ISSN 1866-8836
Клеточная терапия и трансплантация

Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in patients with inherited disorders undergoing allogeneic stem cell transplantation

Tatiana A. Bykova, Anna A. Osipova, Varvara N. Ovechkina, Alexander N. Galimov, Anna A. Dotsenko, Alexander L. Alyanskiy, Ivan S. Moiseev, Elena V. Semenova, Ludmila S. Zubarovskaya, Boris V. Afanasyev

Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Chair of Hematology, Transfusiology and Transplantology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia

Contact: Dr. Tatiana A. Bykova


Graft-versus-host disease (GVHD) remains one of the main life-threatening complications after allo-HSCT, especially in patients with non-malignant diseases. The standard GVHD prophylaxis strategy is mostly based on the use of calcineurin inhibitors alone or in combination with other immunosuppressive drugs(IS). Post-transplant cyclophosphamide (PTCy) is effective GVHD prophylaxis option for adult patients (pts), with only limited data for children. The aim of the present study was to evaluate PTCy as GVHD prophylatic option in pediatric pts with inherited disorders undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Patients and methods

The study included 91 pts, most of them being in pediatric age (median age – 3 y.o., range 7 month – 30 y.o.) with different inherited disorders (β-thalassemia, 9; bone marrow failure syndromes, 26; storage diseases, 41; primary immunodeficiency disorders, 15) were enrolled in retrospective study. Donor type was as follows: matched/mismatched unrelated (MUD/MMUD), 67; matched related donor (MRD), 14; haploidentical (haplo), 10 cases. The following conditioning regimens were applied: myeloablative (MAC), 39; reduced-intensity (RIC), 52. Graft source was: bone marrow (BM) in 69 cases, peripheral blood stem cells (PBSC), in 22 patients. PTCy-based GVHD prophylaxis (50 mg/kg on days +3, +4) was administered in 31 cases, standard GVHD prophylaxis based on calcineurin inhibitors was used in 60 pts.


Cumulative incidence (CI) of aGVHD grade 2-4 was 42%, grade 3-4 aGVHD was in 20% of patients. PTCy-based GVHD prophylaxis reduced CI of aGVHD (34% vs 57%, p=0.02). Another factors associated with reduction of aGVHD incidence were as follows: MAC (37% vs 58% among RIC pts, p=0.05); MRD (14% vs 30% in haplo group vs 59% in MUD/MMUD group, p=0.015); BM as a transplant source (41% vs 74% in PBSC group, p=0.02), male donors vs female ones (40 vs 65%, p=0.008). In multivariate analysis, BM graft (HR 2.3 95%CI 1.2-4.3, p=0.009), male donors (HR 0.4 95%CI 0.2-0.7, p=0.005); PTCY (HR 0.4 95%CI 0.2-0.9, p=0.04) were predictive for reduced CI of aGVHD. 5-year overall survival (OS) was 65%. The following factors improved OS, as follows: recipient age at transplant under 5 y.o. (79% vs 39%, p=0.000); time from diagnosis to allo-HSCT less than 22 months (73% vs 37%, p=0.002); long-term stable engraftment (73% vs 18%, p=0.000). In multivariate analysis, only engraftment was predictive for OS rates (HR 0.2, 95%CI 0.1-0.63, p=0.003).


PTCy-based GVHD prophylaxis can be an effective option for reducing risk of acute GVHD. Using related donors, bone marrow as transplant source and MAC regimen can reduce CI of GVHD. Performing allo-HSCT early after the diagnosis and at younger age may improve OS in the patients with inherited disorders.


Inherited disorders, children, hematopoietic stem cell transplantation, GvHD prophylaxis, cyclophosphamide.

Volume 8, number 3

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