Nonmyeloablative Second Transplants are Associated with Lower Nonrelapse Mortality and Superior Survival Than Myeloablative Second Transplants

Allogeneic hematopoietic stem cell transplantation (SCT) for patients who have previously undergone allogeneic or autologous SCT is potentially curative, but dangerous. To identify patient, disease, and treatment characteristics associated with outcome, we analyzed prognostic factors in 98 consecutive patients who underwent second transplants using allogeneic donors at the Cleveland Clinic between May 1987 and October 2008. Inclusion criteria included age ≥18 years, first SCT either autologous or allogeneic, and second SCT allogeneic. Patients whose second transplant was myeloablative (MA) had shorter survival (median 3.2 versus 14.7 months, P < .001) than patients whose second transplant was nonmyeloablative (NMA). In multivariable analysis, MA second transplant was associated with a higher risk of NRM (hazard ratio [HR] 2.01, P = 0.022) and death (HR 2.13, P = 0.002). Improved survival after NMA second transplant occurred primarily in patients without acute leukemia and when the first transplant was autologous. Among 17 patients transplanted within 3 months of first transplant, mortality was 100% and median survival was 2.3 months. MA transplantation within 3 months of prior SCT carries an unacceptably high rate of NRM. NMA second transplants were associated with substantially less NRM and despite a higher incidence of relapse, significantly improved survival compared to MA second transplants

Risk Factors for 30-Day Hospital Readmission following Myeloablative Allogeneic Hematopoietic Cell Transplantation (allo-HCT)

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all-cause mortality (hazard ratio [HR]Adj = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation

Cigarette Smoking Is Associated with Increased Rates of Fungal Infection and Increased Mortality After Allogeneic Transplantation

Abstract Abstract 2321 Introduction: Prior reports on the effect of smoking on outcomes of stem cell transplantation (SCT) have demonstrated an increased mortality for smokers but have not examined the incidence of fungal infection1-2. Tobacco cigarettes contain aspergillus spores that could serve as a source of fungal infection in immunocompromised patients after allogeneic SCT3. To determine the impact of smoking on transplant outcomes, we retrospectively analyzed data from patients undergoing allogeneic SCT at the Cleveland Clinic and compared the survival and incidence of fungal infection in patients who have smoked cigarettes with those who have never smoked. Methods: We identified 237 consecutive patients using the following inclusion criteria: age ≥18, and myeloablative allogeneic SCT for hematologic malignancy between 2004 and 2009. Survival was estimated using the Kaplan-Meier method and compared according to prospectively-collected smoking history. Smokers were more likely than nonsmokers to be male (59.0% vs. 45.5%, P = 0.046), caucasian (92.8% vs. 84.4%, P= 0.06) and have an unrelated donor (63.9% vs. 48.1%, P = 0.02) but were similar in terms of median age (45 vs. 46, P = 0.85) and hematopoietic stem cell transplant comorbidity index (36.1% low, 27.7% intermediate, 36.1% high vs. 39.0%, 30.5%, 30.5%, P = 0.68). In addition, we analyzed the incidence of fungal infection in 145 consecutive patients with a diagnosis of acute myeloid leukemia (AML) who underwent allogeneic SCT between 1994 and 2009. We categorized the type of fungal infection as possible, probable or proven using the Revised Infectious Diseases Society of America (IDSA) guidelines. Results: 154 of 237 (65.0%) patients who underwent allogeneic transplant had never smoked and 83 (35%) had a history of at least some cigarette smoking. 4 year survival was 42.3% for nonsmokers and 26.4% for smokers (P = 0.004). Multivariable analysis demonstrated a hazard ratio of 1.56 for overall mortality after allogeneic transplantation for smokers (95% confidence interval 1.10 – 2.22, P = 0.013). A Kaplan-Meir survival curve for smokers and nonsmokers is shown below. Patients with AML who had a history of cigarette smoking had a higher incidence of proven or probable fungal infection after allogeneic SCT than nonsmokers (16.3 % vs. 2.9%, P < 0.001). Conclusion: Cigarette smoking is independently associated with increased mortality after allogeneic SCT. Although the effects of cigarette smoking are likely multifactorial, a significantly higher incidence of fungal infections may contribute to the poorer outcomes of smokers after transplantation. References: 1. Marks, D, et al. The Effect of Smoking on Allogeneic Transplant Outcomes. BBMT. 2009;15(10), 1277–1287. 2. Ehlers, SL et al. al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. BMT, May 2010. 3. Verweij, PE, et al: Fungal contamination of tobacco and marijuana. JAMA. 2000;284(22), 2875. Disclosures: No relevant conflicts of interest to declare

Impact of Day 28 Absolute Lymphocyte Count On Outcome of Hematopoietic Cell Transplant (HCT) in CR1 for Adult Patients with Acute Lymphoblastic Leukemia

Abstract Abstract 1472 Introduction: Despite significant advances in survival rates for pediatric Acute Lymphoblastic Leukemia (ALL) patients (pts), long-term survival rates for adults with ALL have remained below 40%. An absolute lymphocyte count (ALC) < 350/μL at Day 28 of induction therapy is predictive of poor outcome [event-free survival (EFS) and overall survival (OS)] in adults with newly diagnosed ALL. It is unknown, however, whether ALC at Day 28 is also predictive of outcome in those patients who undergo allogeneic HCT in CR1. We hypothesized that the prognostic impact of ALC at Day 28 might be nullified by HCT in CR1 due to the graft versus leukemia effect. Methods: We conducted a retrospective chart review of 90 adult pts (≥ 18 yrs of age) with de novo ALL who underwent HCT while in CR1 during the years 1998–2011 at the Cleveland Clinic and Stanford, 66 of whom were evaluable for data analysis. Institutional review board approval was obtained at each institution. Prior studies identified an ALC of 350/ μL at Day 28 of induction therapy as a cut-off predictive of outcome. Therefore, we evaluated this number as well as other cut-offs. Cytogenetic (CG) risk was ascribed by CALGB criteria. We also evaluated the impact of gender, age at diagnosis, CG, and WBC at diagnosis. The Kaplan-Meier method was used to summarize OS and EFS, which were measured from HCT to death and the first of relapse/death, respectively. The log-rank test was used for univariable analysis of categorical factors and the Cox proportional hazards model, stratified by institution, was used for multivariable analysis and univariable analysis of measured factors. Patient characteristics: Median age: 38 yrs (range 19–66); Gender: 58% (38) male; CG risk: 57 (86%) poor, 5 (8%) miscellaneous, 4 (6%) normal; 64 (97%) B-cell lineage; median WBC at diagnosis 18.1 K/μL (range 0.9–432); median Day 28 ALC 440/μL (range 0–2450). The majority of pts (50, 76%) received a vincristine/prednisone/anthracycline-based induction regimen, with the remainder receiving a high-dose cytarabine based regimen. The median interval between the start of induction and CR was 28 days and the median interval from CR to HCT was 3.2 months (0.2–10.8). Results: Median EFS and OS have not been reached; 1-year EFS is estimated to be 57% ± 6%, and 2-year OS 57% ± 7%. In univariable analyses age > 50 (EFS) and WBC at diagnosis ≥ 40 K/μL (EFS and OS) were associated with worse outcomes (all p ≤ 0.04). A Day 28 ALC < 250/μL (but not < 350/μL) was also associated with decreased EFS [HR 2.27 (1.08–4.79), p=0.03] (Figure 1) with a trend towards worse OS [HR 1.89 (0.89–4.04), p=0.10]. WBC and Day 28 ALC remained statistically significant prognostic factors for RFS on multivariable analysis; HRs 2.89 (1.38–6.05), p=0.005 and 2.25 (1.06–4.78), p=0.04, respectively. Conclusion: ALC at Day 28 remains prognostic for outcome in newly diagnosed ALL pts undergoing HCT in CR1. Further characterization of the lymphocytes in pts with high ALCs and their potential role in preventing relapse is needed. Disclosures: No relevant conflicts of interest to declare

Prognostic Factors for Post-Transplant Outcomes in Patients with Myelodysplastic Syndromes (MDS)

Abstract Abstract 2015 Allogeneic hematopoietic stem cell transplantation (AlloSCT) remains the only curative option for MDS. Several retrospective studies evaluated the impact of various prognostic factors (i.e. cytogenetic risk group, WHO classification, ferritin level etc.) on post-transplant outcomes of pts with MDS, however comprehensive analyses including a cytogenetic abnormalities detected by SNP array (SNP-A) karyotyping method have not been performed. We have analyzed prognostic factors of post-AlloSCT outcomes among 74 pts with MDS (2000–2010) including the predictive value of SNP-A abnormalities. Cox proportional hazards analysis was used to identify univariable prognostic factors for acute GVHD (aGVHD), chronic GVHD (cGVHD), disease relapse, relapse free (RFS) and overall survival (OS). Multivariable prognostic factors were identified by stepwise Cox proportional hazards analysis. The median time from MDS diagnosis to transplant for all pts was 6 mos (range, 0.2– 141 mos). The median age at transplant was 51 yrs; 32% of the pts had a hematopoietic cell transplant co-morbidity index (HCT-CI) score ≥ 3; 69% had ≥1 prior chemotherapies; and only 30% were in remission prior to their transplant. 27 pts (37%) had RAEB-2, 11 (15%) had RAEB-1, and 9 (12%) had treatment-related MDS. 42 pts (58%) belonged to an intermediate-2 or higher IPSS risk category. 23 pts (31%) had adverse karyotype (complex or monosomy 7) detected by metaphase cytogenetics (MC). SNP abnormalities were identified in 58% of patients; 79% of all patients with SNP abnormalities had lesions not previously detected by traditional cytogenetic techniques. Median pre-transplant ferritin level was 1127 (range, 9–5201). 73% of the pts received myeloablative conditioning. In 61% of cases stem cells were harvested from the bone marrow. Matched related donors accounted for half of the cases. Twelve pts (16%) died within 100 days of transplant and 39 pts (53%) within the median follow up of 36 mos (range, 5–114). MDS relapse occurred in 22 pts (30%). The rates of grade II-IV aGVHD and extensive cGVHD were 49% and 24% respectively. Disease relapse was the most common cause of death (31%) followed by aGVHD (18%) and cGVHD (13%). In univariate analysis, aGVHD was associated with myeloablative (p<0.01) and non-TBI (p=0.01) containing regimens. Disease relapse was associated with increased number of prior chemotherapy regimens (p=0.04), whereas the OS was associated with higher level of pre-transplant ferritin level (p=0.01). In multivariable analysis, only high pre-transplant ferritin level predicted for worse OS (p=0.01) and only myeloablative conditioning predicted aGVHD (p=0.01). When the group with complex cytoegenetics or ≥3 SNP abnormalities was compared with the rest of the patients, relapse occurred more frequently and RFS and OS was reduced, however the high risk group was too small to detect a statistically significant difference. Our data demonstrate elevated pre-transplant ferritin level to be the only independent predictor for inferior OS in pts with MDS undergoing AlloSCT. The prognostic role of SNP-A abnormalities in addition to chromosomal lesions detected by MC in post-transplant setting needs to be validated in a larger group of MDS pts. Disclosures: Sekeres: Celgene: Consultancy, Honoraria, Speakers Bureau

Impact of Day 28 Absolute Lymphocyte Count on Outcome of Adult Patients with Acute Myeloid Leukemia

Abstract Introduction: Lymphocyte recovery after induction chemotherapy (IC) predicts outcome in adult patients (pts) with acute myeloid leukemia (AML) (Behl et al. Leukemia 2006; 20: 29-34). However, it is unknown whether absolute lymphocyte count (ALC) recovery after IC predicts outcome in those pts who are then treated with allogeneic hematopoietic stem cell transplant (AHCT) in first complete remission (CR1). We hypothesized that the prognostic impact of ALC might be nullified by AHCT in CR1 due to the abrogation of normal immunologic recovery. In this study, our aims were to (1) evaluate the impact of Day 28 ALC on all AML pts receiving IC and (2) to specifically, evaluate the impact of Day 28 ALC on the subset of AML pts proceeding to AHCT in CR1. Methods: A retrospective chart review of 180 adult AML pts (≥ 18 years of age) who were treated with IC during the years 2001- 2012 at the Cleveland Clinic was performed. Institutional Review Board approval was obtained. Pts with acute promyelocytic leukemia were excluded . Ninety-four of the 180 pts received AHCT in CR1. A total of 141 AML pts receiving IC and a total of 66 pts receiving IC and then receiving AHCT in CR1 were eligible for data analysis because Day 28 ALC was missing in the remainder of the pts. Prior studies in AML identified an ALC of < 500/ µL at Day 28 of IC as predictive of overall survival. We stratified Day 28 ALC into the following categories: (a)< 250/ µL (b) < 350/ µL (c) < 500/ µL and (d) < 500/ µL for Max ALC [Max ALC was defined as the maximum ALC value between days 26 and 30 after the initiation of IC]. Other variables collected included age at diagnosis, WBC at diagnosis, and cytogenetic (CG) risk. CG risk was ascribed by CALBG criteria. The Kaplan-Meier method was used to summarize overall survival (OS) and relapse-free survival (RFS), which were measured for all pts from the time of diagnosis. The log-rank test was used for univariate analysis of categorical factors and the Cox proportional hazards model was used for measured factors and multivariate analysis. We performed two separate analyses : one for all AML pts (n=141); and a second analysis only focusing on those receiving AHCT in CR1 (n=66). Results: Pt characteristics for the entire AML cohort: The median age was 58.0 years (20.0-80.0); 46.1% female. The median WBC at diagnosis was 11.6 K / µL (range 0.7-220.7) and median Day 28 ALC was 400/ µL (0-2.4). Twenty-seven pts (19.7%) had favorable CG, 84 (61.3%) intermediate, and 26 (19.0%) unfavorable. Most pts (91%) received "7+3" IC and 93 (66%) also received at least 1 cycle of post-remission chemotherapy. On univariate analysis, age ≥60 (HR 2.72, p< 0.001), CG risk (HR 2.13, p < 0.001), Day 28 ALC < 250/ µL (HR 1.60, p=0.022), Day 28 ALC < 350/ µL (HR 1.57, p=0.029), and max ALC < 500/ µL (HR 1.54, p=0.035) were associated with a worse OS from the initiation of treatment. Low ALC was associated with both a higher incidence of refractory disease and death during induction (p=0.015). In our second analysis of pts undergoing AHCT in CR1, although not statistically significant, max ALC < 500/ µL (during IC) was associated with a trend towards decreased OS from the start of treatment on both univariate (HR 1.88,p= 0.13) and multivariate (HR 2.16, p=0.075) analysis. Conclusions: Max ALC < 500/ µL is predictive of outcome in AML pts undergoing IC, and there is a suggestion that this effect may not be abrogated by AHCT. A larger study will be needed to further confirm these findings. Therapies to improve lymphocyte recovery may be important in the treatment of AML. Disclosures Sekeres: Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees

Impact of allogeneic hematopoietic stem cell transplant (HSCT) on patients harboring the spliceosome mutation SRSF2

7008 Background: Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations (mut) in spliceosome genes U2AF1 and SRSF2 predict poor outcome in MDS and related diseases. The purpose of this study was to investigate the role of HCT on the prognostic impact of U2AF1 and SRSF2 in myeloid malignancies. Methods: 123 patients (pts) with MDS (33%), AML (51%), MPN (10%), and MDS/MPN (5%) receiving an allogeneic HCT from 2003-2012 for whom genomic DNA was available from a time when the disease was active, were evaluated for mut in U2AF1 and SRSF2 by direct sequencing. Data were analyzed using competing risks methods (relapse and non-relapse mortality, NRM), proportional hazards (overall survival, OS) and logistic regression models (GVHD). Results: Median time of follow up was 38 months (range 1.5-108). Median age at HCT was 51 yrs (range 18-71). 53 (43%) pts were in remission and 70 (57%) had active disease prior to HCT. 20 (16%) pts had low, 48 (39%) intermediate and 32 (26%) high risk cytogenetics respective to their disease, (per CALGB criteria for AML, IPSS-MF for MPN and IPSS-R for MDS), with missing data on 23 (19%) pts. 89 (72%) had myeloablative transplants, and 34 (28%) received reduced intensity regimens. 54 (44%) had related, 52 (42%) unrelated and 17 (14%) cord blood donors. SRSF2 mut were detected in 13 (11%) pts and U2AF1 in 2 (2%) pts. Due to the low incidence of U2AF1 mut in our cohort, further analysis was focused on SRSF2. There were no significant differences in baseline characteristics between mut and wild-type (wt) pts except SRSF2 mut tended to occur in older AML pts (median age 64 vs 50 yrs, p=0.0004). SRSF2 mut and wt had similar OS (p=0.95), relapse (p=0.28), NRM (p=0.45) and rates of acute (p=0.41) and chronic (p=0.67) GVHD. Results were similar, adjusting for factors such as age, disease type, cytogenetics, comorbidity, transplant type and stem cell source. Conclusions: SRSF2 has previously been associated with dismal outcomes in MDS pts, with 5 yr-OS of <20%. In this cohort of transplanted pts, SRSF2 mut had similar outcomes to wt, suggesting HSCT may compensate for the adverse impact of SRSF2

Impact of Mutations in the Spliceosome Machinery and Ring Sideroblasts in Patients with Myeloid Malignancies Who Received Conventional Chemotherapy or Allogeneic Hematopoietic Cell Transplantation

Abstract Abstract 1973 Mutations in the spliceosome machinery have recently been identified in myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and MDS/MPN overlap syndromes. Somatic alterations in SF3B1, U2AF1 and SRSF2 are the most frequently affected spliceosome genes in myeloid malignancies with the frequencies of any of the 3 genes being 39% in low risk MDS, 11% in high risk MDS/AML (primarily U2AF1), and 24% in MDS/MPN, (primarily SRSF2). While SF3B1 mutations as well as ring sideroblasts (RS) appear to be associated with improved survival and lower risk of leukemic evolution, mutations of U2AF1 and SRSF2 appear to be associated with poorer outcomes. Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for many myeloid malignancies, however, the prognostic role of SF3B1, U2AF1 or SRSF2 mutations in patients (pts) undergoing high intensity chemotherapy (HIC) and HCT has yet to be investigated. We evaluated 404 pts with the diagnosis of AML (n=96), MDS and MDS/MPN (n=294), MPN (n=13), and congenital sideroblastic anemia (n=1). 35 pts received HIC defined as treatment with 7+3, high dose cytarabine, clofarabine, or other comparable chemotherapy in the context of a clinical trial. 97 pts underwent a myeloablative (n=69) or reduced intensity (n=28) allogeneic HCT from an HLA matched related (n=39), unrelated (n=50) or cord blood (n=8) donor from April 2003 until August 2011. Median age of the whole cohort was 69 and those who underwent BMT at time of transplant was 52 (range 19–70). We performed direct sequencing for the three most commonly mutated spliceosome genes, SF3B1 (exon 13–16), SRSF2 (exon 1 and 2) and U2AF1 (exon 2–6). Given the close association between SF3B1 mutations and RS, we analyzed the impact of the presence or absence of RS on the outcomes associated with the type of therapy received. We found a total of 24 SF3B1 mutations in MDS and MDS/MPN (primarily in pts with RS), 37 SRSF2 mutations in MDS and MDS/MPN (primarily CMML), and 13 U2AF1 mutations in MDS, MDS/MPN and secondary AML. Among pts with MDS and MDS/MPN, significant overall survival (OS) differences were found between SF3B1 mutant and wild type (WT), (83 vs. 31 months, p=0.001) and U2AF1 or SRSF2 mutant (18 vs. 37 months, p=0.007). The U2AF1 mutation by itself was more strongly associated with poor outcome (8 vs. 37 months, p<0.0001), compared to an SRSF2 mutation (26 vs. 36 months, p=0.16). Analysis of survival according to treatment type revealed that no pts who underwent HIC or HCT carried an SF3B1 mutation. The presence of RS was also associated with improved survival (38 vs. 25 months, p=0.04), and this benefit remained if pts received HIC (18 vs. 9 months, p=0.04). However, this benefit became non-significant if pts underwent HCT. There were 19 pts who had either an U2AF1 or SRSF2 mutation that underwent HIC. Although it appeared that having either mutation was associated with worse survival, (9 vs. 21 months), it did not reach statistical significance (p=0.46). Among pts who underwent HCT, there were 10 pts who carried either an U2AF1 or SRSF2 mutation. Those pts with mutations appeared to have superior survival with HCT compared to WT, (53 vs. 34 months), but this did not reach statistical significance (p=0.54). Among pts with either an U2AF1 or SRSF2 mutation, those who underwent HCT had a superior survival (53 vs. 17 months, p=0.05) compared to those who received conventional chemotherapy, defined as HIC or low intensity chemotherapy (LIC), such as hypomethylating agents. There was no difference in survival between receiving HCT or conventional chemotherapy in pts who were WT for U2AF1 or SRSF2 (34 vs. 31 months, p=0.08). Consistent with previous findings of improved survival and loss of SF3B1 with leukemic progression in MDS and MDS/MPN pts, we found no SF3B1 mutations in our cohort of pts receiving HIC or HCT. In contrast, we found poorer outcomes with SRSF2 or U2AF1 mutations. Although the incidence of these mutations was rare in our cohort of pts, we found statistically significant survival benefit for pts with these mutations if they underwent HCT compared to conventional chemotherapy. This is the first study evaluating the impact of spliceosomal mutations on the survival outcomes of pts undergoing HCT. Our preliminary findings of improved survival with HCT in poorer-risk spliceosome mutations is provoking and further molecular analysis is ongoing. Disclosures: Maciejewski: NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding

The Impact of Molecular Lesions in Post-Transplant Acute Myeloid Leukemia (AML) in Correlation with Cytogenetic Abnormalities

Abstract Abstract 4137 Relapse remains the most common cause of treatment failure in allogeneic hematopoietic stem cell transplantation (AlloHCT) for AML. Several risk factors (i.e. older age, persistent disease at transplant, adverse cytogenetics, secondary AML, non-myeloablative conditioning regimen) have been identified as predictors for post-transplant AML recurrence. In addition, the adverse prognostic influence of specific mutations (DNMT3, ASXL1, IDH1/2, RUNX1, TET2, TP53 etc.) has been identified in both de novo and secondary AML treated with standard chemotherapy regimens. The impact of these mutations on clinical outcomes following AlloSCT, however, remains largely unexplored. Consequently, we conducted this study to investigate the prognostic role of molecular lesions including metaphase (MC) and SNP array (SNP-A) cytogenetic defects and somatic mutations in patients undergoing AlloHCT. A total of 186 patients were identified who received myeloablative AlloHCT for AML (2000–2010) and had pre-transplant diagnostic leukemic sample available for testing. We performed SNP-A karyotyping and sequencing for RUNX1, DNMT3, TP53, ASXL1, CBL, IDH1/2, NPM1, FLT3ITD and TET2 gene mutations and correlated the results with clinical outcomes following AlloHCT. SNP-A based karyotyping helped to upstage the cytogenetics by inclusion of previously undetected cryptic abnormalities.Cox proportional hazards analysis was used to identify prognostic factors for relapse, relapse free (RFS) and overall survival (OS). Analysis was based on 103 patients (55%) who had data on cytogenetics. Of these 103 patients, 42 (41%) had disease relapse following transplantation and 58 (56%) died within the median follow up of 39 months (range, 8–133) following their myeloablative AlloSCT. The frequencies of mutations were estimated; for example, FLT3, NPM1, DNMT3, ASXL1, IDH1/2, CBL, RUNX1 and TP53 were detected in 18%, 13%, 14%, 9%, 9%, 4%, 2% and 2% of the cases, respectively. Overall, mutations were present in 35% of AML cases, and were exclusive to those with intermediate or favorable risk cytogenetics. Various combinations were encountered, however in those with 2 concomitant mutations, NPM1 was present in all cases. In patients with intermediate risk cytogenetics (n=83) and those with mutational abnormalities the leukemia relapse rate was 40% and 38%, respectively. In particular, among patients harboring NPM1 mutation relapses occurred in those who were positive for either DNMT3 or FLT3ITD. Lower rate of relapse (25%) was observed in patients with ASLX1 and IDH1/2 mutations. In one case of aggressiveTP53 mutation the patient was alive and leukemia free 3 years after her AlloHCT. In multivariable analysis, complex cytogenetics was an independent predictor for inferior RFS (HR=1.97, 95% CI, 1.04–3.7) and OS (HR=1.96, 95% CI, 1.04–3.7).Older age at transplant (per 10 yr increase, HR=1.24, 95% CI, 1.01–1.5) was associated with poorer OS, whereas higher comorbidity score (HR=1.86, 95% CI, 1.04–3.3) was associated with poorer RFS. There was no significant difference in post-transplant outcomes between patients in intermediate risk cytogenetics with detected genetic mutations (excluding isolated NPM1) and those with no detectable mutations. Our preliminary results suggest that myeloablative AlloHCT could minimize the prognostic impact of adverse molecular markers in AML. These mutations potentially serve as important biomarkers in determining the management of AML. Further studies designed to determine their precise role are planned. Disclosures: No relevant conflicts of interest to declare