ALBERT

Description: Background : Introducing a new antifungals and diagnostic procedures has improved prognosis of the invasive aspergillosis (IA) in hematological patients. The number of patients with IA who are candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increased. The influence of IA on survival and on allo-HSCT related complications has not been investigated in a prospective study. Aim: to estimate impact of prior proven and probable IA on outcome of allo-HSCT compared to patients without IA. Methods: In prospective observational single center study 362 allo-HSCT recipients (336 - first and 26 - second allo-HSCT) were included from Jan 2012 to Dec 2014. The median age was 34 y, males - 54%. Most of pts had high-risk acute leukemia (70%). Allo-HSCT with MUD were performed in 57%, MRD - 24%, haplo - 11%, MMUD - 8%, predominantly with RIC (80%). All patients with lesions in CT scan before allo-HSCT have undergone bronchoscopy with BAL microscopy, culture and GM test. EORTC/MSG 2008 criteria were used for the diagnosis of proven and probable IA as well as to evaluate response to therapy. "Active" invasive IA - IA diagnosed just before allo-HSCT. All patients were observed with the median 2 years follow up. We analyze status of pts before HSCT, donor types, source of HSCT, CMV status, conditioning regimens and type of immunosuppression, relapse or progression of IA, relapse of underlying disease, duration of antifungal therapy and prophylaxis, acute and chronic GvHD. The cumulative incidences were determined with cumulative incidence method. Differences between the two cohorts were verified with Gray test. Overall survival after allo-HSCT was estimated with Kaplan-Meier method and cohorts were compared by log-rank test. Results: Incidence of IA before allo-HSCT was 20% (n=72/362). According to EORTC/MSG 2008 criteria 92% of pts had probable IA and 8% - proven IA. The main sites of IA were lungs - 95%, central nervous system - 3%, and colon - 3%, other sites were observed in a combination with lungs involvement: sinuses - 5%, spleen - 3%, and liver - 3%. The median time from IA to allo-HSCT was 3 months (3 days - 30 months). Antifungal therapy before allo-HSCT was used in 69% pts (voriconazole - 95%, other - 5%) with the median duration of therapy - 2 months. Complete response to antifungal therapy was registered in 19 (26%) patients, partial response or stabilization - 31 (43%), and "active IA" - 22 (31%). After allo-HSCT all patients received antifungal therapy with voriconazole (first line - 31%, continuation of treatment - 43%, and secondary prophylaxis - 26%). Median length of treatment was 166 days (37 - 394) with the median duration to effect 99 days (31 - 217). No toxicity of the antifungal treatment was registered. Cumulative incidence of relapse or progression of IA at 2 year after allo-HSCT was 14% (n=10). "Active" underlying disease before D+100 post transplant was the only risk factor for the relapse or progression of IA after allo-HSCT (6% vs 33%, p=0,007). 100-days OS after allo-HSCT was 77%, 2-year OS after allo-HSCT was 62%. There was no significant difference in OS in patients with or without IA prior to allo-HSCT (57% vs 65%, p=0,3). Duration of antifungal therapy before HSCT (

Description: Introduction. Stromal microenvironment posses a key role in the regulation of both normal hematopoiesis and its reconstitution after hematopoietic stem cell transplantation (HSCT). Recent data supports the idea that bone marrow stromal cells (BMSC) also have genetic aberrations and may tightly involved in the pathogenesis of HSCT complications. These findings justify the need for more detailed study of genetic aberrations in BMSC. The aim of this study was to evaluate genetic aberrations inBMSC and check the ability to gain them in coculture system. Materials and methods. The interaction of BMSC with hematopoietic tumor cell lines bearing specific genetic aberrations (BCR-ABL fusion transcript for K-562 and JAK2 V617F mutation for Uke-1 cell line) was investigated in stromal cells harvested from 17 patients and 8 healthy donors. We performed cultivation of BMSC monolayer and tumor cells suspension using semipermeable membrane plates inserts with different pore size (0,4 μm and 3,0 μm) in order to exclude direct cell-to-cell contact. We looked also forexisting specific genetic aberrations (point mutations and fusion transcripts) in BMSC of patients with the respective aberration in their leukemic clone. For this purpose we used both karyotyping (7 patients) and RQ-PCR method. BMSC were examined by flow cytometry to evaluate the possible contamination with cells of hematopoietic lineage. Results. We investigated the BMSC karyotype in seven patients and only one case led us to a remarkable finding. The clonal chromosomal rearrangement t(1;7) was detected in 25% of BMSC metaphases. Interestingly, this aberration was never detected in patient's leukemic cells. Moreover, at the moment of this investigation patient had full clinical and hematological remission, full donor chimerism and no signs of minimal residual disease (MRD). We also examined BMSC from leukemia patients bearing recurrent genetic abnormalities and in one case the leukemia-specific marker was detected by RQ-PCR - we observed expression of ETV6-RUNX1 gene (≈0,02%) in BMSC by patient with t(12;21) acute lymphoblastic leukemia. At the moment of BMSC culture initiation ETV6-RUNX1 expression in patient's bone marrow was detected at high level (ETV6-RUNX1/ABL*100=321%). Before carrying out RNA extraction BMSC were harvested after the second passage and no contamination with CD45+/CD34+ cells by flow cytometry was observed (50,000 events collected from the sample). When BMSCs and Uke-1 cell line were cocultured by using of 3,0 μm pore culture dishes inserts, the BMSC population gained the Jak2V617F mutation (allele burden ≈ 30,39%). We reproduced similar experiments with the K-562 cell line and got similar results - CD45+ cells were also detected in BMSC population (≈ 30%). Moreover we detected CD45+ non-cellular particles by flow cytometry analysis. Implying K-562 cells are not likely to cross the semipermeable membrane (3,0 μm pores versus 20,0 μm cells as measured during microscopy). Besides BCR-ABL gene expression in BMSC was detected by RQ-PCR (BCR-ABL/ABL*100=19%). We repeated same test with 0,4 μm pore inserts and without them in order to check implication of cell-to-cell interaction. We didn't obtain any similar results with smaller pores, but the fusion transcript was detected in CD45- BMSC population when these two cell populations weren't devided. Both findings point out at possible horizontal gene transfer mediated by membrane vesicles larger than 0,4 μm and direct whole cell fusion. Conclusion Our data stands for the existence of horizontal gene transfer between leukemic clone and BMSC. This process seems to be mediated by membrane vesicles larger than 0,4 μm in size, though cell fusion can also take place. We also confirmed the fact BMSCs can bear clonal genetic rearrangements which are not specific to tumor cell populations. These findings show tight interaction between tumor and microenvironment cells and can partly explain nature of PCR-based MRD persistence in complete remission. Disclosures No relevant conflicts of interest to declare.

Description: Background. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with acute myeloid leukemia (AML). The conditioning regimen administered for this patient based on busulfan combined with cyclophosphamide (BuCy), fludarabine (BuFlu) or some other agents. Comparisons of myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) have demonstrated a various results between relapse and toxicity in a few reports. We supposed, that dose intensity of busulfan across regimens may affect treatment outcomes. The goal of this retrospective study was to evaluate the impact dose of busulfan to overall survival (OS), transplant-related mortality (TRM), relapse-free survival (RFS), toxicity, the incidence of primary graft failure and acute graft-versus-host disease (GVHD) in transplantation in children and adolescents with AML. Material and methods. We analyzed 110 AML pediatric patients with the median age 9 y.o. (range 1-19), who underwent first allo-HSCT with busulfan based (per os and IV) conditioning in R.M. Gorbacheva Memorial Institute from 2002 to 2018. Patients were divided into 3 groups: Bu1 - patients, who received busulfan at the dose 8-10 mg/kg, n=34 (31%), in Bu2 - dose of busulfan was 12 mg/kg, n= 35 (32%), in Bu3 - dose of busulfan was 〉12 mg/kg, n= 41 (37%). In Bu1 busulfan was combined with Flu in 31 pts (91%) and Cy in 3 (9%); in Bu2 - with Flu in 12 (34%) , Cy in 7 (20%) and other agents in 16 (46%); in Bu3 - with Cy in 32 (78%), with Flu in 7 (17%) and other agents in 2 pts (5%) (p 〈 0.001). Patients in Bu2 received more Cy based GVHD prophylaxis regimens (69% vs 44% in Bu1, vs 29% in Bu3, p = 0.003) and more HAPLO grafts (51% vs 29% in Bu1, vs 15% in Bu3, p = 0.003). The complete remission at the HSCT was observed in 79 % in Bu1, 49% in Bu2, 61% in Bu3 p=0,02. Probabilities of OS, RFS, TRM were estimated by using the Kaplan-Meier method. Incidence of toxicity, acute GVHD and primary graft failure - by using Mann - Whitney U-test. Results. Transplant engraftment was achieved in 95 (86%) of patients. Graft failure occurs in the 5 patients of Bu1 group (15%), in the 6 pts of Bu2 (17%) and in the 4 pts of Bu3 (10%), p=0,7. Median follow-up was 2 years for Bu1 and Bu3, 1 year for Bu2. OS was similar (Bu1=59% vs Bu2=60% vs Bu3=51%), p=0,7. OS of pts with CR before HSCT was 70% in Bu1, 82% in Bu2, 60% in Bu3, p=0,3 and 14%, 39%, 38% for pts with progression disease (PD), respectively, p=0,5. RFS was 74% in Bu1, 82% in Bu2, 64% in Bu3 at CR, p=0,4; 43%, 39% and 38% in pts with progression, respectively, p=0,9. Median of RFS were also similar for the pts in PD, (4 months in Bu1, 5 months in Bu2 and Bu3), p=0,9 and not achieved for pts at CR. Drug related toxicity grade 3-4 experienced in 35% pts in Bu1, 29% in Bu2, in 54% in Bu3, p=0,04. Mucositis and toxic hepatitis were the most common adverse events. Sinusoidal obstruction syndrome (SOS) experienced in 8 pts from different group: 4 from Bu2 (11%), 3 from Bu3 (7%) and only 1pts from Bu1 (3%) with previously treated of gemtuzumab ozogamicin, p=0,4. The most pts with SOS (3/5) had PD at the HSCT. Cumulative incidence of acute GVHD grade 2 (15% vs 14% vs 10%, p=0,8) were not different. Acute GVHD grade 3-4 was observed a bit more often in Bu3 (34%), than in Bu1 (18%) and Bu2 (17%), p=0,09. TRM up to +100 days was also higher in Bu3 (15%), than in Bu2 (6%) and Bu1 (0%), p=0,05. Conclusions. The transplant results of children with similar disease status of AML, received conditioning with various dose of busulfan, were not associated with significant differences in overall outcomes. The higher dose busulfan may increase incidence of toxicity grade 3-4 (p=0,04) and acute GVHD grade 3-4 (p=0,09) with increasing of early TRM (p=0,05). Disclosures Moiseev: Celgene: Consultancy, Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Pfizer: Other: Travel grants; MSD: Other: Travel grants; BMS: Other: Travel grants; Takeda: Other: Travel grants.

Description: Background: Allo-HSCT with myeloablative conditioning (MAC) has traditionally been performed in patients with ALL and has been associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities or in elderly patients. In contrast to the adults, the RIC pediatric experience is still sparse. The aim: to compare efficacy of reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) for allo-HSCT in children suffering from very high risk (VHR) ALL. Patients and methods: This was a retrospective analysis performed in 233 patients (pts) with ALL (age - from 4 month till 18 y.o. (mediana 11 y.o.)), who received allo-HSCT at R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation between 12/2000 and 12/2017. MAC (busulfan or treosulphan containing) was used in 159 pts: 1st CR - 26 pts, 2nd CR -57 pts, 3rd or 4th CR 23 - pts, relapse -53 pts. Allo-HSCT with RIC was performed in 74 pts: 1st CR - 14 pts, 2nd CR -29 pts, 3rd or 4th CR - 12 pts, relapse -20 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melfalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). The disease status was not different between groups (p=0.674) Indication for RIC allo-HSCT was poor performance status (Lanskoy/Karnovsky=0,5x109/l was D+18 (range D+8-48). Transplant engraftment was observed in 64 pts (86%) after RIC and 150 pts (93%) after MAC (p=0,224). OS pts after RIC allo-HSCT performed in 1 CR 70% and after MAC - 85% (p=0,043), in 2 CR 56% after RIC and 49% after MAC (p=0,436), in 3 or 4 CR 34% after RIC and 25% after MAC (p=0,394). OS in patients with active disease was 16% in RIC-group and 18% in MAC-group (p=0,432). The transplant-related mortality rate was 18% after RIC and 20% after MAC (p=0,40). Risk of relapse was 37% after RIC and 42% after MAC (p=0,39). Acute GVHD II-IVgr developed in 32% pts after RIC and 33% after MAC (p=0,883), early infections were diagnosed in 63% in RIC-group, and 59% in MAC-group (p=0,356). Early toxic complications were observed (CTC): mucositis III-IV gr in 13% pts after RIC and in 54% pts after MAC (p=0,001), nephrotoxicity in 7% pts and in 21% pts (p=0,042), hepatitis gr II-III in 24% pts and in 57% pts, respectively (p=0,034), neurological complications in 22% pts and 42% pts, resp. (p=0,046). Conclusion: RIC allo-HSCT of VHR ALL in 2,3 or 4 CR pts ≤ 18 y.o. is effective and comparable with MAC allo-HSCT. Early toxic complications after RIC were less frequent. Possibly, the use of RIC can maintain efficacy while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Disclosures Moiseev: Pfizer: Other: Travel grants; BMS: Other: Travel grants; MSD: Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Celgene: Consultancy, Other: Travel grants; Takeda: Other: Travel grants.

Description: Background. In the expanding population of immunocompromised patients rare fungi have emerged as important pathogens, causing invasive infections associated with high morbidity and mortality. The number of publications on the invasive fungal diseases caused by rare pathogens (rare IFD) after hematopoietic stem cell transplantation (HSCT) and chemotherapy is limited. Patients and methods. We design the retrospective study in order to investigate the epidemiology of rare IFD in large cohort of patients after HSCT and chemotherapy for 11-year period. From 2008 to 2018 in R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation (CIC725) were performed 3209 HSCT including 2118 allogeneic (allo-HSCT) and 1037 autologous HSCT (auto-HSCT). During the observation period 41 probable and proven rare IFD (EORTC/MSG 2008 criteria) cases were diagnosed in children and adults with hematological malignances and non-malignant hematological diseases after allo-HSCT (n=30), auto-HSCT (n=2), and chemotherapy (n=9). The median age was 24 (2-59) y.o., males - 61%(n=25). The median follow up time for rare IFD cases was 3 months; for survivors - 30 months. Results. Incidence of rare IFD in HSCT recipients was 1,3%, it was higher after allo-HSCT (1,4%) than auto-HSCT (0,2%) (p

Description: Abstract 1953 Objective. Graft-vs-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) causing significant morbidity and transplant-associated mortality. Acute GVHD (aGVHD) has been observed in approximately 60% of HLA-identical sibling transplants and up to 80% of unrelated donor grafts. Chronic GVHD (cGVHD) occurs in 50–70% of patients and frequently requires long-term systemic immunosuppressive treatment. Corticosteroids are considered to be the gold standard of first-line therapy for GVHD. Patients not responding to steroids have a dismal prognosis, being at risk of lifethreatening infections and severe organ toxicities. Extracorporeal photopheresis (ECP) has objective activity in the treatment of both acute and chronic steroid-refractory GVHD patients. Methods. The study included 82 patients (pts) after allo-HSCT, 34 with aGVHD and 48 with cGVHD. The age was from 2 to 55 y.o. (median 22 y.o.). Treatment aGVHD included tacrolimus or cyclosporine A basic immunosuppressive therapy with steroids (2 mg/kg) as a first line ± MAB. ECP combined with first line or used as third line, after MAB. Therapy cGVHD also included steroids (1 mg/kg) as a first line, imatinib or MMF used as a second line. ECP combined with first or second line therapy. Group aGVHD included: unrelated-HSCT – 20 pts, related-HSCT – 7 pts, haplo-HSCT – 7 pts; grade of aGVHD: II – 16 pts, III – 6 pts, IV – 12 pts; organs involvement: skin – 31 pts, GIT – 14 pts, liver – 7 pts. Group cGVHD included: unrelated-HCT – 26 pts, related-HCT – 12 pts, haplo-HCT – 10 pts; steroid-depended forms – 26 pts, steroid-refractory – 12 pts, steroid-intolerance – 10 pts; severity of cGVHD: moderate cGVHD – 15 pts, severe cGVHD – 33 pts; organs involvement: skin – 44 pts, mucosa – 27 pts, GIT – 11 pts, liver – 9 pts, lungs – 10pts. Infection complications (IC): for aGVHD group – total frequency - 73%, n=25 (bacterial – 53%, n=18, reactivation CMV – 61%, n=21, invasive fungal infection – 29%, n=10), the most frequent – lung infection and urinary tract infection. For cGVHD group: total frequency – 73%, n=35 (bacterial – 60%, n=29, reactivation CMV – 41%, n=20, invasive fungal infection – 56%, n=20), the most frequent – invasive pulmonary aspergillosis. Results. Response to therapy was observed in 23 pts (67%) with aGVHD and in 36 cases with cGVHD (75%). Factors affecting the achievement of response were severity of GVHD: II grade aGVHD vs III, IV – 93% vs 44%, (p=0,015); «moderate GVHD» vs «severe chronic» - 94% vs 77%, (p=0,024) and confirmed infection in pts with cGVHD (69% vs 93% in pts without infection, p=0,045). Probability of overall survival (OS) at 3 years was 54% for aGVHD, and 71% for cGVHD. Factors affecting to OS were achievement of response (70% vs 16 for aGVHD, p=0,001; 88% vs 33% for cGVHD, p=0,000), severity of aGVHD (77% for II grade vs 37% for III, IV). Evaluating the effectiveness of various schemes of immunosuppressive therapy for aGVHD we did not reveal significant differences for achievement response or OS between combination of ECP and first line therapy and using ECP after MAB, but IC were more common in last group (60% vs 100%, p=0,078). For group with cGVHD, pts treated only by combination steroid and ECP had a worse response then scheme including ECP and imatinib or MMF: 82% vs 65%, p=0,088%, OS pts receiving imatinib was better (85% vs 61%, p=0,041); frequency of IC was similar. Conclusion. ECP is effective for steroid-resistance forms of GVHD. It shows the best results in cases of II grade aGVHD and moderate cGVHD. The use of MAB doesn't influence frequency of treatment response or OS, but it increases incindence of IC. As concerns cGVHD, better results are documented in combination of ECP and imatinib or MMF. Disclosures: No relevant conflicts of interest to declare.

Description: Background .Blinatumomab is a monoclonal BITe antibody recently introduced for the treatment of relapsed and refractory (r ) B-ALL. Response rate reaches 65-85% in different subgroups of patients but currently there is no reliable methods to predict response. Using results of the analysis of the efficacy of blinatumomab therapy in heterogenic cohort r/r B-ALL patients, including adults and children, we built a mathematical model to predict response to this antibody. Patients and methods.A total of 128 pts with r B-ALL were included in the analysis, 52 children and 76 adults. Median age was 19 years (1-52). Hematological relapse (hr/r) and persistent measurable residual disease - molecular relapse (mr/r) were in 54% and 46% patients, respectively. Significant predictors of response in the multivariate analysis were used in the modeling for assessment of the probability of response to blinatumomab therapy. For validation of adjusted logistic regression parameters a k-fold cross-validation was performed. Confidence intervals for the model efficiency scores were calculated. Results. The response rate to blinatumomab in the study cohort was 75%. In the univariate and multivariate analysis the following parameters had the highest significance for response: patient age (OR=12,06, 95% CI 3,6-40, p

Description: INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for high-risk acute myeloid leukemia (AML).The preparative regimen consisting of busulfan and cyclophosphamide (BuCy) is considered as one of the classical myeloablative conditioning regimens (MAC); however, it is associated with significant early and long-term toxicities, leading to a high rate of transplant-related mortality (TRM). P urpose: To compare toxicities and outcomes of BuCy and FluBu12 conditioning in the pediatric population. Methods: We retrospectively analyzed 71 pediatric high-risk AML patients in CR1/2 (n=51, 71,8%) and R/R disease (n=20, 28,2%) received allo-HSCT from MSD (n=16, 22,5%), MUD (n=43, 60,6%) and Haplo donor (n=12, 16,9%). BuCy and FluBu conditioning regimens were used in 47 (66,2%) and 24 (33,8%) patients respectively. Median age was 6 years (0-17). GVHD prophylaxis was PTCy±CNI±m-TOR inhibitor in 32 (45%) or ATG±CNI in 39 (55%) patients. The primary end points were TRM, relapse-free survival (RFS), graft-versus-host disease (GVHD) free, relapse free survival (GRFS) and overall survival (OS). Secondary end points included neutrophil engraftment, sinusoidal obstruction syndrome (SOS), acute and chronic GVHD. Patient were censored at the time of death or last follow-up. Probabilities of OS, RFS and GRFS were estimated using Kaplan-Meier curves. TRM was defined as any death that occurred in the absence of disease relapse; relapse was a competing risk for this event. Results: Engraftment rate was 91% and 87,5% in patients received BuCy and FluBu, respectively (p=0,4). There was a trend to lower day 100 TRM after FluBu (4,1% vs 14,9% after BuCy, p=0,07). Overall survival at 2 years did not differ as well (BuCy 48,9%, FluBu 56%, p=0,5). BuCy showed borderline higher RFS at 2 years (70,2% vs 52%, p=0,06). The composite endpoint GRFS did not differ between two study cohorts being 31,8% and 29,2% at 2 years for BuCy and FluBu (p=0,7). We observed a tendency towards a higher incidence of III0-IV0 aGVHD and cGVHD following BuCy when compared with FluBu: 57,1% vs 41% (p=0,06) and 46,5% vs 28,5% respectively (p=0,2). No significant differences were found between the BuCy and FluBu groups in risk of SOS (6% and 8%, respectively). Conclusions: The optimal conditioning regimen for children with AML is still a matter of debate. Our results suggest that FluBu represents a valid myeloablative regimen, able to provide lower TRM, aGVHD and cGVHD. This conditioning might become an alternative approach in patients with a high risk of severe post-transplant complications. Disclosures No relevant conflicts of interest to declare.

Description: Background: Traditionally, children with AML undergo аllo-HSCT with myeloablative conditioning (MAC). It is known that MAC is associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities. But there is no conclusive evidence to support efficacy of RIC allo-HSCT in children suffering from different malignant diseases including AML. The aim: To compare efficacy of different intensity conditioning regimens in children with high risk (HR) AML (according to AML-BFM protocols 1998 and 2004) and to identify factors which have a prognostic significance for overall survival (OS). Patients and methods: Retrospective analysis was performed in 192 patients (pts) with AML (median age of 10 years (0.5-18 y.o.), who received allo-HSCT at R.M. Gorbacheva Research Institute between 08/2000 and 09/2019. MAC (busulfan- or treosulfan-based) were used in 109 pts: 1st CR - 46 pts (MRD+ n=11), 2nd CR - 18 pts, 3rd CR - 1 pt, relapse - 44 pts. Allo-HSCT with RIC were performed in 83 pts: 1st CR - 32 pts (MRD+ n=13), 2nd CR -19 pts, 3rd CR - 4 pts, relapse -28 pts (p=0,674). RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Indication for RIC allo-HSCT was poor performance status (Lansky/Karnofsky score ≤70%), or organ dysfunction due to previous therapy, or infectious complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 30 pts (16%), from matched unrelated donor - in 98 pts (51%), haploidentical - in 64 pts (33%) and the donor distribution was not different between groups (p=0,878). Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (53%). OS were estimated using Kaplan-Meier curves. Univariate analyses were performed using the log rank test for OS, Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment 〉=0,5x109/l was D+16 (range D+8-52). Engraftment was observed in 67 pts (81%) after RIC and 94 pts (86%) after MAC (p=0,231). OS after RIC allo-HSCT in the 1st CR was 76% and after MAC - 68% (p=0,014), in 2nd CR 50% after RIC and 54% after MAC (p=0,058), in advanced disease 14% after RIC and 16% after MAC (p=0,394). The transplant-related mortality rate was 19% after RIC and 22% after MAC (p=0,546). Risk of relapse was 28% after RIC and 26% after MAC (p=0,456). Factors influencing OS after MAC were: 1) Remission status at the moment of allo-HSCT (р=0.001); 2) Presence of aGVHD grade I-II (р=0,005); 3) Relapse or MRD+ status after allo-HSCT (р=0.012); 4) Lansky score 〉70% (р=0,024). Factors influencing OS after RIC were: 1) Remission status at the moment of allo-HSCT (1st remission) (p=0,001); 2) Lansky score 〉70% (р=0,004). Conclusion: The effectiveness of RIC and MAC is comparable in children with HR AML, but RIC demonstrated better results in 1st CR. The presence of I-II grade aGVHD had positive effect in MAC. Factors influencing OS in both groups were disease status at the moment of allo-HSCT and performance status before allo-HSCT The use of RIC can be effective in patients, especially those who have undergone allo-HSCT in the 1st remission, while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Multicenter studies are warranted, especially for patients in the first CR, where long-term complications are of most importance. Disclosures No relevant conflicts of interest to declare.

Description: Background: Relapse of ALL remains the major cause of transplant failure. Relapse incidence after allo-HSCT is described in 30-40% of patients. Patients with ALL receive allo-HSCT with MAC more often because after RIC more relapses are expected. The aim: To compare the frequency of relapse after allo-HSCT with RIC vs with MAC and to analyze the factors influencing the risk of relapse depending on the intensity of conditioning regimens. Patients and methods: Between 12/2000 and 09/2019 at RM Gorbacheva Research Institute a total of 235 children with ALL (median age of 10 years (0,5-18), underwent allo-HSCT. MAC (busulfan- or treosulfan-based) were used in 163 pts: 1st CR - 30 pts (MRD+ n=13), 2nd CR - 58 pts, 3rd or 4 CR - 27 pts, relapse - 48 pts. Allo-HSCT with RIC were performed in 72 pts: 1st CR - 12 pts (MRD+ n=9), 2nd CR - 29 pts, 3rd or 4 CR - 14 pts, relapse -17 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Matched related allo-HSCT was performed in 37 pts (16%), matched unrelated - in 128 pts (54%), haploidentical-in 70 pts (30%). Cumulative incidence functions were used to estimate relapse incidence and NRM in a competing risk setting. Univariate analyses were performed using Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5,4 and 4,5 years for МАС and RIC, respectively. Relapses were diagnosed in 105 pts (44%) during 1-39 months after allo-HSCT (median 7.5 months) (90% relapses were during first 18 mo), 74 pts after MAC; 31 pts after RIC (p=0,549). Relapses occurred significantly less frequent (p=0,007) in patients who had CR at the moment of allo-HSCT - 61 pts (35%) (RIC -32%; MAC -37%) compared patients who had a relapse or primary resistance 44 pts (68%) (RIC-74%; MAC - 65%). The risk of relapse after MAC is influenced by the presence of acute GVHD (p=0,007), the source of HSCs (PBSC vs BM, p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). The risk of relapse after RIC is influenced by the presence of acute GVHD (p=0,042), age at the moment of allo-HSCT 1-10 years (p=0,032), and the status of the disease (CR vs relapse) at the moment of allo-HSCT (p=0,001). Multivariable analysis confirmed a significant impact of disease status at the moment of allo-HSCT whit MAC (p=0,001) and with RIC (p=0,002). Presence of aGVHD was additional factor associated with lower relapse risk in multivariate analysis in pts after MAC (p=0,005). Patients with active disease at the moment of HSCT had higher relapse-free survival after RIC (RIC-23% vs MAC- 12%, p=0,012). Salvage patients in whom the relapse was documented after HSCT had 28% and 38% probability of long-term OS after RIC and MAC, respectively (p=0,572). Conclusion: Relapse incidence after allo-HSCT with MAC and with RIC is comparable. The most significant factor affecting the risk of relapse is the status of the disease at the moment of allo-HSCT. Disclosures No relevant conflicts of interest to declare.