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undergo SCT respectively. Patients with annual income >46K and 35-45K were 53.9 and 29.6 % more likely to get SCT than patients in the 30K group. Patients treated at academic facility were three times more likely to get SCT compared to those in community setting. Conclusion: In our NCDB data analysis, age, race, health care funding, type of health care facility and annual income were noted to be significant predictors of SCT in patients with AML.
indicated that MRD pre-HSCT was the only impact factor on DFS after transplant in AML (p¼0.000). Conclusions: We have demonstrated that MRD pre-conditioning for patients with AML has significant impact on DFS after allogeneic HSCT but not patient age, cytogenetics, donor source and conditioning regimen. Allogeneic HSCT has attenuated the influence of cytogenetics on DFS in AML.
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Myeloablative Timed Sequential Busulfan is Safe and Appears Promising in Older Patients with AML/MDS Uday R. Popat 1, Genevieve Lyons2, Roland Bassett 3, Julianne Chen 4, Ben C. Valdez 4, Jitesh D. Kawedia 5, Sairah Ahmed 4, Amin M. Alousi 1, Paolo Anderlini 4, Qaiser Bashier2, Stefan O. Ciurea 4, Chitra Hosing 4, Roy B. Jones 2, Partow Kebriaei 4, Issa F. Khouri 2, David Marin4, Yago Nieto 4, Amanda Olson 4, Betul Oran 4, Simrit Parmar 2, Krina Patel 4, Muzaffar H. Qazilbash 4, Katy Rezvani 4, Nina Shah 4, Elizabeth J. Shpall 4, Borje S. Andersson 6, Richard E. Champlin 1. 1 Stem Cell Transplantation and Cellular Therapy, UT MD Anderson Cancer Center, Houston, TX; 2 The University of Texas MD Anderson Cancer Center, Houston, TX; 3 Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX; 4 Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; 5 Pharmacy Research, Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX; 6 Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
Minimal Residual Disease by Flow Cytometry PreConditioning has Significant Impact on Disease-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Yue Lu1, Tong Wu1, Yan-Li Zhao1, Xing -Yu Cao1, De-Yan Liu1, Hui Wang2, Min Xiong1, Jian-Ping Zhang1, Jia-Rui Zhou1, Rui-Juan Sun1, Zhi-Jie Wei1, Shu-Quan Ji1, Dao-Pei Lu1. 1 Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China; 2 Hematopathology, Hebei Yanda Lu Daopei Hospital, Langfang, China Introduction: It has been well known that minimal residual disease (MRD) pre-conditioning has remarkable impact on disease-free survival (DFS) after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with acute lymphoblastic leukemia, but the effect of MRD before transplant on the outcomes of allogeneic HSCT in acute myeloid leukemia (AML) is still unclear. Objective: In present study, the effect of MRD by flow cytometry (FCM) pre-conditioning on DFS after allogeneic HSCT in AML was investigated. Methods: Between April 2012 and December 2014, consecutive 168 patients with AML in CR1 who underwent allogeneic HSCT in our hospital were analyzed retrospectively. The median age was 23 (1.8 to 64) years old. Children (14 years) were 51 (30.4%) and adults (>14 years) were 117 (69.6%) cases. The median disease course was 8 (2-37) months. Cytogenetics in good-, intermediate-, high-risk were 40 (23.8%), 89 (53.0%), and 39 (23.2%) cases. Donor sources were identical sibling (IS) in 44 (26.2%), unrelated (UR) in 23 (13.7%), and haploidentical (HI) in 101 (60.1%) cases. Myeloablative conditioning regimens were administered with either busulfan (Bu) plus cyclophosphamide (Cy)/fludarabine (Flu)-based in 150 (89.3%) or TBI plus Cy/ Flu-based in 18 (10.7%) patients. ATG was used in UR and HI transplant. Unmanipulated bone marrow (BM) and peripheral blood stem cells (PBSC) for IS and HI HSCT, and PBSC for UR transplant. Cyclosporine, short-term methotrexate, and mycophenolate mofetil were employed for GVHD prophylaxis. MRD in BM before conditioning was detected by FCM. MRD was 0% in 140 (83.3%), 0.01% to 0.1% in 3 (1.8%), 0.1% to 1% in 17 (10.1%), and 1% to 3% in 8 (4.8%) patients. Results: With the median follow up 16 (6-39) months, twoyear DFS was 81.6%. Two-year DFS after transplant for patients with AML was 52.9% vs 87.0% with or without MRD (p<0.0001). The levels of MRD has remarkable influence on DFS post-HSCT in AML (87.0% for MRD 0%, 66.6% for MRD 0.01% to 0.1%, 57.1% for MRD 0.1% to 1%, 28.5% for MRD1% to 3%, respectively (p<0.0001). Univariate analysis showed that DFS after HSCT in AML was not associated with patient age (children vs. adults, 86.3% vs. 80.0%, p¼0.53), cytogenetics (good- vs. intermediate- vs. high-risk, 86.5% vs. 82.4% vs. 73.8%, p¼0.62), donor source (IS vs. UD vs. HI, 87.0% vs. 84.8% vs. 77.8%, p¼0.51), and conditioning regimen (Bu-based vs. TBI-based, 82.1% vs. 78.7%, p¼0.92). Multivariate analysis
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Background: Reduced intensity conditioning regimen (RIC) extends allogeneic hematopoietic cell transplantation (HCT) to older patients and patients with comorbidities. Compared to myeloablative (MA) conditioning, RIC has higher rate of relapse but lower rate of non-relapse mortality (NRM), resulting in similar survival. To further improve survival for older patients, a MA regimen with low NRM is needed. We hypothesized that a myeloablative busulfan dose could be safely administered over a longer period of time. We previously reported safety of two MA schedules of busulfan targeting busulfan exposure (AUC) of 16,000 and 20,000 mmolmin. Because the regimen with AUC of 20,000 was well tolerated, we further expanded this study and hereby report results in patients with AML/MDS treated with busulfan AUC of 20000 mmol-min. Methods: All patients received a fixed dose of IV busulfan 80 mg/m2 per day on day -13 and -12 in the outpatient clinic. Subsequently they were hospitalized (on day -7) and received fludarabine 40 mg/m2 day followed by IV busulfan daily for 4 days (day -6 to -3). The dose of busulfan on day -6 to -3 was adjusted to achieve a total AUC of 20,000 mmol-min based on pharmacokinetic studies done on day -13 and day -6. GVHD prophylaxis was Tacrolimus (day -2 onwards) and mini dose methotrexate 5mg/m2 on days 1, 3, 6 and 11. Patients with AML or MDS were eligible for the study if they had adequate organ function and an HLA 8/8 matched related or unrelated donor. On this study, we enrolled patients who were otherwise suitable for RIC. When the study began, upper age limit for eligibility was 70 years, but this was increased to 75 years during the course of the study once safety of this regimen was established. Results: Sixty six patients, 21 with MDS and 45 with AML, were enrolled on the study. Median age was 65 years (range 29-75 years) years. Stem cell donor was HLA identical sibling for 21 (32%) patients and HLA- matched (8/8) unrelated for 45 (68%) patients. 23 (35%) of the patients had poor-risk
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disease based on cytogenetic studies. Of the 45 AML patients, 14 (31%) patients were in remission and 31 (69%) had active disease at the time of transplant. With a median follow up of 7.8 months (range 1.3-35) for surviving patients, 1 year overall survival (OS), progression free survival (PFS), relapse rate and non-relapse mortality were 65% (CI 50%-80%), 56% (CI 41%-71%), 21% (CI 10%-33%) and 19% (CI 9%-32%), respectively. At day 100, cumulative incidence of acute grade 2-4 GVHD was 36% (24%-47%) and grade 3-4 GVHD was 9% (4%-18%). OS data in different subgroups are summarized in the figure below. Conclusion: Myeloablative timed sequential busulfan regimen is safe and appears promising in older patients with AML/MDS.
20 Allogeneic Stem Cell Transplantation for t(3;3)(q21;q26)/ Inv(3)(q21;q26) Acute Myeloid Leukemia e Report from the Acute Leukemia Working Party of the EBMT Kazimierz Halaburda 1, Myriam Labopin 2, Mohamed Houhou3, Dietger Niederwieser 4, Jürgen Finke 5, Liisa Volin 6, Johan A. Maertens 7, Jan Cornelissen 8, Noel Milpied9, Gernot Stuhler10, Nicolaus Kröger 11, Jordi Esteve 12, Mohamad Mohty 13, Arnon Nagler 14. 1 Department of Hematopoietic Stem Cell Transplantation, Instytut Hematologii i Transfuzjologii, Warsaw, Poland; 2 EBMT Paris study office / CEREST-TC, Paris, France; 3 Mr., Hopital Saint-Antoine APHP, Acute Leukemia Working Party, Paris, France; 4 Division of Haematology & Oncology, University of Leipzig, Leipzig, Germany; 5 Dept of Medicine, Haematology & Oncology, Freiburg University Medical Center, Freiburg, Germany; 6 Third Department of Medicine, Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland; 7 Dept. of Hematology, University Hospital Gasthuisberg-Leuven, Leuven, Belgium; 8 Department of Hematology, Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, Netherlands; 9 BMT unit, CHU Bordeaux, Bordeaux, France; 10 Centre for Bone Marrow and Blood Stem Cell Transplantation, Deutsche Klinik für Diagnostik, Wiesbaden, Germany; 11 Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany; 12 Hospital Clínic, Hematology department, IDIBAPS, Barcelona, Spain; 13 Clinical Hematology and Cellular Therapy Department, Saint Antoine Hospital, Paris, France; 14 Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel
Background: AML with t(3;3)/inv(3) is listed as a separate entity in WHO 2008 classification and regarded as very high risk leukemia with extremely poor survival (about 8 months). The 3q21/3q26 abnormality result in EVI1 overexpression due to GATA2 enhancer reposition from 3q21 to EVI1 locus at 3q26 with additional, activating RAS/RTK signaling mutations. This rare leukemia is typically characterized by primary resistance to chemotherapy or early relapse after achieving CR. We asked whether allogeneic stem cell transplantation (HSCT) translates into LFS benefit. Methods: 106 pts reported to the ALWP of the EBMT between 1995 - 2013 with confirmed and verified t(3;3)(q21;26) or inv(3)(q21;26) translocation were included. The primary end-point was LFS. Results: The median year of HSCT was 2007. Median follow up was 47 months (14-171). Time from diagnosis to transplant was 162 days (46-2800). The median age of the pts was 46.6 years (18.4-76.1); 54.7% were male. De novo AML constituted 87.7%, secondary AML 2.7% and MDS transformed to AML 9.4%. Inv (3) was diagnosed in 66%, while t(3;3) in 34% of the pts, respectively. Concomitant cytogenetic aberrations included chromosome 7 abnormalities and complex karyotype were observed in 74/106 (70%) and in 23/ 106 (23%) of pts, respectively. 57 pts (53.8%) were transplanted while in active disease (refractory e 40, first relapse -17) and 49 were in CR. 66 pts (62.3%) received myeloablative conditioning, most frequently Cy/TBI (31.1%) or Bu/Cy (22.6%). 40 pts (38.7%) received reduced intensity conditioning. In 44 transplants (41.5%) the donor was a matched sibling, while in 54 (50.9%) it was unrelated. Peripheral blood stem cells were used as the graft 81 (76.4%) transplants. As for outcome, 7 pts did not engraft. 63% of the pts transplanted with active disease achieved CR. At 2 years probability of NRM was 17% (10.5-24.8), while 2y LFS for the whole group was 18.7% (11.2-26.1), OS 24.2% (11.2-26.1), GvHD-freerelapse-free survival (GFRS) was 13.1% (6.6-19.5), and RI rate was 64.3% (54.2-72.7). In 14 relapsing pts second transplantation was performed and in 17 pts DLI was used (14 for relapse and 3 preemptive). 2y LFS and OS were significantly higher for patients transplanted in CR versus those transplanted with active disease: 21.9% vs. 15.8% (p¼0.05) and 32% vs. 17.5% (p¼0.06), respectively. In multivariable Cox analysis CR at transplantation was the only factor associated with LFS and OS. CR at transplantation was also the only significant factor for decreased NRM (p¼0.02) and improved GRFS (p¼0.01). Conclusion: This is the largest study of HSCT in AML pts with t(3;3)/inv(3) indicating that t(3;3)/inv(3) leukemia remains an extremely high risk entity with low LFS and OS probability even with transplantation. Results are better in pts transplanted in CR. For those not achieving CR novel agents and experimental treatment modalities are most probably indicated.
21 Impact of Donor Activating KIR2DS5 and KIR2DS2 on Outcome of Allogeneic Hematopoietic Cell Transplantation (AlloHCT) in Patients with Acute Myeloid Leukemia (AML) Ketevan Gendzekhadze 1, Monzr M. Al Malki 2, Ryotaro Nakamura 2, Guido Marcucci 2, Andy Dagis3, Joycelynne Palmer 3, Auayporn Nademanee 2, Stephen J. Forman 2, David Senitzer 1. 1 HLA, City of Hope National Medical Center, Duarte, CA; 2 Hematology/ Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA; 3 Information Sciences, City of Hope National Medical Center, Duarte, CA