Side Effects Of Immunosuppressive Therapy(IST) Of Aplastic Anemia In Children
Authors: Salamonowicz Malgorzata , Pawelec Katarzyna , Matysiak Michal , Panasiuk Anna , Kowalczyk Jerzy , Balwierz Walentyna , Zaleska-Czepko Ewa , Chybicka Alicja , Szmyd Krzysztof , Bubala Halina , Szczepanski Tomasz , Wysocki Mariusz , Kurylak Andrzej , Wachowiak Jacek , Szpecht Dawid , Mlynarski Wojciech , Bulas Monika , Krawczuk-Rybak Maryna , Leszczynska Elzbieta , Urasinski Tomasz , Kaczorowska-Hac Barbara , Balcerska Anna , Peregud-Pogorzelski Jaroslaw 
Published: October 2019

Abstract

Introduction
Acquired aplastic anemia is very rare disease characterized by and pancytopenia and hypoplastic bone marrow. In 70% of cases the etiology is idiopathic but some cases can be caused by drugs, chemical substances and viruses. One of the main pathophysiological mechanism of aplastic anemia is immune-mediated destruction of hematopoietic cells. As a result of that the immunosuppressive therapy (IST) persists the treatment of choice in patients with severe acquired aplastic anemia (SAA), who don’t have matched sibling donor. Since few last years there is a discussion if it is still the best way of treatment. We wanted to show the side effects of IST during the therapy of SAA using the rabbit antithymocyte globulin(r-ATG)

Methods
The group of 55 children ( 32 boys, 23 girls) with SAA and vSAA (very severe aplastic anemia) treated with r-ATG , steroids, CSA, and/or GSF-CS was retrospectively analyzed. The median age of the children was 10 years (range 6mth-17,5 years). Response rate was assessed on days 84, 112,180, 360. Kaplan–Meier estimator, univariate analysis and multivariate Cox regression models were used to estimate the influence of side effects for PFS (progression free survival) and EFS( event free survival).

Results
Infectious complications (fever of unknown origin-FUO-26,92%, stomatitis -19,23% and sepsis -17,03% ) were the most common side effects of IST. The most common etiology were : E. coli, P. aureginosa, S. aureus, Kl. pneumonie, E. fecium, E. cloace. There was a significant association between EFS and infectious side effects (p=0,00093- log rank). Among side effects of r-ATG fever (30,30%) and dyspnoe (24,24%) were the most common.After CSA mainly gingival hyperplasia, hirsutysm and hypertension were observed. The most common hemorrhagic side effects of IST were skin petechiae. The other were central nervous system bleeding, gastrointestinal tract bleeding. There was significant correlation between the hemorrhagic side effects and PFS(p= 0,0144 log rank).After the G-CSF therapy muscular pains, and capillary leak syndrome, was observed but it didn’t influence survival. Among all patients 15 deaths was observed (27,27%)-5 early and 10 late deaths. Infections were the main causes of death. The relapse rate was 1,81%. The 2-year probability of not having relapse was 87,68%. Relapse free survival was 75,16% at 5 and 10 years. There was one transformation to paroxysmal nocturnal hemoglobinuria (PNH). There were no transformation to MDS or AML.Discussion. Infections are the most common side effects during the IST with r- ATG. Hemorrhagic side effects and infectious complications are very important factors which can affect the survival rate in children with SAA.

Disclosures:
Szczepanski: Octapharma AG: Investigator Other.