PO-07. Optimal model of GvHD prophylaxis in unrelated hematopoietic stem cell transplants in children with malignant diseases
Natalya V. Sidorova1, Kirill I. Kirgizov1, Alexey S. Slinin1,2, Elena B. Machneva1,3, Ekaterina A. Pristanskova3, Veronika V. Konstantinova3, Alexandra E. Burya3, Oksana L. Blagonravova3, Elena A. Skorobogatova3
1 N. N. Blokhin National Medical Centre of Oncology, Moscow, Russia
2 Dmitry Rogachev Federal Research Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
3 Republican Pediatric Clinical Hospital, N. Pirogov Russian Research Medical University, Moscow, Russia
Contact: Dr. Natalya V. Sidorova, e-mail: valerevna25@mail.ru
Summary
Introduction
Graft-versus-host disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). GvHD prophylaxis is the key element of posttransplant therapy. We aimed for a retrospective analysis of different GvHD prevention modes after allo-HSCT from unrelated donors in children with malignant diseases.
Patients and methods
During the period 2003-2019, we performed 143 matched unrelated donor (MUD) HSCT in the children from 2 main clinical groups: (1) myeloproliferative diseases (n=100); (2) patients with lymphoid proliferation (n=43). Their gender distribution was as follows: males, 69.2% (n=99); females, 30.8% (n=44). The age median was 8.0 y.o. (8 months to 17 y.o.). 135 patients (94.4%) received 1st HSCT, and 2nd transplant was carried out in 8 cases (5.6%). Stem cell sources were bone marrow (76%, n=109), or peripheral blood stem cells (24%, n=34). 110 pts (77%) received 10/10 MUD HSCT and 33 pts (23%) had 9/10 HLA matches. The conditioning regimen contained various agents, according to the treatment protocols for particular diseases. GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolic acid (MMF) in following combinations: Tacro/Mtx (n=58), Tacro/MMF (n=59), Tacro/Mtx+MMF (n=2), CsA/Mtx (n=15), CsA/Mtx+MMF (n=4), CsA/MMF (n=3). The duration of observation was from 3 months up to 16 years (median 8.9 years).
Results
The overall survival (OS) was 61.4%, the 2-year relapse-free survival (RFS) was 73.2%. The aGVHD incidence was 68.5%, with 16.7% of severe aGVHD (stage 3-4). In our study, the overall survival (OS) rates showed significant differences, depending on the regimens of aGVHD prevention (p=0.01). The lower rate of aGVHD incidence was observed in group with CsA/Mtx/MMF (50%), however, with the OS rate of 50%. The incidence of aGVHD in patients who received Csa/mtx was 73% (n=11), with higher OS rate (80%). Severe aGVHD (3-4 St) was most often observed with Tacro/MMF prophylaxis regimen (27%, p=0.84), at low OS level (38.2%). The incidence of chronic GVHD was higher in Tacro/Mtx/MMF group (50%). The frequency of cGVHD in other groups was 25 to 33%, without significant differences. The 2-y RFS did not differ significantly for all groups (p=0.67).
Conclusion
A decrease in aGVHD frequency did not have a significant effect on OS. The choice of agents for the GvHD prevention does not affect the level of 2-year RFS. However, it significantly increases the level of OS reaching 80% (p=0.01) when using the CSA/Mtx combined regimen.
Keywords
Unrelated donor, allogeneic hematopoietic stem cells transplantation, graft-versus-host disease, GvHD prophylaxis.
