PO-07. Post-transplant Cyclophosphamide (PTCy), abatacept and vedolizumab in GvHD prophylaxis in hematopoietic stem cells transplantation from matched unrelated and haploidentical donors in pediatric acute leukemia patients
Margarita E. Perminova, Larisa N. Shelikhova, Andrey B. Abrosimov, Maria A. Dunaykina, Maria A.Klimentova, Maria A. Ilyushina, Yakov O. Muzalevsky, Dmitriy N. Balashov, Alexey A. Maschan, Michael A. Maschan
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Contact: Dr. Margarita A. Perminova, phone: +7 (913) 005-37-74, e-mail: margaritaperm92@gmail.com
Summary
Graft-versus-host disease (GvHD) remains a key factor, which induces significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). High-dose post-transplantation cyclophosphamide (PTCy) targets alloreactive donor T cells proliferating early after HSCT, promotes regulatory T cell and prevents severe GvHD. The effectiveness of PTCy-based regimens varies depending on graft source and intensity of the preparative regimen. Further improvement of GvHD control with novel targeted agents is an important clinical goal.
Our purpose was to evaluate safety and effects of abatacept and vedolizumab in addition to PTCy in unmanipulated haploidentical and matched unrelated transplantation (MUD) among pediatric patients with leukemia.
Materials and methods
Twenty-eight pediatric patients with acute leukemia (acute myeloid leukemia, 12 cases) and acute lymphoblastic leukemia (n=16), with a median age of 8.1 years (0.5-16.8) underwent allogeneic HSCT. At the time of HSCT, 26 patients were in complete remission, 12 patients had a refractory status. 1st HSCT was performed in all cases. All the patients received myeloablative conditioning based on total body irradiation (n=13), or treosulfan (n=15). In 25 cases, a haploidentical donor was used; in 3 cases, >9/10 HLA-compatible unrelated donor. Bone marrow (BM), or peripheral blood stem cells (PBSC) were used as a graft source in 26 and 2 cases, respectively. GvHD prophylaxis consisted of cyclosporin A from day -1, post-transplant cyclophosphamide at D+3, +4, abatacept on D+7, +14, +28, +45, +60, and vedolizumab at the days -1, +14, +28. The median follow-up was 196 days.
Results
Engraftment was recorded in 28 patients (100%), the median engraftment time was 21 days for neutrophil counts, and 23 days for blood platelets. On the 30th day, all patients had MRD-negative remission and donor chimerism. One patient died on +D60 from causes unrelated to the underlying disease (consequences of veno-occlusive liver disease). Cumulative incidence of transplant-associated mortality was 4%. The cumulative incidence of acute GvHD II-IV was 31%; grade III-IV, 7%. Skin lesions were registered in all cases, with a good response to systemic immunosuppressive therapy. Involvement of liver and intestines was not noted. There were no cases of chronic GvHD during the observation period. Event-free and overall survival was 96%.
Conclusion
Preliminary data suggest that addition of vedolizumab and abatacept to the PtCy-based GvHD prophylaxis is not associated with increased toxicity and may reduce the incidence of gut GvHD. This approach can be further tested in a prospective trial aiming to increase the anti-leukemic efficacy of HSCT.
Keywords
Acute leukemia, allogeneic HSCT, posttransplant cyclophosphamide, abatacept, vedolizumab.
