ALBERT

Description: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curative treatment for myelodysplastic syndrome (MDS). Relapse, infections and graft-versus-host disease (GvHD) are the main causes of treatment failure. We compared the outcomes of patients receiving T cell depleted (TCD) grafts at Memorial Sloan-Kettering Cancer Center (MSKCC) with patients receiving unmodified grafts at MD Anderson Cancer Center (MDACC) for advanced MDS (RAEB-1 and 2). Adult patients transplanted between 2001 -2012 were included in this retrospective analysis. All recipients of TCD grafts (N=60) received myeloablative conditioning (MAC) and antithymocyte globulin (ATG) to prevent graft rejection. None of them received post-transplant GvHD prophylaxis. Of the 129 recipients of unmodified grafts, 87 received MAC and 42 reduced intensity conditioning (RIC); GvHD prophylaxis consisted of tacrolimus and mini-dose methotrexate in the majority of patients (N=113). ATG was given to all matched unrelated donor (MUD) recipients. Patients in the unmodified group had more therapy-related MDS (MDS-t), very poor risk cytogenetics by IPSS-R at diagnosis and bone marrow (BM) blast count 〉5% at transplant. Only the TCD group had mismatched donors (Table 1). Univariate analysis identified a lower incidence of grade II-IV acute GvHD in the TCD group with 100-day cumulative incidence (CI) of 13.3% vs. 34.1% in the unmodified group (p=0.031). There was no difference in grade III-IV acute GvHD with a 10% CI in both groups at day-100 (p=0.546). The incidence of chronic GvHD was lower in the TCD group with a CI at 3-yrs of 3.4% vs. 44.3% in the unmodified group (p 〈 0.001). The non-relapse mortality (NRM) in both groups was similar. CIs at day 100, 1yr, and 3 yrs in the TCD group were 8.3%, 20.2% and 32.7% vs. 12.4%, 22.5% and 28.1% in the unmodified group (p=0.628). Relapse was lower in the TCD group, with CI at 1 and 3 yrs of 8.5% and 15.5%, vs. 31.0% and 39.4% in the unmodified group (p=0.002). Since the unmodified recipients had worse disease characteristics, further analyses in patients with good/intermediate risk cytogenetic showed that the relapse incidence was similar between these subgroups, with 3-yr CIs of 7.9% in TCD vs. 18% in unmodified group (p=0.185). The most common causes of death in the TCD group were infections (32%) and relapse (28%), while in the unmodified group it was relapse (55%), GVHD (20%) and infections (13%). Considering the differences in disease characteristics between the groups, multivariate regression models were performed for relapse-free survival (RFS) and overall survival (OS) adjusting for MDS-t, high-risk cytogenetics at diagnosis and high blast count at HSCT. No significant differences were observed between the groups for RFS (HR=1.44, p=0.128) and OS (HR= 1.35, p=0.236) (Table 2). High-risk cytogenetics at diagnosis (very poor risk) was the only significant prognostic factor for RFS (HR=5.32, p

Description: Introduction The effect of CMV reactivation after allo-HCT on relapse and overall survival (OS) in patients with acute myeloid leukemia (AML) and myelodysplatic syndrome (MDS) is controversial (Green et al blood 2013, Elmaagacli et al Blood 2011, and Erard et al Hematologica 2006). Methods We retrospectively analyzed the effect of CMV reactivation on OS and cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) in AML and MDS patients older than 〉 18 years who had received allo-HCT between 2005-2011 and had not died within 30 days of receiving allo-HCT at MD Anderson Cancer Center. The effect of any CMV antigenemia on allo-HCT outcomes was evaluated by comparing any CMV antigenemia with no CMV antigenemia. Because of potential immunomodulatory effect of CMV infection, the effect of prolonged antigenemia (defined as CMV antigenemia with duration more than 12 days, the median duration of antigenemia for the cohort) on transplant outcomes was analyzed by comparing patients with prolonged antigenemia with patients with no CMV antigenemia or CMV antigenemia with ≤ 12 days. All patients underwent surveillance by pp65 antigenemia test. Preemtive therapy was initiated for 〉 3 pp65 Ag cells/million WBC's. Kaplan-Meier survival curves were used to estimate OS and the log-rank test was used to assess group differences. CIR and NRM were determined using the competing risks method; competing risk for CIR was death and for NRM was relapse. Group differences in CIR and NRM were assessed using Gray's test. Results Table 1 shows baseline characteristics. Comparing R+/D+, R-/D-, R-/D+, and R+/D- groups, the incidence of any CMV antigenemia after HCT was 48%, 16.7%, 13.5%, and 50.9%, respectively (p 0.15) and CIR (p 〉 0.61) in all cohort as well as AML and MDS subgroups. Comparing any antigenemia vs. no antigenemia, CIR at 3 years was 34.6% vs. 35.2% in all cohort, 36.7% vs. 36.6% in AML patients, and 29.5% vs. 30.0% in MDS patients, respectively. In patients with CMV antigenemia, duration of antigenemia ranged from 1 to 535 days (median 12 days). We then investigated the effect of prolonged CMV antigenemia on transplant outcomes. Patients with CMV antigenemia 〉 12 days compared with combined group of ≤ 12 days or no CMV antigenemia had a lower cumulative incidence of relapse and a higher NRM, resulting in a similar OS (Fig. 1). Such a difference was seen in AML but not in MDS subgroup. We then investigated the effect of duration of CMV antigenemia in patients with CMV reactivation. Comparing 1-12 days of antigenemia vs. more than 12 days of antigenemia, CIR at 3 years was 41.9% vs. 26.7% (p = 0.003) in all cohort, 45.8% vs. 26.4% (p = 0.001) in AML patients, and 32.1% vs. 27.4% (p = 0.68) in MDS patients, respectively. Conclusion Prolonged CMV antigenemia is associated with decreased relapse in patients with AML, but not in MDS. Lower relapse is offset by increased NRM resulting in no change in OS. In contrast with published data, lower rate of relapse was not found when any antigenemia was compared with no antigenemia. Disclosures: No relevant conflicts of interest to declare.

Description: In the present analyses, we sought to determine the impact of disease characteristics at diagnosis and at HSCT including pre-transplant MDS therapy and depth of response, stem cell source and intensity of conditioning regimen on disease outcomes after HSCT. Between 2000 and 2012, 291 MDS patients with a median age of 55 years (range, 18-71) were transplanted with a matched related donor (MRD, n=131), matched unrelated donor (MUD, n=114) or mismatched donors (MMD (n=46). The study cohort had high-risk features including 117 patients (40.2%) with therapy-related MDS (tx-MDS) and 78 (27.3%) with MK+. Histological subtype was RAEB-1 and -2 in 122 (41.9%) and CMML in 26 (8.9%) patients. Therapy prior to HSCT was chemotherapy only (chemo, n=81), hypomethylating agents only (HMA, n=100) and both (chemo+HMA, n=50). There were 74 untreated patients prior to HSCT. Of 74, 45 (60.8%) had tx-MDS, 48 (64.9%) had MRD and proceeded with HSCT with a median of 4.7 months. Among different therapy groups; histological subtype and disease status at HSCT, donor type and conditioning intensity were not different (Table 1). The median age among therapy groups were different with 54 vs. 57 and 59 observed in chemo, HMA and chemo+HMA (p

Description: Introduction Allogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients. Methods All 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively. The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant. Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT. Results Median follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively. Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22). The independent prognostic factors for PFS were a blast count of 〈 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45). Conclusion We conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. Figure 1. Progression free survival Figure 1. Progression free survival Disclosures Alousi: Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.

Description: Introduction: Despite the successes of treatment with tyrosine kinase inhibitors (TKIs) in patients with CML, allogeneic hematopoietic stem cell transplantation (ASCT) continues to be a potentially curative option for patients with advanced disease of who fail TKI therapy. Here we analyzed outcomes of patients with advanced CML (aCML) (beyond first chronic phase-CP1) who received an ASCT at our institution to identify factors associated with improved survival. Methods:207 consecutive patients withaCML treated at The University of Texas MD Anderson Cancer Center after year 2000 were included. The median age was 44 years (range 2-70 years), 135 (65%) were male, 77% had less than 5% bone marrow (BM) blasts, 129 (65%) had persistentPh-chromosome positive, and 176 patients (85%) were less than a major molecular response at transplant. Forty of 114 tested patients (35%) had resistant BCR-ABL mutations and 10 patients (8.7%) had T315I mutation at transplant. Conditioning regimen wasmyeloablative (MAC) in 140 patients (68%). Donors were matched related (MRD), matched unrelated (MUD),haploidentical (HAPLO), mismatched unrelated (MMUD), umbilical cord blood (UCB) and 1Ag mismatched related (MMRD) in 79 (38%), 75 (36%), 18 (9%), 17 (8%), 11 (5%) and 7 (3%) patients, respectively. The median time from diagnosis to transplant was 27 months (range 1-318 months) while the median follow-up duration was 20 months (range 1-194 months). Results:At 30 days post-transplant, 180 of 200 tested patients (90%) and 134 of 201 tested patients (67%) achieved a complete cytogenetic and at least a major molecular response, respectively. The response to transplant by day 30assessment correlated significantly with the disease status before transplant. A higher percentage of patients who experienced cytogenetic response before transplant experienced molecular response post-transplant (77%) compared with those who did not (61%; p=0.027). For the entire group, the 1-year cumulative incidence (CI) of acute GVHD (aGVHD) grade II-IV and grade III-IV were 41% and 15%, respectively; 5-year CI of extensive chronic GVHD (cGVHD) was 31%.Haploidentical transplant patients had lesscGVHD compared with HLA matched donor transplants (14% vs. 32% for HLA matched transplants). The CI of non-relapse mortality at 100 days and 1 year was 14% and 30%, respectively. Sixty-five patients (31%) had molecular relapse after transplant, which correlated with the degree of disease control before transplant. The CI of cytogenetic and molecular relapse at 5 years was 22% and 31%, respectively. Overall the 5-year survival (OS), progression free survival (PFS) and GVHD-free, relapse-free survival (GRFS)was49%, 34%, and 22%, respectively. Adjusting for all significant measures, percentage of BM blasts before transplant and donor type were significantly associated with PFS and GRFS (Table1, Figure 1).Haplodenticaltransplant patients had longer PFS and GRFS compared with other donor types including matched related or unrelated donor (5-year GRFS for HAPLO, MRD, MUD, MMUD, UCB and MMRD were 53%, 19%, 23%, 29%, 9%, and 0%, respectively; p=0.033) (Table 1, Figure 1). Cytogenetic and molecular response before transplant as well as year of transplant did not predict survival after transplant. Conclusions: ASCT is curative for a proportion of patients withaCML. PFS and GRFS are favorably influenced by percentage of BM blasts and donor type, withhaploidentical donor having at least as good outcomes as HLA matched donors, while molecular and cytogenetic response before transplant do not appear to correlate with survival post-transplant. Table 1 Multivariable analysis for PFS and GRFS Table 1. Multivariable analysis for PFS and GRFS Figure 1 PFS and GRFS based on percentage of BM blasts before transplant and donor types Figure 1. PFS and GRFS based on percentage of BM blasts before transplant and donor types Disclosures Cortes: Arog: Research Funding; Teva: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Research Funding; Ambit: Research Funding. Champlin:Intrexon: Equity Ownership, Patents & Royalties; Ziopharm Oncology: Equity Ownership, Patents & Royalties. Ciurea:Spectrum Pharmaceuticals: Other: Advisory Board; Cyto-Sen Therapeutics: Equity Ownership.

Description: Introduction Outcomes after allogeneic stem cell transplant (AHSCT) are influenced by both disease and patient related factors. We hypothesized that combining hematopoietic stem cell transplant comorbidity-age index (HCT-CI/Age) and the refined disease risk index (DRI-R) would better predict survival post-transplant and developed a hematopoietic cell Transplant-composite risk (HCT-CR) model, which we tested in a group of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated at MD Anderson Cancer Center (MDACC). Methods The study included consecutively treated patients, 18 years of age or older, with AML and MDS who received first AHSCT at MDACC between 2005-2016. Donors were HLA-matched related (MRD), HLA-matched unrelated (MUD), 9/10 MUD (MMUD), haploidentical (HAPLO) and 9/10 MRD (MMRD). To develop this model, patients were assigned into 4 groups: 1. Patients with low/intermediate DRI-R and HCT-CI/Age 3 (intermediate-risk); 3. Patients with high/very high DRI-R and HCT-CI/Age 3 (very high-risk). Primary endpoint was 5-year overall survival (OS); other outcomes assess were progression-free survival (PFS), non-relapse mortality (NRM) and relapse rate. The stability of the HCT-CR model was tested by bootstrap resampling. The discrimination power of the HCT-CR model on OS was compared with that of the DRI-R, HCT-CI/Age and cytogenetic risk model by the Harrell C-concordance index. Results The analysis included 942 patients (492 male and 450 female) with a median age of 53 years (range 18-65 years). Cytogenetic data at diagnosis was available in 928 (98.5%) patients and was favorable, intermediate and adverse cytogenetic risk in 63 (7%), 523 (56%) and 342 (37%), respectively. Fifty-five (6%), 399 (43%), 392 (42%) and 82 (9%) patients had low, intermediate, high and very high DRI-R, respectively. The HCT-CI/Age was available in 922 (98%) patients with the median score of 3 (range 0-18). Donor types included MRD (n=377), MUD (n=416), MMUD (n=68), HAPLO (n=73) and MMRD (N=8). Using the HCT-CR model, patients were stratified into 4 risk groups: low (N=272), intermediate (N=168), high (N=284) and very high-risk (N=184), with significantly different survival. The 5-year OS rates for patients in low, intermediate, high and very high-risk group were 57%, 48%, 34%, and 26%, respectively (P

Description: MDS is a heterogeneous group of hematopoietic stem cell disorders. Various prognostic models have been established to categorize patients with MDS including the International Prognostic Scoring System (IPSS), the Revised-IPSS (r-IPSS) and MDACC Scoring System. In this analysis, we compared those three classification schemas for their outcome predictability after HSCT. We analyzed 291 MDS patients with a median age of 55 (interquartile range (IQR) 47-60.7 years) who underwent HSCT between January 2001 and December 2011. Histology by WHO classification included RA/RARS 48 (16.5%), RCMD 28 (9.6%), RAEB-1 59 (20.2%), RAEB-2 63 (21.7%), MDS unclassified 67 (23%), and CMML 26 (9%). Of 291, 117 patients (40.2%) had therapy related MDS (t-MDS). Conditioning regimen was myeloablative in 201 patients (69.1%) and reduced intensity in 90 patients (30.9%). Donors were matched related (MRD), matched unrelated (MUD), mismatched (MMD) in 131 (45%), 114 (39.2%) and 46 (15.8%) patients respectively. Risk categorization was performed by IPSS, r-IPSS and MDACC scoring systems at the time of diagnosis. IPSS, r-IPSS and MDACC scoring systems could be assessed in 239 (82.1%), 241 (82.8%) and 231 (79.4%) patients respectively. The median follow up time of 109 survivors was 45 months. The median time from diagnosis to HSCT was 7.3 months (IQR 4.6-12.4 months). Three-year overall survival (OS) was 38.1% (95%CI 32.3-43.9) with 3-year event free survival (EFS) of 34.2% (95%CI 28.4-40). Cumulative relapse incidence (RI) at 3-year was 28.8% (95%CI 23.3-34.5). Cumulative incidence of treatment related mortality (TRM) at 3 year post-transplant was 27.9% (95%CI 22.6-33.6). In univariate analysis, IPSS and r-IPSS were able to differentiate 2 risk groups for OS and EFS. High risk group per IPSS and very high risk group per r-IPSS had lower OS with hazard ratio (HR) of 2.4 to 3.1, lower EFS with HR of 2.2 to 2.7. While IPSS could not predict RI, very high risk group by r-IPSS had higher RI with HR of 3.6 compared with lower risk groups. Both IPSS and r-IPSS did not identify different risk groups for TRM. On the other hand, MDACC scoring system was able to identify 4 different risk groups for EFS and OS in univariate analysis. Three-year OS was 68%, 46.1%, 30.3% and 11.4% for patients with MDACC risk score of 0-4, 5-6, 7-8 and ≥9 respectively (p

Description: Cardiac involvement in light chain amyloidosis (AL) predicts poor prognosis and is associated with higher treatment related mortality and morbidity during autologous stem cell transplantation (ASCT). We studied the outcomes of AL patients with cardiac involvement undergoing ASCT at our center between January 2002 and December 2012. Out of a total of 264 AL patients, 53 patients had cardiac involvement according to the International Consensus Criteria (Gertz M et al. AJH 2005) and 27 underwent ASCT. Cardiac staging was assessed using the Revised Prognostic Staging System for Light Chain Amyloidosis (Kumar S et al, JCO 2012). Hematologic and cardiac responses were evaluated before and at 1 year after ASCT using the guidelines established by the 10th International Symposium on Amyloid and Amyloidosis (Gertz M et al. AJH 2005). The median age of the patients was 53 years (range 36-74) with a median duration from diagnosis to ASCT of 6 months (range 3-95). The estimated median follow up for the entire cohort was 41 months (range 6-173). Twenty-four patients (89%) had an additional organ involvement, besides heart. Cardiac stage ≥3 was seen in 14 patients. The median troponin-T, Troponin-I, BNP and NT-proBNP levels and free light chain difference (FCL-diff) were 0.054 ng/ml, 0.05 ng/ml, 376 pg/ml, 1888 pg/ml, and 116.4 mg/l respectively (table1). Twenty-four patients (89%) received induction chemotherapy and 22 of those (81%) received novel chemotherapy agents. Eighteen patients (66.6%) achieved at least PR prior to ASCT. Four patients (14.8%) received reduced doses melphalan conditioning (140-180 mg/m2). One-year transplant related mortality (TRM) was 3.7% (1 patient died at day 11 post-transplant due to cardiac event). At 1-year post ASCT, overall HR was seen in 24 patients (89%) (CR=26% and PR=63%) while 3 patients (11%) had cardiac responses. At the time of last follow up, 17 patients (63%) were alive. The median overall survival (OS) from diagnosis and from ASCT was 58 months (95% CI; 46-69) and 46 months (95% CI; 36-55) respectively (figure1). The median progression free survival (PFS) was 25 months (95% CI; 6-44). Cumulative incidence of hematologic relapse at 3 year was 38.5% (95%CI 23.7-62.5). Cardiac progression at last follow up was seen in 1 patient (3.7%). Negative factors affecting OS included lack of induction therapy prior to ASCT and NT-proBNP more than 5000 pg/ml. We conclude that ASCT is well tolerated in patients with high-risk cardiac amyloidosis and the incorporation of induction therapy can improve overall outcomes of these patients.Figure1.Overall SurvivalFigure1. Overall SurvivalTable1Patient CharacteristicsBaseline characteristicsTotal (N=27)Interquartile rangeMedian age (year)5336-71Gender: male (%)20 (74.1)Median time from diagnosis to transplant, (month)63-95Receive induction chemotherapy (%)24 (88.9)Receive novel induction chemotherapy (%)22 (81.5)Light chain type (%)-Kappa-Lambda.6 (22.2) 21 (77.8)Other organ involvement (%)24 (88.9)History of cardiac complications prior ASCT (%)17 (63)History of cardiac complications after ASCT (%)20 (74.1)ICU admission prior ASCT (%)3 (11.1)Cardiac event prior ASCT (%)17 (62.9%)Median FLC-diff (mg/l) (N=15)116.415-1168Median EF (%) (N=19)6030-82Median IVS (mm.) (N=14)1.350.7-2.1Median Troponin-T (ng/ml) (N=20)0.0190.01-0.22Median Troponin-I (ng/ml) (N=19)0.060.03-9.09Median BNP (pg/ml) (N=23)37615.2-1782Median NT-proBNP (pg/ml) (N=12)1888.519-9911Median serum calcium (mg/dl)9.27-11Median serum albumin (g/dl)3.92.4Median Creatinine (mg/dl)1.01-9Median B2 microglobulin (mg/l)3.151-15Median 24-hr urine protein (mg)574120-36006Median serum M protein (g/dl)0.50-4Median LDH (IU/l)377146-770Median BM plasma cell (%)110-58Cardiac stage at diagnosis.Stage 11Stage 25Stage 36Stage 48Cardiac stage at transplant.Stage 13Stage 25Stage 34Stage 46 Disclosures: No relevant conflicts of interest to declare.

Description: Introduction An HLA-matched unrelated donor (MUD) has been accepted as the next best option for patients who do not have a matched-related donor (MRD) available. However, identification of a MUD may be challenging due to donor availability for some populations. In addition, the MUD search and procurement of stem cell product usually takes much longer than that of a related donor, many patients may develop progressive disease or become medically unfit while waiting for a MUD transplant, which might have a negative impact on overall survival. Therefore, in this study we hypothesized that certain groups of patients may not benefit from performing a MUD search and sought to evaluate availability of a MUD donor, ability to proceed to transplant with a MUD, as well as transplant outcomes for all patients who had a MUD search started at our institution. Methods All consecutive patients with a diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who had a MUD search performed between 2013 and 2015 were included. All patients had high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1 performed by DNA sequencing and had unrelated donor search by the NMDP. According to standard operating procedures, a MUD search was initiated when no MRD was available, or as soon as HLA typing was completed. If no 10/10 MUD was available, the choice between a 9/10 MUD, haploidentical or umbilical cord blood (UCB) was based on the treating physician's decision. Results The analysis included 242 patients with a median age of 58 years (range 9-80 years), 123 patients (51%) were male, 182 patients (75%) were Caucasian and 190 (79%) had common haplotypes. One hundred thirteen patients (47%), 35 (14%), 43 (18%) and 49 (20%) were in complete remission, primary induction failure (PIF), relapse/refractory and newly diagnosed, respectively. One hundred sixty (66%) patients had a 10/10 MUD identified. The majority of Caucasians (85%) had common haplotypes compared with only 58% of patients with other races (P

Description: Introduction CK AML patients have high relapse rate and poor outcomes when treated with conventional chemotherapy. Allogeneic hematopoietic stem cell transplantation (AHSCT) may cure this disease; however, relapse rate remains a major limitation and survival is one of the worst amongst AML patients. Here we aimed to identify prognostic factors associated with survival in patients with AML and CK using combined data from the EBMT and MDACC. Methods A total 1,342 consecutively transplanted patients with CK (〉3 cytogenetic abnormalities) AML reported to EBMT (N=1,118) and at MDACC (N=224) between 01/2000-12/2015 were included.The median age was 52 years (range 18-76 years), 335 patients (25%) were older than 60 years. Seven hundred and twenty-nine patients (54.3%) were male, 239 patients (17.8%) had secondary AML. Disease status before transplant was CR1, CR2 and activediseasein 877 (65.3%), 77 (5.7%) and 388 (29%), respectively. Donors were matched related (MRD), matched unrelated (MUD) and mismatched unrelated (MMUD) in 749 (55.8%), 513 (38.2%) and 80 (6%), respectively. Conditioning regimens were various, mostly eitherbusulfan-based (53.7%) or TBI-based (26.7%). Seven hundred and thirty-nine patients (55%) and 603 patients (45%) receivedmyeloablativeconditioning (MAC) and reduced intensity conditioning (RIC), respectively. The main stem cell source was peripheral blood (81%). In vivo T-cell depleted (TCD) methods were used in 665 patients (50%). Median time from diagnosis to transplant was 5.1 months (range 2-387 months) while the median follow-up duration was 35.5 months (range 8-174 months). Results Engraftment occurred in 96.3%, 69.7% and 30.3% had full and mixed donorchimerism, respectively. At 2 year post-transplant, the cumulative incidence (CI) of acute GVHD grade II-IV and grade III-IV was 26.3% and 8.4%, respectively, whereas CI of chronic GVHD was 30.9% with extensive chronic GVHD 17.8%. Leukemia free survival (LFS), overall survival (OS), CI of relapse, non-relapse mortality (NRM) at 2 years for the whole group was 31.3%, 36.8%, 51.1% and 17.6%, respectively, while 2-year GVHD-free, relapse-free survival (GRFS) was 19.8%. LFS, OS, GRFS, CI of relapse and NRM at 2 years for patients transplanted in CR1 was 38.4%, 44.5%, 23.8%, 46% and 15.7%, respectively. For patients with active disease these outcomes were 14.6%, 18.5%, 9.6%, 63.5% and 21.9%, respectively (Figure A, B). Patients ages 40-60 years transplanted in CR1 with MAC demonstrated lower relapse (40.2% vs. 51% with RIC, p=0.005), offset by a higher NRM (18.2% vs 9.8% RIC, p=0.037), associated with higher incidence of acute GVHD, and a non-significant difference in LFS (Figure C, D). In multivariable analysis (MVA) for the entire group, advanced age, transplantation in active disease, secondary AML and presence of deletion or monosomy 5 or 7 predicted poor LFS and OS. All of these factors as well as year of transplant (before 2010) also predicted poor GRFS, while conditioning intensity (MAC vs RIC) and donor type did not influence survival outcomes. Prognostic factors for relapse were age, secondary AML, active disease at transplant and presence of deletion or monosomy 5, while prognostic factors for NRM were older age, active disease, use of a mismatched unrelated donor and deletion or monosomy 7. Conclusions In this largest analysis of complex karyotypes AML patients, relapse remains the most common cause of treatment failure with 45% for patients in CR1 and 63.5% for patients not in remission relapsing after transplant. The only modifiable factorsat this time are performing transplantation in CR1 as soon as the donor is available. Control of GVHD might allow younger patients receiving MAC to have a lower NRM and improved LFS. Novel approaches are needed to decrease relapse rate and improve survival in these patients. Table Multivariable analysis for patients with CK AML. Table. Multivariable analysis for patients with CK AML. Figure A. CI of relapse for all patients and patients in CR; B. LFS for all patients and patients in CR; C. CI of relapse for patients age 40-60 years in CR with MAC, RIC; D. LFS for patients age 40-60 years in CR with MAC, RIC. Figure. A. CI of relapse for all patients and patients in CR; B. LFS for all patients and patients in CR; C. CI of relapse for patients age 40-60 years in CR with MAC, RIC; D. LFS for patients age 40-60 years in CR with MAC, RIC. Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.