Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.

Eltrombopag treatment in thrombocytopenia following hematopoietic stem cell transplantation: A multicenter real-world experience.

INTRODUCTION: Thrombocytopenia is among the most common complications following hematopoietic stem cell transplantation and is associated with increased mortality and morbidity with no standard treatment yet. In this multicenter and retrospective study, we aim to present our multi-center experience of Eltrombopag treatment in patients with isolated thrombocytopenia following HSCT. MATERIAL-METHOD: A total of 73 patients from 5 centers who underwent autologous or allogeneic stem cell transplantation, had no primary disease relapse, all of whom had neutrophil engraftment, complete chimerism, and who were diagnosed with Prolonged Isolated Thrombocytopenia (PIT) or Secondary Failure Of Platelet Recovery (SFPR) were included in the study. The patients were initiated on Eltrombopag at a dose of 50-150 mg. Complete response was defined as a platelet count >50×109/L for 7 consecutive days with no transfusion support. RESULTS: A total of 50.3% of the patients underwent Autologous and 49.7% Allogeneic Stem Cell Transplantation, 54.8% were diagnosed with PIT, and 45.2% were diagnosed with SFPR, and the treatment with 50-150 mg/day Eltrombopag was initiated on the median day +42. Complete response was achieved in 71.2% of these patients on the median day 23 of the treatment. No significant effects of the initial dose (50-150 mg/day) were detected in the Complete Response in the multivariate analysis on response. An insufficient number of Megakaryocytes in the bone marrow before Eltrombopag treatment was determined as an independent risk factor in determining the response (OR 3.57, 95% CI 1.21-10.55). The overall survival of the patients who did not respond to Eltrombopag was found to be significantly worse than that of patients who responded (p=0.022, HR:2.74, 95% CI 1.12-6.54). CONCLUSION: As a result of the present study, Eltrombopag treatment was found to be effective and safe in thrombocytopenia that develops following hematopoietic stem cell transplantation. It was concluded that its use may be more effective in patients with sufficient bone marrow megakaryocytes before the treatment and an initial dose of 50 mg/day may be appropriate in terms of cost, effectiveness, and toxicity. Large-scale randomized and controlled prospective studies are needed to determine the roles of Eltrombopag treatment in patients with post-transplant PIT and SFPR.

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: first reported case.

Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare and challenging complication associated with poor prognosis and limited treatment options. Emerging T-cell directing therapies, such as bispecific antibodies (bsAbs) and chimeric antigen receptor T cells (CAR-T), have shown remarkable success in treating MM, but their efficacy in CNS involvement remains unclear. Elranatamab, a humanized bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3-expressing T cells, has demonstrated promising results in relapsed refractory MM. However, its efficacy in treating CNS-MM has not been reported. We present a case of a 37-year-old male MM patient with CNS involvement who has been successfully treated with Elranatamab.

Newly onset cytopenias not always indicate a relapsing AML after allogeneic HSCT, a case of non-destructive post transplant lymphoproliferative disorder.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an effective option for the treatment of intermediate and high-risk Acute myeloid leukemia (AML). Post-transplant lymphoproliferative disorder (PTLD) is related to the intensity of post-transplant immunosuppression. Although Epstein-Barr virus (EBV) seropositivity and reactivation can be a major risk factor for PTLD. A few PTLDs could be EBV negative. There are a very limited number of PTLD cases following HSCT in patients with AML. We present a differential diagnosis of cytopenias after allo-HSCT. This is the first report of an AML patient developing bone marrow EBV-negative PTLD relatively late in their post-transplant course.

Management of out-of hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation in 2021.

INTRODUCTION: Over the last decade, eCPR programs have become more and more popular, at least amongst high-volume centers. Despite its rise in popularity and promising outcome, strategies concerning pre- and post-implantation of VA-ECMO remain at least debatable. Besides, integrating the appropriate set-up, managing anticoagulation, implementing LV-venting, and predicting neurological outcome play important roles in caring for thise highly selective patient-collective. We sought to present our institutional´s techniques for establishing an eCPR program and managing patients peri- and post implantation in eCPR-runs. AREAS COVERED: This manuscript covers the majority of clinical concerns and parameters for establishing an eCPR program and its recent advantages. We will describe a safe way of cannulation, setting anticoagulation goals, strategies for LV-venting and ICU-treatment. Also included, an elaboration on neurological and cardiac prognostication. EXPERT OPINION: We advocate ultrasound-guided cannula placement in eCPR patients. Also, we emphasize the importance of using stiffer wires and smaller arterial cannula sizes due to the different physiological parameters of OHCA patients. After cannulation, we aim for lower flow goals, the concept of 'partial VA-ECMO,' and lower anticoagulatory targets. LV-venting with Impella should remain an individual case to case decision.

Adequate anticoagulation and ECMO therapy in COVID-19 patients with severe pulmonary embolism.

SARS-CoV-2 (COVID-19) infections have been recently shown to be associated with a high rate of thromboembolic events due to pro-coagulative mechanisms that have not yet been fully understood. This paper reports on a 55-year-old female COVID-19 patient with severe ARDS and pulmonary embolism (PE) complicated by cardiogenic shock after 12 days of hospitalization under initial prophylactic anticoagulation with low molecular weight heparin (LMWH). An ultima-ratio va (veno-arterial) ECMO implantation and subsequent rapid upgrade to vvaECMO due to insufficient oxygenation was performed. The patient developed severe coagulopathy with intrapulmonary bleeding. The present report aims to highlight and discuss the pros and cons of various anticoagulation strategies in COVID-19 patients focusing on current scientific debates to address this frequently observed complication in the current situation worldwide.

SAVR versus TAVI: What about the Hemodynamic Performance? An In Vivo and In Vitro Analysis.

BACKGROUND: Surgical aortic valve replacement (SAVR) is nowadays discussed whether it remains the gold standard of treatment. In the last decade, there has been a tremendous increase in transcatheter aortic valve implantation (TAVI) due to the growing expertise and excellent results of the catheter-based approach. We, therefore, retrospectively compared the rapid deployment valve (RDV), the Edwards Intuity valve (IEV), with the Edwards Sapien 3 (S3V) with regard to post-procedural hemodynamics. METHODS: A total of 246 patients treated with TAVI or SAVR between February 2009 and November 2015 were included. One-hundred twenty-five patients were analyzed in the SAVR group and compared with 121 patients undergoing TAVI. Transvalvular pressure gradients (PGs) and the incidence and extent of aortic regurgitation (AR) were compared post-procedurally by echocardiography for each valve size. In vitro hemodynamics were analyzed by placing both valves into an aortic silicone phantom connected to a pulsatile flow pump and measured using phase-contrast magnetic resonance imaging (4D flow MRI). RESULTS: Post-procedurally, mean transvalvular PGs for the 23 mm valves were 9 (7;11.5) versus 13 (9;18) (p < 0.001), whereas maximum PGs were 16.5 (14;22) versus 25.5 mm Hg (17.5;34) (p < 0.001) in IEV and S3V patients, respectively. The 21 mm IEV showed significantly lower transvalvular PGs compared with the 23 mm S3V: mean PGs: 11 (8;13) versus 13 (9;18) (p < 0.05); maximum PG: 19.5 (13;24) versus 25.5 (18;34) mm Hg (p < 0.05). Analysis revealed significantly lower post-procedural transvalvular PGs for larger valves sizes. With respect to AR, the incidence of AR was significantly lower in IEV group (p < 0.05). In vitro velocities and turbulent kinetic energy values showed similar results between both valves. CONCLUSION: Implanted RDVs presented a lower incidence of paravalvular regurgitation and were associated with significantly lower post-procedural transvalvular PGs, especially for small valve sizes. Our data might support the application of rapid deployment aortic valves in patients with small aortic annulus in the TAVI era.

Determination of risk factors for pacemaker requirement following rapid-deployment aortic valve replacement.

OBJECTIVES: Rapid-deployment aortic valve replacement (RD-AVR) potentially reduces procedure times providing excellent haemodynamic results compared to standard tissue aortic valve replacement. However, concerns have been raised regarding higher rates of postoperative pacemaker (PPM) requirement compared to standard aortic valve replacement. In this study, we sought to determine the PPM rate and its potential risk factors in RD-AVR patients. METHODS: Between 2011 and 2017, 193 patients underwent RD-AVR. The main outcome investigated was PPM. Other outcome parameters included hospital mortality, major morbidity, length of stay and discharge condition. Predictors of PPM were determined using multivariable regression models. RESULTS: Isolated RD-AVR was performed in 72 (37%) patients and 121 (63%) patients underwent combined RD-AVR [coronary artery bypass grafting (n = 110), mitral repair (n = 6) and others (n = 5)]. Aortic cross-clamp and cardiopulmonary bypass times were 57.1 ± 25.1 min and 90.0 ± 40.1 min in the overall RD-AVR population and 39.4 ± 13.5 min and 67.6 ± 24.5 min, respectively, in isolated RD-AVR procedures. PPM occurred in 20 (10.4%) patients. Multivariable analysis revealed bypass grafting of the circumflex artery [odds ratio = 2.8] and preoperative right branch bundle block (odds ratio = 11.7) as independent predictors for PPM. CONCLUSIONS: RD-AVR is a safe and simple procedure resulting in favourable short aortic cross-clamp and cardiopulmonary bypass times and considerable low gradients in postoperative echocardiography. PPM following isolated RD-AVR remains in the range of standard aortic valve replacement. However, patients undergoing concomitant coronary artery bypass grafting, particularly of the circumflex artery, face a 3-fold increased risk for PPM implantation enhanced if right branch bundle block is present. Follow-up examination is necessary to determine whether these patients remain pacer dependent during long-term follow-up.

Rapid Deployment Aortic Valve Replacement: Excellent Results and Increased Effective Orifice Areas.

BACKGROUND: The aim of this study was to evaluate the effects of rapid deployment aortic valve replacement (RDAVR) on surgical outcome and hemodynamics compared with standard aortic valve replacement (AVR). METHODS: One hundred sixty-three RDAVR patients (isolated, n = 67; combined with coronary artery bypass graft surgery [CABG], n = 96) were compared with a propensity matched control group (n = 163). Primary endpoints included association between valve type and procedure times, prosthesis size, transvalvular gradient, and indexed effective orifice area. Secondary endpoints were postoperative mortality and morbidity. RESULTS: Aortic cross-clamp and cardiopulmonary bypass times in the RDAVR group were 55 ± 23 and 88 ± 38 minutes, respectively, compared with 77 ± 22 and 105 ± 38 minutes in the control group (p < 0.001). In the subgroup of patients undergoing isolated RDAVR (n = 67 of 163), the aortic cross-clamp and cardiopulmonary bypass times were 38 ± 13 and 66 ± 22 minutes, respectively, compared with 55 ± 14 and 81 ± 18 minutes in the control group (n = 67 of 163; p < 0.001). The RDAVR patients received larger prostheses (23.3 ± 1.8 mm) compared with standard AVR (22.8 ± 1.5 mm; p = 0.002). Mean transvalvular gradients and indexed effective orifice areas were 9 ± 5 mm Hg and 1.11 ± 0.11, respectively, in the RDVAR group compared with 13 ± 5 mm Hg and 0.95 ± 0.08 in the control group (p < 0.001). Hospital mortality was similar in both groups (1.8%, n = 3 of 163; p = 1.000). Postoperative pacemaker rates were 3.5% (n = 3 of 67) for isolated RDAVR versus 3.0% (n = 2 of 67; p = 0.649) for isolated AVR and 12.5% (n = 12 of 96) for RDAVR/CABG versus 4.2% (n = 4 of 96; p = 0.032) for AVR/CABG. CONCLUSIONS: RDAVR facilitates reduced aortic cross-clamp and cardiopulmonary bypass times compared with standard AVR, particularly in patients undergoing concomitant procedures, allowing the use of larger prostheses and resulting in lower transvalvular gradients and higher indexed effective orifice area compared with standard AVR. Therefore, RDAVR may help to overcome patient-prosthesis mismatch in some patients.

Brentuximab vedotin related bilateral Purtscher-like retinopathy unresponsive to pulse steroid therapy and intravitreal aflibercept injection.

We describe a 36-year-old woman with a relapsing Hodgkin's lymphoma who developed a severe bilateral sudden visual loss almost three weeks after the initiation of brentuximab therapy. Ancillary fundus tests yielded bilateral severe retinal arteriolar occlusion 360° and serous macular retinal detachment. No visual improvement could be achieved despite the pulse corticosteroid therapy and a single bilateral intravitreal aflibercept administration cessation of the brentuximab therapy. Unfortunately, she succumbed to respiratory failure almost six weeks after the diagnosis of Purtscher-like retinopathy.

Urinary kidney injury molecule-1 levels as a marker of early kidney injury in hypertensive patients.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is a type 1 tubular cell transmembrane protein that is found in high levels in early stages of acute kidney injury and is stated to have predictive value in the early diagnosis of chronic kidney diseases. In this study, the hypothesis was that higher levels of KIM-1 would be detected in hypertensive patients for the early detection of nephropathy. With this goal, urinary KIM-1 levels of hypertensive cases were compared with those of healthy controls, and associations of KIM-1 levels with microalbuminuria and glomerular filtration rate (GFR) were investigated. METHODS: The study included a total of 80 patients aged ≥20 years (55 male, 25 female, mean age: 57.21±9.12 years). The patient group consisted of 40 patients (28 males, 12 females, mean age: 57.58±8.79 years) who had had hypertension for at least 5 years, and the control group consisted of 40 healthy subjects (27 female, 13 male, mean age: 56.85±9.53 years). Groups were compared based on demographic, anthropometric and biochemical data, and urinary KIM-1 levels. Correlation analysis was made to assess the association of KIM-1 levels with microalbuminuria and GFR. Levels of urinary KIM-1 enzyme were measured using linked immunosorbent assay (ELISA). RESULTS: KIM-1 levels were found to be 0.86±0.48 ng/mg creatinine in the patient, and 0.71±0.46 pg/mL in the control groups (P>0.05). A positive correlation was detected between KIM-1 levels and both systolic blood pressure and duration of disease (r=0.308, P=0.032 and r=0.339, P=0.032, respectively). CONCLUSIONS: While not supporting the hypothesis that KIM-1 levels may increase in hypertensive patients as an early indicator of hypertensive nephropathy, these findings suggested that this molecule might be associated with kidney injury in hypertensive nephropathy due to its positive correlation with the duration of hypertension.