Contributions
Abstract: PB2443
Type: Publication Only
Background
Immunological tolerance after bone marrow transplantation (BMT) depends on complex interaction between graft and host cells and includes cytokine production and reception. Both host and graft cells may carry different polymorphic alleles in appropriate genes that may alter these processes. Possible impact of cytokine gene polymorphisms on the BMT outcome have not been thoroughly studied yet.
Aims
To measure possible correlation of overall survival, reconstitution time and level of GVHD with CCR5-delta 32 (rs333), CCR2-64I (rs1799864), SDF1-3'A (rs1801157), IL6 -572 C/G (rs1800796) polymorphisms in host and graft cells.
Methods
Forty three patients 18 to 64 years old (median age 32), 13 males and 30 females who received allogeneic hematopoietic transplantation in the National Research Center for Hematology were included in the study. Stem cell source was bone marrow in 14 cases and mobilized peripheral stem cells in 29 cases. 26 patients were diagnosed with AML, 9 with ALL, 3 with AA, 2 with MDS, 2 with CML and 1 with MPN/CLL. DNA of donors and recipients were analyzed for CCR5-delta 32(rs333), CCR2-64I(rs1799864), SDF1-3'A(rs1801157), IL6 -572 C/G (rs1800796) polymorphisms by means of allele-specific PCR. Genetic data were correlated with overall survival, reconstitution time, frequency of acute or chronic GVHD after BMT. Infectious complications where analyzed at days 0-30 and at days 30-120 after transplantation. SAS software was used for statistical analysis. Kaplan-Meier estimates, Log-Rank test and chi-square were used for group comparison.
Results
Patients were divided according to each polimorphysm issue into 4 groups: 1/ no mutant alleles in both recipient and donor; 2/ equal number of mutant alleles in recipient and donor; 3/ donor has less mutant alleles than recipient (0 vs 1, 0 vs 2, 1 vs 2); 4/ donor has more mutant alleles than recipient. All groups were equal in graft source, diagnosis, disease stage, gender and age. No correlations of most polymorphic alleles with overall survival, reconstitution time, frequency of a GVHD and infectious complications at day 30 were found. In the cases where donor carried more mutant CCR2 alleles than recipient hematopoesis reconstitution time was significantly longer than in other cases (p<0.0001) (Fig 1). Infectious complications were also more frequent at day 30-120 (р<0,0016): 10 of 11 patients who received transplant from a donor carrying more mutant CCR2 alleles than recipient (91%) vs 8 of 32 patients in other groups (22-50%).
Conclusion
Cytokine polymorphic alleles of donors and recipients may alter bone marrow transplantation outcome. Decreased reconstitution rate and increased levels of infectious complications could be registed in patients who received transplant from donors carrying mutant CCR2 alleles. More patient samples and extended cytokine gene panels are required for further studies.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Cytokine, Donor, Polymorphism, Transplant
Abstract: PB2443
Type: Publication Only
Background
Immunological tolerance after bone marrow transplantation (BMT) depends on complex interaction between graft and host cells and includes cytokine production and reception. Both host and graft cells may carry different polymorphic alleles in appropriate genes that may alter these processes. Possible impact of cytokine gene polymorphisms on the BMT outcome have not been thoroughly studied yet.
Aims
To measure possible correlation of overall survival, reconstitution time and level of GVHD with CCR5-delta 32 (rs333), CCR2-64I (rs1799864), SDF1-3'A (rs1801157), IL6 -572 C/G (rs1800796) polymorphisms in host and graft cells.
Methods
Forty three patients 18 to 64 years old (median age 32), 13 males and 30 females who received allogeneic hematopoietic transplantation in the National Research Center for Hematology were included in the study. Stem cell source was bone marrow in 14 cases and mobilized peripheral stem cells in 29 cases. 26 patients were diagnosed with AML, 9 with ALL, 3 with AA, 2 with MDS, 2 with CML and 1 with MPN/CLL. DNA of donors and recipients were analyzed for CCR5-delta 32(rs333), CCR2-64I(rs1799864), SDF1-3'A(rs1801157), IL6 -572 C/G (rs1800796) polymorphisms by means of allele-specific PCR. Genetic data were correlated with overall survival, reconstitution time, frequency of acute or chronic GVHD after BMT. Infectious complications where analyzed at days 0-30 and at days 30-120 after transplantation. SAS software was used for statistical analysis. Kaplan-Meier estimates, Log-Rank test and chi-square were used for group comparison.
Results
Patients were divided according to each polimorphysm issue into 4 groups: 1/ no mutant alleles in both recipient and donor; 2/ equal number of mutant alleles in recipient and donor; 3/ donor has less mutant alleles than recipient (0 vs 1, 0 vs 2, 1 vs 2); 4/ donor has more mutant alleles than recipient. All groups were equal in graft source, diagnosis, disease stage, gender and age. No correlations of most polymorphic alleles with overall survival, reconstitution time, frequency of a GVHD and infectious complications at day 30 were found. In the cases where donor carried more mutant CCR2 alleles than recipient hematopoesis reconstitution time was significantly longer than in other cases (p<0.0001) (Fig 1). Infectious complications were also more frequent at day 30-120 (р<0,0016): 10 of 11 patients who received transplant from a donor carrying more mutant CCR2 alleles than recipient (91%) vs 8 of 32 patients in other groups (22-50%).
Conclusion
Cytokine polymorphic alleles of donors and recipients may alter bone marrow transplantation outcome. Decreased reconstitution rate and increased levels of infectious complications could be registed in patients who received transplant from donors carrying mutant CCR2 alleles. More patient samples and extended cytokine gene panels are required for further studies.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Cytokine, Donor, Polymorphism, Transplant