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IMPACT OF AB0 INCOMPATIBILITY ON ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION OUTCOME: A SINGLE-CENTER RETROSPECTIVE STUDY
Author(s): ,
Andrea Busani
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Giorgia Saporiti
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Tatiana Zollner
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Elena Tagliaferri
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Federica Grifoni
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Francesca Gaia Rossi
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Cristina Manera
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Nicola Stefano Fracchiolla
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
,
Agostino Cortelezzi
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
Francesco Onida
Affiliations:
Ematologia - Centro Trapianti Midollo - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Via Francesco Sforza 35,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan,MILANO,Italy
(Abstract release date: 05/17/18) EHA Library. Onida F. 06/14/18; 216054; PB2449
Francesco Onida
Francesco Onida
Contributions
Abstract

Abstract: PB2449

Type: Publication Only

Background

Hematopoietic stem cell transplantation (HSCT) is used to treat a range of hematological malignant and non-malignant conditions including autoimmune, metabolic and immunodeficiency diseases. Because major histocompatibility genes are inherited independently of blood group system genes, approximately 40-50% of all allogeneic HSCTs are performed across the AB0-blood group barrier. Due to the widespread expression of AB0 antigens on a variety of human tissues other than erythrocytes, AB0 incompatibility may have an impact on the outcome of allogeneic HSCT that goes beyond the well-known immune-hematological complications such as immediate hemolysis due to the presence of isoagglutinins and delayed hemolysis due to passenger B lymphocytes.

Aims
With this retrospective study, we aimed to assess the impact of AB0 mismatch on allogeneic HSCT outcomes, including non-relapse mortality, overall and relapse-free survival, post-transplant PRC transfusion requirement, as well as relapse rate and incidence of graft- failure and acute GvHD.

Methods

Retrospectively collected data from 169 consecutive patients undergoing allogeneic HSCT between 01/2008 and 10/2017 at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Hospital in Milan, Italy, were analyzed. Kaplan Meier estimates were used for survival outcomes while cumulative incidences were analyzed by competing risk analysis.

Results

The patient series included 98 AB0-identical, 29 major incompatible, 32 minor AB0-mismatched and 10 bidirectionally incompatible transplants. Mean overall survival for groups of patients undergoing AB0-identical, major AB0 mismatch and minor AB0 mismatch HSCT were 66 months (95% CI [55 ;77]), 47 months (95% CI [28; 65) and 46 months (95% CI [31; 61]), respectively.

Non-relapse mortality in the three groups were significantly different by Gray’s test with point estimates of 12%, 29% and 26% at 5 years, respectively, whereas no significant differences were observed for relapse rate and graft failure incidence. Although not statistically different, incidence of acute grade III-IV GvHD was twice as high in patients transplanted from minor AB0-mismatched donors than in the AB0 identical group (16% vs 8%). Following transplantation, PRC transfusion requirement was significantly higher in the major AB0 mismatch then in the AB0-identical transplanted patients (median 14 vs 7, p=0.01). Of note, a weak positive correlation was found between the anti-donor A/B IgG titers measured prior HSCT and the total number of RBC transfusions administered one year after HSCT.

One case of PRCA occurred in one 0+ 50-year-old woman who received peripheral blood-derived hematopoietic stem cells from an A+ HLA-identical 32-year-old male sibling after myeloablative conditioning for AML in first complete remission. Anti-A IgG isoagglutinin titers prior to transplantation were 1:256. The patient received a total of 46 RBC products in the year following transplantation and resolution occurred during danazole treatment.

Conclusion

In our patient cohort, both major and minor AB0 mismatching were associated with a significantly higher NRM. Major ABO mismatching associated to higher PRC transfusion requirement. Possible more frequent occurrence of severe acute GvHD is also suggested in minor AB0-mismatched transplants.

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): ABO blood group, HSCT, Survival prediction

Abstract: PB2449

Type: Publication Only

Background

Hematopoietic stem cell transplantation (HSCT) is used to treat a range of hematological malignant and non-malignant conditions including autoimmune, metabolic and immunodeficiency diseases. Because major histocompatibility genes are inherited independently of blood group system genes, approximately 40-50% of all allogeneic HSCTs are performed across the AB0-blood group barrier. Due to the widespread expression of AB0 antigens on a variety of human tissues other than erythrocytes, AB0 incompatibility may have an impact on the outcome of allogeneic HSCT that goes beyond the well-known immune-hematological complications such as immediate hemolysis due to the presence of isoagglutinins and delayed hemolysis due to passenger B lymphocytes.

Aims
With this retrospective study, we aimed to assess the impact of AB0 mismatch on allogeneic HSCT outcomes, including non-relapse mortality, overall and relapse-free survival, post-transplant PRC transfusion requirement, as well as relapse rate and incidence of graft- failure and acute GvHD.

Methods

Retrospectively collected data from 169 consecutive patients undergoing allogeneic HSCT between 01/2008 and 10/2017 at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Hospital in Milan, Italy, were analyzed. Kaplan Meier estimates were used for survival outcomes while cumulative incidences were analyzed by competing risk analysis.

Results

The patient series included 98 AB0-identical, 29 major incompatible, 32 minor AB0-mismatched and 10 bidirectionally incompatible transplants. Mean overall survival for groups of patients undergoing AB0-identical, major AB0 mismatch and minor AB0 mismatch HSCT were 66 months (95% CI [55 ;77]), 47 months (95% CI [28; 65) and 46 months (95% CI [31; 61]), respectively.

Non-relapse mortality in the three groups were significantly different by Gray’s test with point estimates of 12%, 29% and 26% at 5 years, respectively, whereas no significant differences were observed for relapse rate and graft failure incidence. Although not statistically different, incidence of acute grade III-IV GvHD was twice as high in patients transplanted from minor AB0-mismatched donors than in the AB0 identical group (16% vs 8%). Following transplantation, PRC transfusion requirement was significantly higher in the major AB0 mismatch then in the AB0-identical transplanted patients (median 14 vs 7, p=0.01). Of note, a weak positive correlation was found between the anti-donor A/B IgG titers measured prior HSCT and the total number of RBC transfusions administered one year after HSCT.

One case of PRCA occurred in one 0+ 50-year-old woman who received peripheral blood-derived hematopoietic stem cells from an A+ HLA-identical 32-year-old male sibling after myeloablative conditioning for AML in first complete remission. Anti-A IgG isoagglutinin titers prior to transplantation were 1:256. The patient received a total of 46 RBC products in the year following transplantation and resolution occurred during danazole treatment.

Conclusion

In our patient cohort, both major and minor AB0 mismatching were associated with a significantly higher NRM. Major ABO mismatching associated to higher PRC transfusion requirement. Possible more frequent occurrence of severe acute GvHD is also suggested in minor AB0-mismatched transplants.

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): ABO blood group, HSCT, Survival prediction

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