chronic graft versus host disease and immunosuppression burden is significantly lower following...

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detected because the time interval between the last sample harvest and hematological relapse was to long (median, 71 days). In ve of these patients, DNA was available at the time of the last sample harvest before relapse and showed a complete donor chimerism. In two patients, we diagnosed a molecular relapse using WT1 gene expression. At that time, both children revealed a complete donor chimerism. In both patients, long-term molecular remission was achieved by immunotherapy. In conclusion, quantitative analysis of WT1 gene expression is a valuable tool for monitoring of MRD before and after HSCT. This approach is very useful for early diagnosis and treatment of molecular relapse after HSCT. MRD measurement using WT1 gene expression is more sensitive for the detection of impending relapse than the analysis of chimerism. 19 Chronic Graft Versus Host Disease and Immunosuppression Burden Is Signicantly Lower Following Adult Cord Blood Transplantation Versus Matched Unrelated Donor Transplantation Jonathan A. Gutman 1 , Han Myint 1 , Choon Kee Lee 1 , Clayton Smith 1 , Vu Nguyen 2 , Daniel Aaron Pollyea 1 . 1 University of Colorado, Aurora, CO; 2 University of Colorado, Aurora, CO Adult umbilical cord blood (UCB) transplant has emerged as an important option for patients lacking matched related (MRD) and matched unrelated donors (MUD). Numerous studies have demonstrated comparable overall survival (OS) between these donor sources as well as decreased classic chronic GVHD (cGVHD) following UCB transplantation as compared to MUD. We compared cGVHD incidence and immunosuppression burden in consecutive patients under- going UCB (n¼29) versus peripheral blood MUD transplant (n¼51) at our center between June 2009 and February 2013. NIH consensus criteria were used to grade cGVHD. Among UCB patients, median age at transplant was 49 (range 22-71) versus 55 (range 18-72) among MUDs. Twelve UCB patients underwent myeloablative conditioning and 17 patients un- derwent non-myeloablative (NMA) conditioning for acute leukemia (n¼17), MDS (n¼5), CLL (n¼2), NHL (n¼4), and CML (n¼1). GVHD prophylaxis was CSA and MMF. Forty-eight MUD patients were 10/10 matched and three patients were 8/8 matched (DQ mismatched). Seventeen patients underwent myeloablative conditioning (TAC/MTX GVHD prophylaxis) and 34 patients underwent NMA conditioning (TAC/MMF GVHD prophylaxis) for acute leukemia (n¼19), NHL (n¼15), MDS (n¼6), CLL (n¼4), Other (n¼6). At two years post- transplant, cumulative incidence (CI) of moderate to severe cGVHD was 30% following MUD versus 7% following UCB (p¼0.02). Among patients not experiencing competing risks of relapse or transplant related mortality (TRM) prior to onset of cGVHD, median time to being off immunosuppression was 307 days among UCB patients (n¼15) versus not reached among MUD patients (n¼33) (p<0.001). Among 15 UCB pa- tients, one patient remains on immunosuppression (227 days post-transplant). Two patients restarted immunosuppression due to recrudescent symptoms, but both patients subse- quently tapered again and remain off immunosuppression. All 15 patients remain alive. Among 33 MUD patients, seven patients stopped immunosuppression and four subsequently restarted for recrudescent GVHD symptoms. All four remain on immunosuppressive therapy. Five of the 33 patients sub- sequently died of complications related to GVHD. One year OS is not signicantly different between UCB and MUD patients (65% UCB versus 67% MUD). Cumulative incidence of relapse and TRM are also non-signicant comparing UCB and MUD patients (one year CI relapse 21% UCB versus 17% MURD, CI TRM 11% UCB versus 17% MUD). These data conrm the low incidence of classic cGVHD following CBT. We demonstrate a markedly lower immunosuppression burden following UCB versus MUD transplant without decreased OS, increased relapse, or TRM. Combined with the rapid availability of UCB, this nding has led our center to move primarily to UCB when a MRD is not available. Assessment of early and late costs of transplant using this donor selection approach is ongoing. 20 Value of a Consensus Panel to Adjudicate Cause-Specic Mortality after Unrelated Donor Allogeneic Hematopoietic Cell Transplantation (URD-HCT) for Use As the Primary Endpoint in a Genome-Wide Association Study (GWAS) Theresa Hahn 1 , Lara Sucheston-Campbell 2 , Leah Preus 2 , Kenan Onel 3 , Xiaochun Zhu 4 , Song Liu 5 , Li Yan 5 , David Tritchler 6 , Marcelo C. Pasquini 7 , Philip L. McCarthy 1 . 1 Medicine, Roswell Park Cancer Institute, Buffalo, NY; 2 Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY; 3 Pediatrics, University of Chicago, Chicago, IL; 4 CIBMTR, Medical College of Wisconsin, Milwaukee, WI; 5 Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY; 6 Biostatistics, SUNY University at Buffalo, Buffalo, NY; 7 CIBMTR, CIBMTR/Medical College of Wisconsin, Milwaukee, WI Cause-specic death (CSD) due to transplant-related com- plications (TRM) after URD-HCT is often multi-factorial. Consensus adjudication panels (CP), commonly used in clinical trials, are rarely used in observational research. Given the risk of endpoint misclassication due to CSD complexity Abstracts / Biol Blood Marrow Transplant 20 (2014) S27eS44 S35

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Page 1: Chronic Graft Versus Host Disease and Immunosuppression Burden Is Significantly Lower Following Adult Cord Blood Transplantation Versus Matched Unrelated Donor Transplantation

Abstracts / Biol Blood Marrow Transplant 20 (2014) S27eS44 S35

detected because the time interval between the last sampleharvest and hematological relapse was to long (median, 71days). In five of these patients, DNAwas available at the timeof the last sample harvest before relapse and showed acomplete donor chimerism. In two patients, we diagnosed amolecular relapse using WT1 gene expression. At that time,both children revealed a complete donor chimerism. In bothpatients, long-term molecular remission was achieved byimmunotherapy. In conclusion, quantitative analysis of WT1gene expression is a valuable tool for monitoring of MRDbefore and after HSCT. This approach is very useful for earlydiagnosis and treatment of molecular relapse after HSCT.MRD measurement using WT1 gene expression is moresensitive for the detection of impending relapse than theanalysis of chimerism.

19Chronic Graft Versus Host Disease andImmunosuppression Burden Is Significantly LowerFollowing Adult Cord Blood Transplantation VersusMatched Unrelated Donor TransplantationJonathan A. Gutman 1, Han Myint 1, Choon Kee Lee 1,Clayton Smith 1, Vu Nguyen 2, Daniel Aaron Pollyea 1.1University of Colorado, Aurora, CO; 2University of Colorado,Aurora, CO

Adult umbilical cord blood (UCB) transplant has emerged asan important option for patients lacking matched related(MRD) and matched unrelated donors (MUD). Numerousstudies have demonstrated comparable overall survival (OS)between these donor sources as well as decreased classicchronic GVHD (cGVHD) following UCB transplantation ascompared to MUD. We compared cGVHD incidence andimmunosuppression burden in consecutive patients under-going UCB (n¼29) versus peripheral blood MUD transplant(n¼51) at our center between June 2009 and February 2013.NIH consensus criteria were used to grade cGVHD. AmongUCB patients, median age at transplant was 49 (range 22-71)versus 55 (range 18-72) among MUDs. Twelve UCB patientsunderwent myeloablative conditioning and 17 patients un-derwent non-myeloablative (NMA) conditioning for acuteleukemia (n¼17), MDS (n¼5), CLL (n¼2), NHL (n¼4), and CML(n¼1).GVHDprophylaxiswasCSAandMMF. Forty-eightMUDpatients were 10/10 matched and three patients were 8/8matched (DQ mismatched). Seventeen patients underwentmyeloablative conditioning (TAC/MTX GVHD prophylaxis)and 34 patients underwent NMA conditioning (TAC/MMFGVHD prophylaxis) for acute leukemia (n¼19), NHL (n¼15),

MDS (n¼6), CLL (n¼4), Other (n¼6). At two years post-transplant, cumulative incidence (CI) of moderate to severecGVHD was 30% following MUD versus 7% following UCB(p¼0.02). Among patients not experiencing competing risksof relapse or transplant relatedmortality (TRM) prior to onsetof cGVHD, median time to being off immunosuppressionwas307 days among UCB patients (n¼15) versus not reachedamong MUD patients (n¼33) (p<0.001). Among 15 UCB pa-tients, one patient remains on immunosuppression (227 dayspost-transplant). Twopatients restarted immunosuppressiondue to recrudescent symptoms, but both patients subse-quently tapered again and remain off immunosuppression.All 15 patients remain alive. Among 33 MUD patients, sevenpatients stopped immunosuppression and four subsequentlyrestarted for recrudescent GVHD symptoms. All four remainon immunosuppressive therapy. Five of the 33 patients sub-sequently died of complications related toGVHD. One year OSis not significantly different between UCB and MUD patients(65% UCB versus 67% MUD). Cumulative incidence of relapseand TRM are also non-significant comparing UCB and MUDpatients (one year CI relapse 21% UCB versus 17% MURD, CITRM 11% UCB versus 17% MUD). These data confirm the lowincidence of classic cGVHD following CBT. We demonstrate amarkedly lower immunosuppression burden following UCBversus MUD transplant without decreased OS, increasedrelapse, or TRM. Combined with the rapid availability of UCB,this finding has led our center tomove primarily toUCBwhena MRD is not available. Assessment of early and late costs oftransplant using this donor selection approach is ongoing.

20Value of a Consensus Panel to Adjudicate Cause-SpecificMortality after Unrelated Donor AllogeneicHematopoietic Cell Transplantation (URD-HCT) for Use Asthe Primary Endpoint in a Genome-Wide AssociationStudy (GWAS)Theresa Hahn 1, Lara Sucheston-Campbell 2, Leah Preus 2,Kenan Onel 3, Xiaochun Zhu 4, Song Liu 5, Li Yan 5,David Tritchler 6, Marcelo C. Pasquini 7, Philip L. McCarthy 1.1Medicine, Roswell Park Cancer Institute, Buffalo, NY; 2CancerPrevention and Control, Roswell Park Cancer Institute, Buffalo,NY; 3Pediatrics, University of Chicago, Chicago, IL; 4CIBMTR,Medical College of Wisconsin, Milwaukee, WI; 5Biostatistics &Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY;6Biostatistics, SUNY University at Buffalo, Buffalo, NY; 7CIBMTR,CIBMTR/Medical College of Wisconsin, Milwaukee, WI

Cause-specific death (CSD) due to transplant-related com-plications (TRM) after URD-HCT is often multi-factorial.Consensus adjudication panels (CP), commonly used inclinical trials, are rarely used in observational research. Giventhe risk of endpoint misclassification due to CSD complexity