ISSN 1866-8836
Клеточная терапия и трансплантация

PO-05. Everolimus with tacrolimus for graft-versus-host disease prophylaxis in children with acute leukemia and JMML after allo-HSCT

Olesya V. Paina, Liubov A. Tsvetkova, Polina V. Kozhokar, Аnastasia S. Frolova, Zhemal Z. Rakhmanova, Elena V. Semenova, Alexander D. Kulagin, Ludmila S. Zubarovskaya

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

Dr. Liubov A. Tsvetkova, phone: +7 (921) 643-39-05, e-mail:

doi 10.18620/ctt-1866-8836-2021-10-3-1-148


Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a new-generation mammalian target of rapamycin inhibitors, combines immunosuppressive properties with antineoplastic effect. Everolimus has demonstrated efficacy in the prevention of allograft rejection after solid organ transplantation. Everolimus has a convenient pharmacological form (dispersible tablets) for and shorter half-life and thus had lack of nephrotoxicity and more clinically manageable than sirolimus for prophylaxis and treatment GVHD in children. Data of the using everolimus in children after allo-HSCT are limited. Aim of this study was evidence of safety and efficiency of using everolimus for GVHD prophylaxis in children with acute leukemia and juvenile myelomonocytic leukemia (JMML) after allo-HSCT from donors with different HLA-compatibility.

Patients and methods

We included 12 children with the median age 2 years old (1-3 y.o.) who underwent allo-HSCT in 2020-21 and received everolimus for GVHD prophylaxis at of the RM Gorbacheva Memorial Research Institute. Four patients (33%) had acute lymphoblastic leukemia, 6 pts (42%) – acute myeloid leukemia, 3 pts (25%) – JMML. Allo-HSCT from haploidentical donor was performed in 11/12 (92%) children, from matched unrelated donor (MUD) in one child. Remission of disease at the allo-HSCT was observed in 8/12 (67%), relapse/refractory disease – in 4/12 (33%) patients. All children received myeloablative regimen of conditioning (MAC) with GVHD prophylaxis posttransplant cyclophosphamide (PTCY), everolimus, tacrolimus. Busulfan-based conditioning regimen was administered in 10/12 (83%) pts. Everolimus was given orally on day -3 and a starting dose of 1.6 mg/m2/day. The dose was subsequently adjusted to achieve a target blood concentration between 3 and 5 ng/ml. We studied overall survival (OS), disease free survival (DFS), GVHD-free, relapse free survival (GRFS) by Kaplan-Meier method. Also, we investigated incidence of acute GVHD, chronic GVHD, primary graft failure, toxicities and infectious complications.


Engraftment was achieved in 11/12 (92%) of children. At the median follow up 9 months (1.5-17 months) OS was 100%, disease-free survival – 75%. Toxicities and infectious complications 3-4 grade developed in 5/12 of the patients (42%). However, we did not observe thrombotic microangiopathy, nephrotoxicity, hepatotoxicity. The most common complication was oral mucositis, that associated with MAC. Acute GVHD 2nd grade occurred in 4/12 (33%) of children. We did not see acute GVHD 3-4 grades in our patients. Most patients had cutaneous GVHD. Chronic GVHD was registered in 6/12 (50%) of patients, severe grade as overlap syndrome – in one child. GFRS was 42% at the median follow-up of 9 months.


We have shown that everolimus in combination with tacrolimus and PTCY after MAC did not increase the rates of adverse events and severe form of GVHD, leading to early transplant mortality, in children after allo-HSCT from haploidentical donors and MUD. The significant benefits of everolimus compared with sirolimus is its convenience when using in infants and children.


Allo-HSCT, graft-versus-host disease, everolimus, children.

Volume 10, Number 3

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doi 10.18620/ctt-1866-8836-2021-10-3-1-148

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