ISSN 1866-8836
Клеточная терапия и трансплантация

IC-03. Pulmonary complications in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with different intensity conditioning regimens and GVHD prophylaxis (post-transplant cyclophosphamide vs ATG)

Anastasia S. Frolova, Olesya V. Paina, Alisa G. Volkova, Polina V. Kozhokar, Zhemal Z. Rakhmanova, Liubov A. Tsvetkova, Kirill A. Ekushov, Elena V. Babenko, Alexander L. Alyanskiy, Ildar M. Barkhatov, Elena V. Semenova, Ludmila S. Zubarovskaya

RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia

Contact: Dr. Anastasia S. Frolova, e-mail: mukhinova.anastasia@mail.ru

doi 10.18620/ctt-1866-8836-2020-9-3-1-152

Summary

Introduction

Although pulmonary complications occur in 40-60% of pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, it is still unclear whether the diagnosis, disease stage, conditioning regimens, or graft-versus-host disease (GVHD) prophylaxis influence their incidence. Our aim was to assess the pulmonary complications rates in the children with acute leukemia after allo-HSCT with different conditioning and acute GVHD prophylaxis, i.e., post-transplant cyclophosphamide (PTCy) versus ATG regimens.

Patients and methods

A total of 208 patients (pts) subjected to allo-HSCT in 2000-2018 were included in the analysis. The median age was 10 years (range 0-18). The underlying diagnoses were AML (n=94, 45%) and ALL (n=114, 55%). The disease status at the time of allo-HSCT was 1st or 2nd remission. Conditioning regimens were myeloablative (MAC) in 128 (62%), and reduced-intensity (RIC) in 80 (38%) pts. In 121 case (58%), the HSC source was bone marrow (BM), in 83 (40%) peripheral blood stem cells (PBSC). In 4 cases (2%), BM+PBSC combination was used. In 15 pts (7%), allo-HSCT was performed from matched related; in 152 (73%), from unrelated, and in 41 (20%), from haploidentical donor. The following ATG-based aGVHD prevention regimens were used in 96 pts (46%), PTCy was administered to 112 (54%) patients ± calcineurin inhibitor (CsA/Tacro) ± Cellsept ± sirolimus. Pulmonary lesions were assessed via X-ray and CT imaging, and functional respiratory tests. Overall survival (OS) was evaluated by Kaplan-Meier method.

Results

Pulmonary complications following allo-HSCT were seen in 60.1% and 59.3% of RIC- and MAC-treated pts allo-HSCT, accordingly. In RIC group, the 5-year OS pts with and without pulmonary complications was 43.8% and 71.9% (p=0.017); in the MAC group, OS was 55.5% vs 78.4% (p=0.025), accordingly. For the subgroup free of pulmonary complications, the PTCy-based aGVHD prophylaxis was associated with better 5-year OS (86.4%) compared to ATG recipients, in which it was 64.1% (p=0.05). However, there is only a trend to significant difference in the patients with pulmonary complications who showed 5-year OS of 58.8% versus 42.1% for PTCy- and ATG-treated recipients, accordingly (p=0.067). The 5-year OS was not affected by presence or absence of pulmonary complications in the pts with aGVHD (53.3% vs 65.9%, accordingly; p=0.268), while in cGVHD subgroup their presence was associated with 5-year OS decrease from 83.3% to 60.3% (p=0.036). The donor compatibility or sex, HSC source, or conditioning regimen did not influence the pulmonary complications rate (p>0.05).

Conclusion

Development of pulmonary complications reduces 5-year OS in the pts with ALL or AML receiving allo-HSCT in 1st or 2nd remission, regardless of the conditioning regimen. Five-year OS was better in PTCy vs ATG recipients with or without pulmonary complications. Also, presence of pulmonary complications is a stronger negative predictor of survival in the pts with concurrent cGVHD, as compared to aGVHD group.

Keywords

Pulmonary complications, allo-HSCT, children.


Volume 9, Number 3
09/30/2020

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doi 10.18620/ctt-1866-8836-2020-9-3-1-152

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