Gene polymorphism analysis as predictor for development of invasive aspergillosis after allogeneic stem cell transplantation

Ref ID: 18546

Author:

L. Gil, M. Pieronkiewicz, A. Mol, D. Poplawski, A. Schneider,
K. Lewandowski, M. Komarnicki

Author address:

University oF Medical Sciences (Poznan, PL)

Full conference title:

Annual Meeting of the EBMT, 38th

Abstract:

Invasive aspergillosis (IA) continues to be a major cause of
morbidity and mortality in patients undergoing alloSCT. The aim
of the study was to analyze molecular risk of IA development
and outcome in pts qualifi ed for alloSCT, based on gene polymorphism studies.
Material and Methods: Two new tetra-primer ARMS-PCR’s
(Amplifi cation Refractory Mutation System) were designed
using Lasergene Primer Select software for TLR4 and UGTA1
SNP. IFGN and TNFR2 polymorphisms were screened with
published primers but using new PCR conditions, common to
all reactions. Gene polymorphisms were analyzed in a cohort
of 111 pts with acute leukemias (79), chronic leukemias (10)
or lymphoid malignances (22) and their sibling (53) or unrelated (58) donors. Pts were conditioned with myeloablative (50)
or reduced intensity (61) regimen and grafted with 3.8 (0.9-
5.2)x10
6
/kg of CD34+ cells. Standard defi nitions for neutropenic, bacterial, fungal and viral infections were used.
Results: Neutrophil recovery occurred in all pts at a median
21 (range; 12-38) days. Infectious complications included neutropenic fever in 102 (92%), CMV infection in 45 (40.5%) and
documented IA in 22 (19%) pts (proven-5 and probable-17).
Acute GVHD 2-4 grade was seen in 41 (37%), while chronic
extensive in 9 (8%) pts. The only pretransplant factor (donor/
recipient gene polymorphisms, age, sex, diagnosis, disease
stage) signifi cant for development of documented IA by logistic regression analysis was recipient TLR4 SNP (p=0.023,
HR 4.0). Among transplant-related factors (dose and source
of stem cells, intensity of conditioning, neutropenia duration,
GVHD) signifi cant for IA development was GVHD occurrence
(p=0.005, HR=5.1). Over a median follow-up of 14.5 (range;
1.5-65.5) months, 89 (80%) pts were alive with median survival 16.5 (95%CI=1.5-66.6) months. Among 22 (20%) deaths,
10 were related to IA. Factors signifi cant for death from infections by univariate analysis was GVHD occurrence (p=0.007,
HR 3.9) documented IA (p<0.001, HR 7.0) and CMV infection (p=0.034, HR 2.5). Factors predicting death from infection by multivariate analysis was only diagnosis of documented IA (p=0.003, HR 23.3). No factors predicting the outcome of IA pts were identifi ed. Conclusion: High mortality rate of IA after alloSCT remains a concern. TLR4 1063A>G SNP strongly predicts IA development. IA risk analysis based on gene polymorphism may help
in stratifi cation of pts to offer an individualized treatment.

Abstract Number: O356

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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