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Fludarabine, Melphalan, and Alemtuzumab Conditioning Regimen in High Risk Leukemia: The Arkansas Experience
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
transplantation. While ATG may decrease graft rejection and graft vs host disease (GVHD), these benefits might be offset by an increased relapse and infection risk. Recent randomized data from Europe demonstrated a reduction in chronic GVHD in acute myeloid leukemia (AML) patients undergoing matched related donor (MRD) Allo-SCT; randomized data in the United States is pending. We studied the ability of ATG as administered via our institutional protocol to facilitate engraftment and prevent GVHD in AML patients. Methods: We retrospectively studied the effect of ATG in 267 AML patients undergoing Allo-SCT. Donor sources included MRD, matched unrelated (MUD), and umbilical cord blood (UCB). Both myeloablative and non-myeloablative regimens were included. GVHD prophylaxis was with tacrolimus and mini-methotrexate and Co-Morbidity Index was defined by Sorror et al (HCT-CI). Cytogenetic risk as poor, intermediate, or favorable was based on the Southwest Oncology Group classification. Per institution protocol, ATG was administered to a subgroup of patients who had not received immunosuppressive chemotherapy within 3 months at a dose of 1.5 mg/kg day × 3 of Thymoglobulin® prior to Allo-SCT. Results: There were no significant differences between the ATG group (n = 24) and those transplanted without (n = 243) in regards to disease status at transplant, HCT-CI, cytomegalovirus serostatus, cytogenetic risk, and regimen intensity. Of note, the non-ATG group stem cell source was more likely to be peripheral blood (PBSC) (P ≤ .001) and related donor graft type (P ≤ .001). There was no difference in engraftment rates in the two groups. There was no increase in infection related mortality in the ATG group (HR 1.54, P = .32), no difference in transplant related mortality (TRM) (P = .29) and survivals were similar (Figure 1). The cumulative incidence of acute GVHD II-IV was lower but not statistically significant and no differences in chronic GVHD were seen in the ATG group. There was no increased risk of relapse overall in the ATG group (HR 1.48, P = .30). Conclusions: ATG can be safely administered to facilitate engraftment in patients at high risk for rejection and did not lead to an increase in relapse. Although we did not see a decrease in either acute or chronic GVHD, this may be due to more PBSC stem cell source and a higher percent of sibling donors in the non-ATG group. We await the results of a US randomized phase III trial (NCT01295710) examining the use of ATG for non-high risk patients.
S295
406 Health Care Utilization Costs Incurred during Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in Children and Adolescent and Young Adults (AYA): A Comparative Study Lauren C. Smith 1, Joseph Stanek 2, Sarah O’Brien 2, Rolla Abu-Arja 2, Rajinder Bajwa 2, Edwin M. Horwitz 2, Jeffery J. Auletta 2,3, Dean Lee 2, Hemalatha G. Rangarajan 2. 1 Pediatrics, Nationwide Children’s Hospital, Columbus, OH; 2 Hematology, Oncology and Bone Marrow Transplant, Nationwide Children’s Hospital, Columbus, OH; 3 Host Defense Program and Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH Background: Hematopoietic cell transplant (HCT) an established treatment strategy in acute myeloid leukemia (AML), is associated with significant cost. When compared to children (age <15y) with AML, adolescents and young adults (AYA: ages 15-39y) with AML receiving HCT have an increased risk for transplant-related morbidity and mortality. Whether AYA transplants are associated with increased resource utilization remains undefined. Therefore, we conducted a national database study to compare inpatient costs incurred during HCT for AML in children and AYA. Methods: Transplant and inpatient-adjusted cost data from admit up to one year post-transplant, of AML patients who underwent HCT during 2011-2015, was obtained from the Pediatric Health Information (PHIS) database utilizing ICD-9 codes for AML (205.xx) and HCT (41.xx). Results were summarized using descriptive statistics and compared using nonparametric methods. Results: 554 (378 pediatric, 176 AYA) HCT recipients were included for analysis. The median length of stay (LOS) and number of intensive care unit days at initial or subsequent admissions did not differ between the groups. Eighty percent of total median adjusted costs (major contribution from pharmacy costs) occurred during initial admission in both groups with AYA incurring significantly greater costs ($825,289 vs. $733,304, P < .0345). AYA had significantly greater prevalence of chronic GVHD (7.8 vs. 4.5%, P < .01), renal complications (55.4 vs. 45.8%, P = .0005), pain (21.3 vs. 10.9%, P < .0001) and fungal infections (18.1 vs. 10.7%, P < .0001). Day 100 transplant related mortality (13.7 vs 15%) and overall mortality at one year (22.7 vs 19.3%) was similar in both groups. Cord blood recipients in both groups had greater median LOS (51 vs. 43 days, P < .0001) and initial admit costs ($954,104 vs. $727,056, P < .0001) than other graft sources. Conclusion: When compared to children, AYA undergoing HCT for AML incurred higher inpatient costs at initial admission and had greater prevalence of transplant-related complications.
407 Fludarabine, Melphalan, and Alemtuzumab Conditioning Regimen in High Risk Leukemia: The Arkansas Experience Rahul Ravilla 1, Dinesh Atwal 2, Sasapu Appalanaidu 1, Pooja Motwani 1, Peter Emanuel 1, Yogesh Jethava 1, Muthu Veeraputhiran 1. 1 Hematology-Oncology, University of Arkansas for Medical Sciences, Little Rock, AR; 2 Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
Figure 1. Overall survival.
Introduction: Fludarabine, melphalan and alemtuzumab (Campath) [FMC] based reduced intensity conditioning (RIC) regimen has been promising with lower incidence of acute/
S296
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
chronic GVHD and comparable non-relapse mortality (NRM) rate. The Arkansas allogeneic transplant program uses FMC regimen as the predominant RIC for matched sibling and matched unrelated donor hematopoietic cell transplant (HCT). We conducted a retrospective analysis of our FMC based transplant outcomes. Methods: Ten consecutive patients from 2015-16 who underwent FMC based Allogeneic HCT and had completed 100 days post-transplant were identified. FMC regimen: Fludarabine 30 mg/m2/d intravenously (IV) for 5 days (day -7 to -3) campath 20 mg IV daily for 4 days (day -8 to day -5) and melphalan 140 mg/m2 on day -2. Post-transplant immunosuppression was started on day-2 with tacrolimus. Results: The patient characteristics are listed in Table 1. The median age was 54 years (range 34-64). Majority of them were male (60%) and Caucasians (90%). AML was the most common diagnoses (60%) followed by ALL (30%) and CLL (10%). All of them had high risk leukemia based on cytogenetics and relapse criteria with 7 patients (70%) in CR (MRD –ve); 2 patients (20%) MRD +ve and 1 patient (10%) with CLL in partial remission at time of transplant. All patients received peripheral blood stem cells from 10/ 10 HLA matched donors (Sibling 4; unrelated donors 6). The median stem cell dose was 5 × 106/kg (range: 3.1 to 6 × 106/kg) body weight and all patients attained neutrophil and platelet engraftment. A total of 3 patients (30%) developed mild acute GI GVHD (Grade II) out of which 2 patients had concomitant mid acute skin GVHD (Grade II); all of them had complete response to systemic steroids. Six patients had CMV viremia (range 97123 to 500) and 1 patient had adeno-viremia. Two patients died of infection (one each from CMV colitis; day 108 and adeno virus related colitis; day 145) while 2 other relapsed 100 days post-transplant. The NRM mortality at day 100 was 0. Mixed donor chimerism was observed at day 100 for CD3 and CD33 subsets were present in 5 (Median 91%; range 9, 100) and 4 patients (median 99%; range 63,100) respectively. Two patients received DLI for persistent mixed chimerism with conversion to full donor chimerism. Conclusion: FMC regimen offers complete protection from severe forms of acute GVHD (grade 3 or 4); acceptable NRM and short term relapse rate in high risk leukemia. Long term follow up is needed to assess relapse free survival, chronic GVHD and OS.
Table 1 Patient Characteristics Characteristic
N = 10
Median Age Race Caucasian African American Type of malignancy AML ALL CLL Median Karnofsky performance score Disease status Complete remission Complete remission with MRD positive Partial remission Donor relation Matched unrelated donor Sibling Donor and Recipient CMV mismatch
54 (34-64) 90% 10% 60% 30% 10% 85 (60-100) 70% 20% 10% 60% 40% 30%
408 Post Hoc Analysis of Defibrotide for Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Post-Hematopoietic Stem Cell Transplantation in Subgroups of Patients with and Without Leukemia Paul G. Richardson 1, Angela R. Smith 2, Brandon M. Triplett 3, Nancy A. Kernan 4, Stephan A. Grupp 5, Joseph H. Antin 6, Leslie Lehmann 7, Robert Ryan 8, Robin Hume 8, William Tappe 9, Robert J. Soiffer 6. 1 Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 2 Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN; 3 Bone Marrow Transplantation and Cellular Therapy, St Jude Children’s Research Hospital, Memphis, TN; 4 Pediatric BMT Service, Memorial Sloan Kettering Cancer Center, New York, NY; 5 Pediatric Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA; 6 Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 7 Center for Stem Cell Transplantation, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 8 Jazz Pharmaceuticals, Inc., Palo Alto, CA; 9 Jazz Pharmaceuticals, Palo Alto, CA Introduction: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication of conditioning for hematopoietic stem cell transplant (HSCT). Reported incidence post-HSCT is ~13.7%. In patients with concomitant multi-organ dysfunction (MOD; eg, renal or pulmonary), mortality may be >80%. Defibrotide is approved in the US to treat hepatic VOD/SOS with renal and/or pulmonary dysfunction post-HSCT, and in the EU to treat severe hepatic VOD/SOS post-HSCT. Methods: In an expanded-access treatment (T-IND) program, patients with VOD/SOS diagnosed by Baltimore/modified Seattle criteria or biopsy were given defibrotide 25 mg/kg/ day in 4 divided doses for a recommended ≥21 days. Day +100 post-HSCT survival and safety were analyzed post hoc for leukemia and nonleukemia primary disease subgroups. Results: Of 752 post-HSCT patients in the T-IND program enrolled as of April 18, 2015, 413 (55%) had leukemias (55% male; median age: 18y [range: .3-74.0y]; 61% with MOD); of these, 50% had acute myeloid leukemia (AML; median age 23y) and 37% had acute lymphoid leukemia (ALL; median age 16y). There were 339 (45%) patients with nonleukemia diagnoses (60% male; median age of 6y [range: .1-71.0y]; 52% with MOD); of these, diagnoses in ≥10% were neuroblastoma (20%), myelodysplastic syndrome (13%), and non-Hodgkin lymphoma (10%). The observed Day +100 survival rate was 51.2% for all HSCT patients, 46.2% for leukemia patients (45.4% for AML and 42.8% for ALL), and 57.2% in nonleukemia patients. In patients with MOD, Day +100 survival rates in the leukemia and nonleukemia groups were 40.8% and 56.5%, respectively; in patients without MOD, rates were 54.6% and 58.0%, respectively. Adverse events (AEs) occurred in 71.4% of patients with leukemia and 63.4% in the nonleukemia group; AE rates were similar in patients with and without MOD. AEs leading to death occurred in 37.3% of the leukemia and 28.3% of the nonleukemia groups. Investigator-assessed treatmentrelated AEs (TRAEs) occurred in 19.9% of the leukemia and 21.8% of the nonleukemia groups. TRAEs in >2% of patients were pulmonary hemorrhage (3.6%/6.2% in leukemia/ nonleukemia patients), gastrointestinal hemorrhage (3.1%/ 4.1%), epistaxis (2.7%/2.7%), and hypotension (2.2%/2.9%).
transplantation. While ATG may decrease graft rejection and graft vs host disease (GVHD), these benefits might be offset by an increased relapse and infection risk. Recent randomized data from Europe demonstrated a reduction in chronic GVHD in acute myeloid leukemia (AML) patients undergoing matched related donor (MRD) Allo-SCT; randomized data in the United States is pending. We studied the ability of ATG as administered via our institutional protocol to facilitate engraftment and prevent GVHD in AML patients. Methods: We retrospectively studied the effect of ATG in 267 AML patients undergoing Allo-SCT. Donor sources included MRD, matched unrelated (MUD), and umbilical cord blood (UCB). Both myeloablative and non-myeloablative regimens were included. GVHD prophylaxis was with tacrolimus and mini-methotrexate and Co-Morbidity Index was defined by Sorror et al (HCT-CI). Cytogenetic risk as poor, intermediate, or favorable was based on the Southwest Oncology Group classification. Per institution protocol, ATG was administered to a subgroup of patients who had not received immunosuppressive chemotherapy within 3 months at a dose of 1.5 mg/kg day × 3 of Thymoglobulin® prior to Allo-SCT. Results: There were no significant differences between the ATG group (n = 24) and those transplanted without (n = 243) in regards to disease status at transplant, HCT-CI, cytomegalovirus serostatus, cytogenetic risk, and regimen intensity. Of note, the non-ATG group stem cell source was more likely to be peripheral blood (PBSC) (P ≤ .001) and related donor graft type (P ≤ .001). There was no difference in engraftment rates in the two groups. There was no increase in infection related mortality in the ATG group (HR 1.54, P = .32), no difference in transplant related mortality (TRM) (P = .29) and survivals were similar (Figure 1). The cumulative incidence of acute GVHD II-IV was lower but not statistically significant and no differences in chronic GVHD were seen in the ATG group. There was no increased risk of relapse overall in the ATG group (HR 1.48, P = .30). Conclusions: ATG can be safely administered to facilitate engraftment in patients at high risk for rejection and did not lead to an increase in relapse. Although we did not see a decrease in either acute or chronic GVHD, this may be due to more PBSC stem cell source and a higher percent of sibling donors in the non-ATG group. We await the results of a US randomized phase III trial (NCT01295710) examining the use of ATG for non-high risk patients.
S295
406 Health Care Utilization Costs Incurred during Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in Children and Adolescent and Young Adults (AYA): A Comparative Study Lauren C. Smith 1, Joseph Stanek 2, Sarah O’Brien 2, Rolla Abu-Arja 2, Rajinder Bajwa 2, Edwin M. Horwitz 2, Jeffery J. Auletta 2,3, Dean Lee 2, Hemalatha G. Rangarajan 2. 1 Pediatrics, Nationwide Children’s Hospital, Columbus, OH; 2 Hematology, Oncology and Bone Marrow Transplant, Nationwide Children’s Hospital, Columbus, OH; 3 Host Defense Program and Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH Background: Hematopoietic cell transplant (HCT) an established treatment strategy in acute myeloid leukemia (AML), is associated with significant cost. When compared to children (age <15y) with AML, adolescents and young adults (AYA: ages 15-39y) with AML receiving HCT have an increased risk for transplant-related morbidity and mortality. Whether AYA transplants are associated with increased resource utilization remains undefined. Therefore, we conducted a national database study to compare inpatient costs incurred during HCT for AML in children and AYA. Methods: Transplant and inpatient-adjusted cost data from admit up to one year post-transplant, of AML patients who underwent HCT during 2011-2015, was obtained from the Pediatric Health Information (PHIS) database utilizing ICD-9 codes for AML (205.xx) and HCT (41.xx). Results were summarized using descriptive statistics and compared using nonparametric methods. Results: 554 (378 pediatric, 176 AYA) HCT recipients were included for analysis. The median length of stay (LOS) and number of intensive care unit days at initial or subsequent admissions did not differ between the groups. Eighty percent of total median adjusted costs (major contribution from pharmacy costs) occurred during initial admission in both groups with AYA incurring significantly greater costs ($825,289 vs. $733,304, P < .0345). AYA had significantly greater prevalence of chronic GVHD (7.8 vs. 4.5%, P < .01), renal complications (55.4 vs. 45.8%, P = .0005), pain (21.3 vs. 10.9%, P < .0001) and fungal infections (18.1 vs. 10.7%, P < .0001). Day 100 transplant related mortality (13.7 vs 15%) and overall mortality at one year (22.7 vs 19.3%) was similar in both groups. Cord blood recipients in both groups had greater median LOS (51 vs. 43 days, P < .0001) and initial admit costs ($954,104 vs. $727,056, P < .0001) than other graft sources. Conclusion: When compared to children, AYA undergoing HCT for AML incurred higher inpatient costs at initial admission and had greater prevalence of transplant-related complications.
407 Fludarabine, Melphalan, and Alemtuzumab Conditioning Regimen in High Risk Leukemia: The Arkansas Experience Rahul Ravilla 1, Dinesh Atwal 2, Sasapu Appalanaidu 1, Pooja Motwani 1, Peter Emanuel 1, Yogesh Jethava 1, Muthu Veeraputhiran 1. 1 Hematology-Oncology, University of Arkansas for Medical Sciences, Little Rock, AR; 2 Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
Figure 1. Overall survival.
Introduction: Fludarabine, melphalan and alemtuzumab (Campath) [FMC] based reduced intensity conditioning (RIC) regimen has been promising with lower incidence of acute/
S296
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
chronic GVHD and comparable non-relapse mortality (NRM) rate. The Arkansas allogeneic transplant program uses FMC regimen as the predominant RIC for matched sibling and matched unrelated donor hematopoietic cell transplant (HCT). We conducted a retrospective analysis of our FMC based transplant outcomes. Methods: Ten consecutive patients from 2015-16 who underwent FMC based Allogeneic HCT and had completed 100 days post-transplant were identified. FMC regimen: Fludarabine 30 mg/m2/d intravenously (IV) for 5 days (day -7 to -3) campath 20 mg IV daily for 4 days (day -8 to day -5) and melphalan 140 mg/m2 on day -2. Post-transplant immunosuppression was started on day-2 with tacrolimus. Results: The patient characteristics are listed in Table 1. The median age was 54 years (range 34-64). Majority of them were male (60%) and Caucasians (90%). AML was the most common diagnoses (60%) followed by ALL (30%) and CLL (10%). All of them had high risk leukemia based on cytogenetics and relapse criteria with 7 patients (70%) in CR (MRD –ve); 2 patients (20%) MRD +ve and 1 patient (10%) with CLL in partial remission at time of transplant. All patients received peripheral blood stem cells from 10/ 10 HLA matched donors (Sibling 4; unrelated donors 6). The median stem cell dose was 5 × 106/kg (range: 3.1 to 6 × 106/kg) body weight and all patients attained neutrophil and platelet engraftment. A total of 3 patients (30%) developed mild acute GI GVHD (Grade II) out of which 2 patients had concomitant mid acute skin GVHD (Grade II); all of them had complete response to systemic steroids. Six patients had CMV viremia (range 97123 to 500) and 1 patient had adeno-viremia. Two patients died of infection (one each from CMV colitis; day 108 and adeno virus related colitis; day 145) while 2 other relapsed 100 days post-transplant. The NRM mortality at day 100 was 0. Mixed donor chimerism was observed at day 100 for CD3 and CD33 subsets were present in 5 (Median 91%; range 9, 100) and 4 patients (median 99%; range 63,100) respectively. Two patients received DLI for persistent mixed chimerism with conversion to full donor chimerism. Conclusion: FMC regimen offers complete protection from severe forms of acute GVHD (grade 3 or 4); acceptable NRM and short term relapse rate in high risk leukemia. Long term follow up is needed to assess relapse free survival, chronic GVHD and OS.
Table 1 Patient Characteristics Characteristic
N = 10
Median Age Race Caucasian African American Type of malignancy AML ALL CLL Median Karnofsky performance score Disease status Complete remission Complete remission with MRD positive Partial remission Donor relation Matched unrelated donor Sibling Donor and Recipient CMV mismatch
54 (34-64) 90% 10% 60% 30% 10% 85 (60-100) 70% 20% 10% 60% 40% 30%
408 Post Hoc Analysis of Defibrotide for Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Post-Hematopoietic Stem Cell Transplantation in Subgroups of Patients with and Without Leukemia Paul G. Richardson 1, Angela R. Smith 2, Brandon M. Triplett 3, Nancy A. Kernan 4, Stephan A. Grupp 5, Joseph H. Antin 6, Leslie Lehmann 7, Robert Ryan 8, Robin Hume 8, William Tappe 9, Robert J. Soiffer 6. 1 Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 2 Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN; 3 Bone Marrow Transplantation and Cellular Therapy, St Jude Children’s Research Hospital, Memphis, TN; 4 Pediatric BMT Service, Memorial Sloan Kettering Cancer Center, New York, NY; 5 Pediatric Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA; 6 Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 7 Center for Stem Cell Transplantation, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 8 Jazz Pharmaceuticals, Inc., Palo Alto, CA; 9 Jazz Pharmaceuticals, Palo Alto, CA Introduction: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication of conditioning for hematopoietic stem cell transplant (HSCT). Reported incidence post-HSCT is ~13.7%. In patients with concomitant multi-organ dysfunction (MOD; eg, renal or pulmonary), mortality may be >80%. Defibrotide is approved in the US to treat hepatic VOD/SOS with renal and/or pulmonary dysfunction post-HSCT, and in the EU to treat severe hepatic VOD/SOS post-HSCT. Methods: In an expanded-access treatment (T-IND) program, patients with VOD/SOS diagnosed by Baltimore/modified Seattle criteria or biopsy were given defibrotide 25 mg/kg/ day in 4 divided doses for a recommended ≥21 days. Day +100 post-HSCT survival and safety were analyzed post hoc for leukemia and nonleukemia primary disease subgroups. Results: Of 752 post-HSCT patients in the T-IND program enrolled as of April 18, 2015, 413 (55%) had leukemias (55% male; median age: 18y [range: .3-74.0y]; 61% with MOD); of these, 50% had acute myeloid leukemia (AML; median age 23y) and 37% had acute lymphoid leukemia (ALL; median age 16y). There were 339 (45%) patients with nonleukemia diagnoses (60% male; median age of 6y [range: .1-71.0y]; 52% with MOD); of these, diagnoses in ≥10% were neuroblastoma (20%), myelodysplastic syndrome (13%), and non-Hodgkin lymphoma (10%). The observed Day +100 survival rate was 51.2% for all HSCT patients, 46.2% for leukemia patients (45.4% for AML and 42.8% for ALL), and 57.2% in nonleukemia patients. In patients with MOD, Day +100 survival rates in the leukemia and nonleukemia groups were 40.8% and 56.5%, respectively; in patients without MOD, rates were 54.6% and 58.0%, respectively. Adverse events (AEs) occurred in 71.4% of patients with leukemia and 63.4% in the nonleukemia group; AE rates were similar in patients with and without MOD. AEs leading to death occurred in 37.3% of the leukemia and 28.3% of the nonleukemia groups. Investigator-assessed treatmentrelated AEs (TRAEs) occurred in 19.9% of the leukemia and 21.8% of the nonleukemia groups. TRAEs in >2% of patients were pulmonary hemorrhage (3.6%/6.2% in leukemia/ nonleukemia patients), gastrointestinal hemorrhage (3.1%/ 4.1%), epistaxis (2.7%/2.7%), and hypotension (2.2%/2.9%).