ISSN 1866-8836
Клеточная терапия и трансплантация

IC-05. Ruxolitinib as a treatment of steroid-refractory acute and chronic graft-versus-host disease in children

Anna A. Zvyagintseva, Ivan S. Moiseev, Tatyana A. Bykova, Olesya V. Paina, Anna A. Osipova, Ludmila S. Zubarovskaya

RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia

Contact: Dr. Anna A. Zvyagintseva, phone: +7 (931) 211-64-04, e-mail:

doi 10.18620/ctt-1866-8836-2022-11-3-1-132


Acute and chronic steroid-refractory “graft-versus-host disease” (srGVHD) is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), indicating the inefficiency of glucocorticosteroids, which are the standard of the first line therapy. There are no standards of 2nd-line therapy for srGVHD. There is evidence of the successful use of JAK-inhibitors as a treatment for GVHD in adults and in children over 12 y.o. There are no data of the use the Ruxolitinib in the pediatric cohort up to 12 y.o. Our objective was to evaluate the efficacy and safety of ruxolitinib in the treatment of srGVHD after allo-HSCT in children.

Patients and methods

The study included 68 patients (49 boys and 19 girls) with srGVHD who received ruxolitinib in the second or subsequent lines of therapy. The median age – 5.5 y.o. (1-18). The largest number of patients were diagnosed with acute leukemia (ALL – 25, AML – 14, JMML – 5), MPS I type – 6, aplastic anemia – 5, and 7 patients had non-malignant diseases. Allo-HSCT from match related donor was performed in 3 patients, match unrelated donor – 22, haploidentical – 43. Myeloablative and non-myeloablative conditioning regimens were performed in an equal number of patients. All patients received cyclophosphamide-containing GVHD prophylaxis. Thirty-seven patients had acute GVHD (aGVHD), 31 – chronic GVHD (cGVHD). At the time of inclusion in the study, 10 patients had grade II aGVHD, 15 – grade III, and 12 grade IV aGVHD. Skin lesions 2-4 gr. observed in 89%, gastrointestinal tract 2-4 gr. – 48%, liver 3-4 gr. – 8%. Eight patients had moderate cGVHD and 22 – severe. The most frequently was the skin lesion of 2-3 (87%), mucous membranes of 2-3 (41%) and eye damage of mild severity (48%). The median dose of ruxolitinib was 0.3 mg/kg for aGVHD and 0.25 mg/kg for cGVHD. Median intake was 122 days for aGVHD, 341 days for ccGVHD.


Complete response rate in patients with aGVHD was 64%, partial – 18%. The complete response rate for cGVHD was 35%, partial – 51%. No response or disease progression occurs in 15% with aGVHD and 12% with cGVHD. Median time to overall response was 32 days (6-110) for aGVHD and 50 days (7-496) for ccGVHD. The most common complication was the development of hematological toxicity in the form of thrombocytopenia 3-4 degrees (50%) and neutropenia 3-4 degrees (59%). Long-term use of IST led to an isolated increase in liver transaminases of 3-4 degrees was in 33% of patients. Due to the long-term use of immunosuppressive therapy 63% of patients with aGVHD and 54% of patients with cGVHD had viral infections, which required systemic antiviral therapy. The overall survival of patients with aGVHD was 59%, with cGVHD – 86% (p=0.07). The severity of GVHD, the time to achieve an overall response, the type of allo-HSCT didn’t significantly affect the overall survival in both acute and cGVHD (p>0.1). Also, there was no effect on the overall survival of the fact of the addition of bacterial, viral or fungal infections during therapy with Ruxolitinib.


Ruxolitinib showed good efficacy with relatively low toxicity and can be used as an option for the treatment of acute and chronic GVHD as a 2nd or subsequent line of therapy in a pediatric cohort of patients.


Graft-versus-host disease, steroid-refractory, ruxolitinib, hematopoietic stem cell transplantation.

Volume 11, Number 3

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doi 10.18620/ctt-1866-8836-2022-11-3-1-132

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