Non-Infectious Pulmonary Toxicity after Allogeneic Hematopoietic Cell Transplantation (HCT): A Center for International Blood and Marrow Transplant Research (CIBMTR) Study

Introduction Early non-infectious pulmonary toxicity (NIPT) is a significant HCT complication and comprises diffuse alveolar hemorrhage (DAH), idiopathic pneumonia syndrome (IPS), and cryptogenic organizing pneumonia (COP) with an overall incidence ranging 1-10%. Treatment options are primarily immunosuppressive therapy and supportive care with limited efficacy. Mortality in IPS, for example, approaches 60-80% (PMID: 21531955). Therefore, to better identify potentially high-risk patients (pts) we performed a registry-based analysis of the incidence, risk factors, and outcomes of early NIPT after HCT. Methods This retrospective study included adult pts undergoing allogenic HCT for hematologic malignancies and non-malignant disorders as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008-2017). Data analyses were divided into four common disease categories (AML/ALL, CML/MDS/MPN, NHL/CLL/PCD, and non-malignant diseases) to minimize statistical interactions in the multivariate model. The primary outcome was the incidence of and risk factors for individual NIPT and a composite of the three NIPT (IPS, DAH, COP); the secondary outcome was overall survival (OS). Multivariable Cox proportional hazards regression models were developed to identify the risk factors for NIPT and OS. In addition to baseline pre-transplant covariates, post-transplant neutrophil recovery (>500/mcL x 3 consecutive days), platelet recovery (>20k/mcL x 3 consecutive days, without transfusion in 7 previous days) and grade 2-4 acute GVHD were included as time-dependent covariates in the multivariable models. Results Characteristics of 21,587 adult pts are shown in Table 1. Median age at HCT was 54 years, 59% were male, and 39% had KPS <90. Median follow-up was 49 months. Per the HCT-Comorbidity Index (HCT-CI), 15% and 24% of pts had a severe (FEV1 and/or DLCO≤65%, dyspnea at rest, requiring supplemental oxygen) and moderate (FEV1 and/or DLCO 66-80%, dyspnea on slight activity) pulmonary comorbidity, respectively. Pre-transplant, 3% of pts had a history of mechanical ventilation, 5% had a history of pulmonary fungal infection, and 40% reported a smoking history. Most pts had a matched sibling or unrelated donor (68%) and received peripheral blood graft (71%). Myeloablative conditioning was used in 49% pts, and 39% received total body irradiation (TBI). Table 2 shows the cumulative incidence of early NIPT amongst pts in the four disease categories. Multivariable analysis in the AML/ALL group identified TBI-based conditioning, grade 2-4 acute GVHD, HCT-CI score of 1-3, and prior autologous HCT were associated with increased risk of NIPT, while platelet recovery decreased the risk of NIPT. In the CML/MDS/MPN group, smoking history, grade 2-4 acute GVHD and HCT-CI scores of 2-5+ were associated with increased risk of NIPT, while non-TBI and non-myeloablative TBI conditioning and platelet recovery were associated with a lower risk. In the NHL/HD/CLL/PCD group, a higher risk of NIPT was seen with severe pulmonary comorbidity pre-HCT and chronic GVHD, while platelet recovery and non-TBI regimens were associated with a lower risk. In the non-malignant disease group, both neutrophil and platelet recovery were associated with a lower risk of NIPT. Furthermore, the multivariable analysis for OS (Table 2) showed across all disease groups, NIPT increased the risk of mortality (vs. no NIPT; HR of 4.3 in AML/ALL, 4.1 in CML/MDS/MPN, 3.5 in NHL/CLL/PCD, 6.8 in non-malignant diseases; p<0.0001). Conclusions This large registry-based analysis of allogeneic HCT pts highlights several risk factors for the development of early NIPT including smoking history, severe pulmonary comorbidity, myeloablative TBI conditioning, and acute and/or chronic GVHD. Identification of these risk factors can enhance appropriate selection of pts prior to HCT. We also found that post-transplant, platelet and neutrophil recovery was associated with a reduced risk of NIPT. Furthermore, early NIPT is associated with a several-fold higher mortality risk in the current era despite significant advances in supportive care. Future studies are needed to optimize risk factors such as conditioning regimen and graft source selection to reduce the risk of early NIPT. Disclosures Ustun: Kadmon: Honoraria. Hamilton:Syndax Pharmaceuticals: Consultancy, Honoraria. Majhail:Anthem, Inc.: Consultancy; Incyte: Honoraria; Nkarta Therapeutics: Honoraria; Mallinckrodt: Honoraria. Sorror:Jazz Pharmaceutical: Other: Honorarium for Advisory role. . Stadtmauer:Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Novartis, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy. Pasquini:Bristol Myers Squibb: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Other; Novartis: Research Funding; Kite: Research Funding.

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Analysis of Risk Factors Determining Incidence and Outcome of Infections in Children and Adults after Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood-2018-99-113787 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3364-3364

Author(s):

Jan Styczynski ◽

Krzysztof Czyzewski ◽

Sebastian Giebel ◽

Jowita Fraczkiewicz ◽

Malgorzata Salamonowicz ◽

...

Keyword(s):

Risk Factors ◽

Acute Leukemia ◽

Bacterial Infections ◽

Acute Gvhd ◽

Viral Infections ◽

Chronic Gvhd ◽

Multivariable Analysis ◽

Risk Of Death ◽

Increased Risk ◽

Cmv Reactivation

Abstract BACKGROUND: Recent EBMT analysis showed that infections are responsible for 21% of deaths after allo-HCT and 11% after auto-HCT. However, the risk, types and outcome of infections vary between age groups. The aim of the study is the direct comparison of risk factors of incidence and outcome of infections in children and adults. PATIENTS AND METHODS: We analyzed risk factors for the incidence and outcome of bacterial, fungal, and viral infections in 650 children and 3200 adults who received HCT between 2012-2015. The risk factors were determined by multivariable logistic regression analysis. RESULTS: A total number of 395/650 (60.8%) children and 1122/3200 (35.0%) adults were diagnosed for microbiologically confirmed infection, including 345/499 (69.1%) and 679/1070 (63.5%), respectively after allo-HCT, and 50/151 (33.1%) and 443/2130 (20.8%) respectively, after auto-HCT. At 2 years after HCT, the incidences of microbiologically documented bacterial infection were 36.0% and 27.6%, (p<0.001) for children and adults, respectively. Incidences of proven/probable invasive fungal disease (IFD) were 8.4% and 3.7% (p<0.001), respectively; and incidences of viral infection were 38.3%, and 13.5% (p<0.001), respectively. Overall, 31/650 (4.8%) children and 206/3200 adults (6.4%) have died after these infections. The distribution of deaths was different in children (35.5% bacterial, 48.4% fungal, 16.1% viral) and adults (61.7% bacterial, 24.7% fungal, 13.6% viral). BACTERIAL INFECTIONS: In multivariable analysis, the risk of infections was higher after allo-HCT (HR=1.8; p<0.001). In allo-HCT patients, the risk was higher in children (HR=2.1; p<0.001), in patients with acute leukemia (HR=1.6; p<0.001), matched unrelated (MUD) vs matched family-donor (MFD) HCT (HR=1.6; p<0.001), mismatched unrelated (MMUD) vs MFD HCT (HR=2.0; p<0.001), myeloablative vs reduced-intensity conditioning (RIC) (HR=1.3; p<0.001), delayed (>21d) hematological recovery (HR=3.3; p<0.001), acute GVHD before infection (HR=1.7; p<0.001), and chronic GVHD before infection (HR=1.4; p=0.014). In auto-HCT patients, the risk was higher in children (HR=1.7; p<0.001), and in patients with delayed hematological recovery (HR=2.8; p<0.001). In patients with multiple myeloma (MM) the risk was decreased (HR=0.7; p=0.005). FUNGAL INFECTIONS: The risk of proven/probable IFD was higher after allo-HCT (HR=5.4; p<0.001). In allo-HCT patients, the risk was higher in children (HR=3.9; p<0.001), in patients with acute leukemia (HR=3.8; p<0.001), MUD vs MFD HCT (HR=1.5; p=0.013), MMUD vs MFD HCT (HR=2.5; p<0.001), delayed hematological recovery (HR=3.3; p<0.001), acute GVHD before infection (HR=1.5; p=0.021), and chronic GVHD before infection (HR=2.2; p<0.001). In auto-HCT patients, the risk was higher in children (HR=1.8; p=0.025). Patients with MM were at decreased risk of IFD (HR=0.6; p=0.005). VIRAL INFECTIONS: In multivariable analysis, the risk of infections was higher after allo-HCT (HR=6.1; p<0.001). In allo-HCT patients, the risk was higher in children (HR=1.3; p=0.010), in patients with acute leukemia (HR=1.7; p<0.001), MUD vs MFD HCT (HR=2.0; p<0.001), MMUD vs MFD HCT (HR=3.3; p<0.001), myeloablative vs RIC (HR=1.8; p=0.050), acute GVHD before infection (HR=1.5; p<0.001) and chronic GVHD before infection (HR=2.7; p=0.014). Among auto-HCT patients, diagnosis of MM brought decreased risk of viral infections (HR=0.5; p<0.001). DEATH FROM INFECTION: In allo-HCT patients, adults (HR=3.3; p<0.001), recipients of MMUD-HCT (HR=3.8; p<0.001), patients with acute leukemia (HR=1.5; p=0.023), chronic GVHD before infection (HR=3.6; p=0.014), CMV reactivation (HR=1.4; p=0.038) and with duration of infection treatment >21 days (HR=1.4; p=0.038) were associated with increased risk of death from infection. Among patients with bacterial infections, the risk was higher in G- infections (HR=1.6; p=0.031). Among auto-HCT patients, no child died of infection. In adults, the risk of death was higher if duration of treatment of infection was >21 days (HR=1.7; p<0.001). In patients with MM the risk was decreased (HR=0.4; p<0.001). CONCLUSIONS: The profile of infections and related deaths varies between children and adults. MMUD transplants, diagnosis of acute leukemia, chronic GVHD, CMV reactivation and prolonged infection are relative risk factors for death from infection after HCT. Disclosures Kalwak: Sanofi: Other: travel grants; medac: Other: travel grants.

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Impact of Targeted Immunotherapies and Novel Cytogenetic and Clinical Risk Groups on Outcome after Allogeneic Hematopoietic Stem Cell Transplant (AlloHCT) for Acute Lymphoblastic Leukemia (ALL): The Mayo Clinic Cohort

Blood ◽

10.1182/blood-2019-122068 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2588-2588

Author(s):

Zaid Abdel Rahman ◽

Michael G. Heckman ◽

Kevin C. Miller ◽

Patricia Greipp ◽

Matthew R Spiegel ◽

...

Keyword(s):

High Risk ◽

Tyrosine Kinase ◽

Targeted Therapies ◽

Mayo Clinic ◽

Lower Risk ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Risk Groups ◽

Increased Risk ◽

The Impact

Introduction Novel high-risk groups have been identified in adult ALL, including secondary (sALL) and Philadelphia-like ALL (Ph-like, based on CRLF2, IgH, ABL2, JAK2 and other tyrosine kinase translocations), and those with minimal residual disease >0.1% (MRD+) after induction therapy. Novel targeted therapies are now routinely incorporated into 1st line regimens, including tyrosine kinase inhibitors (BCR-ABL1-pos), rituximab (CD20+) and blinatumomab (Blina) for MRD+. The impact of these novel high risk groups and therapies after alloHCT is unknown; therefore, we evaluated their impact on overall survival (OS), relapse rate (REL), non-relapse mortality (NRM) and acute and chronic GVHD. Methods We evaluated pts receiving 1st Allo-HCT for ALL at Mayo Clinic (Rochester, Phoenix, and Jacksonville) from 2008-2018 for outcomes of interest, specifically the impact of novel therapies and risk groups. Associations of patient factors with outcomes were examined using univariable (UVA) and multivariable (MVA) Cox proportional hazards regression models, where the cause-specific hazard of the given outcome was modeled to account for the competing risk of death. Results We identified 261 consecutive AlloHCT recipients during the study period. Median age at transplant was 48 years (18-72) and 147 (56.3%) were male. The median comorbidity (HCT-CI) score was 2 (0-8). 213 pts (81.6%) had B-lineage ALL, of which 85 (32.6%) were BCR-ABL-pos, 17 (6.5%) Ph-like (identified by FISH), 16 (6.1%) hypoploidy/near triploidy (Hy/Tri), and 67 (25.7%) pre-B ALL NOS. The remaining 48 (18.4%) had T-ALL. 30 pts (11.5%) had sALL (i.e. prior chemo/radiotherapy for another malignancy). HyperCVAD was the most common 1st line regimen (68.2%). 243 (93.1%) pts achieved Complete Remission (CR1) after induction therapy, and 203 (77.8%) were in CR1 at the time of alloHCT. Blina was administered for MRD+ in 14 pts (5.4%), and for relapsed/refractory ALL (R/R) in 13 (27% of R/R pts), 7 of whom received Blina as initial therapy for R/R. Donors were matched unrelated in 149 (57.1%), matched related in 98 (37.5%), and haploidentical in 14 (5.4%). Peripheral blood (PB) grafts were used in 233 (89.3%). 103 (54.5%) were donor:recipient (D:R) sex-matched, and 86 D:R mismatched [47 (24.9%) M:F; and 39 (20.6%) F:M]. Myeloablative conditioning was used for the majority (78.5%) mostly with Cy/TBI (60.5%). Standard GVHD prophylaxis regimens were used. Outcomes Median follow-up after transplant was 22.4 months (0.5-135), and 51 (19.5%) had REL. The 1, 2 and 5-year survival rates were 71.9%, 64.9%, and 54.1%, respectively (Figure 1). Acute GVHD developed in 144 (55.2%) and chronic GVHD in 100 (38.3%). Ph-like ALL, Blina for MRD+, Blina for R/R, sALL and CD20-pos had no independent impact on OS. In contrast, age>60, Hy/Tri, and >CR1 at alloHCT were associated with worse OS in UVA, however, in MVA only pre-B ALL NOS was associated with better OS. Female:male D:R status was associated with inferior OS. Blina for R/R disease was associated with increased risk of REL in UVA [HR 5.26 95% CI (1.33, 20.00), p=0.017], whereas other novel high risk groups had no impact on REL. In contrast, T-ALL, Hy/Tri and >CR1 at AlloHCT were associated with increased REL in UVA, but only T-ALL and Hy/Tri continued to predict for increased REL in MVA. Secondary ALL was associated with increased NRM in UVA [HR 1.96 95% CI (1.07, 3.57), p=0.028], whereas other novel high risk groups had no impact on NRM. In contrast, age>60, >CR1 at AlloHCT and D:R sex mismatch were associated with higher NRM in UVA, but only sex mismatch and >CR1 at AlloHCT were associated with higher NRM in MVA. TBI use was associated with higher risk of acute GvHD (p=0.008) and ATG use with lower risk chronic GVHD (p<0.001). Similarly non-PB grafts were associated with a lower risk of chronic GVHD (p=0.005). Results for OS, REL, NRM, acute and chronic GVHD analysis are shown in Table 1. Conclusion Novel high risk groups (CD20+, Ph-like and sALL) do not appear to adversely impact OS after alloHCT, although sALL was associated with increased risk of NRM. Interestingly, pre-B-ALL NOS appear to be associated with favorable OS. Novel targeted therapies also do not independently predict outcome, with the exception of Blina for R/R ALL which may be associated with REL after subsequent alloHCT (a subgroup for whom novel maintenance strategies should be explored). Our analysis highlights the importance of allo-HCT for novel high risk ALL subgroups. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Foran:Agios: Honoraria, Research Funding.

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Interferon in Polycythemia Vera (PV) Yields Improved Myelofibrosis-Free and Overall Survival

Blood ◽

10.1182/blood-2020-141796 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 31-32

Author(s):

Ghaith Abu-Zeinah ◽

Spencer Krichevsky ◽

Tatiana Cruz ◽

Gabriela Hoberman ◽

Niamh Savage ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Lower Risk ◽

Research Funding ◽

Multivariable Analysis ◽

Interferon Alfa ◽

Single Center ◽

Cytoreductive Treatment ◽

Disease Modifying ◽

Disease Modifying Treatment

Introduction: Polycythemia vera (PV) progression to myelofibrosis (MF) is associated with significant morbidity and mortality. Recombinant interferon alfa (rIFN-α) is the only disease-modifying treatment shown to reverse marrow fibrosis, but the myelofibrosis-free survival (MFS) and overall survival (OS) benefit associated with rIFN-α treatment is yet to be determined. In our preliminary analysis of 306 PV patients (pts) (Abu-Zeinah et al. ASH 2019), those treated with rIFN-α had a longer MFS and OS compared to those treated with hydroxyurea (HU) or phlebotomy-only (PHL-O). Herein, we present the final analysis comparing MFS and OS of 470 PV pts treated with rIFN-α, HU, or PHL-O. Methods: This single-center retrospective study at Weill Cornell Medicine (WCM) was approved by the WCM institutional review board. Pts were identified by an automated query of the electronic medical record system for the diagnosis of PV and were included if they met the PVSG criteria (1974-2007), WCM criteria (2008-2016) (Silver et al. Blood 2013), and the WHO 2016 criteria (2016-2020). Post-PV MF (PPVMF) diagnosis was made according to IWG-MRT criteria. Both intention-to-treat (ITT) and on-treatment analyses compared the MFS and OS by treatment group and duration, respectively. In the ITT analysis, pts were grouped to rIFNa or HU according to the first treatment they received for at least one year or to PHL-O if no cytoreductive treatment was given. MFS and OS were estimated using Kaplan-Meier methods and the log-rank test compared survival between treatment arms in ITT analysis. Multivariable analysis of PPVMF risk and mortality was performed using a Cox proportional hazards model. Results: The 470 PV pts identified had a median age of 54 years (range 20-94) at diagnosis; 229 (49%) were women. The median follow-up was 10 years (range 0-45). The primary treatment was rIFN-a in 94 (20%), HU in 188 (40%), other drugs or combinations in 55 (12%), and PHL-O in 133 (28%). The median age at diagnosis for rIFN-a, HU and PHL-O groups was 49, 58 and 54 years respectively (p <0.001) (Table 1). The median MFS for all pts was 23.8 years and for rIFN-a, HU, and PHL-O groups was 32.5, 22.6, and 20.5 years respectively (p <0.001) (Fig 1A-B). The median OS for all pts was 26.7 years and for rIFN-a, HU, and PHL-O groups was 27.7, 25.9 and 21.3 respectively (p<0.01) (Fig 1C-D). In multivariable analysis including age, sex, CV risk factors and thrombosis history, the rIFN-a group had a lower risk of MF compared to the HU group (HR = 0.42, p =0.008) and the PHL-O group (HR = 0.24, p<0.001). Likewise, the rIFN-a group had a lower risk of death compared to the HU group (HR = 0.33, p=0.01) and the PHL-O group (HR 0.3, p=0.001) independent of age. The HU group had a lower risk of PPVMF compared to PHL-O (HR 0.45, p=0.005) but no OS difference. Analysis of longitudinal bone marrow samples showed significantly less MF 2-3 fibrosis in rIFN-a compared to the HU and PHL-O groups (Figure 2). Time on treatment multivariable analysis showed that rIFN-a reduced PPVMF by 6% and all-cause mortality by 8% per year (HR = 0.94, p <0.001 and HR = 0.92, p<0.001 respectively), independent of age, thrombosis history, CV risk factors, or other treatments. On the other hand, HU was not associated with a risk reduction of either MF or mortality. The discontinuation rate of rIFN-a or HU due to toxicity was similar at 2.2 and 2.8 per 100 patient-years. Discussion: This is the largest single center study in PV using universal diagnostic criteria showing the MFS and OS advantage with rIFN-a over HU or PHL-O, and its similar rates of toxicity to HU. The evidence suggests that early cytoreductive treatment rather than PHL-O is advantageous. Treatment with PHL-O was associated with a higher risk of MF than either rIFN-a or HU. Conclusion: Our results support early use of rIFN-a as a safe, disease-modifying treatment of rigorously defined PV to delay and potentially prevent PPVMF, and prolong overall survival of PV pts. Disclosures Ritchie: Jazz pharmaceuticals: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Abbvie: Honoraria; Sierra Oncology: Honoraria; Incyte: Speakers Bureau; Novartis: Honoraria. Silver:PharmaEssentia: Speakers Bureau. OffLabel Disclosure: Interferon alfa has been used off label in the treatment of MPN for decades

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Validation of Minnesota Acute GVHD Risk Score and Identification of New Factors Associated with Initial Response to Steroids: Not All GVHD Is Created Equal

Blood ◽

10.1182/blood-2018-99-113085 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 67-67

Author(s):

Margaret L. MacMillan ◽

Shernan G. Holtan ◽

Armin Rashidi ◽

Todd E. DeFor ◽

Claudio G Brunstein ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Steroid Therapy ◽

Early Onset ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Risk Scores ◽

Increased Risk ◽

Better Than

Abstract Introduction: We recently reported on the Minnesota acute GVHD Risk Score that is based on the number of involved organs and severity of GVHD at onset. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. Patients with HR GVHD were 3 times less likely to respond to steroid therapy and had >2 fold increased risk of mortality and transplant-related mortality (TRM) than patients in the standard risk (SR) GVHD group. This GVHD Risk Score more accurately predicts response, survival and TRM than other published GVHD risk scores based upon clinical grading criteria (BBMT.2015,21:761). Methods: To validate this Risk Score, we examined a new cohort (2008-2016) of 355 patients (median age 49 years, range <1-75) at the University of Minnesota diagnosed with acute GVHD and treated with prednisone 60 mg/m2/d for 14 days, followed by an 8-week taper. Results: All patients had >6 months follow-up after steroid initiation (median 3.2 years). 79 (22%) patients had HR GVHD and 276 (78%) had SR GVHD. Demographics were similar in the two groups (Table). Overall response [complete response (CR)+partial response (PR)] was significantly higher in the 276 SR vs 79 HR GVHD patients at day 14 (71% vs 56%, p<0.01), day 28 (74% vs 59%, p=0.02) and day 56 (68% vs. 49%, p<0.01) after steroid initiation (Figure A). Day 28 CR/PR did not differ by initial GVHD grade being 64%, 77%, 65% and 50% for grade I, II, III and IV (p=0.07). HR GVHD was observed in 31% single UCBT recipients, 19% double UCBT recipients and 22% BMT/PBSCT recipients. Notably, Day 28 responses were significantly higher in UCB recipients than others (Figure B). In multiple regression analysis, the odds of day 28 CR/PR were lower in HR vs SR GVHD patients (OR 0.5, 95% CI 0.3-0.8) and in HLA matched URD donor vs other recipients (OR 0.5, 95% CI,0.3-1.1, p<0.01). OR of response was 2 fold higher in UCB (OR 2.2, 95% CI,1.3-3.7, p=0.01) vs. BM/PBSC recipients. Factors significantly associated with greater 2 year TRM included HR GVHD (HR 1.4, 95% CI,1.0-1.9, p=0.05), age ≥60 years (HR 1.7, 95% CI,1.1-2.8, p=0.02) and high risk HCT-comorbidity index (HCT-CI; HR 1.6, 95% CI,1.1-2.2, p=0.01). Similarly, mortality at 2 years was higher in HR GVHD (HR 1.7, 95% CI,1.2-2.4, p<0.01), high risk HCT-CI (HR 1.8, 95% CI,1.3-2.5, p<0.01), and recipients of URD grafts HR 1.9, 95% CI,1.1-3.1, p=0.01). Mortality was lower in early onset GVHD (HR 0.95, 95% CI,0.92-0.99, p=0.04). Two years after initiation of steroid therapy, 92 patients developed chronic GVHD for a cumulative incidence of 26% (95% CI 21-31%). No differences in the incidence of chronic GVHD were observed in those with SR and HR acute GVHD (28% vs 20%, p=0.54). Risks of chronic GVHD however were significantly lower in UCB recipients (HR 0.6, 95% CI,0.5-0.9, p=0.01) and in early onset GVHD (HR 0.95, 95% CI,0.92-0.98, p<0.01), but were higher in patients with high risk HCT-CI (HR 1.7, 95% CI,1.2-2.3, p<0.01). Conclusions: This analysis confirms that the Minnesota GVHD Risk Score is a valuable, immediately available bedside tool to define risk in patients with acute GVHD and predicts outcomes better than GVHD clinical grades. These results also demonstrate the importance of age, HCT-CI, graft source, and time to onset of GVHD on outcomes after GVHD therapy. Notably, UCB recipients have better responses to steroid therapy and lower subsequent risk for chronic GVHD than other donor sources. These data suggest that a tailored approach to upfront GVHD therapy based upon the Minnesota acute GVHD Risk Score and other risk factors should be considered in order to improve outcomes in patients with acute GVHD. Further studies are needed to explore why cord blood recipients with acute GVHD respond better than BM/PBSC recipients with a similar severity of GVHD. Disclosures MacMillan: Angiocrine: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy; Equillium: Consultancy. Holtan:Incyte: Consultancy. Brunstein:Gamidacell: Research Funding. Wagner:Magenta Therapeutics: Consultancy, Research Funding; Novartis: Research Funding. Blazar:Kadmon Corporation, LLC: Consultancy, Research Funding. Weisdorf:SL Behring: Consultancy; Equillium: Consultancy; FATE: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Consultancy.

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Survival after T-Cell Replete Haploidentical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor (MUD) Transplant for Lymphoid Malignancies

Blood ◽

10.1182/blood.v126.23.194.194 ◽

2015 ◽

Vol 126 (23) ◽

pp. 194-194 ◽

Cited By ~ 1

Author(s):

Alberto Mussetti ◽

Abraham Sebastian Kanate ◽

Mohamed A Kharfan-Dabaja ◽

Kwang Woo Ahn ◽

Alyssa DiGilio ◽

...

Keyword(s):

Mortality Risk ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Study Cohort ◽

Platelet Recovery ◽

Post Transplant ◽

Gvhd Prophylaxis ◽

Significant Difference ◽

Conditioning Regimens

Abstract Background: The use of haploidentical hematopoietic cell transplantation (HCT) using post- transplant cyclophosphamide (PT-Cy), calcineurin inhibitors (CNI) and mycophenolate as graft-versus-host disease (GVHD) prophylaxis is rapidly increasing in patients (pts) lacking suitable HLA-matched donors. Herein we compare outcomes of haploidentical HCT using this GVHD prophylaxis with 8/8 allele-level MUD HCT. Methods: Included are 917 adult (>18) lymphoma pts who underwent allogeneic HCT between 2008 and 2013. All pts received non-myeloablative or reduced-intensity conditioning regimens. The study cohort was divided into 3 groups; haploidentical (n=185), MUD without (w/o) antithymocyte globulin (ATG; n=491) and MUD with (w/) ATG (n=291). The primary end-point was overall survival (OS). Secondary endpoints included cumulative incidence (Cum-Inc) of acute GVHD, chronic GVHD, non-relapse mortality (NRM), relapse/progression (rel/prog) and progression-free survival (PFS). The study had an 83% power to detect an 11% difference in OS. Results: The baseline characteristics are shown in Table 1. Pts in the haploidentical group received conditioning with Flu/CY/2Gy TBI and PT-Cy + CNI and mycophenolate as GVHD prophylaxis, while the two MUD cohorts received fludarabine-based (+ an alkylator or 2GyTBI) conditioning and CNI-based GVHD prophylaxis. Graft source was bone marrow in 93% of the haploidentical pts and peripheral blood in 94% and 91% of MUD w/o ATG and MUD w/ ATG pts, respectively. The 28-day neutrophil recovery and platelet recovery were 94%, 97%, 97% (p=0.32) and 63%, 89%, 84% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups respectively. Cum-Inc of grade II-IV acute GVHD at day100 and chronic GVHD at 1 year was 27%, 40% and 49% (p=0.07) and 13%, 51% and 33% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups, respectively. On multivariate analysis (MVA) higher risk of chronic GVHD was seen in MUD w/o ATG (RR=5.85, 95%CI 3.96-8.64; p<0.0001) and MUD w/ ATG (RR=3.64, 95%CI 2.37-5.59; p<0.0001) groups relative to the haploidentical cohort. The 3 year NRM was 17%, 22% and 26% in the haploidentical, MUD w/o ATG and MUD w/ ATG groups (p=0.08), respectively. On MVA a trend towards higher NRM was noted in MUD w/ ATG cohort, RR 1.54 (95%CI 0.98 - 2.41, p=0.06), relative to the haploidentical group. Among the haploidentical, MUD w/o ATG and MUD w/ ATG cohorts the 3 year Cum-Inc of rel/prog was 36% vs. 28% vs. 36%, PFS was 47% vs. 49% vs. 38% and OS was 60%, 62% and 50% (Figure), respectively. MVA demonstrated no significant difference between the three groups in terms of rel/prog (p=0.27) and PFS (p=0.07). Compared to the haploidentical group, the two MUD groups did not have a significantly different mortality risk (inverse of OS; p>0.05), but compared to MUD w/ ATG, the MUD w/o ATG pts had a reduced mortality risk (RR=0.67; p=0.001). We tested for a transplant center effect on survival and found none. Conclusion: With lower-intensity conditioning regimens the early (up to 3 years) survival outcomes are comparable between conventional MUD transplants (w/ or w/o ATG) and haploidentical HCT with PT-Cy approach. Chronic GVHD was significantly lower with haploidentical HCT. Prospective, randomized confirmation of these findings is necessary before wide spread adoption of haploidentical HCT over MUD transplants in lymphomas.Table 1.Haploidentical N=185 (%)MUD w/o ATG N=491 (%)MUD w/ ATG N=241 (%)p-valueAge @ HCT, median (range)55 (18-75)55 (19-74)55 (20-73)0.13Male sex118 (64)301 (61)163 (68)0.25White race149 (81)469 (96)227 (94)<0.001KPS ≥ 90145 (78)311 (63)153 (63)<0.001HCT-CI≥355 (30)175 (36)88 (37)<0.001Histology NHL Hodgkin139 (75) 46 (25)386 (79) 105 (21)193 (80) 48 (20)<0.001Months from diagnosis to HCT, median (range)31 (<1-255)34 (<1-342)32 (4-460)0.19High LDH @ HCT16 (31)31 (33)11 (27)<0.001BM +ve @ HCT6 (12)5 (5)2 (5)0.35Extranodal disease @ HCT18 (35)20 (21)6 (15)0.11Prior lines of therapy, median (range)3 (1-7)3 (1-12)3 (1-8)0.41Remission @ HCT CR PR Refractory Untreated / missing72 (39) 99 (54) 10 (5) 4 (2)215 (44) 215 (44) 55 (11) 6 (1)100 (41) 96 (40) 40 (17) 5 (2)0.02Disease Risk Index Low Intermediate High45 (24) 126 (68) 13 (7)199 (41) 263 (49) 48 (10)75 (31) 129 (54) 37 (15)<0.001Median follow-up, months (range)36 (5-73)35 (4-74)35 (<1-75) Figure 1. Figure 1. Disclosures Armand: Infinity: Consultancy, Research Funding; Merck: Consultancy, Research Funding; BMS: Research Funding; Sequenta, Inc.: Research Funding. Smith:Celgene: Consultancy; Pharmacyclics: Consultancy. Sureda:Seattle Genetics Inc.: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.

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Incidence, Risk Factors and Outcomes of Sclerotic Chronic Graft-Versus-Host Disease (GVHD) Phenotype After Allogeneic Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v118.21.322.322 ◽

2011 ◽

Vol 118 (21) ◽

pp. 322-322

Author(s):

Yoshihiro Inamoto ◽

Barry Storer ◽

Effie W. Petersdorf ◽

Paul A. Carpenter ◽

Stephanie J. Lee ◽

...

Keyword(s):

Risk Factors ◽

Malignant Disease ◽

Acute Gvhd ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Factors Associated ◽

Increased Risk ◽

Unrelated Donors ◽

Recurrent Malignancy

Abstract Abstract 322 Background: A sclerotic GVHD phenotype represents one of the most severe late complications of allogeneic hematopoietic cell transplantation (HCT), sharing some clinical similarities with systemic sclerosis. The incidence and risk factors of sclerotic chronic GVHD and its association with major transplant outcomes are not well established. Patients and methods: We analyzed 986 consecutive patients who received systemic therapy for chronic GVHD after a first allogeneic HCT performed between 2000 – 2008 in Seattle for malignant and nonmalignant diseases. Chronic GVHD was diagnosed by the NIH consensus criteria. Sclerotic GVHD was defined when manifestations of cutaneous sclerosis, fasciitis or joint contracture were first documented in the medical record. Multivariate Cox regression analyses accounted for patient and donor age per decade, donor type, HLA matching, ABO matching, diagnosis and disease risk, stem cell source, patient gender, intensity of conditioning regimen, use of total body irradiation (TBI) or rabbit antithymocyte globulin in the conditioning regimen, and GVHD prophylaxis. Risk factors considered at the onset of chronic GVHD were prior acute GVHD, prior severe (stage 3 and 4) skin acute GVHD, eosinophilia, thrombocytopenia, progressive onset, extent of skin involvement, and bronchiolitis obliterans. Overall mortality (OM), nonrelapse mortality (NRM; malignant disease only) and recurrent malignancy (malignant disease only) were compared between patients with and without sclerotic features using time-dependent Cox models. Results: Of the 986 patients, median age was 47 (0–78) years, 776 (79%) were Caucasian, 950 (96%) had malignant diseases, 407 (41%) had HLA-matched related donors, 356 (36%) had HLA-matched unrelated donors, and 223 (23%) had HLA-mismatched related or unrelated donors. The median time from HCT to chronic GVHD was 5.3 (2.5–46) months; 73 patients (7%) presented with sclerotic features at initial diagnosis and 142 patients (14%) developed sclerosis after the onset of chronic GVHD. The cumulative incidence of sclerotic GVHD was 20% (95%CI, 18–23) at 36 months after onset of chronic GVHD, and median onset of sclerosis was 7.9 months after onset of chronic GVHD (Figure). In multivariate models (Table), factors associated with an increased risk of sclerotic GVHD were mobilized blood cell graft, female recipient, TBI >450cGy, and prior severe skin acute GVHD. Factors associated with a decreased risk of sclerotic GVHD were HLA-mismatched donors and ABO major mismatch. Risks of OM, NRM and recurrent malignancy in patients with sclerotic features did not differ statistically from patients without sclerotic features (hazard ratio (HR) 0.97, 95% CI 0.7–1.3, p=0.83; HR 0.94, 95% CI 0.6–1.4, p=0.78; HR 0.73, 95% CI 0.5–1.2, p=0.17, respectively). Conclusion: Sclerotic GVHD is an underestimated phenotype of chronic GVHD. Female predominance in sclerotic chronic GVHD is similar to that in systemic sclerosis. Risks of major transplant outcomes do not differ statistically between patients with and without sclerotic chronic GVHD phenotype. Mechanisms that account for the decreased risk of sclerosis associated with HLA and ABO mismatching and for the increased risk associated with prior severe skin acute GVHD warrant future investigation. Disclosures: No relevant conflicts of interest to declare.

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Unrelated Donor Bone Marrow Transplants in Children

Cell Transplantation ◽

10.1177/096368979400300508 ◽

1994 ◽

Vol 3 (5) ◽

pp. 413-420 ◽

Cited By ~ 12

Author(s):

Alfred Grovas ◽

Stephen A. Feig ◽

Sheryl O'rourke ◽

Leonard Valentino ◽

Fran Wiley ◽

...

Keyword(s):

Bone Marrow ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Marrow Transplant ◽

Myelogenous Leukemia ◽

Unrelated Donor ◽

Short Course ◽

Increased Risk ◽

Disease Free

Only a small proportion of children who might benefit from bone marrow transplant (BMT) have an HLA-identical sibling. To provide this potentially curative therapy to patients without a matched related donor, marrow transplants using less well matched related donors or unrelated donors (identified through computerized donor registries) have been performed. We report the outcome of 24 consecutive unrelated donor BMT's performed on children. Eligible diagnosis included acute leukemia (AL) (n = 15), chronic myelogenous leukemia (CML) (n = 4), myelodysplastic syndrome (MDS) (n = 3), and severe aplastic anemia (SAA) (n = 2). All donor/recipient pairs were sero-matched at 5 or 6 of the 6 HLA A, B, and DR antigens. Several different preparative regimens were used, but fractionated total body irradiation (TBI) was used in 20 patients. All recipients received graft-versus-host-disease (GVHD) prophylaxis with cyclosporine-A (CSA), four with short course methotrexate (MTX), 14 in combination with short course MTX and methylprednisolone (MPS), and five in combination with a mouse monoclonal antibody to CD5, coupled to the A-chain of ricin (Xomazyme-65). One patient received CSA and MPS alone after a T-cell depleted marrow transplant. Twenty of 23 evaluable recipients engrafted (87%). Two patients with CML never engrafted and had autologous marrow recovery, one patient with SAA died at 128 days without evidence of engraftment, and there was one early death at day + 9. Fourteen of 20 patients (70%) with stable donor-derived hematopoiesis developed significant acute GVHD ≥ grade II). Eleven of 15 engrafted patients who survived > 100 days after BMT developed chronic GVHD (73%). Thirteen patients survive, 10 disease-free; 2 yr actuarial survival and disease-free survival are 47% and 41%, respectively. Of the 19 engrafted patients with leukemia or MDS, only three have relapsed. The actuarial relapse risk at 2 yr is 24%. Unrelated donor transplants in children are associated with an increased risk of GVHD and nonengraftment compared to matched sibling transplants. Increased donor age is significantly associated with a greater risk of acute GVHD.

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Pre-transplant Marital status and Hematopoietic Cell Transplantation Outcomes

Current Oncology ◽

10.3747/co.27.6327 ◽

2020 ◽

Vol 27 (6) ◽

Author(s):

J. Tay ◽

S. Beattie ◽

C. Bredeson ◽

R. Brazauskas ◽

N. He ◽

...

Keyword(s):

Social Support ◽

Marital Status ◽

Cell Transplantation ◽

Acute Gvhd ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Multivariable Analysis ◽

Hematopoietic Cell ◽

Increased Risk ◽

The Impact

Background Evidence regarding the impact of pre-hematopoietic cell transplantation (HCT) marital status on post-HCT outcomes is conflicting. Methods We identified patients, ≥40-years within the Center for International Blood and Marrow Transplant Research registry who received a HCT between January 2008 and December 2015. Pre-HCT marital status was declared as either 1) Married/living with a partner, 2) Single/never married, 3) Separated/divorced, and 4) Widowed. We performed multivariable analysis to determine the association of marital stsatus with post-HCT outcomes. Results We identified 10,226 allogeneic and 5,714 autologous HCT patients with a median follow-up of 37 months (range 1-102) and 40 months (range 1-106) respectively. There was no association between marital status and OS in both allogeneic (p=0.58) and autologous (p=0.17) settings. However, marital status was associated with grade 2-4 acute GVHD (p<0.001) and chronic GVHD (p=0.04). There was an increased risk of grade 2-4 acute GVHD in separated patients compared with married patients [HR 1.13, 95%CI (1.03-1.24)], while single patients had a reduced risk of grade 2-4 acute GVHD [HR 0.87, 95%CI (0.77-0.98)]. The risk of chronic GVHD was lower in widowed patients [HR 0.82, 95%CI (0.67-0.99)] compared with married patients. Conclusions OS post-HCT is not influenced by marital status, but there are associations between marital status and grade 2-4 acute and chronic GVHD. Future research should consider measuring social support using validated scales, patient and caregiver reports of caregiver commitment, and assess health-related quality of life together with health-care utilization to better appreciate the impact of marital status and social support.

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SNP12 and SNP13 Variants of NOD2/CARD15 Gene of Donor and Recipient as Independent Risk Factors for Severe Intestinal and Pulmonary GVHD after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.3242.3242 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3242-3242

Author(s):

Alexandra Holowiecka-Goral ◽

Jerzy Wojnar ◽

Sebastian Giebel ◽

Elzbieta Grudziecka ◽

Malgorzata Oczko ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Hematopoietic Stem ◽

Increased Risk ◽

Card15 Gene ◽

The Impact ◽

Grade Iii

Abstract Background: Presence of any of single nucleotide polymorphism (SNPs) of the NOD2/CARD15 gene have been recently proven to correlate with higher rate of GvHD after allogeneic hematopoietic stem cell transplantation - alloHSCT (Holler E et al; Blood2006,107,4189). Mutated variants lead to impaired antibacterial response. As NOD2/CARD15 is expressed not only in monocytets/macrophages but also in both intestinal and bronchial epithelial cells these organs seem to be a major target for developing advanced GvHD. Patients and methods: The impact of each single donor (D) and recipient (R) SNPs (8,12,13) of NOD2/CARD15 gene on the incidence of acute GvHD (grade II-IV, grade III-IV, intestinal), chronic GvHD (overall, extensive, pulmonary), survival, and non-relapse mortality was evaluated in a setting of 72 patients treated with alloHSCT in single BMT center in Katowice between Jan 2000 and Jun 2005. Median patient age was 33 (11–52) years. In 70/72 cases hematological malignancies were indication for alloHSCT. Conditioning regimen was myeloablative in all cases, bone marrow was used as the only source of stem cells in 74% of patients. GVHD prophylaxis consisted of CsA, Mtx and, in case of URD-HSCT - antithymocyte globulin. Results: In univariate and multivariate analysis, including other potential risk factors, the presence of SNP12 in the recipient was associated with increased incidence of intestinal acute GVHD (75% vs. 29%; RR 4,37, p=0,03), overall chronic GVHD (100% vs. 50%, RR 4,72; p=0,003), extensive chronic GVHD (80% vs. 24%; RR 5,12; p=0,02), and pulmonary chronic GVHD (47% vs. 9%; RR 5,97; p=0,02). SNP13 in the recipient resulted in increased incidence of grade III–IV acute GVHD (45% vs. 12%; RR 4,66; p=0,01), intestinal acute GVHD (64% vs. 24%; RR 4,21, p=0,005), and extensive chronic GVHD (55% vs. 25%; RR 3,59; p=0,03). SNP13D in the donor contributed to increased risk of pulmonary chronic GVHD (36% vs. 8%; RR 6,58; p=0,01). In this single centre analysis we were not able to demonstrate the impact of NOD2/CARD15 SNPs on survival. Conclusion: The presence of particular mutations of NOD2/CARD15 in the recipient and/or the donor is associated with increased risk of severe acute and chronic GVHD. In particular, intestines and lungs appear to be target organs of these complications. Our findings may contribute to optimization of immunosuppressive and gastrointestinal decontamination regimens based on individual risk assessment for GVHD.

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A Phase II Study of Allogeneic Transplantation for Older Patients with AML in First Complete Remission Using a Reduced Intensity Conditioning Regimen: Results From CALGB 100103/BMT CTN 0502

Blood ◽

10.1182/blood.v120.21.230.230 ◽

2012 ◽

Vol 120 (21) ◽

pp. 230-230 ◽

Cited By ~ 9

Author(s):

Steven M. Devine ◽

Kouros Owzar ◽

William Blum ◽

Daniel DeAngelo ◽

Richard M. Stone ◽

...

Keyword(s):

Complete Remission ◽

Total Dose ◽

Research Funding ◽

Antithymocyte Globulin ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Marrow Transplant ◽

Reduced Intensity Conditioning ◽

First Complete Remission ◽

Reduced Intensity

Abstract Abstract 230 The prognosis for patients (pts) with acute myeloid leukemia (AML) who are aged 60 years or older at the time of initial diagnosis is poor. Even for pts achieving a first complete remission (CR1), prospects for long-term survival are poor due to the very high risk of relapse. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with conventional chemotherapy when performed in younger pts with AML in CR1. However, the toxicity of this approach in older pts is prohibitive. A reduced intensity conditioning (RIC) regimen may mitigate the risk of early toxicity and while early results in older AML pts have been encouraging and suggest disease free survival (DFS) rates above 30% at 3 yrs (Farag et al, Biol Blood Marrow Transplant 2011), most data are retrospective and pts have not been treated uniformly. We therefore sought to determine the effectiveness of a uniform RIC regimen given to older pts with AML in CR1 on a prospective multi-center phase II trial conducted by the Alliance (formerly Cancer and Leukemia Group B (CALGB)) and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The study, activated in 2004, was initially limited to recipients of a matched related donor (MRD) graft but was amended in 2006 to include matched unrelated donor grafts (URD). The primary endpoint of the study was 2-year DFS. We hypothesized that DFS at 2-years would exceed 20% and powered the study to detect a 2-year DFS probability of 35% for URD recipients. We focused the primary analysis on URD recipients since the majority of older pts require an URD graft. Eligible pts were from 60–74 years old inclusive, had AML in CR1 following induction chemotherapy, availability of a 6/6 MRD or 8/8 URD, and absence of significant end-organ damage prior to transplantation. Adverse events (AE) were initially recorded according to NCI-CTCAE v3.0, amended to v4.0 in 10/2010. Accrual was completed in 12/2011. 132 pts were registered at 21 centers and 123 transplanted (MRD (47%); URD (53%). All donor grafts were mobilized and collected following G-CSF (PBSC). The median age of pts was 65 (range 60–74) and 76 pts (62%) were male. At diagnosis, 67% had an intermediate risk karyotype, 20% adverse risk, <1% favorable, and in 11% data were missing. More than 90% achieved CR following standard “7+3” based induction. CR1 was achieved after 1 (59%) or 2 (41%) induction cycles. Consolidation therapy was administered for one (50%) or two (24%) cycles and 17% received no consolidation with data missing in 9%. All but the initial 8 MRD recipients (who received fludarabine and busulfan alone) were conditioned with the same regimen containing fludarabine (30mg/m2/day × 5), busulfan (6.4mg/kg IV total dose), and antithymocyte globulin (ATG; thymoglobulin) (7.5mg/kg total dose). Only one case of primary graft failure was reported. With a median follow-up of 3.3 yrs, the results in the 123 transplanted pts are depicted below: Event Cumulative incidence at 100 days* or 2yrs† 95% CI Acute GVHD 2-4 9.4%* 4.1–15% Acute GVHD 3-4 3.4%* 1.2–6.7% Chronic GVHD 26%† 17–34% Relapse 47%† 37–57% Treatment related mortality (TRM) 14%† 7.2–21% Event Probability at 2 yrs 95% CI DFS 39% 30–50% DFS URD only 38% 26–55% Overall survival (all pts) 46% 36–57% The rates of both acute and chronic GVHD as well as TRM were relatively low. There were 81 grade 3–5 non-hematologic AE recorded, including 7 grade 5 (4 infections, 1 each cardiac, pulmonary, and second malignancy). Relapse was the most common cause of death. In conclusion, the results of this first prospective US cooperative group trial conducted in a homogeneously treated group of older AML patients in CR1 demonstrate the feasibility and effectiveness of RIC allografting using MRD or URD PBSC grafts. DFS appears better following a RIC allograft compared to results achieved historically after conventional therapies, warranting prospective comparison in pts with contemporary cytogenetic and molecular disease characterization. Future research should also focus on preventing disease relapse after RIC allografting in this population. Disclosures: Devine: Sanofi: Honoraria, Research Funding. Off Label Use: Antithymocyte globulin for GVHD prophylaxis is included in the abstract. Vij:Millennium: Speakers Bureau. Shea:Otsuka: Research Funding.

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