THE JAK2 46/1 HAPLOTYPE IS ASSOCIATED WITH ACUTE GRAFT-VERSUS-HOST DISEASE IN ACUTE MYELOID LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
(Abstract release date: 05/19/16)
EHA Library. Meggyesi N. 06/09/16; 133056; E1507
Dr. Nora Meggyesi
Contributions
Contributions
Abstract
Abstract: E1507
Type: Eposter Presentation
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be the most effective treatment option for certain hematological malignancies, however the favorable outcome of the procedure could be jeopardized by graft-versus-host disease (GvHD). Cytokines play a well established role in the mechanism of acute GvHD (aGvHD) and many of the involved cytokines relay their signal through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
Aims
In the present work, we investigated whether recipient and donor JAK2 46/1 haplotype could affect allo-HSCT outcomes, such as aGvHD, relapse rate and mortality in AML patients.
Methods
We examined the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 adult patients diagnosed with AML, who received first allo-HSCT in complete remission (CR) between January 2007 and December 2013 at our single center. For identification of JAK2 rs12343867 from genomic DNA LightCycler melting curve analysis (LightCycler 480II, Roche Diagnostics) was performed.
Results
Presence of JAK2 46/1 haplotype was associated with higher frequency of aGvHD grades II-IV (carrier vs. non-carrier recipients 42% vs.19% p=0.008 and carrier vs. non-carrier donors 40% vs. 21%, p=0.038). We confirmed significantly higher risk if both, recipient and donor were 46/1 haplotype carriers compared to those where recipient and donor were non-carriers (OR=5.242, 95% CI=1.784-15.404, p=0.003). Relapse free survival (RFS) did not differ between 46/1 haplotype carrier and non-carrier recipients (2-year RFS 69.1±6.1% vs. 54.2±6.9%, respectively, p=0.25), but we found significant alterations in the cause of death between the subgroups. In the 46/1 haplotype group the major causes of death were transplantation related complications, including aGvHD (18/21, 86%), while 3 deaths (14%) were attributed to relapse. In the non-46/1 haplotype subgroup 48% died of relapsing leukemia, while non-relapse mortality accounted for 52% (p=0.024). If donors were 46/1 carriers, patients more often died of transplantation related complications (81% vs. 50%, p=0.049). The relapse rate was comparable in patients transplanted from a carrier or a non-carrier donor. Survival analysis according to the donor haplotype showed a favorable RFS in the non-46/1 haplotype group (2-year RFS 71±6 vs. 53±7%, p=0.033). The difference in 2-year RFS rates remained significant in the four recipient-donor groups [64±8% (non-carrier recipient, non-carrier donor), 82±8% (carrier recipient, non-carrier donor), 36±11% (non-carrier recipient, carrier donor) and 61±8% (carrier recipient, carrier donor); p=0.038).
Conclusion
Although the exact pathomechanism is yet to be explored, our findings suggest that recipient and donor JAK2 46/1 haplotypes might be involved in the regulation of aGvHD.
Session topic: E-poster
Keyword(s): Acute graft-versus-host disease, Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant
Type: Eposter Presentation
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be the most effective treatment option for certain hematological malignancies, however the favorable outcome of the procedure could be jeopardized by graft-versus-host disease (GvHD). Cytokines play a well established role in the mechanism of acute GvHD (aGvHD) and many of the involved cytokines relay their signal through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
Aims
In the present work, we investigated whether recipient and donor JAK2 46/1 haplotype could affect allo-HSCT outcomes, such as aGvHD, relapse rate and mortality in AML patients.
Methods
We examined the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 adult patients diagnosed with AML, who received first allo-HSCT in complete remission (CR) between January 2007 and December 2013 at our single center. For identification of JAK2 rs12343867 from genomic DNA LightCycler melting curve analysis (LightCycler 480II, Roche Diagnostics) was performed.
Results
Presence of JAK2 46/1 haplotype was associated with higher frequency of aGvHD grades II-IV (carrier vs. non-carrier recipients 42% vs.19% p=0.008 and carrier vs. non-carrier donors 40% vs. 21%, p=0.038). We confirmed significantly higher risk if both, recipient and donor were 46/1 haplotype carriers compared to those where recipient and donor were non-carriers (OR=5.242, 95% CI=1.784-15.404, p=0.003). Relapse free survival (RFS) did not differ between 46/1 haplotype carrier and non-carrier recipients (2-year RFS 69.1±6.1% vs. 54.2±6.9%, respectively, p=0.25), but we found significant alterations in the cause of death between the subgroups. In the 46/1 haplotype group the major causes of death were transplantation related complications, including aGvHD (18/21, 86%), while 3 deaths (14%) were attributed to relapse. In the non-46/1 haplotype subgroup 48% died of relapsing leukemia, while non-relapse mortality accounted for 52% (p=0.024). If donors were 46/1 carriers, patients more often died of transplantation related complications (81% vs. 50%, p=0.049). The relapse rate was comparable in patients transplanted from a carrier or a non-carrier donor. Survival analysis according to the donor haplotype showed a favorable RFS in the non-46/1 haplotype group (2-year RFS 71±6 vs. 53±7%, p=0.033). The difference in 2-year RFS rates remained significant in the four recipient-donor groups [64±8% (non-carrier recipient, non-carrier donor), 82±8% (carrier recipient, non-carrier donor), 36±11% (non-carrier recipient, carrier donor) and 61±8% (carrier recipient, carrier donor); p=0.038).
Conclusion
Although the exact pathomechanism is yet to be explored, our findings suggest that recipient and donor JAK2 46/1 haplotypes might be involved in the regulation of aGvHD.
Session topic: E-poster
Keyword(s): Acute graft-versus-host disease, Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant
Abstract: E1507
Type: Eposter Presentation
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be the most effective treatment option for certain hematological malignancies, however the favorable outcome of the procedure could be jeopardized by graft-versus-host disease (GvHD). Cytokines play a well established role in the mechanism of acute GvHD (aGvHD) and many of the involved cytokines relay their signal through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
Aims
In the present work, we investigated whether recipient and donor JAK2 46/1 haplotype could affect allo-HSCT outcomes, such as aGvHD, relapse rate and mortality in AML patients.
Methods
We examined the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 adult patients diagnosed with AML, who received first allo-HSCT in complete remission (CR) between January 2007 and December 2013 at our single center. For identification of JAK2 rs12343867 from genomic DNA LightCycler melting curve analysis (LightCycler 480II, Roche Diagnostics) was performed.
Results
Presence of JAK2 46/1 haplotype was associated with higher frequency of aGvHD grades II-IV (carrier vs. non-carrier recipients 42% vs.19% p=0.008 and carrier vs. non-carrier donors 40% vs. 21%, p=0.038). We confirmed significantly higher risk if both, recipient and donor were 46/1 haplotype carriers compared to those where recipient and donor were non-carriers (OR=5.242, 95% CI=1.784-15.404, p=0.003). Relapse free survival (RFS) did not differ between 46/1 haplotype carrier and non-carrier recipients (2-year RFS 69.1±6.1% vs. 54.2±6.9%, respectively, p=0.25), but we found significant alterations in the cause of death between the subgroups. In the 46/1 haplotype group the major causes of death were transplantation related complications, including aGvHD (18/21, 86%), while 3 deaths (14%) were attributed to relapse. In the non-46/1 haplotype subgroup 48% died of relapsing leukemia, while non-relapse mortality accounted for 52% (p=0.024). If donors were 46/1 carriers, patients more often died of transplantation related complications (81% vs. 50%, p=0.049). The relapse rate was comparable in patients transplanted from a carrier or a non-carrier donor. Survival analysis according to the donor haplotype showed a favorable RFS in the non-46/1 haplotype group (2-year RFS 71±6 vs. 53±7%, p=0.033). The difference in 2-year RFS rates remained significant in the four recipient-donor groups [64±8% (non-carrier recipient, non-carrier donor), 82±8% (carrier recipient, non-carrier donor), 36±11% (non-carrier recipient, carrier donor) and 61±8% (carrier recipient, carrier donor); p=0.038).
Conclusion
Although the exact pathomechanism is yet to be explored, our findings suggest that recipient and donor JAK2 46/1 haplotypes might be involved in the regulation of aGvHD.
Session topic: E-poster
Keyword(s): Acute graft-versus-host disease, Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant
Type: Eposter Presentation
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be the most effective treatment option for certain hematological malignancies, however the favorable outcome of the procedure could be jeopardized by graft-versus-host disease (GvHD). Cytokines play a well established role in the mechanism of acute GvHD (aGvHD) and many of the involved cytokines relay their signal through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
Aims
In the present work, we investigated whether recipient and donor JAK2 46/1 haplotype could affect allo-HSCT outcomes, such as aGvHD, relapse rate and mortality in AML patients.
Methods
We examined the association of recipient and donor JAK2 46/1 haplotypes and allo-HSCT outcome in a cohort of 124 adult patients diagnosed with AML, who received first allo-HSCT in complete remission (CR) between January 2007 and December 2013 at our single center. For identification of JAK2 rs12343867 from genomic DNA LightCycler melting curve analysis (LightCycler 480II, Roche Diagnostics) was performed.
Results
Presence of JAK2 46/1 haplotype was associated with higher frequency of aGvHD grades II-IV (carrier vs. non-carrier recipients 42% vs.19% p=0.008 and carrier vs. non-carrier donors 40% vs. 21%, p=0.038). We confirmed significantly higher risk if both, recipient and donor were 46/1 haplotype carriers compared to those where recipient and donor were non-carriers (OR=5.242, 95% CI=1.784-15.404, p=0.003). Relapse free survival (RFS) did not differ between 46/1 haplotype carrier and non-carrier recipients (2-year RFS 69.1±6.1% vs. 54.2±6.9%, respectively, p=0.25), but we found significant alterations in the cause of death between the subgroups. In the 46/1 haplotype group the major causes of death were transplantation related complications, including aGvHD (18/21, 86%), while 3 deaths (14%) were attributed to relapse. In the non-46/1 haplotype subgroup 48% died of relapsing leukemia, while non-relapse mortality accounted for 52% (p=0.024). If donors were 46/1 carriers, patients more often died of transplantation related complications (81% vs. 50%, p=0.049). The relapse rate was comparable in patients transplanted from a carrier or a non-carrier donor. Survival analysis according to the donor haplotype showed a favorable RFS in the non-46/1 haplotype group (2-year RFS 71±6 vs. 53±7%, p=0.033). The difference in 2-year RFS rates remained significant in the four recipient-donor groups [64±8% (non-carrier recipient, non-carrier donor), 82±8% (carrier recipient, non-carrier donor), 36±11% (non-carrier recipient, carrier donor) and 61±8% (carrier recipient, carrier donor); p=0.038).
Conclusion
Although the exact pathomechanism is yet to be explored, our findings suggest that recipient and donor JAK2 46/1 haplotypes might be involved in the regulation of aGvHD.
Session topic: E-poster
Keyword(s): Acute graft-versus-host disease, Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant
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