Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Steroid refractory psoriasiform cutaneous graft versus host disease successfully treated by extracorporeal photopheresis: a case report.

Graft-versus-host disease (GVHD) is a frequent complication occurring after allogeneic hematopoietic stem cell transplantation. It can be classified as acute and chronic GVHD based on the time of onset following transplantation and clinical presentation. Cutaneous involvement is the most common feature of acute GVHD, with maculopapular exanthema and perifollicular papular lesions. Steroid refractory GVHD is associated with a significant morbidity and mortality. We present a very rare case with acute cutaneous GVHD mimicking psoriasis vulgaris occurring after allogeneic peripheral blood stem cell transplantation for chronic lymphocytic leukemia. The patient's rash resembled psoriasis vulgaris and showed histologic features of both psoriasis and acute GVHD. Despite concomitant cyclosporine A and methylprednisolone therapy no response was obtained. Therefore, we administered extracorporeal photopheresis and achieved the desired therapeutic effect.

Origin of the effects of optical spectrum and flow behaviour in determining the quality of dry fig, jujube, pomegranate, date palm and concentrated grape vinegars.

In this study, we focused on physical characterization and quality control of dry fig, jujube, pomegranate, date palm and concentrated grape vinegars using UV spectroscopy method and rheology technique. The optical spectra and flow behaviour of the vinegars were analysed in detail in the selected specific wavelength, shear rate and frequency ranges, respectively. It was determined that the peak values seen in the UV spectra of the vinegars were caused by the organic acid and phenolic compound concentration. The peak values in the UV spectra of the vinegars wavelength range of 190 nm to 240 nm and 250 nm to 300 nm were caused by the organic acid and phenolic compound concentration, respectively. In this context, it was predicted that concentrated grape vinegar, which has the highest absorbance value, has higher organic acid content and more antibacterial/antioxidant properties compared to the others. It is thought that the optical energy gaps of vinegars are related to the organic acid concentration and the release time. Flow properties of the vinegars were non-Newtonian thickening fluids (dilatant fluids) and compatible with the Power law model. The stable flow of the vinegars in the high shear rate region was interpreted as having a successful production process and being of good quality.

Investigation of the traditional organic vinegars by UV-VIS spectroscopy and rheology techniques.

Optical, rheological and metabolic properties of the apple, hawthorn, artichoke, grape, rosehip and blackberry organic vinegar produced by deep culture method (handmade traditional method) were analysed using UV-Vis spectroscopy and rheology techniques. Flow behaviours for all samples were analysed in the shear rate range of 10-3 to 103 1/s and in frequency range of 10-3 to 103rad/s, respectively. Absorption spectra for six organic vinegars was observed two peaks around 215 and 285nm due to the presence of phenolic compounds and organic acids such as acetic. The effects of optical transitions of organic molecules on the absorption coefficient values for vinegars were determined. Optical energy band gaps of all samples were found to be consistent with Planck's radiation approach known as Rayleigh-Jeans law and Tauc law. The rheological/flow properties of the all vinegars were found to be relevant with non-Newtonian flow behaviour and Ostwald-de Waele model. From the results of optical and rheological analysis, which determines the quantity and quality characteristics of all organic vinegars, it was concluded that these vinegars are in a level that people can drink easily.

Is Cytomegalovirus Surveillance Necessary for Patients With Low Reactivation Risk in an Autologous Hematopoietic Cell Transplantation Setting?

BACKGROUND: In an autologous hematopoietic cell transplantation (AHCT) setting, routine cytomegalovirus (CMV) surveillance is not indicated except in high-risk situations. On the other hand, some studies reported increased CMV reactivation in AHCT setting as a result of incorporation of novel agents into treatment algorithms, such as bortezomib and rituximab. We retrospectively analyzed CMV reactivation and infection rates in patients with no high-risk features, who were treated with AHCT. METHODS: During January 2010 to November 2015, all consecutive, CMV-seropositive patients were included. The viral copy numbers were measured twice a week from the start of the conditioning regimen until engraftment, once a week for the remaining time period until day 30 after AHCT and once weekly only for patients who had been diagnosed with CMV reactivation before and who developed primary/secondary engraftment failure during 31 to 60 days after AHCT. RESULTS: One hundred one (61.6%) men and 63 (38.4%) women were included in the study. The median age of study cohort was 51 years (range, 16-71 years). The indications for AHCT were Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma in 44 (26.8%), 41 (25%), and 79 (48.2%) patients, respectively. CMV reactivation occurred in 60 (37%) patients, and 13 patients (8%) received pre-emptive ganciclovir treatment. CONCLUSIONS: On the basis of our results, it might be stated that CMV surveillance may be recommended during 40 days after AHCT in countries with a high CMV prevalence, even in patients without high-risk features regarding reactivation. Additionally, the risky conditions necessitating CMV screening after AHCT must be re-defined in the era of novel agents.

Electrolyte free water clearance could be an early sign of renal dysfunction in renal transplant patients.

Data on free water excretion capacity of renal transplant recipients are scant. The aim of this study was to evaluate the ability of electrolyte free water clearance (E-CH(2)O) by the allograft in renal transplant patients and the effects of various immunosuppressive drugs. Renal transplant recipients with good graft function (creatinine < 1.5 mg/dL) as well as controls were divided into five groups according to their immunosuppressive regimen: group I, azathioprine (n = 15); group II, cyclosporine (n = 28); group III, tacrolimus (n = 28); group IV healthy controls (n = 20); and group V renal transplant donors (n = 16). Following a 12-hour fast, we administered oral water loading (20 mL/kg) with urine collection for 3 hours. We calculated creatinine clearance for 3 hours and E-CH(2)O. No matter which immunosuppressive drug, the E-CH(2)O of recipients (groups I, II, and III) was lower than that of donors or healthy controls. The creatinine clearance of the cyclosporine arm was significantly lower than all of the other groups. Decreased E-CH(2)O in renal transplant patients might be due to diminished water input to the loop of Henle related to subclinical allograft insufficiency as a result of posttransplantation pathology and/or immunosuppressive drug therapy or the transport of water into the extrarenal interstitium as a result of vascular endothelial dysfunction due to the pretransplant uremic milleu.

Secondary amyloidosis causing nephrotic syndrome in a patient with non-Hodgkin's lymphoma: quite a rare diagnosis.

Secondary amyloidosis is usually a complication of chronic inflammation. Amyloidosis cases during the course of non-Hodgkin's lymphoma (NHL) are usually of AL-type, only one NHL patient with secondary amyloidosis has been reported. Our 79-year-old male patient visited us with multiple lymphadenopathies, and he was diagnosed with nodal marginal zone B-cell lymphoma. After four cycles of combined chemotherapy; his urea, creatinine levels started to increase and he developed nephrotic-range proteinuria. His rectal biopsy demonstrated amyloid deposition in submucosal vessel walls. The patient has been under hemodialysis for 10 months and his lymphoma is still in partial remission. We presented this case because it is the second NHL patient who developed secondary amyloidosis during his disease course.