COVID-19 in a Post-transplant Heart Recipient Who Developed Aggressive Lymphoma: A Biphasic Course During Rituximab Treatment.
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ABSTRACT:
SUBMITTER: Clerico M
PROVIDER: S-EPMC8196101 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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COVID-19 in a Post-transplant Heart Recipient Who Developed Aggressive Lymphoma: A Biphasic Course During Rituximab Treatment.
Clerico Michele M Dogliotti Irene I Calcagno Andrea A Grimaldi Daniele D Leone Sarah S Ragaini Simone S Boffini Massimo M Caracciolo Daniele D Ferrero Simone S Barbero Cristina C Zanotto Elisa E Stroffolini Giacomo G Cavallo Rossana R Rinaldi Mauro M Bruno Benedetto B Cavallo Federica F
HemaSphere 20210612 7
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Project description:ObjectiveThe effects of recipient body mass index (BMI) on waitlist strategies, waitlist outcomes, and post-transplant outcomes among adult patients listed for heart transplantation under the updated 2018 allocation system have not been well characterized.MethodsThe United Network of Organ Sharing data set between October 2015 and March 2021 was analyzed, and patients were grouped based on recipient BMI and whether listing occurred in the old (pre-October 2018) or new allocation system.ResultsListing strategies differed by BMI group, but trends of increased use of temporary mechanical support and decreased use of durable support remained among all BMI groups, except those with BMI > 35 kg/m2 . Waitlist outcomes improved among all BMI cohorts in the new allocation system, including among patients with BMI 30-34.9 and >35 kg/m2 , although patients with higher BMIs continued to have longer waitlist times. Post-transplant outcomes in the new allocation system are worse for patients with BMI > 30 kg/m2 (hazard ratio: 1.47; confidence interval: 1.19-1.82; p < .001).ConclusionsThe 2018 change to the heart transplant allocation system was associated with similar changes in the use of mechanical support for listing strategy across BMI ranges, except in the most obese, and improved waitlist outcomes across all BMI ranges. Post-transplant outcomes in the new allocation system are worse for patients with BMI > 30 kg/m2 compared to patients with BMI < 30 kg/m2 . These findings have important clinical implications for our understanding of the ongoing influence of BMI on waitlist courses and post-transplant outcomes among patients listed for heart transplantation.
| S-EPMC9320797 | biostudies-literature
Project description:The addition of high-dose cytarabine to rituximab/bendamustine (RB) induction could improve outcomes for transplant-eligible patients with mantle cell lymphoma (MCL). We conducted a pooled analysis of 2 phase 2 trials and an off-trial cohort each testing 3 cycles of RB and 3 cycles of rituximab/high-dose cytarabine (RC) followed by autologous stem cell transplantation (ASCT) among untreated, transplant-eligible patients with MCL. Dana-Farber Cancer Institute (DFCI) and Washington University in St. Louis (WUSTL) led separate phase 2 trials testing sequential and alternating cycles of RB/RC, respectively. Patients treated at DFCI with sequential RB/RC off trial were retrospectively identified. Minimal residual disease (MRD) was assessed in the DFCI trial. A total of 88 patients (23 DFCI trial, 18 WUSTL trial, and 47 off trial) received RB/RC; 92% of patients completed induction, and 84% underwent planned consolidative ASCT. Grade 3 or 4 adverse events among trial patients included lymphopenia (88%), thrombocytopenia (85%), neutropenia (83%), and febrile neutropenia (15%). There were no treatment-related deaths during induction and 2 following ASCT. Among 87 response-evaluable patients, the end-of-induction overall and complete response rates were 97% and 90%, respectively. After a median follow-up of 33 months, 3-year progression-free survival and overall survival were 83% and 92%, respectively. Patients undergoing MRD testing experienced prolonged MRD negativity after ASCT with emergence of MRD occurring in only 1 patient who subsequently relapsed. RB/RC followed by ASCT achieves high rates of durable remissions in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT01661881 (DFCI trial) and #NCT02728531 (WUSTL trial).
| S-EPMC7065472 | biostudies-literature
Project description:BK virus nephropathy in kidney transplantation is widely recognized as an important cause of graft dysfunction and loss. In the case of transplants of organs other than kidney, BK virus nephropathy in native kidneys has been recognized as a cause of chronic kidney disease, which is related with immunosuppression; however, the diagnosis is usually late because the renal dysfunction is attributed to other causes, such as toxicity by anticalcineurinic drugs, interstitial nephritis due to medications, hemodynamic changes, diabetes, hypertension, etc. We report a case of BK virus nephropathy in a patient who underwent heart transplantation due to peripartum cardiomyopathy. The kidney biopsy reported active chronic tubulointerstitial nephritis associated with late stage polyomavirus nephritis and the blood viral load for BK virus was positive (logarithm 4.5). The immunosuppressive treatment was reduced, and after two years of follow-up, the patient had stable renal function with a serum creatinine of 2.5 mg/dL (GFR of 23.4 mL/min/1.73m2). We recommend that the BK virus be considered as a cause of renal dysfunction in heart transplant recipients, with the aim of detecting its replication in time to reduce immunosuppressive therapy before irreversible compromise of renal function may manifest.
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Project description:Although cardiac resynchronization therapy (CRT) is an established therapy in selected patients with heart failure with reduced ejection fraction (HFrEF), its role in orthotopic heart transplant (OHT) recipients remains understudied. We describe a case of successful CRT implantation in an OHT recipient for HFrEF and high-grade atrioventricular block. This case highlights the deliberations made given the lack of clinical trial and observational evidence for this therapy in OHT recipients.Learning objectiveThis case demonstrates the feasibility of cardiac resynchronization therapy (CRT) in an orthotopic heart transplant (OHT) recipient and adds to the scarcely reported data on the utility of CRT in this population. Given the exclusion of OHT recipients from the major CRT trials, further research is required to refine the indications for CRT implantation in this population.
| S-EPMC9911931 | biostudies-literature
Project description:BackgroundDespite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects.MethodsAntibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).ResultsThree different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model.ConclusionThis study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo.
| S-EPMC10433160 | biostudies-literature
Project description:BackgroundThe new kidney allocation system in the United States has introduced longevity matching, which gives priority to allocating the best quality organs to wait-listed candidates with the longest predicted survival for the efficient utilization of organs that are of limited availability. The estimated post-transplant survival (EPTS) score was developed in the United States to risk-stratify all wait-listed patients. However, prognostic indices used in Western countries were derived from data that may be different for Korea and do not necessarily reflect prognostic values for Korean deceased donor kidney transplantation. Prognostic indices for Korean wait-listed candidates therefore need to be developed from Korean data.MethodsWe analyzed 6,731 adult solitary kidney transplant patients for candidate risk prediction using the national data from the Korean Network for Organ Sharing (KONOS) and National Health Insurance Data Sharing Service (NHISS). Cox regression analysis was used to model the risk of patient death.ResultsThe Korean EPTS (K-EPTS) score was developed based on four recipient parameters (age, diabetes mellitus, hepatitis C virus, and duration of dialysis) that showed a significant association with post-transplant survival. K-EPTS scores showed good discrimination (C-statistics 0.690; 95% confidence interval, 0.666-0.715). Moreover, the ability of the K-EPTS score to discriminate patient survival was better than that of the EPTS according to the criteria of the United Network for Organ Sharing (US-EPTS) score (P<0.001).ConclusionsThe K-EPTS score, which was developed based on Korean national data, is expected to contribute to the assessment of recipient prognosis and efficient utilization of deceased donor kidneys.
| S-EPMC9235339 | biostudies-literature
Project description:Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014-2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥70, 40-69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98-9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95-9.43); portal thrombus (aHR 1.87, 95%CI 1.26-2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34-6.20); and Karnofsky score 10-30% (aHR 2.03, 95%CI 1.13-3.65), 40-60% (aHR 1.65, 95%CI 1.08-2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss associated with older donor age.
| S-EPMC9452632 | biostudies-literature
Project description:We present the case of acute myocardial infarction secondary to spontaneous coronary artery dissection in a patient 2 weeks post orthotopic heart transplantation. (Level of Difficulty: Advanced.).
| S-EPMC9350898 | biostudies-literature
Project description:Purpose: Despite recent advances in the treatment of patients with aggressive lymphomas, still a significant fraction of patients will succumb to their disease. Thus, novel therapeutic strategies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects. Experimental Design: Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Results: Overall, three different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 2/11 cell lines were primarily sensitive to tafasitamab and 2/11 were predominantly sensitive to rituximab treatment, the combination of tafasitamab and rituximab resulted in enhanced cell death in 7/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combinatorial approach of the two antibodies resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model. Conclusions: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to antibody mono treatment in models of aggressive B-cell lymphoma in vitro and in vivo. Translational Relevance: The immunochemotherapy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains the standard of care for newly diagnosed DLBCL patients. However, 30-40% of patients are refractory or relapse after initial response to the immunochemotherapy, indicating a high-unmet medical need for these patients. Tafasitamab and rituximab target the B-cell surface proteins CD19 and CD20, respectively, and both antibodies feature overlapping modes of action , namely direct cytotoxicity, ADCC and ADCP. In this study, we show that the combination of tafasitamab and rituximab had additive and synergistic efficacy both in vitro and in vivo. Our findings shed new light on the underlying mechanism of the combination of both antibodies and lay the ground to translate the results into improved outcome for patients with aggressive lymphoma in future clinical trials.
2023-10-22 | GSE211829 | GEO
Project description:BackgroundRadiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed.MethodsWe retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed.ResultsA total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported.ConclusionThese data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.
| S-EPMC10788030 | biostudies-literature