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Terminal complement blockade by humanised monoclonal antibody eculizumab has been used to treat transplantation-associated thrombotic microangiopathy (TA-TMA) in recent years. This retrospective international study conducted by the Paediatric Diseases (PDWP) and Inborn Error Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT) describes outcome and response of 82 paediatric patients from 29 centres who developed TA-TMA and were treated with eculizumab between January 2014 and May 2019. The median time from hematopoietic stem cell transplantation (HSCT) to TA-TMA manifestation was 92 days (range: 7-606) and from TA-TMA diagnosis to the start of eculizumab treatment 6 days (range: 0-135). Most patients received eculizumab weekly (72%, n = 55) with a standard weight (kg)-based dose (78%, n = 64). Six months from beginning of eculizumab therapy, the cumulative incidence of TA-TMA resolution was 36.6% (95% CI: 26.2-47) and the overall survival (OS) was 47.1% (95% CI: 35.9-57.5). All 43 patients with unresolved TA-TMA died. The cause of death was HSCT-related in 41 patients. This study also documents poor outcome of patients without aGvHD and their frequent concomitant viral infections. Considering recent publications, intensified eculizumab dosing and complement monitoring could potentially improve upon outcomes observed in this study.

Hereditary predisposition has been ever since implicated in the etiology of childhood myelodysplastic syndromes (MDS). Until recently, GATA2 deficiency prevailed as a major germline cause in pediatric primary MDS. In the past 2 years, we and others identified germline mutations in paralogue genes SAMD9 and SAMD9L residing on chromosome 7q21.2 as new systemic diseases with high propensity for MDS with monosomy 7. Although initially, mutations in SAMD9 and SAMD9L genes were associated with MIRAGE and Ataxia-Pancytopenia syndromes, respectively, with recent reports the phenotypes are becoming more intertwined. Nevertheless, the predisposition to MDS with monosomy 7 (-7) remains a common clinical denominator. Both genes are categorized as negative regulators of cellular proliferation and mutations were shown to be activating. Because of their high evolutionary divergence, classical in silico prediction is erratic, thereby establishing in vitro testing as the current gold standard for pathogenicity evaluation. The objectives of this study were to define the prevalence of SAMD9/9L germline mutations in primary pediatric MDS, and to describe the clinical phenotype and outcome. In addition, we aimed to characterize the somatic mutational architecture and develop a functional scoring system. Within the cohort of 548 children and adolescents with primary MDS diagnosed between 1998 and 2016 in Germany, 43 patients (8%) carried SAMD9/9L mutations that were mutually exclusive with GATA2 deficiency and known constitutional bone marrow (BM) failure. MDS type refractory cytopenia of childhood was diagnosed in 91% (39/43), and MDS with excess blasts in 9% (4/43) of mutated cases. Karyotype at diagnosis was normal in 58%, and -7 was detected in 37% of SAMD9/9L cohort. Within MDS subgroup with -7 (n=74), SAMD9/9L mutations accounted for 22% of patients. Notably, the demographics, familial disease, diagnostic blood and BM findings, overall survival (OS) and the outcome after HSCT were not influenced by mutational status in our study cohort (n=548). At the last follow up, 88% (38/43) of SAMD9/9L MDS patients were alive; 35/43 had been transplanted with a 5-year-OS of 85%. Next, we added 26 additional cases with SAMD9/9L mutations diagnosed in Europe within EWOG-MDS studies. In the total cohort of 69 germline mutated patients we found a total of 75 SAMD9/9L mutations, of which 67 were novel. Of those we tested 47 using a HEK293 cell in vitro system and 45/47 mutants inhibited proliferation. While 53/69 patients carried only single germline mutations (missense in 50/53 and truncating in 3/53), in the remaining 16 patients, 11 additional truncating and 7 missense mutations were found. We did not observe an association between germline mutation and phenotype. Immunological issues (e.g. recurring infections, low Ig) were described in 32%/50% of SAMD9/9L-mutated patients, while physical anomalies were very heterogeneous and reported in ~50% of patients in both mutational groups. Intriguingly, genital phenotypes occurred in 40% of SAMD9L, while neurological problems were present in 30% of SAMD9 - mutational subgroups. To elucidate the somatic mutational landscape, we performed whole exome and deep sequencing of 58 SAMD9/9L patients and identified recurrent somatic mutations in known oncogenes that were earlier associated with pediatric MDS: SETBP1 (10%), RUNX1 (7%), ASXL1 (5%), EZH2 (5%), CBL (3%). The identified somatic mutations occurred in association with monosomy 7 background (18/20). Finally, we utilized the results from functional testing of the 47 SAMD9/9L variants as our test cohort to develop combinatorial in silico scoring. The rationale was to decrease the dependency on functional validation. Based on the results of 20 in silico tools we could concatenate a matrix of 5 algorithms to resolve the pathogenicity of >80% of variants. Using this model, all variants predicted as pathogenic showed also growth-restrictive effect in vitro. In summary, pathogenic SAMD9/9L germline mutations account for 8% of primary pediatric MDS and 22% of MDS/-7. The mutations identified are heterogeneous and their effect can be predicted using a combinatorial in silico - in vitro approach. Finally, the clinical outcome and somatic mutational landscape are not influenced by the mutational status. Disclosures Locatelli: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Miltenyi: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Niemeyer:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction Detection of minimal residual disease (MRD) is an important predictor of patient outcome following treatment of B-cell acute lymphoblastic leukemia (B-ALL). We assessed concordance between two MRD assays, with different assay sensitivities, to determine which MRD detection method could support early relapse detection. Immunoglobulin next generation sequencing (Ig NGS) and flow cytometry (FC) were tested in samples from two clinical trials ELIANA (NCT02435849) and ENSIGN (NCT02228096) for pediatric relapsed and refractory B-ALL patients treated with tisagenlecleucel. We also assessed whether using blood with Ig NGS would be comparable to BM testing with FC. Finally we analyzed whether clonal evolution, as detected by Ig NGS, occurred during of the course of therapy for both CD19+ and CD19- relapse patients. Methods In this analysis, bone marrow and peripheral blood specimens at screening (pre-tisagenlecleucel infusion), post-infusion and relapse were tested. Ig NGS was performed in 300 samples from 88 patients. 237 samples from 83 patients also had FC MRD results available. MRD was measured on fresh blood and bone marrow using a 3-tube FC assay (CD10, CD19, CD13, CD20, CD22, CD33, CD34, CD38, CD45, CD58, CD123). The FC MRD assay has a lower limit of sensitivity of 0.01% of white blood cells. Ig NGS detection of MRD was performed using the Adaptive Biotechnology's NGS MRD assay. MRD quantitative values, along with the qualitative MRD calls at each assay sensitivity level (10-4, 10-5 and 10-6) were reported. At baseline, 85 out of 88 samples had informative clones. Results and Conclusions To examine the comparability of flow cytometry and Ig NGS methods in assessing MRD, baseline and post-treatment samples were tested. Baseline samples, which had a high disease burden, showed 100% MRD concordance between both assays. However, post-treatment, where the leukemic burden was dramatically reduced, Ig NGS detected a greater number of MRD positive samples compared to FC, at each sensitivity level tested (10-4, 10-5 and 10-6). At the highest sensitivity level of 10-6, Ig NGS was able to detect 18% more MRD positive post-treatment samples. Importantly, Ig NGS was able to detect MRD positivity 1-4 months ahead of clinical relapse in a small number of relapsed patients, whether relapse was CD19+ or CD19-. This may provide an important window of opportunity for pre-emptive treatment while a patients' tumor burden is still low. In B-ALL, it has previously been described that MRD levels can be one to three logs lower in blood compared to bone marrow (VanDongen JJ et al. Blood 2015). Our results support these findings whereby MRD burden in bone marrow was higher than in blood using both FC and Ig NGS. We next set out to determine if the increased sensitivity afforded by the Ig NGS assay could provide a level of MRD detection in the blood comparable to FC in the bone marrow. In patients with matching data available, Ig NGS was able to detect more MRD positive blood samples than FC MRD positive bone marrow samples. This suggests that monitoring of MRD using Ig NGS in the blood holds the potential to be used as a surrogate for FC MRD in bone marrow. The relationship between MRD and prognosis was examined. Patients who were MRD negative by both Ig NGS and FC at the end of first month post-infusion had better progression-free survival and overall survival compared to those with detectable MRD. Tumor clonality will be further analyzed to understand sub-clone composition at baseline and clonal evolution following tisagenlecleucel treatment. Taken together, these results highlight the importance of using a highly sensitive assay, such as Ig NGS, when monitoring for MRD. MRD detection by Ig NGS holds the potential to identify early response/relapse in patients, which could provide a window of opportunity for additional intervention before morphological relapse. Ongoing studies with larger patient groups will provide further information on the applicability of Ig NGS MRD detection and its association with long-term outcome in tisagenlecleucel-treated pediatric r/r B-ALL patients. Disclosures Pulsipher: Novartis: Consultancy, Honoraria, Speakers Bureau; CSL Behring: Consultancy; Amgen: Honoraria; Adaptive Biotech: Consultancy, Research Funding. Han:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Quigley:Novartis Pharmaceuticals Corporation: Employment. Kari:Adaptimmune LLC: Other: previous employment within 2 years; Novartis Pharmaceuticals Corporation: Employment. Rives:Shire: Consultancy, Other: Symposia, advisory boards ; Amgen: Consultancy, Other: advisory board ; Novartis Pharmaceuticals Corporation: Consultancy, Other: Symposia, advisory boards ; Jazz Pharma: Consultancy, Other: Symposia, advisory boards . Laetsch:Bayer: Consultancy; Eli Lilly: Consultancy; Pfizer: Equity Ownership; Novartis Pharmaceuticals Corporation: Consultancy; Loxo Oncology: Consultancy. Myers:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau. Qayed:Novartis: Consultancy. Stefanski:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Speakers Bureau. Baruchel:Shire: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Servier: Consultancy; Roche: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Travel, accommodations or expenses; Celgene: Consultancy. Bader:Cellgene: Consultancy; Riemser: Research Funding; Medac: Patents & Royalties, Research Funding; Neovii: Research Funding; Novartis: Consultancy, Speakers Bureau. Yi:Novartis Pharmaceuticals Corporation: Employment. Kalfoglou:Novartis Pharmaceuticals Corporation: Employment. Robins:Adaptive Biotechnologies: Consultancy, Employment, Equity Ownership, Patents & Royalties. Yusko:Adaptive Biotechnologies: Employment, Equity Ownership. Görgün:Novartis Pharmaceuticals Corporation: Employment. Bleickardt:Novartis Pharmaceuticals Corporation: Employment. Wong:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Grupp:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Adaptimmune: Consultancy; University of Pennsylvania: Patents & Royalties.

BACKGROUND Tisagenlecleucel is an FDA approved chimeric antigen receptor (CAR)-T cell therapy that reprograms T cells to eliminate CD19+ B cells. ELIANA (NCT02435849) is a phase 2 pivotal study of tisagenlecleucel in pediatric/young adult patients (pts) with CD19+ r/r B-cell acute lymphoblastic leukemia (ALL), the first global trial of a CAR-T cell therapy. The primary objective was met, with an overall remission rate (ORR) of 81% (complete remission [CR] + CR with incomplete blood count recovery [CRi]). Here we present an update of ELIANA, with additional pts and additional 11 mo follow-up from the previous report (Maude et al. N Engl J Med 2018). METHODS Eligible pts were aged ≥3 y at screening and ≤21 y at diagnosis and had ≥5% leukemic blasts in bone marrow. Tisagenlecleucel was centrally manufactured at 2 sites (Morris Plains, NJ, USA and Leipzig, Germany) by lentiviral transduction of autologous T cells with a vector encoding for a second generation 4-1BB anti-CD19 CAR and expanded ex vivo. Tisagenlecleucel was provided to pts at 25 study centers in 11 countries on 4 continents using cryopreserved apheresed mononuclear cells, central production facilities, and a global supply chain. The primary endpoint, ORR within 3 mo and maintained for ≥28 d among infused pts, was assessed by an independent review committee. Secondary endpoints included duration of remission (DOR), overall survival (OS), safety, and cellular kinetics. RESULTS As of April 13, 2018, 113 pts were screened and 97 enrolled. There were 8 manufacturing failures (8%) and 10 pts (10%) were not infused due to death or adverse events (AEs). Following lymphodepleting chemotherapy in most pts (76/79; fludarabine/cyclophosphamide [n=75]), 79 pts were infused with a single dose of tisagenlecleucel (median dose, 3.0×106 [range, 0.2-5.4×106] CAR-positive viable T cells/kg), and all had ≥3 mo of follow-up or discontinued earlier (median time from infusion to data cutoff, 24 mo [range, 4.5-35 mo]). Median age was 11 y (range, 3-24 y); 61% of pts had prior hematopoietic stem cell transplant (SCT). Among the 65 pts with CR/CRi, 64 (98%) were MRD- within 3 mo. Median DOR by K-M analysis was not reached (Figure): responses were ongoing in 29 pts (max DOR, 29 mo and ongoing); 19 pts relapsed before receiving additional anticancer therapy (13 died subsequently); 8 pts underwent SCT while in remission, 8 received additional anticancer therapy (non-SCT) and 1 discontinued while in remission. The probability of relapse-free survival at 18 mo was 66% (95% CI, 52%-77%). Median OS was not reached; OS probability at 18 mo was 70% (95% CI, 58%-79%). Cytokine release syndrome (CRS) occurred in 77% of pts (grade [G] 3/4; 48%; graded using the Penn scale); 39% of pts received tocilizumab for treatment of CRS with or without other anti-cytokine therapies; 48% of pts required ICU-level care for CRS, with a median ICU stay of 7 d. All cases of CRS were reversible. Most common G 3/4 nonhematologic AEs (>15%) other than CRS were neutropenia with a body temperature >38.3°C (62% within 8 wk of infusion), hypoxia (20%), and hypotension (20%). 13% of pts experienced G 3 neurological events, with no G 4 events or cerebral edema. Based on laboratory results, 43% and 54% of pts had G 3/4 thrombocytopenia and neutropenia not resolved by d 28; the majority of events resolved to G ≤2 by 3 mo. 25 post-infusion deaths were reported: 2 within 30 d (1 disease progression, 1 cerebral hemorrhage); 23 after 30 d of infusion (range, 53-859 d; 18 disease progression, 1 each due to encephalitis, systemic mycosis, VOD [hepatobiliary disorders related to allogeneic-SCT], bacterial lung infection, and an unknown reason after study withdrawal). Tisagenlecleucel expansion in vivo correlated with CRS severity, and persistence of tisagenlecleucel along with B-cell aplasia in peripheral blood was observed for ≥2.5 y in some responding pts. Analysis of B-cell recovery and correlation with relapse will be presented. CONCLUSIONS With longer follow-up, the ELIANA study continues to confirm the efficacy of a single infusion of tisagenlecleucel in pediatric and young adults with ALL without additional therapy. AEs were effectively and reproducibly managed globally by appropriately trained personnel at study sites. The achievement of high overall response rates and deep remissions, in combination with the median duration of response and overall survival not being reached, further corroborate previously reported results. Figure. Figure. Disclosures Grupp: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Adaptimmune: Consultancy; University of Pennsylvania: Patents & Royalties. Maude:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rives:Shire: Consultancy, Other: Symposia, advisory boards ; Jazz Pharma: Consultancy, Other: Symposia, advisory boards ; Novartis Pharmaceuticals Corporation: Consultancy, Other: Symposia, advisory boards ; Amgen: Consultancy, Other: advisory board . Baruchel:Celgene: Consultancy; Amgen: Consultancy; Roche: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Travel, accommodations or expenses; Novartis: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Servier: Consultancy. Bittencourt:Novartis Pharmaceuticals Corporation: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria. Bader:Riemser: Research Funding; Cellgene: Consultancy; Medac: Patents & Royalties, Research Funding; Neovii: Research Funding; Novartis: Consultancy, Speakers Bureau. Laetsch:Bayer: Consultancy; Pfizer: Equity Ownership; Eli Lilly: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy; Loxo Oncology: Consultancy. Stefanski:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Speakers Bureau. Myers:Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau. Qayed:Novartis: Consultancy. Pulsipher:CSL Behring: Consultancy; Amgen: Honoraria; Adaptive Biotech: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau. Martin:Novartis Pharmaceuticals Corporation: Research Funding; Jazz Pharmaceuticals: Research Funding. Nemecek:Novartis Pharmaceuticals Corporation: Other: advisory boards. Boissel:Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leung:Novartis Pharmaceuticals Corporation: Employment. Eldjerou:Novartis Pharmaceuticals Corporation: Employment. Yi:Novartis Pharmaceuticals Corporation: Employment. Mueller:Novartis Institutes for Biomedical Research: Employment; Novartis Pharmaceuticals Corporation: Equity Ownership, Other: Patent pending. Bleickardt:Novartis Pharmaceuticals Corporation: Employment.

Introduction: Most pediatric patients (pts) with ALL receive total body irradiation (TBI) for myeloablative conditioning of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unproven whether TBI can be replaced by chemotherapy (CHT). Methods: To compare the outcomes of TBI- versus (vs.) CHT-based conditioning, we performed a retrospective EBMT-registry based study. Children between 2 and 18 years of age (y.) after myeloablative conditioning for first allo-HSCT of bone marrow (BM) or peripheral blood SC (PBSC) from matched sibling (MSD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to consider the covariate "distribution of TBI recipients" for pts who did not receive TBI. Results: In total 3071 pts (CR1: 1504 (49%), CR2: 1567 (51%)) were included. CR1: 1045 pts (69%) received BM and 459 pts (31%) PBSC from MSD (760 (51%)) or UD (744 (49%)). CR2: 1067 pts (68%) received BM and 500 pts (32%) PBSC from MSD (675 (43%)) or UD (892 (57%)). Overall, conditioning was TBI- in 2647 (86%) and CHT-based in 424 pts (14%). Busulfan/Cyclophosphamide (Bu/Cy) and Bu/Cy/Etoposide (Bu/Cy/Eto) were the two most frequently applied CHT combinations in CR1 (68 (32%), 66 (31%)) and CR2 (68 (32%), 52 (25%)). The remaining conditionings included 5 different combinations of chemotherapeutics (other chemo). 1504 pts in CR1 were conditioned with TBI (1291), Bu/Cy/Eto (66) or other chemo (147) with a median follow-up of 4.4, 3.4 and 2.4 y. In weighted univariate analysis no significant differences were detected for LFS (5-y.-LFS, range: 62.4 to 67.5%) and relapse incidence (5-y.-RI, range: 24.0 to 29.0%). In pairwise testing, OS after Bu/Cy/Eto was significantly better compared with TBI (5-y.-OS, 78.7 vs. 66.8%, P=.006). Non-relapse mortality was significantly higher after other chemo (5-y.-NRM, 12.7%, P Other significant influencing factors on LFS were age (5-y.-LFS, 2-11 y. 65.8 vs. 12-18 y. 58.0%, P=.009), y. of HSCT (2008-2012 65.9 vs. 2000-2007 59.6%, P=.035) and donor type (MSD 64.9 vs. UD 59.5%, P=.007). RI was influenced by y. of HSCT (5-y.-RI, 2008-2012 21.7 vs. 2000-2007 26.8%. P=.026). OS was influenced by age (5-y.-OS, 2-11 y. 72.7 vs. 12-18 y. 61.7%, P In weighted multivariable Cox model clustered on EBMT centers, TBI-based conditioning in CR1 was associated with lower RI (HR 0.70, P=.047), lower OS (HR 1.54, P=.017) and higher NRM (HR 3.97, P 1567 pts in CR2 were conditioned with TBI (1356), Bu/Cy (68) or other chemo (143) with a median follow-up of 3.9, 3.2 and 3.1 y. In weighted univariate analysis highly significant differences of survival were detected. TBI-based conditioning resulted in highest 5-y.-LFS of 52.2% (Bu/Cy 41.0%, other chemo 18.4%, P Other significant influencing factors on LFS were age (5-y.-LFS, 2-11 y. 53.5 vs. 12-18 y. 43.0%, P In weighted multivariable Cox model clustered on EBMT centers, TBI-based conditioning in CR2 was associated with higher LFS (HR 0.48, P Conclusion: Conditioning by TBI demonstrated clear superiority in comparison to CHT for children with ALL undergoing HSCT in CR2. For pts in CR1, TBI- and CHT-based conditioning showed similar results. This retrospective data is currently re-evaluated in a prospective, randomized, international trial (ALL SCTped 2012 FORUM). Disclosures Büchner: Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Consultancy. Veys: Bellicum: Research Funding; Servier: Research Funding. Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding.

Christina Peters, Petr Sedlacek, Jean Hugues Dalle, Stelios Graphakos, Antonio Campos, Akif Yesilipek, Jacek Wachowiak, Arjan Lankester, Andrea Pession, Amir Ali Hamidieh, Marianne Ifversen, Jochen Büchner, Gergely Krivan, Franca Fagioli, Arnaud Dalissier; Myriam Labopin; Peter Bader on behalf of the EBMT Pediatric Diseases Working Party Most children with acute lymphoblastic leukemia (ALL) with indication for allogeneic hematopoietic stem cell transplantation (HSCT) receive myeloablative conditioning with a total body irradiation (TBI)-containing regimen. To investigate the outcomes of patients (pts) who did not undergo TBI, we performed a retrospective registry based study on children below 18 years who received a myeloablative chemo-conditioning for a first allogeneic HSCT from different donors between 2000 and 2012. In this analysis, only chemotherapeutic regimens with more than 30 applications were included. In total, 732 pts were included: 313 pts who received bone marrow (BM) or peripheral blood stem cells (PBSC) in 1st CR, 247 pts with BM/PBSC transplantation in CR2, 85 pts and 52 pts who received umbilical cord blood (CB) in 1st or 2nd CR, respectively. The most commonly applied myeloablative chemo-combinations were: Busulfan (Bu)/Cyclophosphamide (Cy) (n=202), Bu/Cy/Etoposide (VP) (n=189), Bu/Cy/Melphalan (Mel) (n=93), Bu/AraC/Mel (n=80), Bu/Fludarabine (Flu)/Thiotepa (Thio) (n=62), Bu/Cy/Thio (n=53, Bu/Cy/Thio (n=53), and Bu/Flu (n=53). 313 pts received either BM or PBSC in CR1 with a median follow up of 26 months (1-156) and we compared Bu/Cy/VP vs the other chemo-conditioning regimens. The Bu/Cy/VP cohort had a longer follow up (med 37 vs. 20 months, p=0.002), pts were younger (med 3,6 vs. 6,5 years, p=0.003) and the median year of transplant was earlier (med 2009 vs. 2010, p=0.03). Donor type, CMV match, gender match, stem cell were comparable. In univariate analysis, conditioning with Bu/Cy/VP was better than all other combinations: relapse incidence (RI) 21% vs 32% (p=0.05), leukemia-free survival (LFS) 72 vs 54% (p=0.004), overall survival (OS) 79 vs 68% (p=0.03) and chronic GVHD (cGVHD) 9% vs 19% (p=0.014). Engraftment and incidence and severity of acute GVHD were similar and non- relapse mortality (NRM) was 7% vs 13% (p=0.10). Other significant influencing factors were: interval between diagnosis and transplantation below or beyond 208 days (NRM 6% vs 16%, p=0.015), donor sibling vs other (RI 35% vs 23%, p=0.01, NRM 5% vs 16%, p=0.001) and in vivo T cell depletion (TCD) vs no TCD (RI 35% vs. 19%, p=0.003; NRM 20% vs 4%, p=0.0001). In the cox model, conditioning type (Bu/CY/VP vs other), age, year of transplantation, interval from diagnosis to transplant, donor type, stem cell source and in vivo TCD were evaluated. For LFS only BU/CY/VP was associated with better outcome (p=0.004, HR .52), RI was lower after Bu/Cy/VP (HR .54, p=0.02), NRM was higher in pts older than 4,6 years (p=0.02, HR 2,48) and after TCD HSCT (p=0.01, HR 9,13) and OS was best after Bu/Cy/VP (p=0.03, HR 0.57). We conclude that omission of TBI is feasible for children who undergo first allogeneic HSCT in first or second complete remission. The combination of busulfan, cyclophosphamide and etoposide resulted in better LFS and OS with less NRM and RI for children who received bone marrow or peripheral blood stem cells in CR1. These observations should be the basis for prospective trials in homogenous patient groups. Disclosures No relevant conflicts of interest to declare.