Intensive Consolidation Therapy Research Articles

The Outcome of Outpatient Intermediate and High Dose Cytarabine Consolidation Chemotherapy in Patients with Acute Myeloid Leukemia. The Experience of King Fahad Specialist Hospital in Dammam, Saudi Arabia

Background: Adult patients with Acute Myeloid Leukemia (AML) have traditionally been hospitalized for the duration of intensive consolidation chemotherapy until blood count recovery to avoid complications. Recently, there has been a trend to shift the care of AML patients treated with intensive chemotherapy from inpatient to outpatient settings to reduce treatment costs and save beds. Methods and materials: A retrospective study of AML patients who received cytarabine consolidation chemotherapy between the 1st of August 2016 and the 31st of December 2023 at King Fahad Specialist Hospital in Dammam, Saudi Arabia was performed. Results: Over a period of 7 years and 4 months, 62 patients received a total of 127 cycles of intensive consolidation chemotherapy at outpatient setting. At diagnosis: 12 patients had extramedullary disease, and 17 patients had adverse cytogenetic abnormalities. Following the 127 cycles of chemotherapy, 38 episodes of febrile neutropenia were encountered, and 46 hospital admissions were required. No complications were encountered following 62.2% of the cycles of consolidation therapy and no early mortality due to intensive consolidation therapy was reported. Out of 62 patients studied, 36 patients underwent various forms of hematopoietic stem cell transplantation. Disease relapses were encountered in 24 patients and the 5-year incidence of relapse for the entire group of patients was 42%. The 5-year leukemia-free survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 43%, 38%, and 50% respectively. The 5-year overall survival for the: entire study patients, transplanted patients, and non-transplanted patients were: 44%, 34%, and 65% respectively. At the end of follow-up: 37 patients (59.68%) were alive, 24 patients (38.71%) were dead, and the fate of 1 patient (1.61%) was unknown as the patient moved to another hospital. Conclusion: Administration of intensive consolidation chemotherapy for patients with AML at outpatient setting is safe, feasible, and cost-effective. The incidence of infectious complications was relatively low. No early treatment-related mortality due to intensive consolidation therapy was encountered. Outpatient administration of intensive consolidation therapy can save beds, reduce hospital costs, and is associated with short-term and long-term outcomes that are comparable to inpatient administration of consolidation therapy.

The Occurrence of Infection and TP53 Mutation Are Risk Factors for Cardiovascular Toxicity of Acute Myeloid Leukemia Induction Therapy

Introduction: For almost 50 years,induction therapy (IT) is the standard of care for acute myeloid leukemia (AML) patients. Nevertheless, little is known about cardiovascular (CV) toxicity during IT. We aimed to describe CV events (CVE)occurring during IT and to identify clinical, hematological and molecular risk factors of such events. Methods: Two hundred and twenty-four patients of 18 years or more (median age 61 (51;67) years, 58% males), treated with ITbetween 2014 and 2021 were enrolled in this study. Two hundred and one (90%) received an anthracycline-based IT, the others received gemtuzumab ozogamicin as part of a clinical protocol research. Survival from the time from initiation of IT until death or until the initiation of the second course of therapy (either salvage regimen in case of primary refractory or relapsed AML, or intensive consolidation therapy in case of response) was considered. The primary endpoint was the time to occurrence of the first CVE after IT initiation, with death as a competing event. Multivariate analysis included significant covariate, identified by univariate models among initial characteristics and occurrence of infection (coded as time dependent covariate). Results: Hematological characteristics were as follows: European LeukemiaNet (ELN) 2022 risk of myelodysplastic neoplasm (MDS)/AML was low, intermediate and adverse in 13%, 29% and 58% of patients respectively. Main mutations encounters were: DNMT3A, FLT3, NPM1, TET2, NRAS, RUNX1, ASXL1, IDH2, PTPN11, BCOR, SRSF2, WT1 and TP53. Main CV risk factors were tobacco (36%), arterial hypertension (35%), obesity (24%), hyperlipidemia (22%), diabetes mellitus (11%). Baseline left ventricular ejection fraction (assessed by transthoracic echocardiography) was >45% in all patients, >55% in 95% of patients. Seventy-five patients (33%) presented a CVE during IT. Eighty-six percent of CVE were severe (grade 3 or more). Patients presenting CVE during IT were significantly older (p=0.02) and presented more often a past history of dilated cardiomyopathy (p=0.04), arterial hypertension (p=0.005) or dyslipidemia (p=0.005). At baseline, CVE patients presented a greater left auricle volume (p=0.005), higher tricuspid regurgitation grade (p=0.01), and more often a right ventricular dilatation or a significative valvopathy (respectively p=0.01 and p=0.03). There was no difference in CVE occurrence between patients treated with and without anthracyclin (p=0.2). Competing risk models identified the following adverse characteristic for the risk of first CVE, namely the occurrence of the first infectious event (Hazard ratio [HR]= 2.43, p=0.005), TP53 mutation (HR=1.79, p=0.04). No other clinical characteristics nor mutation (including TET2 and DNMT3A) were identified. Multivariate analyses demonstrated that TP53 mutation (HR=1.78, p=0.04) and occurrence of infection (HR=2.29, p=0.008) retained independent prognostic value, see Table 1. In a response stratified model, only TP53 mutation was a risk factor of first CVE (HR=2.46, p=0.008). Conclusions: CVE occurred in 33% of patients during IT and were severe. The major adverse role of onset of infection for CVE occurrence after IT could overcome the prognostic value of mutations usually associated with CV risk in the healthy population (i.e. TET2, DNMT3A, ASXL1, ...). TP53 mutation was the only molecular abnormality associated with CVE, in agreement with the increased risk of doxorubicin-induced cardiac toxicity in a mouse model of TP53 clonal hematopoiesis developed by Sano et al. These results suggest that TP53 mutated patients could benefit from careful CV monitoring and optimization of primary prevention treatment.

Impairment of health-related quality of life for children with acute lymphoblastic leukemia over the first year of therapy: A report from the DFCI ALL Consortium.

Children treated for acute lymphoblastic leukemia (ALL) receive prolonged treatment, resulting in toxicities that affect health-related quality of life (HR-QoL). Longitudinal assessment of HR-QoL allows improved understanding of experiences with ALL. Parent-proxy and child self-report HR-QoL over the first year of chemotherapy were evaluated in the context of DFCI Protocol 05-001, a phase 3 therapeutic trial for childhood ALL. HR-QoL was assessed with the Pediatric Quality-of-Life inventory (PedsQL) domains for Pain and Hurt, Procedural Anxiety, Treatment Anxiety, Emotional Functioning, General Fatigue, and Sleep/Rest Fatigue. Total of 281 subjects participated, with 141 contributing at least one child report and 280 at least one parent report. Children with ALL experienced impairment in HR-QoL by both patient and parent report compared to the published PedsQL reference population at each time point on each subscale. Agreement between parent and child assessment of HR-QoL impairment was high, particularly among those for whom HR-QoL was not impaired. During the consolidation phase, which included intensive asparaginase administration, multivariable models demonstrated more impairment in Treatment Anxiety and Procedural Anxiety for children treated with intramuscular asparaginase than intravenous asparaginase, but randomized groups were otherwise similar in HR-QoL. Impairments in fatigue, both General and Sleep/Rest, were evident throughout and worse during intensive asparaginase therapy. This report examines HR-QoL for children with ALL during treatment longitudinally by parent and patient report across multiple domains. Children with ALL demonstrated substantial impairment in HR-QoL, particularly related to fatigue during intensive consolidation therapy including asparaginase.

Double-Blind, Placebo Controlled, Randomized, Multicenter, Phase II Study to Assess the Efficacy of the High Affinity CXCR4 Inhibitor BL-8040 As Addition to Consolidation Therapy in AML By the SAL and OSHO Leukemia Study Groups

Background: Leukemia-cell-stroma interactions are an attractive therapy target in AML. The CXC chemokine receptor 4 (CXCR4) and its ligand CXCL12 (SDF-1) are expressed and secreted by myeloid leukemia blasts and play an essential role in the migration, homing, differentiation, proliferation, and retention of myeloid blasts within the protective bone marrow (BM) niche. The high-affinity CXCR4 antagonist BL-8040 is directly toxic for AML blasts and interrupts the interaction between blasts and the protective BM microenvironment. Objective: The aim of this clinical trial was to evaluate the impact of BL-8040 in combination with standard consolidation therapy on relapse free survival (RFS) in patients with acute myeloid leukemia (AML) in first complete remission (CR, CRp, CRi). Methods: Adult patients ≥ 18 years with documented 1st CR/CRi/CRp, after induction therapy with cytarabine and an anthracycline, and not scheduled for allogeneic stem cell transplantation were randomized in a 1:1 ratio to receive two cycles (≥ 60 years) or three cycles (<60 years) of high-dose cytarabine plus BL-8040 or placebo as consolidation therapy. The dosage of cytarabine was 1g/m² per dose for subjects older than 60 years and 3 g/m² per dose for subjects younger than 60 years. Results: Between November 2015 and November 2019, 134 patients of the originally planned number of 202 were recruited at 29 trial sites, 6 patients violated inclusion and/or exclusion criteria and were excluded. Considering the results of the interim analysis, the data monitoring committee recommended to stop recruitment. Thus, no further patients were enrolled. One hundred and twenty-eight patients were randomized (63 placebo; 65 BL-8040). Baseline characteristics were balanced between treatment arms: median age 61 vs 63 years; 2010 ELN favorable or intermediate-risk 95% vs 98%; CXCR4 expression 38% vs 30% in the BL-8040 and standard arm, respectively. Overall median follow-up time was 25.4 months. Median RFS was similar between arms 10.3 months [95% CI 8.0,12.0] for the BL-8040 arm and 11.5 months [95% CI 8.6,24.1] for the placebo arm (two-sided p=0.98 by log-rank test).The median OS was not reached at the time point of the analysis. Intention to treat (ITT) analyses revealed no difference between placebo and BL-8040, neither for the total cohort, nor for the subset of patients with expression of CXCR4 with respect to RFS (Hazard ratio (HR) 1.0, 95% CI 0.7,1.6, p =0.9, and HR 0.9, 95% CI 0.1,2.9, p =0.9,respectively) or overall survival (OS; HR 1.1, 95% CI 0.6,2.0, p = 0.8, and HR 2.5, 95% CI 0.4,13.8, p = 0.3, respectively). Regarding safety endpoints, overall, 739 and 576 adverse events were documented in the BL-8040 and placebo arm, respectively. Serious adverse events were similar between therapies. Conclusion: The addition of BL-8040 to intensive consolidation therapy did not improve RFS or OS. Although more side effects were noted, no differences in serious adverse events were observed.

Prognostic value of KIT and other clonal genetic mutations in core-binding factor acute myeloid leukemia

目的评价基于二代测序（NGS）检测技术下的克隆性基因突变对核心结合因子相关急性髓系白血病（CBF-AML）预后的影响。方法回顾性分析2011年7月至2017年8月在苏州大学附属第一医院血液科诊治的195例成人初治CBF-AML患者，其中诱导化疗达完全缓解的患者190例，包括134例RUNX1-RUNXIT1+ AML和56例CBFβ-MYH11+ AML，年龄15～64岁，中位随访时间43.6个月。采用Log-rank检验和Cox回归模型分析临床因素和基因突变对患者总生存（OS）和无病生存（DFS）的影响。结果在195例患者中，KIT基因突变发生率最高（47.6％），其次为NRAS（20.0％）、FLT3（18.4％）、ASXL2（14.3％）、KRAS（10.7％）、ASXL1（9.7％）。按基因功能分类，酪氨酸激酶信号通路基因突变发生率最高（76.4％），其次为染色质修饰相关基因（29.7％）。在接受强化巩固治疗的患者中，CBFβ-MYH11+ AML患者的OS有优于RUNX1-RUNXIT1+ AML患者的趋势（P＝0.062）。染色质修饰相关基因突变仅在RUNX1-RUNXIT1+ AML中检出，但对患者的DFS无明显影响（P＝0.557）。染色质修饰相关基因突变阳性且接受异基因造血干细胞移植（allo-HSCT）的患者预后最好。多因素分析显示KIT exon17突变为影响RUNX1-RUNXIT1+ AML患者DFS的独立危险因素（P<0.001），allo-HSCT能明显改善RUNX1-RUNXIT1+ AML患者的DFS（P＝0.010）。结论合并KIT exon17突变的RUNX1-RUNXIT1+ AML患者预后差，allo-HSCT可改善这部分患者的预后，allo-HSCT也能使染色质修饰相关基因突变阳性患者的预后得到改善。

Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation

BackgroundMore than one-half of high-risk patients with relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) relapse after autologous hematopoietic cell transplantation (auto-HCT). In this phase II study, we investigate the long-term outcomes of high-risk patients with rrDLBCL receiving intensive consolidation therapy (ICT) with OVA (ofatumumab, etoposide, and high-dose cytarabine) prior to auto-HCT. Patients and MethodsThe primary endpoints were the ability of OVA to mobilize peripheral stem cells and the 2-year progression-free survival (PFS) rate following OVA. Secondary endpoints included safety, 2-year overall survival (OS), impact of cell of origin (COO), and the prognostic utility of next-generation sequencing minimal residual disease (MRD) testing. We simultaneously retrospectively assessed the outcomes of DLBCL patients who underwent ICT with a similar regimen at our institution. ResultsTwenty-seven patients received salvage chemotherapy, with a response rate of 25% in patients with germinal center B-cell (GCB)-DLBCL versus 92% in patients with non-GCB-DLBCL (P = .003). Nineteen responding patients underwent ICT with OVA (100% successful stem cell mobilization). The 2-year PFS and OS rate was 47% and 59%, respectively, with no difference based on COO. Similar findings were observed when the study and retrospective cohorts were combined. Neutropenia was the most common toxicity (47%). MRD-negative patients at the completion of salvage had a median OS of not reached versus 3.5 months in MRD-positive patients (P = .02). ConclusionsOVA followed by auto-HCT is effective and safe for high-risk rrDLBCL. Patients with GCB-DLBCL had a lower response to salvage chemotherapy, but no difference in outcomes based on COO was seen after auto-HCT. MRD testing in the relapsed setting was predictive of long-term survival.

The prognostic value of cloned genetic mutations in patients with CBFβ-MYH11 fusion-positive acute myeloid leukemia receiving intensive consolidation therapy

The prognostic value of cloned genetic mutations in patients with CBFβ-MYH11 fusion-positive acute myeloid leukemia receiving intensive consolidation therapy

The prognostic value of cloned genetic mutations detected by second-generation sequencing in RUNX1-RUNX1T1 positive acute myeloid leukemia patients receiving intensive consolidation therapy

目的探讨基于二代测序检测技术下的克隆性基因突变对第1次完全缓解（CR1）状态下接受高剂量化疗或自体造血干细胞移植（强化巩固治疗）的RUNX1-RUNX1T1融合基因阳性急性髓系白血病（AML）预后的影响。方法收集2011年7月至2017年8月在苏州大学附属第一医院CR1状态下接受强化巩固治疗的79例RUNX1-RUNX1T1融合基因阳性AML患者的临床资料，通过Kaplan-Meier曲线、Cox回归模型分析临床因素及突变基因对患者总生存（OS）和无病生存（DFS）时间的影响。结果在79例患者中，检出C-KIT、FLT3、CEBPA、DNMT3A基因突变者分别为25例（31.6％）、6例（7.6％）、8例（8.9％）、1例（1.3％），其中C-KIT exon17及C-KIT exon8突变分别为19例（24.1％）、5例（6.3％），FLT3-ITD突变为5例（6.3％）。初诊白细胞计数越高，患者的OS时间越短（P＝0.030），合并C-KIT exon17突变患者的OS时间（P＝0.010）和DFS时间（P＝0.006）明显缩短，合并FLT3-ITD基因突变患者的OS时间（P＝0.048）和DFS时间（P＝0.071）缩短。多因素分析显示合并C-KIT exon17和FLT3-ITD突变均为影响患者预后的独立因素。结论在接受强化巩固治疗的RUNX1-RUNX1T1融合基因阳性AML患者中，C-KIT exon17、FLT3-ITD基因突变提示预后较差，这将对细化患者危险度分层、个体化治疗、评估预后有指导意义。

Evolving Risk Factors for Mortality, Progression, Myeloid Dysplasia and Survival in Large 2-Decade Single-Centre Autologous Transplant Cohort of Myeloma, Amyloidosis and related Plasma Cell Dyscrasia

Autologous Stem Cell Transplant (ASCT) with High-Dose Melphalan conditioning has been a unchallenged standard for intensive consolidation therapy in younger fitter Multiple Myeloma (MM) since late 1990, & was ratified as increasing PFS & OS, through RCT by various collaborative groups, as well as meta-analysis.However induction regimens have evolved from anthracycline-based infusions (e.g. [C]VAD & DTPACE]), through thal- & now len- alidomide-based IMid regimens (CTD/DTPACE/CRD), alongside advent of proteasome-inhibitors (esp.

FLT3 and NPM1 Are Powerful Determinants of Outcome in Acute Myeloid Leukemia Patients Treated with Autologous Stem Cell Transplantation: An Analysis By the Acute Leukemia Working Party of the EBMT

Background: While intensive consolidation therapy with autologous stem cell transplantation (ASCT) can secure a remission in selected Acute Myeloid Leukemia (AML) patients with intermediate-risk cytogenetics, a substantial proportion will ultimately relapse. Knowledge of the mutational status of FMS like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) and nucleophosmin (NPM) 1 and their possible combinations could further refine a subset of intermediate cytogenetic risk patients who may benefit from ASCT. However, data are limited. We, therefore, set out to evaluate the impact of FLT3-ITD and NPM1 in a large cohort of patients undergoing ASCT.Methods: This was a retrospective analysis of the Acute Leukemia Working Parity of the European Society for Blood and Marrow Transplantation (EBMT) registry. We included 405 de-novo AML patients, from 51 European centers, with intermediate-risk cytogenetics (Grimwade et al., Blood 2010) and complete data on FLT3-ITD and NPM1 status, receiving an ASCT at first complete remission (CR1), between 2000-2014. Leukemia free survival (LFS) was the primary outcome. Secondary outcomes were overall survival (OS), transplantation-related mortality (TRM), and relapse incidence (RI). The latter two were considered as competing events. Univariate and multivariable Cox regression models, adjusted for recipient sex, age, Karnofsky performance status, FLT3/NPM1 combinations, days from diagnosis to transplantation, stem cell source -bone marrow or peripheral blood (PB), and use of total-body irradiation-based conditioning.Results: Patients included had a median age of 52 years and received an autograft at median of 5 months from diagnosis. PB-based autograft and non-TBI conditioning were used in the majority of patients (93% and 90%, respectively). FLT3-/NPM1- was the leading molecular combination (50%), followed by FLT3-/NPM1+ (30%), FLT3+/NPM1+ (11%), and FLT3+/NPM1- (9%). Age, time from diagnosis to transplantation, graft source, and use of TBI were similar between the molecular subgroups. The median year of transplantation was earlier in NPM1- patients (FLT3+/NPM1- 2008, FLT3-/NPM1- 2009, FLT3-/NPM1+ 2010, FLT3+/NPM1+ 2011, p<0.001). In the univariate analysis, age, molecular makers, time from diagnosis to transplantation, and use of TBI were associated with the risk for experiencing an LFS event. Patients in the FLT3-/NPM1+ subgroup had the most favorable outcome (5-years LFS [62%] and OS [74%]). Nonetheless, 5 years following ASCT the RI was 35% (Figure). FLT3+/NPM1- were the least likely to survive due to a tendency to relapse: 5-years LFS (21%), OS (33%),and RI (79%). In a Cox multivariable model, the combination of molecular markers were the strongest predictors of LFS: FLT3-/NPM1+ (reference), FLT3-/NPM1- HR 2.39 (1.65-3.46), FLT3+/NPM1+ HR 2.24 (1.33-3.75), FLT3+/NPM1- HR 5.09 (2.94-8.82). We did not find interactions between molecular markers and other covariates in the model.Conclusions: In this pioneering analysis of CR1-AML patients, with intermediate risk cytogenetics, receiving an ASCT as post-remission therapy, we show that the molecular subgroups of FLT3-ITD and NPM1 are highly prognostic. In line with previous publications in the allogeneic setting, patients with FLT3-/NPM1+ have promising outcomes, while those with FLT3+/NPM1- do poorly. Testing for the role of additional markers, such as isocitrate dehydrogenase (IDH), could further identify populations who may derive the most benefit from ASCT. DisclosuresBaerlocher:Novartis: Research Funding. Foà:NOVARTIS: Speakers Bureau; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD. Haenel:Novartis: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Roche: Honoraria. Zuckerman:Cellect Biotherapeutics Ltd: Consultancy. Mohty:MaaT Pharma: Consultancy, Honoraria.

Cell of Origin and Double Protein Expression As Predictors of Outcome after Autologous Stem Cell Transplant for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Who Undergo Intensive Consolidation Therapy (ICT) and Autologous Stem Cell Transplant (AutoSCT)

Introduction: For patients with relapsed or refractory DLBCL with chemosensitive disease after 2nd line (salvage treatment), AutoHCT is considered the standard of care. Risk factors for progression following AutoHCT include primary refractory disease and early relapse (<12 months after initial chemotherapy. In our institution, we have previously shown that a course of ICT given prior to AutoHCT in patients with these high-risk features results in improved outcomes in DLBCL and other lymphomas (Damon et al, BMT 2008; 42(10):649-57). More recently, cell of origin (COO) subtype and double myc and bcl2 protein expression (DPP) status have been shown to predict outcome to front line treatment but data in the relapsed setting are lacking. We hypothesized that our approach of ICT followed by AutoHCT will increase the likelihood of complete remission (especially in patients with high-risk clinical or biologic features) and improve progression free survival (PFS) following AutoHCT.Methods: Consecutive patients who underwent ICT followed by autoHCT for relapsed/refractory DLBCL at our institution between 2005-2015 and had available tissue samples for review were included in our analysis. ICT was applied per institutional standard to patients with apriori identified high-risk features as described below. This chemotherapy step is utilized for stem cell mobilization following evidence of chemosensitivity and prior to undergoing AutoHCT. COO was determined using the Hans algorithm and DPP status using the Johnson criteria. Following CHR approval, patient's charts and EMR were reviewed to ascertain baseline variables and outcome data. Response was determined using radiologic (CT) and metabolic (PET) imaging for all patients at the time of transplantation. Survival probability was estimated by the Kaplan-Meier method. Comparisons were made using the X2 test and Fisher's exact test, where appropriate.Results: A total of 35 patients were included in this analysis. Out of those, 30 patients received a high-dose etoposide and ara-C-based ICT regimen as described by Damon et al. 13/30 (43.3%) were female, 17/30 (56.7%) were male. Median age at transplant was 56 (range 34-68). The high risk features that lead to this treatment were: early (<12 months) relapse (9/30, 30%) or refractory disease (13/30, 43.3%)to front line therapy or other (8/30, 27.7%). In all, 16/30 (53%) patients achieved CR at the end of salvage therapy, with this proportion increasing to 26/30 (86.7%) CR after ICT. Eventually, 24/30 (80%) of patients were able to continue on to AutoHCT, 23/30 (76.7%) with CBV, 4/30 (13.3%) with BEAM, and 3/10 (10.0%) other. With a median follow up of 20 months, 66% of patients are progression-free at 24 months (Figure 1). In our cohort, 8/30 (27%) were germinal center B-cell origin subtype (GCB), 19/30 (63.3%) were non-GCB subtype and 3 (10.0%) could not be identified. In all, 8/30 (26.7%) were double protein positive, 18 (60.0% were double protein negative and 4 (13.3%) could not be determined. Notably, 15.8% of patients with non-GCB were double protein expressors, compared to 37.5% of patients with GCB (Fisher’s exact p=0.06). Neither COO nor DPP were associated with response rates prior to AutoHCT (p=0.6 and p=0.17 respectively) or with PFS (p=0.32 and p=0.72 respectively and Figures 2a and 2b).Conclusions: Even though COO and DPP status are associated with inferior outcomes in the front-line setting of patients with DLBCL, data in the relapsed setting are limited. In a cohort of high-risk patients with relapsed DLBCL, we confirmed our previously described excellent outcomes with ICT in terms of increased CR rates prior to AutoHCT and a high rate of 2-year PFS. Moreover, while numbers are small, our study suggests that ICT leads to similar outcomes regardless of cell of origin or double protein expression status. [Display omitted] [Display omitted] [Display omitted] DisclosuresMartin:Amgen: Research Funding; Sanofi: Research Funding.

Retrospective Study Evaluating Hematological Remission Rates and Survival in Chinese Adults with Relapsed or Refractory (r/r) Philadelphia Chromosome Negative (Ph-) B-Precursor Acute Lymphoblastic Leukemia (ALL)

Introduction: Outcomes are poor among Chinese adults with r/r ALL. Current recommendations in China for the treatment of adults with Ph- ALL include induction therapy with vincristine or vindesine, anthracyclines/anthraquinones, and corticosteroids; intensive consolidation therapy following complete remission (CR); and hematopoietic stem cell transplantation (HSCT). Currently, there is a lack of studies assessing treatment status and outcomes in Chinese adults with r/r ALL. The objective of this study was to assess the efficacy of currently available treatments for adults with r/r Ph- ALL in China.Methods: Between January 2009 and December 2014, adults with r/r B-precursor ALL and defined Philadelphia chromosome status were identified and enrolled from 14 hematology centers in China. All patients were ≥ 15 years of age at time of de novo (initial) diagnosis of ALL, had no central nervous system involvement at time of relapse, and had no isolated extramedullary relapse. Clinical data were retrospectively collected by chart review. The primary analysis set included only patients with r/r Ph- ALL, defined as meeting 1 of the following criteria: primary refractory, had relapsed within 12 months of first CR, relapsed after first or later salvage, or relapsed within 12 months of HSCT. The primary endpoint was rate of overall response (CR or CR with partial hematologic recovery [CRh]) after last salvage treatment. Key secondary endpoints included rate of CR with incomplete hematologic recovery (CR/CRh/CRi), duration of CR/CRh, rate of allogeneic hematopoietic stem cell transplantation (alloHSCT) realization after CR/CRh, and overall survival (OS).Results: Of 458 eligible patients, 304 (66%) had Ph- ALL, 270 (89%) of whom were in the primary analysis set (female, 46%; median [range] age at diagnosis, 29 (15-73) years). Of these, 45 (17%) had primary refractory disease, 159 (59%) had relapsed within 12 months of first CR, 49 (18%) had relapsed twice or more, and 17 (6%) had relapsed within 12 months post-HSCT. Baseline characteristics at the time of last salvage therapy among patients without prior HSCT included 195 (72%) with no prior salvage, 45 (17%) with 1 prior salvage, and 6 (2%) with ≥ 2 prior salvage treatments. Prior HSCT (n = 24; 9%) included both autologous (n = 8) and allogeneic (n = 16). Among those with prior HSCT, 18 (7%) had prior salvage, 6 (2%) had 1 prior salvage, and none had ≥ 2 prior salvages.Efficacy data at last salvage are presented in the table. Overall, 31% (84/270; 95% confidence interval [CI], 26%-37%) of patients achieved CR/CRh at last salvage. The median time to CR/CRh was 30 days. Median (range) number of therapies to CR/CRh was 1 (1-3). The occurrence of CR/CRh by line of salvage was 104/254 (41%) for 1st line, 13/55 (24%) for 2nd line, and 1/6 (17%) for 3rd line or later. Median (95% CI) duration of CR/CRh at last salvage was 2.7 (2.0-3.8) months with 57% events among 84 patients who achieved CR/CRh. Among CR/CRh responders, 13 of 16 evaluable patients (81%) achieved a minimal residual disease response. Median (95% CI) OS was 4.4 (3.6-5.1) months, with 54 (20%) deaths among 270 patients. At last salvage, 24/84 (29%) responders subsequently received alloHSCT.Conclusions: In this population of Chinese adults with r/r Ph- ALL treated with currently available salvage chemotherapies, CR/CRh responses were low (31%) and prognosis was poor. The median duration of CR/CRh was short (2.7 months), and the alloHSCT realization rate was low among responders. Thus, new therapies are needed to improve treatment outcomes in Chinese adults with primary refractory or relapsed Ph- ALL. [Display omitted] DisclosuresMeng:Amgen: Employment, Equity Ownership.

Effect of idarubicin combined with medium-dose arabinoside in intensive chemotherapy on the prognosis of acute myeloid leukemia

Objective To explore the efficacy and feasibility of idarubicin combined with medium-dose arabinoside in intensive chemotherapy for acute myeloid leukemia(AML). Methods Fifty remittent patients with induced chemotherapy who underwent the intensive consolidation therapy with medium-dose arabinoside from January 2010 to January 2015 in hematology department of General Hospital of Beijing Military Area were considered as the treatment group. The single arabinoside (2 g/m2, 1/12 h, d1-3) treatment for 50 cases in the same period were considered as the control group. Two groups were performed with 6 courses sequential. There were 28 males, 22 females in the treatment group, and average age was 27.6 years (18-52 years), with 3 cases of M1, 27 cases of M2, 8 cases of M4, 12 cases of M5. In the control group, there were 30 males, 20 females, and average age was 26.8 years (16-50 years), with 2 cases of M1, 30 cases of M2, 8 cases of M4, 10 cases of M5. Then the complications and disease-free survival of two groups were observed respectively. Results Follow-up was done until June 2015. In the treatment group, 1 case died of pulmonary infection, 2 cases died of septic shock and 3 cases died of pulmonary infection, 1 case died of septic shock in the control group. The treatment related mortality of both groups were 6% (3/50), 8% (4/50), the related relapse rates were 32% (16/50), 52% (26/50), the disease-free survival rates were 62% (31/50), 40% (20/50) respectively in two groups. Conclusion Compared with the single arabinoside, the intensive consolidation therapy with medium-dose arabinoside and idarubicin for the treatment of AML has gained lower relapse rate and the related mortality, and the DFS rate has been improved significantly, which need further clinical application. Key words: Leukemia, myeloid, acute; Idarubicin; Arabinoside; Intensive consolidation therapy

Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming with Decitabine in Adults with Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS): A Phase 1 Study

Background: Most adults with AML or high-risk MDS will ultimately require salvage therapy. However, the likelihood of achieving a complete remission (CR) with standard salvage regimens is often 15-20% or less. Emerging data suggest that pre-treatment (“priming”) with a hypomethylating agent such as decitabine can sensitize AML cells to chemotherapeutics, prompting a dose-escalation study of MEC preceded by decitabine-priming in relapsed/refractory AML and high-risk MDS.Methods: This single arm study aimed to estimate the maximum tolerated dose (MTD) of decitabine-primed MEC in adults ≥18 years with relapsed/refractory high-risk MDS (>10% blasts) or AML requiring first or subsequent salvage therapy. Previous treatment with hypomethylating agents or MEC (but not the combination) was acceptable. Trial participation required a treatment-related mortality (TRM) score of <9.2, corresponding to an expected TRM of 4% with standard induction chemotherapy. Patients with post-transplant relapse were eligible if graft-versus host disease was well controlled. Excluded were patients with concomitant illness with expected survival <1 year, and active, uncontrolled infection. Cohorts of 6-12 patients were assigned to 1 of 3 total dose levels of decitabine (20mg/m2 for 5, 7, or 10 days) followed by MEC (mitoxantrone 8mg/m2/day x 5 days; etoposide 100 mg/m2/day x 5 days; cytarabine 1 g/m2/day x 5 days) after a break of 5 days. In the case of persistent leukemia, patients were eligible for re-induction provided all non-hematologic toxicities had resolved to grade <2. Patients achieving a CR or CR with incomplete platelet recovery (CRp) could receive 2 additional cycles of decitabine-MEC given at doses identical to those used during induction. Dose-limiting toxicity (DLT) was defined as: 1) any grade 3 non-hematologic toxicity lasting >48 hours that resulted in >7 day delay of the subsequent treatment cycle, with the exception of febrile neutropenia or infection; 2) any grade ≥4 non-hematologic toxicity, with the exception of febrile neutropenia/infection or constitutional symptoms, if recovery to grade ≤2 within 14 days.Results: 30 patients, median age 55 (range: 19-72) years, with primary refractory disease (n=13), first relapse (n=16), or second relapse (n=1) with median duration of prior CR of 4 (range: 1-19) months were enrolled and received a median of 1 (range: 1-3) cycles of therapy. During dose escalation, 1 DLT occurred at each the 2nd and 3rd tested dose level after cycle 1 (septic shock with multi-organ failure in both), identifying a 10-day course of decitabine together with standard dose MEC as the MTD. A total of 12 patients received therapy at the MTD level. 9/30 patients achieved a CR (30%). This CR rate compared favorably relative to a historic control population with patient matching based on duration of prior remission and number of prior salvage therapies (Blood 1996; 88:756), with an observed/expected CR ratio of 1.9. 5 additional patients achieved a CRp, and 1 achieved a CR with incomplete count recovery (CRi) for an overall response rate of 15/30 (50%). Furthermore, 4 patients achieved a morphologic leukemia-free state, 8 had refractory disease, and 3 died before a response was assessed. Of the 15 patients who achieved a remission, 3 remain on study, 9 were taken off protocol to pursue further intensive consolidation therapy including hematopoietic cell transplantation, and 3 have died after a median CR duration of 68 days. In the 15 responders, the median response duration was 68 days (range 0-437), with 6 of these responses ongoing. Overall survival of these 15 patients was longer (median of 211 [range: 59-484] days) than that for patients who failed to achieve remission but lived at least 29 days (i.e. did not experience TRM) (median of 110 [range: 30-303] days). Six patients died within 28 days of treatment initiation for a TRM rate of 20%: 4 from infection, 1 from intracranial hemorrhage, and 1 from unknown cause. Besides grade 3-4 cytopenias, cough, fatigue, nausea and infection/neutropenic fever were the most common adverse events.Conclusion: Decitabine-primed MEC is feasible, well tolerated, and has anti-leukemic activity in relapsed/refractory AML and high-risk MDS. A phase 2 study based on these findings has been initiated. DisclosuresOff Label Use: Off-label use of some of the study drugs for either AML or high-risk MDS.

Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups

SummaryThe most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group.

Autologous (Auto) Peripheral Blood Stem Cell (SCT) As a Consolidation Therapy for Patients with Acute Myeloid Leukemia (AML) in 1st Complete Remission (CR): A Single Institution Experience

Abstract 4505 Introduction:Patients with AML in 1st CR are frequently consolidated with an auto SCT but the role of this modality in the management of AML is still not fully defined. Methods:Retrospective analysis was performed on all patients who underwent an auto SCT for AML in 1st CR at UMass Memorial Medical Center from January 2000 to December 2010. Data was analyzed as of August 2011. The study was approved by UMass Memorial Medical Center IRB. Results:25 Patients were identified from the database. There were 13 males and 12 females. The median age was 46 years range (19–72). Cytogenetics was good risk in 6 patients, intermediate risk in 14, poor risk in 3 and unknown in 2 patients. Induction chemotherapy was standard dose Ara-C based in 13 patients and high dose Ara-C based regimen in 12 patients. Median time from diagnosis to transplant was 133 days range (107–362). Stem cell mobilization regimen consisted of Ara-C/Etoposide (E) in 21 (80%), Cyclophosphamide (Cy) in 3 (12%) and Mitoxantrone/Ara-C/E in 1 (4%). Preparative regimen included Busulfan (Bu) 4/ E in 17 (68%), Bu4/Cy in 5 (20%) and high dose Melphalan in 3 (12%). A median of 4.56 ×106 range (1.05 × 106 – 9.67 × 106 ) CD34 cells/kg were infused. 3 patients failed to engraft. Median time to neutrophil recovery was 11 days range (9 to 16) and platelet recovery was 20 days range (9 to 116). 100 day mortality was 12% (3/25). Median follow of the entire cohort is 6.5 years range (0.6 – 10.7). Total of 9 patients died. The cause of death included disease in 7, sepsis in 1 and unknown in 1 patient. Kaplan Meier estimate for progression free survival (PFS) and overall survival (OS) was 72% and 80% at 6 months and 62% and 61% at 3 years. Conclusion:ASCT is an effective and safe intensive consolidation therapy for patients with AML in 1st CR. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Abstract 5330: Leukemia initiating cells are frequent and oligoclonal in de novo resistant ALL

Abstract Xenotransplantation of primary leukemia cells constitutes an attractive strategy to model disease for translational research, but the consequences of selective pressure on leukemia cells need to be clarified. Here we evaluate the phenotypic and genetic stability of primograft samples that were established by xenotransplantation of ALL cells from a group of patients with very high-risk precursor B-cell ALL, characterized by the persistence of minimal residual disease (VHR-ALL by MRD) after an intensive induction and consolidation therapy. Phenotypic properties remained unchanged, with concordant immunophenotypes in 9-10/10 leukemia-associated markers after up to 5 passages in Nod/scidIL2Rgammanull (NSG) mice and with stable drug response profiles in vitro on bone marrow stroma co-cultures. In 4/6 cases, 100 unsorted ALL cells were sufficient to reconstitute the leukemia. From up to 5 recurrent copy number abnormalities (CNA) detected in diagnostic samples, most were maintained in primografts. Changes in CNAs upon transplantation in NSG mice were few with 0-2 new lesions per case, mostly occurring during the first xenotransplantation. At the single cell level, the pattern of deletions in the CDKN2A/B locus revealed distinct subsets of ALL cells, which could reproducibly be tracked in primografts. These results provide unequivocal data for the existence of clonally closely related but distinct subsets of leukemia initiating cells in ALL, which has important implications for the use of this model for translational research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5330. doi:10.1158/1538-7445.AM2011-5330

Isocitrate Dehydrogenase Gene Mutations In Elderly Patients with Acute Myeloid Leukemia (AML) and Outcome After Treatment with All-Trans Retinoic Acid: A Study of the German-Austrian AML Study Group (AMSLG)

AbstractAbstract 101 Background:We have recently reported that mutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes are present in ~16% of younger adults [<60 years (yrs)] with acute myeloid leukemia (AML) and that they are associated with normal karyotype (NK) AML, in particular with the NPM1mutated/FLT3-ITDnegative genotype. Within this distinct genotype IDH mutations constitute an unfavorable prognostic factor in younger AML.(Paschka et al., J Clin Oncol. 2010;28:3636–43) Our former study in elderly AML patients (pts) suggested the NPM1mutated genotype, and in particular the NPM1mutated/FLT3-ITDnegative genotype, as a predictive factor for outcome after treatment with all-trans retinoic acid (ATRA) given as an adjunct to intensive chemotherapy.(Schlenk RF et al., Haematologica. 2009;94:54–60) To date, there is only scarce data on the frequency and clinical impact of IDH mutations in elderly AML pts, and no study has analyzed the prognostic relevance of these mutations in the context of additional treatment with ATRA. Methods:The molecular analyses were performed on pre-treatment bone marrow (BM) or blood specimens from 732 pts with AML aged ≥60 yrs treated on one of two AMSLG trials [AML HD98B (n=306), AMLSG 06-04 (n=426)]. Mutational screening of exon 4 of both IDH1 and IDH2 was performed by a combination of denaturing high performance liquid chromatography and direct sequencing. Pts were also analyzed for the presence of FLT3-ITD, FLT3-TKD and NPM1 mutations. The treatment on each AMLSG trial incorporated a double induction and intensive consolidation therapy; in the AML HD98B trial pts were randomized for ATRA as adjunct to chemotherapy, whereas in the AMLSG 06-04 trial ATRA was given to all pts, and they were randomized for the administration of valproic acid. Results:A total of 163 IDH mutations were found in 732 (22%) pts. All but one IDH mutation clustered to the previously reported mutational hot spots: IDH1R132 (n=54), IDH2R140 (n=92), IDH2R172 (n=16); one case had both IDH1 and IDH2R172 mutation, and in one case a novel IDH2I170T mutation in addition to a IDH2R172 mutation was detected. IDH mutations were associated with higher platelet counts (P<.001), higher circulating blasts (P<.001), in trend higher BM blasts (P=.08), and were found more frequently in NK-AML (P=.007), AML with mutated NPM1 (P<.001), and AML with the genotype NPM1mutated/FLT3-ITDnegative (P<.001), whereas in complex karyotype IDH mutations were less frequent (P<.001). Among the NPM1 mutated cases the frequency of IDH2R140 mutations (n=40) was twice as high as of IDH1 mutations (n=21). Notably, no IDH2R172 mutation occurred together with a NPM1 mutation or FLT3-ITD. The median follow-up for survival of all pts was 3.56 yrs (95%-confidence interval, 3.24–4.01 yrs). Exploratory outcome analyses did not reveal any impact of IDH mutations on induction success or outcome [relapse-free survival (RFS); OS] in the entire AML cohort, as well as in NK-AML, and on subset analysis of NK-AML exhibiting the NPM1mutated/FLT3-ITDnegative genotype. However, in AML exhibiting the NPM1mutated genotype, pts with IDH1 mutations appeared to have an inferior OS than those with IDH2R140 mutations (P=.05; 3-yr OS rates, 12% vs 42%). In concordance with our previous results, we confirmed in an “as-treated” analysis the beneficial effect for ATRA on outcome in AML exhibiting the NPM1mutated/FLT3-ITDnegative genotype (OS; P=.026) and also the NPM1mutated genotype (OS; P=.0029). Further subset analyses of AML with the NPM1mutated genotype revealed an association of the IDH mutation type (IDH2R140vs IDH1R132vs IDH1/2 wildtype) and response to ATRA treatment. In pts harboring the IDH2R140 mutation OS appeared to be superior when treated with ATRA compared to no ATRA treatment (P=.10; 3-yr OS rates, 48% vs 25%). This beneficial effect of ATRA was also seen in pts with IDH1/2 wildtype (P=.0016; 3-yr OS rates, 30% vs 10%), but not in pts with IDH1 mutations (P=.46; 3-yr OS rates, 17% vs 13%). Conclusions:The overall incidence of IDH mutations in elderly is higher than in younger AML pts. This is mainly attributed to the increased frequency of IDH2R140 mutations (10%) in elderly compared to younger AML pts (~6%). Treatment with ATRA as adjunct to intensive chemotherapy appears to be beneficial in NPM1 mutated NK-AML with IDH2R140 mutation or with IDH1/2 wildtype. Disclosures:Greil:Cephalon: Research Funding.

FLT3-ITD and Age Are the Major Prognostic Factors In Relapsed AML with Normal Karyotype

AbstractAbstract 1719Acute myeloblastic leukemia with normal karyotype (CN-AML) is a heterogenous disease. During the past years, a wide variety of somatic gene mutations has been described in these patients. For several of these mutations, a prognostic impact in first-line therapy of patients with CN-AML has clearly been established in numerous large studies. In contrast, data on the influence of these aberrations on outcome after relapse are limited. We analyzed 98 adult patients up to 60 years of age (median age 47 years) with CN-AML in first relapse for clinical and molecular risk factors for survival. All patients were treated within two prospective multicenter trials. First-line treatment consisted of double induction and intensive consolidation therapy with high dose cytarabine, autologous or allogeneic stem cell transplantation. Leukemic blasts were analyzed for genetic aberrations in the genes FLT3, NPM1, CEBPA, WT1, IDH1 and IDH2. Median duration of first CR was 9.1 months. 33% of the patients had an FLT3-ITD, 50% a mutation in NPM1, 8% in CEBPA, 11% in WT1, 12% in IDH1 and 11% in IDH2. 28% had the genotype NPM1mutated/FLT3-ITDnegative. Seventy-seven of the patients received intensive re-induction chemotherapy after relapse, 17 patients directly received an allogeneic stem cell transplantation and only four patients received no further intensive treatment. A second CR was achieved in 52% of the 77 patients with re-induction. Presence of an FLT3-ITD (OR 0.24; 95% CI 0.07 – 0.80), duration of CR1 < 6 months (OR 0.24; 95% CI 0.06 – 0.92) and age above 47 years (OR 0.31; 95% CI 0.10 – 0.98) were associated with significantly inferior CR2 rates. Median survival after relapse was 9.7 months and six-year survival was 27%. In multivariate analysis, age above 47 years (HR 2.66, 95% CI 1.55 – 4.55) and FLT3-ITD (HR 2.06; 95% CI 1.22 – 3.94) were the only independent prognostic factors for survival. Other clinical or molecular parameters had no impact on survival. Patients with none of these risk factors (n = 27) had a six-year survival of 54%. In patients with one (n = 43) or both (n = 18) of these factors, survival was significantly inferior (15% and 6% six-year survival respectively). This was even true when only patients were considered who received an allogeneic stem cell transplantation after relapse (n = 51). In these patients, six-year survival was 64% when none of these risk factors was present, 24% for one risk factor and 20% for patients with both factors. In conclusion, FLT3-ITD and older age are the major prognostic factors in relapsed CN-AML. Patients with none of these factors have a relatively good outcome after re-induction and allogeneic stem cell transplantation. In contrast, patients with at least one of these risk factors have a dismal prognosis and might be considered for investigational treatment approaches after relapse. Disclosures:No relevant conflicts of interest to declare.

Autologous Hematopoetic Stem Cell Transplantation as An Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

AbstractAbstract 4595Despite advances in our understanding of its pathogenesis, acute myeloblastic leukemia remains difficult to treat. Although initial complete remission can be achieved in a high percentage of patients, relapse occurs in 70–80% of the patients. Two main approaches have been the attempt to eradicate the leukemic clonal cells population via chemotherapy with or without autologous stem cell rescue or to pursue a combined approach using an antileukemic therapy combined with an antileukemic immune response via allogeneic bone marrow transplantation. Autologous transplantation compares favorably against allogeneic bone marrow transplant in several ways. Autologous transplantation can be used as a consolidation therapy in the older population, and lack of a matched donor does not preclude the patients from this treatment.We report a retrospective analysis on 48 patients diagnosed with de novo AML, who did not have an available histocompatible donor, and who underwent autologous transplantation between years 2000–2009 at the University hematology Clinic, Skopje, Macedonia. All patients had ECOG score 1 or less. The patient's age ranged from 17 to 65 years with the median age 41 years. There were 26 males and 22 females. For stem cell mobilization patients received chemotherapy or chemotherapy plus G-CSF. The preparative chemotherapy regimen prior to autologous transplantation consisted of BuCy in 24 patient, BEAM in 22 and BuCyMel was used in the remaining 2 patients. We used bone marrow as primary source of stem cells in 18 patients, and peripheral blood stem cells in remaining 30 patients.The five years overall survival was 52% and the 5 years disease progression free survival were 42%. We analyzed sever factors that can influence the overall survival and the disease free survival such as: age, disease status, stem cell source, chemotherapy regiments prior to transplantation, conditioning regiments, number of mobilized stem cells. Advanced age and bone marrow stem cell source seems to be more influent factors.We report that the clinical results of autologous hematopoietic stem cell transplantation are sufficiently encouraging to warrant future trials that include autologous transplantation as an option for appropriately selected patients with AML in CR1. We conclude that autologous hematopoietic stem cell transplantation is a reasonable and save intensive consolidation for patients with acute myeloblastic leukemia who do not have a suitable HLA–matched donor. Disclosures:No relevant conflicts of interest to declare.