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.

[Extracorporeal photopheresis in the treatment of patients with refractory chronic graft-versus-host disease after allogeneic bone marrow transplantation].

AIM: To evaluate the efficiency of extracorporeal photopheresis (ECP) in the treatment of patients with refractory chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS: The study included 49 patients aged 2 to 55 years. Allo-HSCT was carried out in 38 (79%) patients with acute leukemias, 5 (10%) with chronic leukemias, 4 (8%) with myelodysplastic syndrome/myeloproliferative disease, and 2 (3%) with other hematologic diseases. The patients included in the study had glucocorticosteroid (GCS)-refractory disseminated cGVHD or a history of severe complications from GCS therapy. RESULTS: When evaluating the efficiency of therapy, its response was recorded in 37 (77%) cases; the best results were obtained in patients with hepatic (82%), mucosal (76%), and skin (74%) lesions. The mean severity according to the cGVHD Working Group, National Institutes of Health, and a platelet level of more than 100.10(9)/1 were defined as factors improving a therapy response. In the patients receiving ECP, the overall survival was 70%. The latter was higher in the group of patients who had responded to ECP therapy without involving the gastrointestinal tract in the cGVHD process and in those receiving a combination of ECP and other immunosuppressive drugs. CONCLUSION: ECP is an effective treatment for patients with refractory cGVHD, it may be used in those with a history of severe complications from GCS therapy. ECP allows the dose of GCS to be reduced to the point of complete discontinuation.

[Thermodynamic functions of lysozyme, myoglobin, beta-lactoglobulin, albumin, and poly-L-tryptophane in the temperature range 0-330 K]. / Termodinamicheskie funktsii lizotsima, mioglobina, beta-laktoglobulina, al'bumina i poli-L-triptofana v diapazone temperatury 0-330 K.

The temperature dependence of heat capacity for lysozyme, myoglobin, beta-lactoglobulin, albumin, and poly-L-tryptophan was studied in the temperature range 5-330 K using an adiabatic vacuum calorimeter. The accuracy of measurements was approximately 0.2%. From the data obtained, the thermodynamic functions of these proteins and the polyamino acid Cp degree (T), H degree (T)-H degree (0), S degree (T)-S degree (0), G degree (T)-H degree (0) in the temperature range 0-330 K, and the values of fractal dimension D and intrinsic temperature theta max were calculated.