to day 5 (planned apheresis) and ixazomib 4 mg orally at day 4. Plerixafor 24 mg s.c. was administered if the stem cell mobilization with ixazomib and G-CSF was not sufficient. (3) Results: 19 patients were treated within the study between 06/2020 and 02/2021. The primary endpoint was reached in 17 (89%) patients, with a median of 7.1 × 106/kg CD34+ cells collected within the first apheresis, comparable to previously published results, and only 2 (11%) patients required a second apheresis. Median number of circulating CD34+ cells was 14.0 × 106/L (2.0-95.2) before the administration of ixazomib, and 33.0 × 106/L (4.2-177.0) pre-apheresis. However, 9 (47%) patients required the addition of plerixafor to ensure optimal stem cell collection. (4) Conclusions: The combination of ixazomib and G-CSF showed promising stem cell mobilizing activity in patients with MM prior to HDCT and ASCT. Future larger studies might further investigate the role of ixazomib in stem cell mobilization regimens for MM.
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High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is an option to consolidate remission in Waldenstrom's macroglobulinemia (WM), particularly in selected younger patients with chemosensitive disease. BEAM, consisting of BCNU, etoposide, cytarabine, and melphalan, is often used as a conditioning regimen. However, problems with BCNU, including pneumotoxicity, tolerance, and availability, necessitate the search for alternatives. In this pilot study, we investigated high-dose chemotherapy with BeEAM, in which BCNU is replaced with high-dose bendamustine as an alternative conditioning regimen in six subsequent patients with WM. Bendamustine treatment was well tolerated without unexpected toxicities. The overall response rate was 6/6 patients (2 very good partial responses (VGPR) and 4 PR). After a median follow-up of 72 months, two (33%) patients relapsed. Median progression-free and overall survivals were not reached, and no severe late-onset toxicities were observed so far. In this pilot study, BeEAM conditioning before ASCT seems feasible, safe, and effective in patients with WM.
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(1) Background: First-line therapy in fit MCL patients may comprise high-dose chemotherapy (HDCT) with autologous transplantation to consolidate remission before maintenance treatment. However, optimization of HDCT is an unmet clinical need given the substantial relapse rate of first-line treatment, while the use of bortezomib is a promising candidate to be added to standard HDCT. (2) Methods: We analyzed 11 consecutive patients with MCL who received bortezomib added to standard BeEAM (2BeEAM) HDCT at a single academic institution. We assessed safety, feasibility, toxicities, and survival rates. (3) Results: All patients had stage III or IV disease. We found that six patients (55%) developed new or worsening of preexisting peripheral neuropathy following administration of 2BeEAM HDCT. One patient relapsed within the first six months after HDCT, whereas three patients never reached complete remission. After a median follow-up of 22 months, the PFS was 64% and the OS 64% at the last follow-up assessment. At this time, 55% of patients were in CR. (4) Conclusions: The use of bortezomib added to standard BeEAM HDCT is associated with relevant toxicities, particularly with regards to additional neuropathy. Moreover, the anti-lymphoma efficacy of 2BeEAM HDCT appears to be modest; therefore, other therapeutic options should be evaluated for consolidation in this patient group.
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Postpartum hemorrhage (PPH) remains a major cause of maternal morbidity and mortality. While PPH treatment guidelines exist, data on their effect on reduction in red blood cell (RBC) transfusions and use of hemostatic products are scarce. Continuous evaluation of PPH management is important to assess potential pitfalls and incorporate new treatment options. We retrospectively compared PPH management and administration of RBC and hemostatic products before and after international guideline implementation. The primary endpoint was RBC administration for PPH. Secondary endpoints were hemoglobin trigger for RBC administration, administration of hemostatic products and surgical therapies. In total 235 patients had a PPH, 59 in 2011 and 176 in 2018. In 2018, fewer patients received RBC within 24 h (2018: 10% vs. 2011: 32%, p < 0.001) and 24 h after delivery (2018: 4.5% vs. 2011: 37%, p < 0.001). The number of RBC units transfused per case was significantly lower in 2018 (two vs. four units in 2011, p = 0.013). A significantly reduced transfusion of fresh frozen plasma and platelets was observed in 2018 (p < 0.001 and p = 0.002, respectively). In 2011, additional surgeries for PPH in both the acute and subacute phase were performed more frequently. Local implementation of multidisciplinary PPH guidelines is feasible and was associated with a significant reduction in transfused blood products.
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BACKGROUND: Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is associated with potentially life-threatening toxicities, most commonly cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS). These frequent adverse events are managed with the IL-6 receptor antagonist tocilizumab and/or corticosteroids. The prophylactic and early use of corticosteroids for CRS and ICANS have previously been reported, but eventual negative impacts on CAR T-cell efficacy are feared. METHODS: Retrospective comparative analysis of two patient cohorts with hematological malignancies treated with CAR T-cell therapy: 43 patients received early administration of 10 mg dexamethasone preceding each dose of tocilizumab ("early corticosteroid/ tocilizumab", EcsTcz cohort) vs. 40 patients who received tocilizumab alone ("tocilizumab alone", Tcz cohort) for treatment of low-grade CRS. RESULTS: Despite overall higher CRS incidence (91% vs. 70%; p = 0.0249), no high-grade CRS was observed (0% vs. 10%; p = 0.0497) among patients receiving early corticosteroids in combination with tocilizumab. In terms of neurotoxicity, no worsening regarding incidence of ICANS (30% vs. 33%; p = 0.8177) or high-grade ICANS (20% vs. 14%; p = 0.5624) was observed in the EcsTcz cohort. Moreover, overall response rates (80% vs. 77%; p = 0.7936), complete response rates (50% vs. 44%; p = 0.6628), progression-free survival (p = 0.6345) and overall survival (p = 0.1215) were comparable for both cohorts. CONCLUSIONS: Our study suggests that the early use of corticosteroids in combination with the standard tocilizumab schedule for low-grade CRS following CAR T-cell therapy may significantly reduce the risk of high-grade CRS without negative impact on neurotoxicity or treatment outcome.
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Síndrome da Liberação de Citocina , Imunoterapia Adotiva , Humanos , Síndrome da Liberação de Citocina/etiologia , Receptores de Antígenos de Linfócitos T , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Resultado do TratamentoRESUMO
(1) Background: Upfront treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has relevantly contributed to achieving durable remissions following induction treatment in multiple myeloma (MM) patients. The optimization of HDCT regimens can, therefore, essentially contribute to improving the depth and duration of tumor remissions. To date, melphalan at 200 mg/m2 is the standard HDCT regimen for fit MM patients. In our previous work, we showed promising efficacy and safety results for treosulfan (14 g/m2) and melphalan (200 mg/m2) (TreoMel) in acute myeloid leukemia (AML) patients receiving ASCT. Based on these data, TreoMel became the standard of care for fit MM patients at our institution. (2) Methods: We identified 115 consecutive MM patients who underwent consolidation with TreoMel between 01/2020 and 08/2022 at the University Hospital of Bern. We analyzed the safety and efficacy data, as well as the treosulfan pharmacokinetics, correlating them with tumor responses. (3) Results: A complete response (CR) rate of 84% was achieved, which is comparable to the CR rate reported for the quadruplet combination. The median PFS was 30 months (95% CI: 20.4-not reached), and the 31-month OS rate was 83%. The median area under the curve (AUC) for treosulfan was 952.5 mg*h/L (range: 527.4-1781.4), and the median peak level was 332.3 mg/L (range: 168-554). The treosulfan pharmacokinetics showed no significant correlation with MM responses after HDCT and ASCT. However, female patients had a significantly higher AUC (p = 0.007) and peak value (p = 0.001), and the higher values were associated with longer hospitalizations. (4) Conclusions: Treatment consolidation with TreoMel HDCT demonstrated a promising efficacy and safety profile in our cohort of MM patients and deserves further investigation in prospective studies.
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Efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement remain understudied. Here we analyzed the outcomes of CAR-T cell therapy in r/r DLBCL patients with CNS involvement and compared them with patients without CNS disease. Retrospective and monocentric comparative analysis of patient cohort with r/r DLBCL treated with CAR-T cell therapy: 15 patients with CNS versus 65 patients without CNS involvement. Overall response rates (80% versus 80%; P = 1.0), progression-free survival (P = 0.157), and overall survival (P = 0.393) were comparable for both cohorts. The frequency of cytokine release syndrome was comparable in the CNS and non-CNS cohorts; 93% versus 80%; P = 1.0. Numerically, immune effector-cell-associated neurotoxicity syndrome (all grades) was more frequent in patients with CNS manifestation (53% versus 29%; P = 0.063), although no grade 4 events were documented. Our study suggests that CAR-T cell therapy is effective and feasible in patients with r/r DLBCL and CNS manifestation.