Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

[Rhinosinusitis in Hurler syndrome patients requiring hematopoietic stem cells transplantation]. / Problema rinosinusita u patsientov s sindromom Gurler pri transplantatsii gemopoéticheskikh stvolovykh kletok.

INTRODUCTION: Allogenic transplantation of hemopoetic stem cells (allo-THSC) is one of the most effective treatment methods for Hurler syndrome, aimed at maximal correction of complications related to the genetic disorder. Presence of infection in the recipient is an adverse risk factor, affecting the possibility of starting the conditioning regimen and THSC peforming in general. AIM: To assess the condition of the nasal cavity and paranasal sinuses in Hurler syndrome patients before the allo-THSC, dynamics of these changes after the transplantation taking into account the correction of alpha-L-iduronidase enzyme level with donor blood cells. MATERIAL AND METHODS: From February 2012 to December 2017, In the Raisa Gorbacheva Research Institute of Child Oncology, Hematology and Transplantology of the Pavlov First Saint Petersburg State Medical University, eighteen Hurler syndrome patients (10 girls and 8 boys) received an allo-THSC. Median age at the time of the procedure was 23,5 months (min - 3,4; max - 24,8). Each patient with the shadowing of paranasal sinuses, rhinitis or nasal breathing difficulty received a standard rhinosinusitis treatment before the transplantation, effect of which was insignificant. Symptoms of rhinitis, condition of pharyngeal tonsil and paranasal sinuses were assessed before and auto the allo-THSC. RESULTS: In the post-allo-THSC, with the correction of alpha-L-iduronidase level each evaluated parameter has improved reliably (p-value < 0,05). Comparative analysis of the condition of the nasal cavity and pharyngeal tonsil before and after THSC was conducted on 14 patients out of 18. Rhinitis symptoms decreased in 9 (64,2%) patients; in 11 patients (78,5%) adenoids size reduced. Comparative analysis of the condition of paranasal sinuses was possible in 12 patients out of 18. Sinuses aeration improved in eight (66,6%) if patients. CONCLUSION: Nasal cavity and paranasal sinuses changes in Hurler syndrome patients before and after allo-THSC is poorly studied. Our experience demonstrates the normalization of nasal cavity, pharyngeal tonsila and paranasal sinuses symptoms in the majority of the patients receiving allo-THSC. These symptoms are, it seems a consequence of the underlying disease.

[Dynamics of duration of tracheal forced expiratory noises during long-term isolation in the "Mars-500" experiment].

Dynamics of duration of tracheal forced expiratory noises in a group of volunteers was studied before, during and after 520-days confinement. The duration did not change in most volunteers. Two volunteers demonstrated significant changes of tracheal sounds duration and some spirometric parameters. Increase in duration of tracheal forced expiratory noises and decrease in spirometric parameters reveal ventilatory impairment of obstructive type. Analysis of duration of tracheal forced expiratory noises dynamics during prolonged confinement proves to be a sensitive technique to test ventilatory function changes.

[Influence of changed gas media on acoustic parameters of human forced exhalation].

In previous study it was shown that duration of tracheal forced expiratory noises is promising to reveal negative changes of lung function after dive. The objective is a study of parameters of tracheal forced expiratory noises in changed gas media. The first experiment involved 25 volunteers (22-60 years), performed forced exhalation under normal pressure with air, oxygen-helium and oxygen-krypton mixtures. The second experiment in the chamber involved 6 volunteers (25-46 years), which performed forced exhalation with air under normal pressure (0.1 MPa), and under elevated pressure 0.263 MPa with air and oxygen-helium mixture. In the first experiment the direct linear dependence on gas density was found for forced expiratory noises common duration in the band of 200-2000 Hz and for its durations in narrow 200-Hz bands, excluding high frequency range 1400-2000 Hz. In the second experiment a significant reversed dependence of high frequency durations and spectral energies in 200-Hz bands (1600-2000 Hz) on adiabatic gas compressibility. Individual dynamics of common duration of tracheal forced expiratory noises under model dive of 16.3 m (0.263 MPa) is more then the diagnostic threshold of this parameter for lung function decrease, previously obtained for divers under normal pressure.

[Acoustic and spirometric indices of forced expiration noise in the conditions of 5-day dry immersion].

Dynamic studies of forced expiration (FE) indices involved 7 normal males aged 21 to 25 participating in a 5-d experiment with dry immersion (DI). FE spirometry was conducted simultaneously with registration of tracheal noise with the help of a microphone. Indices included acoustic duration of tracheal noise (Ta), forced lung capacity (FLC), FE volume per a second (FEV1), peak expiratory rate (PER) and time to reach (T(PER)) before DI, on DI days 1 and 4, and next day after completion. PER showed a significant decrease by 8.4% on DI day-1 and rose by 8.9% on DI day-4, though remaining below pre-DI values. Throughout the experiment, FLC and FEV1 did not change on the average. There was a noticeable increase of Ta by 17 % after DI which may suggest strengthening of respiratory resistance and invites further investigation. A moderate negative correlation was stated between TA and the Gensler index (r = -0.63), whereas correlation with the other spirometric indices was weak or absent.