Ignite Creation Date:
2024-05-06 @ 8:48 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02827149
Status:
COMPLETED
Last Update Posted:
2021-08-20
First Post:
2016-07-06
Brief Title:
High Resolution Donor Recipient HLA Matching Level in Unrelated HSCT
Sponsor:
Gruppo Italiano Trapianto di Midollo Osseo
Organization:
Gruppo Italiano Trapianto di Midollo Osseo
Study Overview
Official Title:
High Resolution Donor Recipient HLA Matching Level in Unrelated Hematopoietic Stem Cell Transplantation and Impact on the Transplant Outcome the Italian Experience
Status:
COMPLETED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GITMO-HLA-HR
Brief Summary:
Italian retrospective prospective observational multicentre spontaneous non-interventional non-pharmacological The study aims to analyze in the national Italian experience
1 The compatibility level selected by the Italian Transplant Centres using an high resolution HLA typing at the start of search process for hematopoietic stem cell transplantation from volunteer unrelated donor
2 The transplant outcomes in terms of Overall Survival Disease Free Survival Relapse Rate and Transplant Related Mortality and the correlation with the level of HLA matching pairs of donorrecipient included in the Italian Bone Marrow Donor Registry and Promise registry
3 The possible identification of allelic mismatching combinations characterized by increased cross-reactivity associated with higher incidence of acute or chronic graft-versus-host disease
4 The possible identification of combinations of allelic mismatching characterized by higher permissiveness
1 The compatibility level selected by the Italian Transplant Centres using an high resolution HLA typing at the start of search process for hematopoietic stem cell transplantation from volunteer unrelated donor
2 The transplant outcomes in terms of Overall Survival Disease Free Survival Relapse Rate and Transplant Related Mortality and the correlation with the level of HLA matching pairs of donorrecipient included in the Italian Bone Marrow Donor Registry and Promise registry
3 The possible identification of allelic mismatching combinations characterized by increased cross-reactivity associated with higher incidence of acute or chronic graft-versus-host disease
4 The possible identification of combinations of allelic mismatching characterized by higher permissiveness
Detailed Description:
Haematopoietic allogeneic stem cell transplantation HSCT represents a potentially curative treatment for several haematological disorders but its application depends on the availability of a suitable donor Some data show that in US population the likelihood of finding HR 88 HLA A B C DRB1 matched donor in NMDP registry is about 75 for white Europeans but only 46 for white patients of Middle Eastern or North African descents Moreover this probability decreases for patients belonging to African or Black SouthCentral American group at 18 and 16 respectively Furtherly recent data have reported a significant improvement in the unrelated donor identification over the years In particular they have conducted the unrelated donor searches for 1344 ideal patients in the Be The Match Registry database at 2 time points 2009 and 2012 Their results have shown that 88 high resolution HLA match rate A B Cw and DRB1 for White raised from 68 in 2009 to 72 in 2012 Corresponding match rates were 41 to 44 for Hispanic 44 to 46 for AsianPacific Islander and 27 to 30 for African AmericanBlack race and ethnic groups for 2009 and 2012 respectively The 2012 1010 match rates were 67 for White 38 for Hispanic 41 for AsianPacific Islander and 23 for African AmericanBlack
Current available data confer to HLA mismatch 6-78 a significant increased risk for grades II to IV and III to IV acute graft versus host disease chronic graft versus host disease transplant-related mortality TRM and overall mortality compared with HLA-matched cases 88 However it is not yet clear if type alleleantigen and locus HLA-A -B -C and -DRB1 of mismatch are associated with overall mortality In order to improve the outcome of the unrelated HSCT many efforts are ongoing for identifying permissive and non permissive HLA disparity both for I and II classes HLA Recently several authors have highlighted the crucial role of allelic mismatching Cw combinations in supporting GVL graft versus host disease effect with a consequent decreased risk of relapse p0003 On the contrary Cw disparities as Cw0303 vs Cw0304 or Cw0701 vs Cw0702 seem to be permissiveness in terms of HSCT clinical outcome Contemporarily Japanese meta-analysis on 6967 unrelated HSCT has shown that the presence of HLA-B5101 in the donorrecipient pairs is associated with acute graft versus host disease not only for the strong linkage disequilibrium of HLA-C1402 and -B5101 but also for the effect of HLA-B5101 itself Based on these data mismatched HLA-C1402 should be considered a non-permissive HLA-C mismatch in donor selection because it seems to be a potent risk factor for severe acute graft versus host disease and mortality
Concerning DPB1 HLA loci an algorithm for non-permissive HLA-DPB1 disparities has been described based on T-cell alloreactivity patients with potential clinical implications To confirm this data GITMO analysis has reported an increased but similar overall mortality by non-permissive HLADPB1 disparity in 10 of 10 HR 212 CI 123-364 P 006 and 9 of 10 allele-matched transplantations HR 221 CI 128-380 P 004 both in early-stage and in advanced-stage disease Additionally recent data have reported that among 88 matched cases HLA-DPB1 and -DQB1 mismatch resulted in increased acute graft versus host disease and HLA-DPB1 mismatch is associated with decreased relapse Non-permissive HLA-DPB1 allele mismatch was also associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 88 and 1010 matched cases Based on all these reports the current suggestions concerning the unrelated donor selection consists of a full matching at HLA-A -B -C and -DRB1 unrelated donor for optimal HSCT survival and avoiding non-permissive HLA-DPB1 mismatches in otherwise HLA-matched pairs
In 2009 a previous retrospective Italian analysis performed on 805 couples reported that globally there are no differences in terms of outcomes Overall Survival Disease Free Survival Relapse Rate and Transplant Related Mortality and Graft Versus Host Disease in adult patients with neoplastic diseases transplanted with HLA-matched donor 1010 or 910 However stratifying patients by stage of disease at transplant a single HLA incompatibility significantly increases the risk of mortality in patients who received HSCT in early stage whereas this data is not confirmed for patients transplanted in advanced stage of disease This previous Italian analysis included only 1010 high-resolution typed pairs from 1999 to 2006 excluding all the others couple without a full HLA typing for avoiding confounding results According to Italian Bone Marrow Donor Registry standard extended HR HLA was not a mandatory requirement from 1999 to 2006
From January 2012 all Italian recipients have been typed with HR-HLA typing at the starting of the unrelated donor search process with a consequent advantage in terms of non selected population as object of the present observational trial Moreover the larger size of cohort of patients who underwent unrelated HSCT during a smaller study period of 2 years should lead to a more effective analysis including the assessments of permissive and non-permissive I and II class HLA incompatibilities Finally in order to give a stronger statistical power to this trial particular efforts have been drawn in order to recovery data about the graft versus host disease prophylaxis
Current available data confer to HLA mismatch 6-78 a significant increased risk for grades II to IV and III to IV acute graft versus host disease chronic graft versus host disease transplant-related mortality TRM and overall mortality compared with HLA-matched cases 88 However it is not yet clear if type alleleantigen and locus HLA-A -B -C and -DRB1 of mismatch are associated with overall mortality In order to improve the outcome of the unrelated HSCT many efforts are ongoing for identifying permissive and non permissive HLA disparity both for I and II classes HLA Recently several authors have highlighted the crucial role of allelic mismatching Cw combinations in supporting GVL graft versus host disease effect with a consequent decreased risk of relapse p0003 On the contrary Cw disparities as Cw0303 vs Cw0304 or Cw0701 vs Cw0702 seem to be permissiveness in terms of HSCT clinical outcome Contemporarily Japanese meta-analysis on 6967 unrelated HSCT has shown that the presence of HLA-B5101 in the donorrecipient pairs is associated with acute graft versus host disease not only for the strong linkage disequilibrium of HLA-C1402 and -B5101 but also for the effect of HLA-B5101 itself Based on these data mismatched HLA-C1402 should be considered a non-permissive HLA-C mismatch in donor selection because it seems to be a potent risk factor for severe acute graft versus host disease and mortality
Concerning DPB1 HLA loci an algorithm for non-permissive HLA-DPB1 disparities has been described based on T-cell alloreactivity patients with potential clinical implications To confirm this data GITMO analysis has reported an increased but similar overall mortality by non-permissive HLADPB1 disparity in 10 of 10 HR 212 CI 123-364 P 006 and 9 of 10 allele-matched transplantations HR 221 CI 128-380 P 004 both in early-stage and in advanced-stage disease Additionally recent data have reported that among 88 matched cases HLA-DPB1 and -DQB1 mismatch resulted in increased acute graft versus host disease and HLA-DPB1 mismatch is associated with decreased relapse Non-permissive HLA-DPB1 allele mismatch was also associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 88 and 1010 matched cases Based on all these reports the current suggestions concerning the unrelated donor selection consists of a full matching at HLA-A -B -C and -DRB1 unrelated donor for optimal HSCT survival and avoiding non-permissive HLA-DPB1 mismatches in otherwise HLA-matched pairs
In 2009 a previous retrospective Italian analysis performed on 805 couples reported that globally there are no differences in terms of outcomes Overall Survival Disease Free Survival Relapse Rate and Transplant Related Mortality and Graft Versus Host Disease in adult patients with neoplastic diseases transplanted with HLA-matched donor 1010 or 910 However stratifying patients by stage of disease at transplant a single HLA incompatibility significantly increases the risk of mortality in patients who received HSCT in early stage whereas this data is not confirmed for patients transplanted in advanced stage of disease This previous Italian analysis included only 1010 high-resolution typed pairs from 1999 to 2006 excluding all the others couple without a full HLA typing for avoiding confounding results According to Italian Bone Marrow Donor Registry standard extended HR HLA was not a mandatory requirement from 1999 to 2006
From January 2012 all Italian recipients have been typed with HR-HLA typing at the starting of the unrelated donor search process with a consequent advantage in terms of non selected population as object of the present observational trial Moreover the larger size of cohort of patients who underwent unrelated HSCT during a smaller study period of 2 years should lead to a more effective analysis including the assessments of permissive and non-permissive I and II class HLA incompatibilities Finally in order to give a stronger statistical power to this trial particular efforts have been drawn in order to recovery data about the graft versus host disease prophylaxis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None