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. 2024 Mar 1;109(3):799-808.
doi: 10.3324/haematol.2023.283649.

Lower overall survival in male patients with advanced disease undergoing allogeneic hematopoietic stem cell transplantation is associated with CYP1B1 Leu432Val polymorphism

Norbert Stute  1 , Michael Koldehoff  2
Affiliations

Lower overall survival in male patients with advanced disease undergoing allogeneic hematopoietic stem cell transplantation is associated with CYP1B1 Leu432Val polymorphism

Norbert Stute et al. Haematologica. .

Abstract

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic key enzyme involved in estrogen metabolism, steroid synthesis, and pro-carcinogen activation. In a single-center retrospective study, 382 patients who underwent allogeneic hematopoetic stem cell transplantation and their donors were genotyped for CYP1B1 C432G polymorphism by reverse transcription polymerase chain reaction. One hundred and sixty-nine patients (44%) were homozygous wild-type (wt) gene CC, 157 (41%) heterozygous CG and 56 (15%) homozygous gene mutated GG. Of interest, mutated CYP1B1 was more common in male (62%) than in female patients (48%) P=0.006, unlike in donors. Five-year estimate for overall survival (OS) was 58±4% (CC) versus 48±3% (CG and GG), P=0.048. Surprisingly, this difference was only evident in males (P=0.024): OS 58±6% versus 42±4%, whereas it was virtually absent in females. Importantly, this difference was only evident in male patients with advanced disease (AD) (n=118, P=0.002): OS 44±8% (CC) versus 32±6% (CG) versus 6±6% (GG), whereas it was virtually absent in male patients with early disease. One-year non-relapse mortality in male patients with AD was 8±4% (CC) versus 21±5% (CG) versus 50±12% (GG), P=0.002. Three-year relapse rate in male patients with AD was 31±7% (wt) versus 42±6% (mut), P=0.04. Multivariate analysis for OS in male patients with AD revealed CYP1B1 polymorphism as the only prognostic factor: RR 1.78, P=0.001. In conclusion, these results suggest that male patients with AD and mutant CYP1B1 polymorphism have lower OS after allogeneic hematopoetic stem cell transplantation due to a higher non-relapse mortality and a higher relapse rate.

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Figures

Figure 1.
Figure 1.
Overall survival estimate by CYP1B1 polymorphism. (A) Male patients (N=204): patients with mutant (mut) recipient single nucleotide polymorphism (R SNP) (wt/mut and mut/mut) had lower overall survival (OS) than patients with wild-type (wt) R SNP (wt/wt). (B) Female patients (N=178) displaying no difference (not significant [NS]). R SNP here CYP1B1 C432G polymorphism CC, CG and GG. HSCT: hematopoietic stem cell transplantation.
Figure 2.
Figure 2.
Overall survival estimate in male patients by CYP1B1 polymorphism. (A) Male patients with advanced disease (N=118):
Figure 3.
Figure 3.
Non-relapse mortality estimate in male patients by CYP1B1 polymorphism. (A) Male patients with advanced disease (N=118): male patients with mutant (mut) recipient single nucleotide polymorphism (R SNP) had a higher non-relapse mortality (NRM) than those with wild-type (wt) R SNP. (B) Male patients with early disease (N=86) displaying no difference (not significant [NS]). HSCT: hematopoietic stem cell transplantation.
Figure 4.
Figure 4.
Relapse estimate in male patients by CYP1B1 polymorphism. (A) Male patients with advanced disease (N=118). Male patients with mutant (mut) recipient single nucleotide polymorphism (R SNP) had a higher relapse rate than those with wild-type (wt) R SNP. (B) Male patients with early disease (N=86) displaying no difference (not significant [NS]). HSCT: hematopoietic stem cell transplantation.
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