Contributions
Abstract: PB2448
Type: Publication Only
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment option for certain hematological malignancies. Suppressor of fused (SUFU) is a negative regulator of the hedgehog signaling pathway which is involved in cell proliferation and differentiation, and it interacts with the Glioma transcription factors. Recently, correlation has been shown between the SUFU polymorphism rs17114808 and the incidence of acute graft versus host disease (aGvHD).
Aims
The aim of this study was to investigate the role of SUFU rs17114808 (C>T) polymorphism in the outcome of HSCT.
Methods
We examined the association of recipient and donor SUFU rs17114808 C>T and allo-HSCT outcome in a cohort of 407 adult patients who underwent first allo-HSCT between January 2007 and December 2013 at our single center. 208 patients received stem cells from their siblings, 199 patients from matched unrelated donors (MUD). 227 patients was diagnosed with AML (n=155) or ALL (n=72) and 180 patients with other (MDS [n=31], CML [n=22], MPN [n=20], MM [n=25], CLL [n=25], NHL [39], HL [18]) diseases. In 260 cases myeloablative conditioning (MAC), while in 147 cases reduced intensity conditioning (RIC) was applied. For identification of SUFU rs17114808 from genomic DNA LightCycler melting curve analysis (LightCycler 480II, Roche Diagnostics) was performed.
Results
We did not find any association between recipients’ SUFU rs17114808 C>T polymorphism and HSCT outcome on the whole cohort. In patients with SUFU rs17114808 CT or TT genotype, aGvHD grade II-IV occurred in 68% (67/99), compared to 32% (98/307) in patients with CC genotype (p=1). Relapse occurred in 29% (29/99) T carrier patients and in 25% (76/307) of patients with CC genotype (p=0.428). Similar findings were observed in case of SUFU rs17114808 C>T polymorphism in donors. The frequency of aGvHD was 29% (22/76) in case of T allele carrier donors and 32% (107/336) in patients with wild type (CC) donor (p=0.682). Donors’ SUFU genotype did not influence the relapse rate (22% [17/76] in patients with donors bearing at least one T variant vs. 27% [91/336] for wild type donors). Overall survival did not differ in subgroups with different genotypes of recipients and donors. Based on tests for interaction, subgroup analysis was performed according to diagnosis (acute leukemia vs. other) and conditioning regimen (MAC vs. RIC), but we did not find significant association in the subgroups.
Conclusion
In contrast with a previous study performed in pediatric HSCT patients, our findings suggest that SUFU rs17114808 C>T polymorphism in adult HSCT recipients and donors does not influence the outcome of HSCT.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, SNP
Abstract: PB2448
Type: Publication Only
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment option for certain hematological malignancies. Suppressor of fused (SUFU) is a negative regulator of the hedgehog signaling pathway which is involved in cell proliferation and differentiation, and it interacts with the Glioma transcription factors. Recently, correlation has been shown between the SUFU polymorphism rs17114808 and the incidence of acute graft versus host disease (aGvHD).
Aims
The aim of this study was to investigate the role of SUFU rs17114808 (C>T) polymorphism in the outcome of HSCT.
Methods
We examined the association of recipient and donor SUFU rs17114808 C>T and allo-HSCT outcome in a cohort of 407 adult patients who underwent first allo-HSCT between January 2007 and December 2013 at our single center. 208 patients received stem cells from their siblings, 199 patients from matched unrelated donors (MUD). 227 patients was diagnosed with AML (n=155) or ALL (n=72) and 180 patients with other (MDS [n=31], CML [n=22], MPN [n=20], MM [n=25], CLL [n=25], NHL [39], HL [18]) diseases. In 260 cases myeloablative conditioning (MAC), while in 147 cases reduced intensity conditioning (RIC) was applied. For identification of SUFU rs17114808 from genomic DNA LightCycler melting curve analysis (LightCycler 480II, Roche Diagnostics) was performed.
Results
We did not find any association between recipients’ SUFU rs17114808 C>T polymorphism and HSCT outcome on the whole cohort. In patients with SUFU rs17114808 CT or TT genotype, aGvHD grade II-IV occurred in 68% (67/99), compared to 32% (98/307) in patients with CC genotype (p=1). Relapse occurred in 29% (29/99) T carrier patients and in 25% (76/307) of patients with CC genotype (p=0.428). Similar findings were observed in case of SUFU rs17114808 C>T polymorphism in donors. The frequency of aGvHD was 29% (22/76) in case of T allele carrier donors and 32% (107/336) in patients with wild type (CC) donor (p=0.682). Donors’ SUFU genotype did not influence the relapse rate (22% [17/76] in patients with donors bearing at least one T variant vs. 27% [91/336] for wild type donors). Overall survival did not differ in subgroups with different genotypes of recipients and donors. Based on tests for interaction, subgroup analysis was performed according to diagnosis (acute leukemia vs. other) and conditioning regimen (MAC vs. RIC), but we did not find significant association in the subgroups.
Conclusion
In contrast with a previous study performed in pediatric HSCT patients, our findings suggest that SUFU rs17114808 C>T polymorphism in adult HSCT recipients and donors does not influence the outcome of HSCT.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, SNP