GVHD prevention using a combination of post-transplantation cyclophosphamide in combination with abatacept, vedolizumab and Ruxolitinib in children and young adults with hematoloblastosis after myeloablative conditioning regimen with treosulfan/TBI, etoposide, fludarabine after HSCT from matched unrelated and haploidentical donors
acute lymphoblastic,
myeloblastic,
biphenotypic,
bilinear leukemia,
Patients with ALL outside clinical and hematological remission
Lansky/Karnowski index <70% (supplement No.1)
Heart function: left ventricular ejection fraction <40% according to ultrasound of the heart1
Kidney function: clearance of endogenous creatinine < 70 ml / min
Single group
Conditioning regimen: Treosulfan 42 g/m2/course or total body irradiation 12 Gray/course, Etoposide 60 mg/kg , Fludarabine 150
DrugThe most significant adverse events limiting the use of HSCT from an unrelated donor are graft-versus-host disease (GVHD) and prolonged immunodeficiency associated with the development of severe infectious complications. The use of post-transplant cyclophosphamide for the prevention of GVHD during allogeneic HSCT from unrelated and haploidentical donors has reduced the incidence of acute clinically significant GVHD in children to 25%, chronic GVHD to 12-30%, but the issue of GVHD control still remains extremely relevant. Emerging data on the use of abatacept, a selective blocker of the costimulatory signal from an antigen-presenting cell, in the prevention of intestinal GVHD and data on the effectiveness of Janus-kinase type 1/2 inhibitors (JAK-1/2) in the treatment and prevention of acute GVHD allow us to justify the use of these drugs in combination with post-transplant cyclophosphamide as a promising pharmacological platform for the prevention of GVHD.
1. Cumulative Incidence stage II-IV after HSCT
Estimate the probability of developing acute GVHD stage II-IV after HSCT-
Kaplan Meier overal survival
Explore the safety based on an assessment of the frequency of occurrence severe (3-5 degrees) side effects of conditioning- 100-day transplant-associated mortality
1. Cumulative Incidence stage II-IV after HSCT
Estimate the probability of developing acute GVHD stage II-IV after HSCT
Kaplan Meier event free survival
Explore the safety based on an assessment of the frequency of occurrence severe (3-5 degrees) side effects of conditioning
event-free survival
Probability of developing a relapse of the primary disease, transplantation-associated mortality on the horizon of 100 days, general and event-free survival
Cumulative Incidence of leukocyte engraftment
Probability and kinetics of engraftment of leukocyte and platelet sprouts of donor origin
Cumulative Incidence of platelet engraftment
Probability and kinetics of engraftment of leukocyte and platelet sprouts of donor origin
Cumulative Incidence reactivation of CMV
Probability of reactivation of CMV, EBV, AdV, HHV6 infection
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