Arnon Nagler

Benedetto Bruno

Bipin N. Savani

Christoph Schmid

Didier Blaise

Fabio Ciceri

Frédéric Baron

Gerhard Ehninger

Johan A. Maertens

Johanna Tischer

Jonathan Canaani

Jordi Esteve

Mohamad Mohty

Myriam Labopin

Norbert Gorin

Sebastian Giebel

William Arcese

Xiao-Jun Huang

Yener Koc

Zafer Gulbas

Biology of Blood and Marrow Transplantation

English

Crossref

ABO Mismatching and Haploidentical Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia—a Report from the ALWP of the EBMT

Savani, Bipin N.

Labopin, Myriam

Canaani, Jonathan

Huang, Xiao-Jun

Arcese, William

Tischer, Johanna

Koc, Yener

Bruno, Benedetto

Gulbas, Zafer

Blaise, Didier

Maertens, Johan A.

Ehninger, Gerhard

Baron, Frédéric

Gorin, Norbert

Esteve, Jordi

Schmid, Christoph

Giebel, Sebastian

Ciceri, Fabio

Mohty, Mohamad

Nagler, Arnon

OPUS Augsburg

increased risk of developing IPS (P = .04), and trended towardssignificance for the development of BOS (P = .08). Nineteenof 41(46%) patients with IPS, and 22 of 49(45%) patients withBOS had a preceding EOVI (Tables 1 and 2). Early-onset HHV6infections occurred in 7 of 41 (17%) patients with IPS versus47 of 700 (7%) patients without IPS respectively, P = .02. Therewas no association between early-onset CMV or communi-ty acquired viral (CAV) infections and IPS. In contrast, early-onset CMV infections were associated with an increased riskof developing BOS post-HSCT (P = .03), with no associationbetween early-onset EBV, HHV6, HSV, CAV infections and BOSnoted. The median duration from viral infection to the onsetof IPS was 25 days (range, 1-335 days) and the medianduration from viral infection to the onset of BOS was 465 days(range, 76-1168).Conclusion: HHV-6 infections within the first 100 days post-HSCT are associated with an increased risk of developing IPS,whereas CMV infections occurring during this ‘early” post-HSCT period are associated with an increased risk for thedevelopment of BOS.ALTERNATIVE DONORS17ABO Mismatching and Haploidentical HematopoieticStem Cell Transplantation in Acute Myeloid Leukemia—a Report from the ALWP of the EBMTBipin N. Savani 1, Myriam Labopin 2, Jonathan Canaani 3,Xiao-Jun Huang 4, William Arcese 5, Johanna Tischer 6,Yener Koc 7, Benedetto Bruno 8, Zafer Gulbas 9, Didier Blaise 10,Johan A. Maertens 11, Gerhard Ehninger 12, Frédéric Baron 13,Norbert Gorin 2, Jordi Esteve 14, Christoph Schmid 15,Sebastian Giebel 16, Fabio Ciceri 17, Mohamad Mohty 18,Arnon Nagler 19. 1 Division of Hematology/Oncology,Department of Medicine, Vanderbilt University MedicalCenter, Nashville, TN; 2 Hopital Saint-Antoine, Paris, France;3 Hematology Division, Chaim Sheba Medical Center, TelHashomer, Israel; 4 Institute of Hematology, Peking University,Beijing, China; 5 Dipartimento di Biotechnology Cellurari eEmatologia, Policlinico Universitario Tor Vergata, Rome, Italy;6 Department III of Internal Medicine, Hematopoietic Stem CellTransplantation, Ludwig-Maximilians-University Hospital ofMunich-Grosshadern, Munich, Germany; 7 Medical ParkAntalya, Istanbul, Turkey; 8 University of Torino, Torino, Italy;9 Hematology Oncology, Gebze Anadolu Health Center, Kocaeli,Turkey; 10 Hematology Department, Institut Paoli Calmettes,Marseille, France; 11 Department of Hematology, UniversityHospitals of Leuven, KU LEUVEN, Leuven, Belgium;12 Universitaetsklinikum Dresden, Dresden, Germany;13 Hematology, GIGA-I3, University of Liège, Liège, Belgium;14 Hospital Clínic, Hematology Department, IDIBAPS,Barcelona, Spain; 15 Department of Hematology and Oncology,Klinikum Augsburg, Ludwig-Maximilians-University, Munich,Germany; 16 Department of Bone Marrow Transplantation andOncohematology, Gliwice Branch, Maria Sklodowska-CurieMemorial Cancer Center and Institute of Oncology, Gliwice,Poland; 17 Hematology and Bone Marrow TransplantationUnit, IRCCS San Raffaele Scientific Institute, Milan, Italy;18 Clinical Hematology and Cellular Therapy Department, SaintAntoine Hospital, Paris, France; 19 The Bone MarrowTransplantation Department, Division of Internal Medicine,The Chaim Sheba Medical Center, Tel-Hashomer, IsraelBackground: About 30-50% of HLA-matched hematopoi-etic stem cell transplantation (HCT) are performed withABOmismatch (ABO-MM) donor, which can be classified aseither major, minor or bidirectional. The impact of ABO-MMon clinical outcome after HCT remains controversial and nolarge series is available to study the impact of ABO-MM inpatients (pts) receiving haploidentical-HCT (haplo-HCT).Methods: 837 pts with AML that underwent haplo-HCTfrom January 2005 to December 2014 were analyzed tostudy the long term impact of ABO-mismatching in haplo-HCT. The comparative analysis was performed between ptsreceiving ABO-matched vs. ABO-MM for common outcomevariables.Results: 522 (62%) pts received ABO-matched whereas 315(38%) underwentABO-MMhaplo-HCT including 150 (18%)minor ABOMM (minor-A, 75 [50%]), 127 (15%) major ABO-MM (major-O, 98 [77%]) and 38 (5%) bidirectional ABO-MM(Bidirectional-A, 20 [53%]). Median agewas 42 years (range,18-77) andwas not significantly different between ABO groups(P = .67). The median follow-up period was 36 months (IQR,23-53). Median year of transplantationwas 2011. More thanhalf of ptswere in CR1 and nearly one third of pts were withactive disease prior to transplantation. 497 (59%) pts re-ceived ablative and 340 (41%) reduced intensity or non-ablative conditioning regimen. 219 (26%) of pts received BM,240 (29%)BM+PB, 378 (45%) PB alone and 123 (15%) ex-vivoT-cell depleted grafts. There were no significant differencesin distributions of pts and transplant characteristics amongABO- groups. 771 (94%) pts engrafted and the percentage ofengraftmentwas lower in the major mismatch group (88% vs95% in other group, P = .007). The cumulative incidences (CI)of day 100 grade II-IV acute GVHDwas 31% (III-IV, 10%) andthe 3-year CI of chronic GVHD was 31% (95% CI, 27-34), andwere not significantly different between the ABO-groups(P = .124 and .392). There was no differences in OS, RI, andNRM between ABOgroups. Bidirectional ABO-group had im-proved 3-year LFS (67%) and GFRS (54%) compared to otherABO-group in univariate analysis. Therewas no impact of ABO-MM when T-cells replete and T-depleted groups analyzedseparately. In multivariate analysis, our data showed no sig-nificant differences in OS, LFS, RI, NRM, and chronic GVHDbetween ABO-groups. The analyses were performed sepa-rately for pts receiving PB and BM+/-PB grafts. There was nostatistical difference between ABO-groups for OS, LFS, RI, NRM,GFRS and chronic GVHD in pts receiving PB grafts. However,Table 1Early-onset viral infections and IPS*Total Patientsn = 741IPS (%)n = 41No IPS (%)n = 700PAny viral 229 19 (46) 210 (30) .04CMV 116 4 (10) 112 (16) 0.38EBV 27 4 (10) 23 (3) .06HHV-6 54 7 (17) 47 (7) .02HSV 6 2 (5) 4 (1) .04CAV 26 2 (5) 24 (3) 0.65* Viral infections (excluding BK virus) within first 100 days post-HSCT.Table 2Early onset viral infection and BOS*Total Patientsn = 741BOS (%)n = 49No BOS (%)n = 692PAny viral 242 22 (45) 220 (32) .08CMV 126 14 (29) 112 (16) .03EBV 27 2 (4) 25 (4) 0.70HHV-6 56 5 (10) 51 (7) 0.41HSV 7 1 (2) 6 (1) 0.21CAV 26 0 (0) 26 (4) 0.17* Viral infections (excluding BK virus) within first 100 days post-HSCT.S30 Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391among BM group, pts withminor ABO-MM recipients had sig-nificantly higher acute GVHD (HR 2; 95% CI, 1-4; P = .048)without impacting other transplant outcome.Conclusion: Despite the limitation of a retrospective regis-try based study, our large series shows no significant long termoutcome difference between ABO matched and mismatchedgroups after haplo-HCT in current era.LEUKEMIA18Outcomes of Allogeneic Hematopoietic CellTransplantation for AML with Complex Karyotypes: ARetrospective Study From the Acute Leukemia WorkingParty of the European Society for Blood and MarrowTransplantation and MD Anderson Cancer CenterStefan O. Ciurea 1, Myriam Labopin 2, Emmanuelle Polge 3,Piyanuch Kongtim 4, Gabriela Rondon 1, Gerard Socié 5,Liisa Volin 6, Jakob Passweg 7, Patrice Chevallier 8,Dietrich W. Beelen 9, Noel Milpied 10, Didier Blaise 11,Jan Cornelissen 12, Nathalie Fegueux 13, Mohamad Mohty 14,Bipin N. Savani 15, Richard E. Champlin 1, Arnon Nagler 16.1 Department of Stem Cell Transplantation and CellularTherapy, The University of Texas MD Anderson Cancer Center,Houston, TX; 2 Hopital Saint-Antoine, Paris, France;3 Université Pierre et Marie Curie, Paris, France; 4 Medicine,Faculty of Medicine Thammasat University, Pathumthani,Thailand; 5 Saint Louis Hospital, Paris, France; 6 ThirdDepartment of Medicine, Stem Cell Transplantation Unit,HUCH Comprehensive Cancer Center, Helsinki, Finland;7 University Hospital Basel, Basel, Switzerland; 8 Hematologie,CHU NANTES, Nantes, France; 9 University Hospital of Essen,Essen, Germany; 10 BMT Unit, CHU Bordeaux, Bordeaux,France; 11 Hematology Department, Institut Paoli Calmettes,Marseille, France; 12 Hematology, Erasmus University MedicalCenter, Rotterdam, Netherlands; 13 Centre HospitalierUniversitaire de Montpellier Montpellier, Montpellier, France;14 Clinical Hematology and Cellular Therapy Department, SaintAntoine Hospital, Paris, France; 15 Division of Hematology/Oncology, Department of Medicine, Vanderbilt UniversityMedical Center, Nashville, TN; 16 The Bone MarrowTransplantation Department, Division of Internal Medicine,The Chaim Sheba Medical Center, Tel-Hashomer, IsraelIntroduction: Allogeneic hematopoietic stem cell transplan-tation (AHSCT) is the only curative treatment for CK AMLwhich otherwise has dismal outcomes. Here we aimed toidentify prognostic factors associated with post-transplantsurvival in patients with CK AML using combined data fromthe EBMT and MDACC.Methods: A total 1342 consecutively transplanted patientswith CK (≥3 cytogenetic abnormalities) AML reported to EBMT(N = 1118) and at MDACC (N = 224) between 01/2000-12/2015 were included. The median age was 52 years (range 18-76 years). Seven hundred and twenty-nine patients (54.3%)were male, 239 patients (17.8%) had secondary AML. Diseasestatus before transplant was CR1, CR2 and active disease in877 (65.3%), 77 (5.7%) and 388 (29%), respectively. Donorswere MRD, MUD and MMUD in 749 (55.8%), 513 (38.2%) and80 (6%), respectively. Conditioning regimens were various,mostly either busulfan-based (53.7%) or TBI-based (26.7%).Seven hundred and thirty-nine patients (55%) received MAC.The main stem cell source was PB (81%). Median follow-upduration was 35.5 months (range 8-174 months).Results: Engraftment occurred in 96.3% and 69.7% had fulldonor chimerism. The cumulative incidence (CI) of acuteGVHD grade II-IV and grade III-IV at 2 years was 26.3% and8.4%, respectively, whereas CI of chronic GVHDwas 30.9%withextensive chronic GVHD 17.8%. LFS, OS, CI of relapse, NRMat 2 years for the whole group was 31.3%, 36.8%, 51.1% and17.6%, respectively, while 2-year GVHD-free, relapse-free sur-vival (GRFS) was 19.8%. LFS, OS, GRFS, CI of relapse and NRMat 2 years for patients transplanted in CR1 was 38.4%, 44.5%,23.8%, 46% and 15.7%, respectively (Figure 1A,B). Patients age40-60 years transplanted in CR1 with MAC demonstratedlower relapse compared with RIC (40.2% versus 51%, P = .005),offset by a higher NRM (18.2% versus 9.8%, P = .037), associ-ated with higher incidence of acute GVHD, and a non-significant difference in LFS (Figure 1C,D).In multivariable analysis, advanced age, transplantation inactive disease, secondary AML and presence of deletion ormonosomy 5 or 7 predicted poor LFS and OS. All of thesefactors as well as year of transplant (before 2010) also pre-dicted poor GRFS. Prognostic factors for relapse were age,secondary AML, active disease at transplant and presence ofdeletion or monosomy 5, while prognostic factors for NRMwere older age, active disease, use of a mismatched unre-lated donor and deletion or monosomy 7.Conclusions: In this largest analysis of complex karyotypesAML patients, relapse remains the most common cause oftreatment failure with 45% for patients in CR1 and 63.5% forpatients not in remission relapsing after transplant. The onlymodifiable factors at this time are performing transplanta-tion in CR1 as soon as the donor is available. Novel approachesare needed to decrease relapse rate and improve survival inthese patients.19Analysis of Transplantation Rate and Overall TreatmentEfficacy by Age for Patients Aged 60 to 75 with UntreatedSecondary Acute Myeloid Leukemia (AML) Given CPX-351 Liposome Injection Versus Conventional Cytarabineand Daunorubicin in a Phase III TrialJeffery Lancet 1, Geoffrey L. Uy 2, Jorge Cortes 3,Laura F. Newell 4, Tara L. Lin 5, Ellen Ritchie 6, Robert Stuart 7,Stephen Strickland 8, Donna Hogge 9, Scott R. Solomon 10,Figure 1. (A) CI of relapse for all patients and patients in CR; (B) LFS for allpatients and patients in CR; (C) CI of relapse for patients age 40-60 yearsin CR with MAC, RIC; (D) LFS for all patients age 40-60 years in CR withMAC, RIC.S31Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391

ABO mismatching and haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia: a report from the ALWP of the EBMT

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abo mismatching and haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia a report from the alwp of the ebmt

abo mismatching and haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia a report from the alwp of the ebmt

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