Equivalent Survival Following Fludarabine/Melphalan Reduced Intensity Conditioning with or without Rabbit ATG As Part of GvHD Prophylaxis

Abstract Abstract 1959 Introduction: Reduced intensity conditioning (RIC) prior to allogeneic transplantation allows donor cell engraftment with the maintenance of a graft versus malignancy effect. A recent CIBMTR registry study suggested worse outcomes for patients receiving anti-thymocyte globulin (ATG) as part of the conditioning regimen. To further study the role of ATG when added to a fludarabine and melphalan RIC regimen in the unrelated donor (URD) setting, we have retrospectively studied 76 consecutive patients with advanced hematologic malignancies who underwent URD transplantation. Comparisons were made between cohorts that did or did not receive ATG (given primarily for HLA disparity) for pretransplant graft vs. host disease (GvHD) prophylaxis. Pateints and Methods: Seventy six patients with advanced hematologic malignancies (43% CIBMTR high-risk) received fludarabine and melphalan (FluMel) conditioning with or without pre-transplant rabbit ATG 6 mg/kg as part of GvHD prophylaxis. Twenty five patients who received ATG (24 of whom received grafts from donors mismatched at 1 or 2 HLA loci) were compared with 51 patients who did not receive ATG (45 of whom received grafts from HLA matched donors with six donors mismatched at a single locus). The majority of patients received post-transplant tacrolimus with either methotrexate (MTX) or mycophenolate mofetil for GvHD prophylaxis. With the exception of HLA disparity, pre-transplant patient characteristics were similar between groups (Figure 1). Results: With median follow up of 481 days and 376 days for the ATG and no ATG cohorts, respectively, K-M overall survival estimates were similar, with 2 year OS of 62 vs. 47 percent, respectively, for the ATG vs no ATG groups (p=.34). On multivariate analysis, the inclusion of MTX in GvHD prophylaxis was favorably associated with overall survival (p=.004), and was associated with a significant reduction in the incidence of severe (gr 3–4) acute GvHD (p=.03). There were no significant differences in pre-transplant creatinine, age, or comorbidity index scores between patients who did or did not receive MTX. Conclusions: Fludarabine and melphalan RIC, with or without pre-transplant ATG, produced similar outcomes following URD transplantation, despite the fact that patients receiving ATG in this series were more likely to have received a HLA mismatched graft. The inclusion of MTX for GVHD prophylaxis resulted in less severe acute GVHD and better survival when compared with tacrolimus/MMF. Disclosures: Flowers: Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Kaufman:Merck: Research Funding; Keryx: Consultancy; Novartis: Consultancy; Onyx Pharmaceuticals: Consultancy; Millenium: Consultancy; Celgene: Research Funding. Lonial:Millennium Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Onyx: Consultancy; Merck: Consultancy. Sinha:Celgene: Research Funding.

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Results of a Two-Arm Phase II Clinical Trial Using Post-Transplantation Cyclophosphamide for Prevention of Graft-Versus-Host Disease in Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem-Cell Transplantation

Blood ◽

10.1182/blood.v126.23.152.152 ◽

2015 ◽

Vol 126 (23) ◽

pp. 152-152 ◽

Cited By ~ 2

Author(s):

Sameh Gaballa ◽

Isabell Ge ◽

Riad O. El Fakih ◽

Jonathan E. Brammer ◽

Sa A. Wang ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Disease Risk ◽

Risk Index ◽

Conditioning Regimen ◽

Hematologic Malignancies ◽

Unrelated Donor ◽

Reduced Intensity Conditioning ◽

Equity Ownership ◽

Reduced Intensity

Abstract Allogeneic stem cell transplantation offers curative therapy for many patients (pts) with high-risk hematologic malignancies. Donor availability remains a major limitation for many pts. The introduction of high-dose post-transplant cyclophosphamide (PTCy) has significantly improved the outcomes of pts undergoing haploidentical (HAPLO) stem cell transplants. The choice between a HAPLO or a one-antigen HLA mismatched unrelated donor (9/10 MUD) for pts lacking an HLA-matched donor remains unclear. Methods: We conducted a prospective non-randomized phase 2 clinical trial with two parallel arms, HAPLO (n=60) and 9/10 MUD (n=46) transplants, for pts with advanced hematologic malignancies or aplastic anemia who lacked an HLA-matched unrelated donor type at 10 loci (HLA-A, -B, -C, -DRB1, and -DQB1) using a MEL-based reduced-intensity conditioning regimen. The regimen included a single intravenous dose of MEL 140 mg/m2 (day -7), thiotepa 5 mg/kg (day -6), and four daily IV doses of fludarabine 40 mg/m2 (day -5 to day -2) (FM140). Thiotepa was intermittently available and was replaced by total body irradiation at a dose of 2 Gy on day -1. Pts >55 years (yr) old or with significant comorbidities received a lower MEL dose (100 mg/m2) (FM100). All pts with CD20-positive lymphoma received rituximab (375 mg/m2) on days -13, -6, +1 and +8. GVHD prophylaxis consisted of PTCy 50 mg/kg on day +3 and +4, and tacrolimus and mycophenolate for 6 and 3 months (mo), respectively. The stem cell source was unmodified bone marrow for both arms. Results: Patient characteristics are shown in Table 1. The median follow-up duration was 24 mo in the HAPLO arm and 29 mo in the 9/10 MUD arm. The cumulative incidence (CI) of neutrophil (ANC) recovery at day 45 was 95% and 98% in the HAPLO and 9/10 MUD arm, respectively. The median time to ANC recovery was 18 days in both arms; the median time to platelet recovery was 25 days in the HAPLO arm and 28 days in the 9/10 MUD arm. Primary graft failure developed in two pts in the HAPLO arm (one due to anti-donor HLA antibodies) and one patient in the 9/10 MUD arm. One pt in both arms developed mixed donor chimerism at day 100; otherwise, all pts in both arms achieved full (>95%) donor chimerism. Bone marrow was the graft source in all pts except 2 in the HAPLO arm and 8 in the 9/10 MUD arm who received a peripheral blood graft. The 1-yr overall and progression free survival were 70% and 60%, respectively, in the HAPLO arm (Fig. 1A) and 60% and 47%, respectively, in the 9/10 MUD arm (Fig. 1B). Day 100 CI of grade II-IV aGVHD and III-IV aGVHD were 28% and 3%, respectively, in the HAPLO arm versus 33% and 13%, respectively, in the 9/10 MUD arm; the 2-yr CI of chronic extensive GVHD was 13% and 14% in the two groups, respectively. The 1-yr CI of non-relapse mortality was 21% in the HAPLO arm and 31% in the 9/10 MUD arm, while the 1-yr relapse rate was 19% and 25% in the two groups, respectively. Conclusions: This study establishes PTCy, tacrolimus, and mycophenolate as an effective regimen for GVHD prevention in mismatched transplantation using both haploidentical and mismatched unrelated donor sources. Melphalan-based reduced-intensity conditioning is an effective regimen for a broad range of hematologic malignancies. Prospective randomized studies comparing haploidentical and unrelated donor sources are needed. Table 1. HAPLO (n=60) 9/10 MUD (n=46) Median Age, years (Range) 45 (20-63) 51 (20-64) Sex (M/F) 29/31 23/23 KPS ³90 53 (88%) 40 (87%) <90 7 (12%) 6 (13%) HCT-CI 0-3 50 (83%) 38 (83%) >3 10 (17%) 8 (17%) Disease Risk Index* Very high 5 (8%) 3 (7%) High 18 (30%) 15 (33%) Intermediate 29 (48%) 12 (26%) Low 8 (13%) 12 (26%) NA 0 4 (9%)** Conditioning Regimen FM100 20 (33) 18 (39%) FM140 40 (67%) 28 (61%) Diagnosis AML/MDS 33 (55%) 18 (39%) ALL 7 (11%) 5 (11%) Lymphoma 10 (17%) 13 (28%) Others 10 (17%) 10 (22%) Disease Stage Acute Leukemia CR1/CR2 24 (66%) 9 (56%) CR3 or higher/ CRpx 6 (17%) 5 (31%) Active disease 6 (17%) 2 (13%) Lymphoma CR 3 (30%) 8 (62%) PR 5 (50%) 3 (23%) Chemoresistant 2 (20%) 2 (15%) *Disease Risk Index by Armand et al; xCRp: Complete Remission with incomplete count recovery; **Patients had aplastic anemia. Figure 1. Figure 1. Disclosures Brammer: Celgene: Research Funding. Lee:Ziopharm: Equity Ownership; Cyto-Sen: Equity Ownership; Intrexon: Equity Ownership. Rezvani:Pharmacyclics: Research Funding. Alousi:Therakos, Inc: Research Funding.

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Survival after T-Cell Replete Haplo-Identical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor Transplant for Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v124.21.679.679 ◽

2014 ◽

Vol 124 (21) ◽

pp. 679-679 ◽

Cited By ~ 1

Author(s):

Stefan O. Ciurea ◽

Mei-Jie Zhang ◽

Andrea Bacigalupo ◽

Asad Bashey ◽

Frederick R. Appelbaum ◽

...

Keyword(s):

Overall Survival ◽

Survival Rates ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Reduced Intensity Conditioning ◽

Treatment Groups ◽

Post Transplant ◽

Gvhd Prophylaxis ◽

Reduced Intensity ◽

Donor Transplant

Abstract Background: Increasing numbers of haplo-identical transplants are being performed and the most common approach in the United States includes transplantation of an unmanipulated graft with tacrolimus, mycophenolate and post-transplant cyclophosphamide for GVHD prophylaxis. In this analysis we compare the early outcomes after haplo-identical transplantation with this GVHD prophylaxis with that after conventional HLA-matched unrelated donor transplant approaches (MUD). Methods: Included are 2174 patients with AML aged 21-70 years and transplanted between 2008 and 2012. Cox regression models were built for recipients of myeloablative (N=1245 MUD compared with N=104 haplo-identical) and reduced intensity (N=737 MUD compared with 88 haplo-identical) conditioning transplants. Primary endpoint was 2-year overall survival. With median follow-ups of 2-3 years, surviving patients in all treatment groups were censored at 2-years. Results: Characteristics of recipients of myeloablative transplantation were similar across the two treatment groups except peripheral blood (PB) was the predominant graft with calcineurin inhibitor (CNI) with methotrexate the predominant GVHD prophylaxis for the MUD group compared to predominantly BM grafts with CNI, mycophenolate and post-transplant cyclophosphamide for the haplo-identical group. Most regimens were non-irradiation containing, 74% for MUD and 78% for haplo-identical transplants. Characteristics of recipients of reduced intensity conditioning transplants differed by treatment groups; recipients of MUD transplants were older (median age 62 vs. 57 years), more likely to report performance score 80 or lower, be in first complete remission at transplantation and shorter interval from diagnosis to transplantation. PB was the predominant graft for MUD and BM, for haplo-identical transplants. The conditioning regimen for reduced intensity haplo-identical transplants was uniform (TBI 200 cGy, cyclophosphamide, fludarabine) and for MUD transplants, it was predominantly an alkylating agent and fludarabine (79%). Day-30 cumulative incidence of neutrophil recovery was higher after myeloabative MUD compared with haplo-identical transplants (97% vs. 90%, p=0.01). Neutrophil recovery was not different after MUD and haplo-identical reduced intensity conditioning transplants (96% vs. 93%, p=0.25). Table 1 shows the results of multivariate analysis for non-relapse mortality (NRM), relapse and overall survival. Overall survival is not significantly different after haplo-identical and MUD transplants with either the myeloablative or reduced intensity conditioning approaches. The 2-year survival rates adjusted for age, disease status and interval from diagnosis to transplant after myeloablative MUD and haplo-identical transplantation were 54% (95% CI 51-57) and 47% (95% CI 37-57), respectively (p=0.22). The corresponding 2-year survival rates after reduced intensity conditioning transplantation were 49% (95% CI 45-53) and 53% (95% CI 42-63), p=0.25. We also explored for difference in survival with in vivo T-cell depletion in the myeloablative (HR 0.81, p=0.19) and reduced intensity (HR 1.18, p=0.33) MUD groups compared with the corresponding haplo-identical groups (baseline HR 1.00) and found none. We tested for a transplant center effect on survival and found none. Conclusion: With the available data, 2-year survival rates for AML after myeloablative or reduced intensity conditioning transplants are comparable after conventional MUD transplant approaches and haplo-identical transplant with the post-transplant cyclophosphamide approach. Longer follow-up of haplo-identical transplant recipients as well as confirmation of these findings in a larger population, are needed before wide spread adoption of selecting haplo-identical donors over HLA-matched unrelated donors. Table Transplant Conditioning Regimen Outcomes Myeloablative Hazard Ratio Reduced intensity Hazard Ratio NRM Haplo-identical 1.00 1.00 MUD 1.07; p=0.82 2.35; p=0.03 Relapse Haplo-identical 1.00 1.00 MUD 0.88; p=0.40 0.76; p=0.09 Survival Haplo-identical 1.00 1.00 MUD 0.93; p=0.61 1.13; p=0.46 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Myeloablative Fractionated Busulfan Conditioning Regimen in Older Patients: Results of a Phase II Study

Blood ◽

10.1182/blood-2019-122124 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 256-256 ◽

Cited By ~ 1

Author(s):

Uday Popat ◽

Rohtesh S. Mehta ◽

Roland Bassett ◽

Amanda L. Olson ◽

Julianne Chen ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Advisory Committees ◽

Gvhd Prophylaxis ◽

Very High

Background: Traditionally, pre-transplant conditioning regimen is given over 4-6 days before hematopoietic cell transplant (HCT). Delivering higher dose chemotherapy preparative regimen over a longer time period has not been tested previously. We hypothesized that the delivery of myeloablative dose of busulfan over a 3-week period may reduce toxicity and non-relapse mortality (NRM), without affecting relapse, and tested this in a prospective phase II study. Methods: Patients between 18 and 70 years of age with hematological malignancies and adequate organ function, with 8/8-HLA matched related or unrelated donor were eligible. They received a fixed dose of busulfan 80mg/m2 as outpatient on days -20 and -13. Then, fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. GVHD prophylaxis was cyclophosphamide (PTCy) 50mg/kg on days 3 and 4 and tacrolimus. Mycophenolate mofetil (MMF) was added to later unrelated donor recipients. All patients received standard supportive care. The primary endpoint was day 100 NRM. Results: We enrolled 52 patients with a median age of 62 (range, 39-69) years. Almost half (n=25, 48%) had AML or MDS and the other half (n=26, 50%) had had CML or MPD; 1 (2%) had multiple myeloma. Low, intermediate, high and very-high disease risk index (DRI) was present in 3 (6%), 34 (65%), 14 (27%) and 1 (2%). HCT-comorbidity index was >3 in 23 (44%) and 1-2 (n=23, 44%). A majority (n=32, 62%) had an unrelated donor. With a median follow up of 14 months (range, 3-23), NRM at day 100 was 1.9% (n=1) and 8% (95% CI, 0-15) at 1 year. Overall survival, progression-free survival and relapse at 1-year were 83% (95% CI, 73-95%), 78% (95% CI, 67-91%), and 14% (95% CI, 4-24%), respectively [Table]. There were no graft failures. The median time to neutrophil engraftment was 17 days (range, 13-33) and that of platelets (> 20K/µL, n=45) was 24 days (range, 9-266). Day 100 grade II-IV and III-IV acute GVHD rates were 37% (95% CI, 23-50%) and 6% (95% CI, 0-12%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 9% (95% CI, 0-17%) and 7% (95% CI, 0-14%), respectively. Overall survival at 1-year differed significantly among patients with low/intermediate DRI (94%; 87-100%) and those with high/very high DRI (53%; 31-91%), P=0.001. Conclusion: Myeloablative fractionated busulfan regimen with PTCy GVHD prophylaxis is feasible in older patients, has low incidence of severe acute GVHD, chronic GVHD, and NRM and results in promising overall survival. Table Disclosures Popat: Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; StemLine: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Ciurea:Miltenyi: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder. Kebriaei:Amgen: Research Funding; Pfizer: Honoraria; Jazz: Consultancy; Kite: Honoraria. Nieto:Astra-Zeneca: Research Funding; Affimed: Research Funding; Affimed: Consultancy; Novartis: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Astex pharmaceuticals: Research Funding. Qazilbash:Autolous: Consultancy; Bioclinica: Consultancy; Speaker: Other: Speaker; Amgen: Other: Advisory Board. Molldrem:M. D. Anderson & Astellas Pharma: Other: Royalties. OffLabel Disclosure: Fludarabine & Busulfan as conditioning agent prior to transplant

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The Use of Busulphan As Compared to Melphalan in Combination with Fludarabine in the Reduced Intensity Conditioning Improves Overall Survival in Patients with Lymphoma

Blood ◽

10.1182/blood.v126.23.2007.2007 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2007-2007

Author(s):

Natasha Kekre ◽

Francisco J Marquez-Malaver ◽

Dolores Caballero ◽

Jl Piñana ◽

Albert Esquirol ◽

...

Keyword(s):

Overall Survival ◽

Retrospective Study ◽

Cumulative Incidence ◽

Research Funding ◽

Conditioning Regimen ◽

Multivariable Analysis ◽

Reduced Intensity Conditioning ◽

Gvhd Prophylaxis ◽

Donor Type ◽

Reduced Intensity

Abstract Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC. Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months. Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01]. Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting. Table 1. N= 136 Flu-Bu (n= 61) Flu-Mel (n= 75) P Sex (male) 41 (67.2%) 49 (65.3%) 0.081 Age 42 (SD: 12.3) 48.2 (SD: 12.3) 0.073 Diagnosis:- Hodgkin- NHL 9 (14.8%) 52 (85.2%) 26 (34.7%) 49 (65.3%) 0.008 Type of donor:- Related- Unrelated 25 (41.0%) 36 (59.0%) 36 (48.0%) 39 (52.0%) 0.413 Source of stem cells:-BM-PB -- 61 (100%) 2 (2.7%) 73 (97.3%) 0.502 Dis status at trx:- CR- PR or active dis 31 (50.8%) 30 (49.2%) 38 (50.7%) 37 (49.3%) 0.986 GVHD prophylaxis:- CNI-MTX- SIRO-TKR 42 (68.9%) 19 (31.1%) 34 (45.3%) 41 (54.7%) 0.006 Cause of death:- GvHD- Infection- Relapse- Others 3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%) 11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%) 0.114 Figure 1. Figure 1. OVERALL SURVIVAL: Disclosures Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand:BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding.

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Use of Thymoglobulin with Lower Dose of Busulfan Results in Less Acute Gvhd Following Unrelated Donor Allogeneic Stem Cell Transplantation for AML without Affecting Relapse-Free and Overall Survival

Blood ◽

10.1182/blood-2019-125418 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4488-4488

Author(s):

Dipenkumar Modi ◽

Vijendra Singh ◽

Seongho Kim ◽

Abhinav Deol ◽

Asif Alavi ◽

...

Keyword(s):

Overall Survival ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Advisory Board ◽

Unrelated Donor ◽

Hla Matching ◽

Reduced Intensity Conditioning ◽

Post Transplant ◽

Reduced Intensity

Introduction: Post-transplant relapse and GVHD are two major barriers of success of allogeneic hematopoietic stem cell transplantation (AHSCT) for AML. These outcomes are often dependent on the complex interaction between the post-transplant immunosuppression and the conditioning regimen. We as well as others have used rabbit thymoglobulin for the reduction of both acute and chronic GVHD in unrelated transplant in AML. The interaction between different conditioning regimens and thymoglobulin may play an important role in the outcomes, but it has not been fully investigated. In this study, we compared outcomes of patients undergoing unrelated donor AHSCT for AML using thymoglobulin with either a myeloablative or reduced intensity conditioning regimen. Patients received busulfan/fludarabine (Bu/Flu)-based myeloablative conditioning (MAC) regimen with 4 days of busulfan or reduced intensity conditioning (RIC) regimen using 2 days of busulfan with fludarabine. Since 2 days of busulfan as RIC may have a higher relapse rate, we added low dose TBI (200cGY) to the RIC regimen (Bu/Flu/TBI). Methods: We retrospectively evaluated outcomes of adult AML patients who underwent unrelated donor AHSCT utilizing tacrolimus, mycophenolate (MMF) and thymoglobulin as GVHD prophylaxis. All patients received either a Bu/Flu/TBI-based RIC or a Bu/Fu-based MAC regimen. Thymoglobulin was administered at a total dose of 4.5mg/kg in divided fashion (0.5mg/kg on day-3, 1.5mg/kg on day -2, 2.5mg/kg on day -1). Tacrolimus and MMF were started on day -3. The objectives were to determine the rates of acute and chronic GVHD, overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM) using Cox proportional hazard regression and competing risk models. Results: One hundred twenty-two patients with AML received unrelated donor AHSCT between January 2005 and December 2017. Of these, 88 (72%) patients had de-novo and 34 (28%) had secondary AML. Sixty-four patients received Bu/Flu/TBI-based RIC, and 58 received Bu/Flu as MAC regimen. All patients received peripheral blood stem cells. The patients receiving RIC regimen were older (median age 66 vs 53 years, p<0.001), had higher proportion of patients with normal cytogenetics (47% vs 31%, p=0.02) and 8/8 HLA match (88% vs 64%, p=0.004) as compared to MAC regimen. The 6-month cumulative incidence rate (CIR) of grade III-IV acute GVHD (aGVHD) was 6% in RIC and 26% in MAC regimen (p=0.004). The 2-year CIR of chronic extensive GVHD was 35% and 29% in RIC and MAC regimen, respectively (p=0.50). Median follow-up of surviving patients after RIC and MAC regimen was 4.4 years and 4 years, respectively. Two-year OS after RIC and MAC regimen was 50% and 49%, respectively (p=0.69). Two-year relapse rate with RIC and MAC was 37% and 24%, respectively (p=0.25), whereas two-year NRM with RIC and MAC was 21% and 31%, respectively (p=0.41). Two-year RFS was 43% with RIC and 45% with MAC regimen (p=0.80). In all, CMV and EBV reactivation rates were 34% and 7%, respectively. Eight patients (7%) developed gastrointestinal CMV disease. Multivariable analysis revealed that relapsed and refractory AML at AHSCT was associated with adverse OS (HR 1.71, p=0.04), RFS (HR 1.84, p=0.01) and higher NRM (SHR 2.96, p=0.006) compared to first complete remission. Secondary AML was associated with higher NRM (HR 2.44, p=0.02). No impact of HLA matching and conditioning regimen on OS, relapse, NRM and RFS was observed. Subgroup analysis showed that HLA matching had an interaction with the conditioning regimen for RFS (p=0.03). Otherwise, none of the factors appeared to have any significant interaction with the conditioning regimen for survival outcomes. Conclusion: Our study shows that thymoglobulin when used with lower dose of busulfan (in the form of Bu/Flu/TBI-based RIC regimen) provided significantly lower rate of acute GVHD compared to Bu/Flu-based MAC in AML patients undergoing unrelated donor AHSCT without affecting leukemia-free and overall survival. Disease status at transplant remains a significant predictor of post-transplant outcomes. Disclosures Deol: Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board.

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Rapid Immune Reconstitution after a Reduced-Intensity Conditioning Regimen and a CD3-Depleted Haploidentical Stem Cell Graft for Pediatric Refractory Hematologic Malignancies.

Blood ◽

10.1182/blood.v108.11.5311.5311 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5311-5311

Author(s):

Xiaohua Chen ◽

Gregory A. Hale ◽

Raymond C. Barfield ◽

Ely Benaim ◽

Wing H. Leung ◽

...

Keyword(s):

Stem Cell ◽

Nk Cells ◽

Immune Reconstitution ◽

Acute Gvhd ◽

Conditioning Regimen ◽

Hematologic Malignancies ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Reduced Intensity Conditioning Regimen ◽

Reduced Intensity

Abstract Haploidentical hematopoietic stem cell transplantation (HaploHSCT) from a mismatched family member (MMFM) donor offers an alternative option for patients who lack an HLA-matched donor. The main obstacles to successful haploidentical hematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections, and severe graft-versus-host disease (GvHD). Method: We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin. The graft was immunomagnetically depleted of CD3+ T-cells (CD3 negative selection) and contained a large number of both CD34+ and CD34− stem cells and most other immune cells especailly NK cells. This protocol was used to treat 22 pediatric patients with refractory hematologic malignancies. Results and Discussion: After transplantation, 91% of the patients achieved full donor chimerism. They also showed rapid recovery of CD3+ T-cells, T-cell receptor excision circle counts, TCRβ repertoire diversity and NK-cells during first four months post-transplantation. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft, and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.

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The Prognostic Calculator Easix Predicts Acute Gvhd, Non-Relapse Mortality and Overall Survival in Adult Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

Blood ◽

10.1182/blood-2018-99-111036 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2069-2069

Author(s):

Miriam Sanchez-Escamilla ◽

Patrick Hilden ◽

Molly Maloy ◽

Samira A Fatmi ◽

Doris Ponce ◽

...

Keyword(s):

Overall Survival ◽

Research Funding ◽

Acute Gvhd ◽

Endothelial Damage ◽

Adult Patients ◽

Stress Index ◽

Unrelated Donor ◽

Risk Of Death ◽

Increased Risk ◽

Reduced Intensity

Abstract Keywords Allogeneic transplantation; endothelial damage; biomarkers. Background Endothelial damage is associated with severe complications and increased risk of death after allogeneic hematopoietic cell transplantation (AlloHCT). The recently developed Endothelial Activation and Stress Index (EASIX) is a prognostic tool that uses clinical lab values and has been shown to predict non-relapse mortality (NRM) and overall survival (OS) at onset of acute graft versus host disease (aGVHD) in reduced intensity (RIC) alloHCT (Luft, Lancet Haematol 2017). We hypothesized that EASIX may be valuable for more broadly predicting aGVHD, NRM and OS after AlloHCT, beyond time of onset of aGVHD. Design We evaluated 152 adult patients who received an unmodified RIC AlloHCT from a related or unrelated donor with uniform GVHD prophylaxis of sirolimus/tacrolimus and low-dose MTX for treatment of lymphoid malignancies, between April 2008 and May 2017. The EASIX formula (LDH*Creatinine/platelet counts) was calculated at multiple timepoints (pre-HCT, day 30, day 100, onset TMA and aGVHD). For all EASIX assessments post-HCT, a landmark analysis was conducted at the given timepoint A log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. A one-unit increase in log2 EASIX is associated with a doubling (one-fold increase) of EASIX on the original scale. Kaplan-Meier, cumulative incidence, and cox modeling (cause specific for NRM and aGVHD) were used to evaluate EASIX as it relates to outcomes of interest. Relapse and death or relapse were considered competing risks for NRM and aGVHD respectively. Results The median age at transplant was 54 years (range 23-78), 70% were males, a majority had non-Hodgkin lymphoma (68%), and most had sensitive disease at time of HCT (CR=56%; PR=33%). All patients, except two, received peripheral blood stem cells. Sixty-three patients had an HLA-identical related donor, while the remaining 89 had an unrelated donor transplant (HLA-matched in 75 patients, and HLA-mismatched in 14 patients). HCT-CI was 0 in 49 patients, 1-2 in 41 and ≥ 3 in 62 patients. With a median follow-up in surviving patients of 5.4 years (range, 0.8-10), the 1 and 3 years OS rate was 84.2% (95% CI, 77.3-89.1) and 67.9% (95% CI, 59.6-74.8), respectively. The NRM rate at 1 and 3 years was 7.9% (95% CI, 4.3-12.9) and 16.4% (95% CI, 10.9-22.8), respectively. The 1-year cumulative incidences of grades 1-4, 2-4 and 3-4 aGVHD were 56.6% (95% CI, 48.3-64.1), 42.1% (95% CI, 34.2-49.8) and 7.9% (95% CI, 4.3-12.9), respectively. Post-HCT thrombotic microangiopathy was only observed in 13 patients, representing too few events for EASIX analysis. As expected, HCT-CI was significantly associated with both OS and NRM. Pre-HCT EASIX was significantly associated with increased NRM (HR=1.60 [95% CI, 1.15-2.23], p=0.005) and aGVHD grade 1-4 and 2-4 (HR=1.33 [95% CI, 1.08-1.64], p=0.006 and HR=1.39 [95% CI, 1.10-1.75], p=0.005; respectively), but not OS or grade 3-4 aGVHD (Table 1). EASIX at day 30 and day 100 was significantly associated with both OS and NRM (Figures 1-4). Furthermore, confirming the results of Luft, EASIX calculated at onset of any grade aGVHD was significantly associated with OS (HR=1.34 [1.10-1.63], p=0.004) and NRM (HR=1.47 1.11-1.94], p=0.007). Finally, there was no correlation between HCT-CI and EASIX score. Conclusions We conclude that the EASIX formula, calculated at various timepoints pre and post AlloHCT, is significantly associated with NRM and OS. Pre-HCT EASIX also predicts risk of aGVHD, confirming prior results, EASIX at onset of acute GVHD is a predictor of NRM and OS in adult recipients RIC AlloHCT. EASIX provides an independent and easily accessible tool to predict important AlloHCT outcomes that can be used in addition to HCT-CI to better risk stratify patients. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Perales:Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees; Novartis: Other: Personal fees.

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Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression After Conditioning with Fludarabine and Low-Dose Total Body Irradiation for Recipients of HLA-Matched Sibling or Unrelated Donor Hematopoietic Cell Transplants in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Blood ◽

10.1182/blood.v114.22.3354.3354 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3354-3354

Author(s):

Tara Gregory ◽

Mark W. Brunvand ◽

Peter A. McSweeney ◽

Scott I. Bearman ◽

Michael Maris ◽

...

Keyword(s):

Paroxysmal Nocturnal Hemoglobinuria ◽

Low Dose ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Reduced Intensity Conditioning ◽

Gvhd Prophylaxis ◽

Reduced Intensity Conditioning Regimen ◽

Matched Sibling ◽

Total Body ◽

Reduced Intensity

Abstract Abstract 3354 Poster Board III-242 Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder of hematopoiesis that results in bone marrow failure and myelodysplasia. Hematopoietic cell transplantation is the only curative therapy. The success of allogeneic stem cell transplantation has been limited, in part, by regimen-related toxicity associated with high-dose preparative regimens. Nonrandomized studies suggest that long-term remissions are achievable when using allogeneic SCT as treatment for PNH. Mikolajewska, et al. reported treatment of 7 patients with high risk PNH with a reduced intensity conditioning regimen of fludarabine and total body irradiation (TBI). Mycophenolate mofetil (MMF) and cyclosporine were utilized as graft versus host disease (GvHD) prophylaxis (2008 ASH Annual Meeting Abstracts, 4407). The objective of this study is to evaluate the combination of tacrolimus and MMF as GvHD prophylaxis after conditioning with fludarabine and low dose TBI in PNH patients who are not candidates for conventional ablative allografting. This is a novel approach to immunosuppression incorporating an early but extended taper of tacrolimus on day +80. Patients and Methods: Four patients with PNH underwent allogeneic SCT after a reduced intensity regimen. Patients received fludarabine (30mg/m2/day) on days -4 to -2 and low dose TBI (200 or 400 cGy at 6-7 cGy/min from a linear accelerator) on day 0. Two patients received TBI 200 cGy and three received 400 cGy. One patient failed to engraft with TBI 200 cGy and was transplanted again with TBI 400 cGy. GvHD prophylaxis was with tacrolimus (0.06mg/kg PO BID) starting on day -3 and MMF (15mg/kg PO BID for related and TID for unrelated donors) starting from day 0. All patients received filgrastim-mobilized peripheral blood stem cells from either from an HLA-matched sibling (n=1) or matched unrelated (n=4) donor. Results: The median follow up was 20 (range 3 to 36) months after SCT. One patient who received TBI at 200 cGy failed to engraft after an unrelated transplant. She underwent a second transplant from a different unrelated donor with TBI with 400 cGy with engraftment after the second procedure. The patients engrafted reaching a neutrophil count ≥ 500 a median of 16 (range 15 to 18) days post-transplant. Each achieved eradication of their PNH clone based on subsequent marrow and blood chimerism studies together with absence of clinical signs of PNH. Acute GvHD (grades II-IV) occurred in three patients. Chronic GvHD occurred in two patients. Day 100 mortality was 0% and all four patients are alive with an EGOG status of 0-1. Conclusions: A reduced intensity conditioning regimen consisting of fludarabine and TBI at 200 cGy or 400 cGy with tacrolimus and MMF as post grafting immunosuppression appears well tolerated for performing allogeneic transplants in PNH. Donor cell engraftment with eradication of the PNH clone was observed with this approach. The higher dose of TBI (400 cGy) might be more effective in overcoming graft rejection and warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

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Outcomes with Mismatched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation Following Reduced Intensity Conditioning: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2021-146051 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2863-2863

Author(s):

Moazzam Shahzad ◽

Sibgha Gull Chaudhary ◽

Ezza Tariq ◽

Naira Fatima ◽

Muhammad Arslan ◽

...

Keyword(s):

Cell Transplantation ◽

Research Funding ◽

Acute Gvhd ◽

Meta Analysis ◽

Unrelated Donor ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Unrelated Donors ◽

Matched Donor ◽

Reduced Intensity

Abstract Background: Allogeneic hematopoietic cell transplantation (HSCT) is often the optimal and only potentially curative therapy in several high-risk hematologic malignancies. Although human leukocyte antigen (HLA)-matched donors remain the preferred choice for HSCT recipients, haploidentical and umbilical cord blood HSCT has increased access to transplantation. Despite these advances, many patients lack an appropriate donor, in particular the ethnic minorities. The use of mismatched unrelated donors (MMUD) has increased over the years but concerns regarding increased risk of graft versus host disease (GVHD) and non-relapse mortality (NRM) limits the utility of MMUD HSCT. The intensity of the conditioning regimen has a significant impact on survival in case of mismatched donors. We conducted a systematic review and meta-analysis aimed to investigate the outcomes with MMUD HSCT using reduced intensity conditioning (RIC). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane Library, and ClinicalTrials.gov) from date of inception through February 2021 using the MeSH and entry terms for "hematopoietic stem cell transplantation", OR "hematologic neoplasms", AND unrelated donors" AND "treatment outcome". A total of 2477 records were identified and primary and secondary screening was done. After excluding review, duplicate, and non-relevant articles, we included 6 (4 retrospective, 2 prospective) studies reporting outcomes following RIC MMUD HSCT. The Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data and randomized control trial was used for quality assessment, and all studies were reported as good. Proportions along with a 95% confidence interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). The variance between the studies was calculated using Der Simonian Laird Estimator. Results: We identified 895 participants in the 6 studies, who had MMUD HSCT with RIC. (Table 1) Median age was 57.5 (18-76) years and 56% (n= 415) were males as reported by four studies (n=740). In five studies with available data (n=855), source of the primary graft was peripheral blood (PB) and bone marrow (BM) in 72% (n=614) and 28% (n=241) of the HSCT recipients respectively. After a median follow-up of 48 (3-125) months, we estimated a pooled overall survival (OS) of 62% (95% CI 0.52-0.72, I 2=84%, n=895) at one year and 43.5% (95% CI 0.33-0.54, I 2 =84% n=855) at three years. The pooled incidence of acute GVHD (grade II-IV), acute GVHD (grade III-IV), and chronic GVHD were 37% (95% CI 0.26-0.49, I 2=81%, n=610), 16% (95% CI 0.07-0.29, I 2=87%, n=542), and 28% (95% CI 0.13-0.47, I 2=95%, n=848) respectively. Progression free survival (PFS) and relapse rates (RR) were 46% (95% CI 0.30-0.62, I 2=92%, n=814) and 31% (95% CI 0.24-0.39, I 2=65%, n=814) respectively. The pooled incidence of non-relapse mortality (NRM) was 23% (95% CI 0.09-0.40, I 2=91%, n=707). Kasamon et al. and Shaw et al. reported 1-year OS of 75-79% with MMUD HSCT using fludarabine, cyclophosphamide and 2 Gy total body irradiation RIC, bone marrow graft and post-transplant cyclophosphamide, sirolimus and mycophenolate for GVHD prophylaxis. Conclusion: Mismatched unrelated donor HSCT has shown favorable outcomes with reduced intensity conditioning using a post-transplant cyclophosphamide-based regimen, comparable to the historical outcomes with mismatched related donor (haploidentical) HSCT. MMUD HSCT with RIC can be considered in patients lacking an HLA-matched donor. This strategy will expand access to HSCT in patients with ethnic minorities who often lack a matched donor. Figure 1 Figure 1. Disclosures McGuirk: EcoR1 Capital: Consultancy; Allovir: Consultancy, Honoraria, Research Funding; Gamida Cell: Research Funding; Novartis: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Fresenius Biotech: Research Funding; Bellicum Pharmaceuticals: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding.

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Thiotepa-Fludarabine-Treosulfan (TFT) Conditioning for 2nd Allogeneic Peripheral Blood Hematopoietic Cell Transplantation (HCT) from a Second Unrelated Donor in Patients with Acute Myeloid Leukemia (AML) Relapsed after Prior Allogeneic HCT: A Prospective Multicenter Phase II Trial

Blood ◽

10.1182/blood-2018-99-118999 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 210-210

Author(s):

Jürgen Finke ◽

Claudia Schmoor ◽

Matthias Stelljes ◽

Andreas Burchert ◽

Peter Dreger ◽

...

Keyword(s):

Primary Endpoint ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Allogeneic Hct ◽

Gvhd Prophylaxis ◽

Secondary Endpoints ◽

Full Analysis

Abstract Introduction: Relapse of AML after allogeneic HCT has a dismal prognosis. Long-term survival after 2nd allogeneic HCT has been described in selected patients. Here we tested a specific protocol with a fixed drug combination for myeloablative conditioning and GvHD prophylaxis for 2nd allogeneic HCT from a different unrelated donor. (EudraCT no.: 2012-005414-18, German Clinical Trials Registry no.: DRKS00005126) Methods : Aim of the trial was to show efficacy and safety of a 2nd alloHCT from an unrelated donor after a uniform conditioning with Treosulfan 3x12gm/m2, Fludarabin 3x30mg/m2, and Thiotepa 3x 5mg/kg (TFT), and GvHD prophylaxis with cyclosporine A (CyA) /Mycophenolate and ATG-F (Neovii) 3x10mg/kg. Eligible were adult patients with AML, ECOG ≤ 2, with sensitive or refractory hematologic relapse (≥ 20% blasts) > 6 months after a prior allogeneic HCT , including secondary (s) and/ or tAML. CR prior 2nd HCT was no prerequisite. The primary endpoint of the study was disease-free survival (DFS) defined as being alive and free of disease at 1 year post 2nd HCT. Secondary endpoints were relapse, relapse mortality (RM), NRM, overall survival (OS), acute GvHD, chronic GvHD, engraftment, and adverse events. According to the Fleming one-stage design, 50 evaluable patients had to be included. If 16 or more patients were alive and free of disease at 1 year post 2nd SCT, the regimen could be considered as successful for evaluation in further trials. With this decision rule, it can be shown at one-sided α=0.1 that the probability of DFS at 1 year post 2nd HCT is higher than 23% with a power of 90%, when it is at least 40%. This is a first analysis of the study covering the first year after 2nd HCT of each patient. The analysis is based on the full analysis set, which includes all patients, for whom the conditioning regimen TFT and the GvHD prophylaxis regimen CyA, MPA/MMF, ATG-F has started, and for whom allogeneic HCT from an unrelated donor has been performed. Results: Fifty-two patients were registered for the study from 25th March 2014 up to 10th March 2017 from 9 German centres. The full analysis set includes 50 patients (median age 53.5 years). ECOG was median 1. Donors for 1st allo HCT had been related (n=11 (22.0%)) or unrelated (n=39 (78.0%)) (n=48 PBSCT, n=2 bone marrow). Conditioning for 1st HCT was myeloablative in 23 (46.0%) patients. After 1st HCT, the rate of acute GvHD I-IV was 34.0%, and of chronic GvHD was 40.0%. Median time from 1st HCT to relapse was 17.2 months and from relapse after 1st HCT to 2nd HCT 2.5 months. Thirty-six (72%) patients had received induction chemotherapy for relapse prior to 2nd HCT, 11 (22.0%) patients had received azacytidine or decitabine, and 11 (22.0%) had received donor lymphocyte infusions (DLI). Remission status prior to 2nd HCT was complete remission in 16 (32.0%) patients, chemo-refractory relapse in 33 (66.0%), one patient was in partial remission. With regard to the primary endpoint, 23 (46%, 95%-CI (31.8-60.7%) of the patients were alive and free of relapse at 1 year after 2nd SCT. With regard to the secondary endpoints at 1 year, the cumulative incidence of relapse (95%-CI) was 26 (17-42)%, 9/50 patients (18 (10-33)%) died after relapse of AML, NRM was 14/50 patients (28 (18-44)%, cause: infection n=6, infection after aGvHD n=6, PTLD n=2), OS was 54 (39-66)%. Four patients are alive after relapse. aGvHD rate was 54 (42-70)%, aGvHD III-IV 26 (16-42)%, cGvHD 26 (16-42)%, extensive cGvHD 20 (12-35)%, engraftment rate with ANC > 1.0 x 103/µl was 92 (85-100)%, with platelets > 20 x 103/µl was 80 (70-92)%, and with platelets > 100 x 103/µl was 66 (54-81)%. After 1 year, 4 patients had received DLI for prophylaxis, and 5 patients for mixed chimerism as per protocol. Conclusion: Second alloHCT with an ablative double alkylator containing conditioning regimen with Thiotepa, Fludarabine, and Treosulfan is feasible and can result in sustained disease control in patients with AML relapse after a first alloHCT, and therefore seems to be a valid option in this otherwise detrimental setting. Disclosures Finke: Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding. Stelljes:Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy; Novartis: Honoraria; Amgen: Honoraria; JAZZ: Honoraria. Burchert:Novartis: Research Funding; Bayer: Research Funding; AOP Orphan: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Schub:Affimed: Research Funding. Kobbe:Celgene: Honoraria, Other: Travel Support, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.

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