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SOS) Patients from an Ongoing, Expanded-Access Program
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Methods: Clinical data were collected from the clinical records of Kanagawa Cancer Center. Patients aged 16 years or older who underwent first allo-HCT between January 2002 and December 2013 were evaluated for analysis. The patients divided to 4 risk groups according to the refined DRI (low, intermediate, high, very high). Patient characteristics and survival after allo-HSCT of the four risk groups were analyzed. Those risk groups were also analyzed in the two groups stratified by the HCT-CI scores. Result: Of 298 patients (AML n¼177, ALL n¼79, MDS n¼19, CML n¼10, others n¼13), 17 patients were low group (5.7%), 157 patients were intermediate group (52.7%), 90 patients were high group (30.2%) and 34 patients were very high group (11.4%). Higher proportion of low group received myeloablative conditioning (P¼0.05). Low group patients were younger, compared with other groups (P¼0.01). The HCT-CI score of very high group was higher (P¼0.001). There was no difference in other factors, including sex, sex mismatch, ABO mismatch and donor source. The estimated 4-years overall survival (OS) of low, intermediate, high and very high group was 66.8%, 61.2%, 32.5% and 12.8%, respectively (P<0.001). In the subgroup analysis stratified according to the HCT-CI scores, the 4-years OS of low, intermediate, high and very high group was 70.7%, 67.6%, 41.0% and 16.7% respectively, for patients with HCT-CI scores of 0-2 (P¼0.002). The 4-years OS of low, intermediate, high and very high group was 60.0%, 46.5%, 20.1% and 10.6% respectively, for patients with HCT-CI scores of >2 (P¼0.006). In the multivariate analysis, the hazard ratios for mortality were 0.90 (P¼0.79) in the low group, 1.93 (P<0.001) in the high group and 2.94 (P<0.001) in the very-high group respectively, compared with the intermediate group. Conclusion: These results confirmed the prognostic value of the refined DRI. Furthermore, the current study suggested the refined DRI could be a more useful predictor by combination with pre-transplant comorbidity.
446 Efficacy and Safety of Defibrotide in a Subset Analysis of Late-Onset Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Patients from an Ongoing, Expanded-Access Program Sally Arai 1, Paul G. Richardson 2, Angela R. Smith 3, Brandon M. Triplett 4, Nancy A. Kernan 5, Stephan A. Grupp 6, Joseph H. Antin 2, Leslie Lehmann 7, Wei Liang 8, Robin Hume 9, Alison L. Hannah 9, Bijan Nejadnik 9, Robert J. Soiffer 10. 1 Stanford University Medical Center, Stanford, CA; 2 DanaFarber Cancer Institute, Harvard Medical School, Boston, MA; 3 University of Minnesota, Minneapolis, MN; 4 St Jude Children’s Research Hospital, Memphis, TN; 5 Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; 6 Children’s Hospital of Philadelphia, Philadelphia, PA; 7 Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute/Boston Children’s Hospital, Boston, MA; 8 Jazz Pharmaceuticals, Palo Alto, CA; 9 Jazz Pharmaceuticals, Inc., Palo Alto, CA; 10 Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA Introduction: Hepatic VOD/SOS is a potentially life-threatening complication of conditioning regimens for hematopoietic stem cell transplant (HSCT). Severe VOD/SOS, often defined as VOD/SOS and multi-organ dysfunction (MOD), may be associated with >80% mortality. Although VOD/SOS onset typically occurs <20 or 21 days post-HSCT (per diagnostic criteria), there have been reported cases of later-onset VOD/SOS (up to Day+50 [Carreras E. Br J Haematol.
S303
2015;168:481-91]). Also, late-onset VOD/SOS may be diagnosed after hospital discharge, potentially delaying treatment. Treatment of VOD/SOS with defibrotide is not approved in the US but is available via an ongoing, expandedaccess protocol. Interim data for 649 treated patients (pts) in this study include results from 573 pts post-HSCT with a median age of 14 y, 50% Day+100 survival, and treatmentrelated adverse events (TRAEs) in 22% of pts; here, we provide efficacy and safety data in the subgroup of pts with lateonset VOD/SOS. Methods: The original protocol required VOD/SOS diagnosis by Baltimore criteria or biopsy by Day+35 post-HSCT, with evidence of MOD (renal and/or pulmonary failure) by Day+45. The study was amended to include pts with lateronset VOD/SOS, with or without MOD; VOD/SOS diagnosed by modified Seattle criteria; and VOD/SOS after HSCT or chemotherapy alone. All pts received defibrotide 25 mg/kg/ d (6.25 mg/kg q6h); the recommended minimum treatment duration was 21 days. In this analysis, “late-onset” was defined as diagnosis >30 days post-HSCT. Results: Of 681 pts enrolled as of December 31, 2013, 76 of 649 treated pts (12%) had late-onset VOD/SOS. All pts with late-onset VOD/SOS had HSCT (allogeneic, 93%; autologous, 7%); 55% were male. The median age was 42 y (range: 0.7e68); 72% were 18 y. The most common primary diseases were acute myelogenous leukemia (47%) and acute lymphocytic leukemia (16%); most common graft vs host prophylaxes were tacrolimus (65%), methotrexate (32%), and sirolimus (21%). Day+100 survival by Kaplan-Meier estimate was 35% (95% CI: 25%e46%). AEs occurred in 79% of pts; 25% had TRAEs. The most common TRAEs were gastrointestinal hemorrhage or hypotension (7% each). TRAEs leading to study discontinuation (n¼7) or death (n¼4) were primarily hemorrhage. Conclusions: In this study, current diagnostic criteria requiring onset before day 30 potentially would miss >10% of pts with VOD/SOS, highlighting the need for expanded criteria to include less typical manifestations of VOD/SOS. This subgroup represents a large late-onset VOD/SOS dataset compared with earlier case series, and results should be interpreted in the context of an older population (median age 42). Of note, TRAEs for this subgroup were similar to the overall interim results. Factors contributing to the survival rate in these pts form a potential area for future exploration. Support: Jazz Pharmaceuticals.
447 Comparable Survival with HLA Haploidentical and Mismatched Unrelated Donor Transplants in Patients with AML and MDS Dhruv Bansal 1, Michael Slade 2, Shivaprasad Manjappa 1, Scott R. Goldsmith 2, John F. DiPersio 3, Peter Westervelt 3, Geoffrey L. Uy 3, Ravi Vij 3, Camille Abboud 3, Keith StockerlGoldstein 3, Kathryn Trinkaus 4, Rizwan Romee 3. 1 Department of Hospital Medicine, Washington University School of Medicine, St Louis, MO; 2 Department of Medicine, Washington University School of Medicine, St. Louis, MO; 3 Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO; 4 Biostatistics Shared Resource, Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO Background: Cord blood and HLA haploidentical transplantation (haplo-HCT) remain viable alternative donors for patients with no readily available HLA matched related and unrelated donors. There is currently a paucity of data comparing outcomes of haplo-HCTs and mismatched
Methods: Clinical data were collected from the clinical records of Kanagawa Cancer Center. Patients aged 16 years or older who underwent first allo-HCT between January 2002 and December 2013 were evaluated for analysis. The patients divided to 4 risk groups according to the refined DRI (low, intermediate, high, very high). Patient characteristics and survival after allo-HSCT of the four risk groups were analyzed. Those risk groups were also analyzed in the two groups stratified by the HCT-CI scores. Result: Of 298 patients (AML n¼177, ALL n¼79, MDS n¼19, CML n¼10, others n¼13), 17 patients were low group (5.7%), 157 patients were intermediate group (52.7%), 90 patients were high group (30.2%) and 34 patients were very high group (11.4%). Higher proportion of low group received myeloablative conditioning (P¼0.05). Low group patients were younger, compared with other groups (P¼0.01). The HCT-CI score of very high group was higher (P¼0.001). There was no difference in other factors, including sex, sex mismatch, ABO mismatch and donor source. The estimated 4-years overall survival (OS) of low, intermediate, high and very high group was 66.8%, 61.2%, 32.5% and 12.8%, respectively (P<0.001). In the subgroup analysis stratified according to the HCT-CI scores, the 4-years OS of low, intermediate, high and very high group was 70.7%, 67.6%, 41.0% and 16.7% respectively, for patients with HCT-CI scores of 0-2 (P¼0.002). The 4-years OS of low, intermediate, high and very high group was 60.0%, 46.5%, 20.1% and 10.6% respectively, for patients with HCT-CI scores of >2 (P¼0.006). In the multivariate analysis, the hazard ratios for mortality were 0.90 (P¼0.79) in the low group, 1.93 (P<0.001) in the high group and 2.94 (P<0.001) in the very-high group respectively, compared with the intermediate group. Conclusion: These results confirmed the prognostic value of the refined DRI. Furthermore, the current study suggested the refined DRI could be a more useful predictor by combination with pre-transplant comorbidity.
446 Efficacy and Safety of Defibrotide in a Subset Analysis of Late-Onset Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Patients from an Ongoing, Expanded-Access Program Sally Arai 1, Paul G. Richardson 2, Angela R. Smith 3, Brandon M. Triplett 4, Nancy A. Kernan 5, Stephan A. Grupp 6, Joseph H. Antin 2, Leslie Lehmann 7, Wei Liang 8, Robin Hume 9, Alison L. Hannah 9, Bijan Nejadnik 9, Robert J. Soiffer 10. 1 Stanford University Medical Center, Stanford, CA; 2 DanaFarber Cancer Institute, Harvard Medical School, Boston, MA; 3 University of Minnesota, Minneapolis, MN; 4 St Jude Children’s Research Hospital, Memphis, TN; 5 Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; 6 Children’s Hospital of Philadelphia, Philadelphia, PA; 7 Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute/Boston Children’s Hospital, Boston, MA; 8 Jazz Pharmaceuticals, Palo Alto, CA; 9 Jazz Pharmaceuticals, Inc., Palo Alto, CA; 10 Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA Introduction: Hepatic VOD/SOS is a potentially life-threatening complication of conditioning regimens for hematopoietic stem cell transplant (HSCT). Severe VOD/SOS, often defined as VOD/SOS and multi-organ dysfunction (MOD), may be associated with >80% mortality. Although VOD/SOS onset typically occurs <20 or 21 days post-HSCT (per diagnostic criteria), there have been reported cases of later-onset VOD/SOS (up to Day+50 [Carreras E. Br J Haematol.
S303
2015;168:481-91]). Also, late-onset VOD/SOS may be diagnosed after hospital discharge, potentially delaying treatment. Treatment of VOD/SOS with defibrotide is not approved in the US but is available via an ongoing, expandedaccess protocol. Interim data for 649 treated patients (pts) in this study include results from 573 pts post-HSCT with a median age of 14 y, 50% Day+100 survival, and treatmentrelated adverse events (TRAEs) in 22% of pts; here, we provide efficacy and safety data in the subgroup of pts with lateonset VOD/SOS. Methods: The original protocol required VOD/SOS diagnosis by Baltimore criteria or biopsy by Day+35 post-HSCT, with evidence of MOD (renal and/or pulmonary failure) by Day+45. The study was amended to include pts with lateronset VOD/SOS, with or without MOD; VOD/SOS diagnosed by modified Seattle criteria; and VOD/SOS after HSCT or chemotherapy alone. All pts received defibrotide 25 mg/kg/ d (6.25 mg/kg q6h); the recommended minimum treatment duration was 21 days. In this analysis, “late-onset” was defined as diagnosis >30 days post-HSCT. Results: Of 681 pts enrolled as of December 31, 2013, 76 of 649 treated pts (12%) had late-onset VOD/SOS. All pts with late-onset VOD/SOS had HSCT (allogeneic, 93%; autologous, 7%); 55% were male. The median age was 42 y (range: 0.7e68); 72% were 18 y. The most common primary diseases were acute myelogenous leukemia (47%) and acute lymphocytic leukemia (16%); most common graft vs host prophylaxes were tacrolimus (65%), methotrexate (32%), and sirolimus (21%). Day+100 survival by Kaplan-Meier estimate was 35% (95% CI: 25%e46%). AEs occurred in 79% of pts; 25% had TRAEs. The most common TRAEs were gastrointestinal hemorrhage or hypotension (7% each). TRAEs leading to study discontinuation (n¼7) or death (n¼4) were primarily hemorrhage. Conclusions: In this study, current diagnostic criteria requiring onset before day 30 potentially would miss >10% of pts with VOD/SOS, highlighting the need for expanded criteria to include less typical manifestations of VOD/SOS. This subgroup represents a large late-onset VOD/SOS dataset compared with earlier case series, and results should be interpreted in the context of an older population (median age 42). Of note, TRAEs for this subgroup were similar to the overall interim results. Factors contributing to the survival rate in these pts form a potential area for future exploration. Support: Jazz Pharmaceuticals.
447 Comparable Survival with HLA Haploidentical and Mismatched Unrelated Donor Transplants in Patients with AML and MDS Dhruv Bansal 1, Michael Slade 2, Shivaprasad Manjappa 1, Scott R. Goldsmith 2, John F. DiPersio 3, Peter Westervelt 3, Geoffrey L. Uy 3, Ravi Vij 3, Camille Abboud 3, Keith StockerlGoldstein 3, Kathryn Trinkaus 4, Rizwan Romee 3. 1 Department of Hospital Medicine, Washington University School of Medicine, St Louis, MO; 2 Department of Medicine, Washington University School of Medicine, St. Louis, MO; 3 Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO; 4 Biostatistics Shared Resource, Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO Background: Cord blood and HLA haploidentical transplantation (haplo-HCT) remain viable alternative donors for patients with no readily available HLA matched related and unrelated donors. There is currently a paucity of data comparing outcomes of haplo-HCTs and mismatched