ALBERT

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: Introduction: In spite of the widespread use of second- and third-generation tyrosine kinase inhibitors (TKIs) the prognosis of patients with advanced phase CML (accelerated phase (AP) or blast crisis (BC)) is still dismal. The aim of this study was to compare outcomes in advanced phase CML cohorts based on whether or not these patients received allogeneic hemopoietic stem cell transplantation (allo-HSCT). Patients and methods: A total of 162 patients with AP/BC-CML with (allo-HSCT+TKIs, n=20/62,) or without (n=10/70, TKI) history of allo-HSCT were included in this retrospective study. All patients received allo-HSCT with a reduced-intensity conditioning regimen with fludarabine 180 mg/m2 and busulfan 8-12 mg/kg or melphalan 140 mg/m2. Forty-two patients received TKIs for post-transplant relapse prophylaxis. In the majority of cases dasatinib was used (n=36). In the remaining 80 patients alloHSCT was not performed due to refusal for personal reasons or delay in referral to transplant center. They were included in TKI-group and were treated with chemotherapy+TKIs (60) or TKIs only (20). Eighty-one percent received second or third line TKIs. There were no significant differences in age, sex, comorbidity status, disease phase, and additional chromosomal aberrations incidence between allo-HSCT+TKI and TKI groups (Table 1). Overall survival (OS) was defined as the time from the start of treatment (allo-HSCT/TKI, chemotherapy) to death, event-free survival (EFS) - as the time between commencement of treatment and loss of response or post-transplant relapse, death. Response was defined according to European Leukemia Net and National Comprehensive Cancer Network recommendations. All patients signed an informed consent for processing of personal data; the trial was approved by Pavlov University local ethical committee. Results: The median follow-up was 44 months (1-344). The engraftment was documented in 71 (86%) patients. The cumulative incidence of non-relapse mortality at day 100 and 1 year after allo-HSCT were 10% and 18%, respectively. Grade 2-4 acute graft versus host disease (GVHD) was documented in 21 (29%), grade 3-4 acute GVHD - 14 (20%), chronic GVHD - 18 (27%) including mild, moderate and severe form in 6 (9%), 8 (12%) and 4 (6%) patients, respectively. Two-year cumulative incidence of relapse was 39%. Twenty-four patients received donor lymphocyte infusions and TKIs after relapse, in 4 cases chemotherapy was added. In four cases only TKIs were administered to treat relapse. Nine patients achieved sustained complete molecular response (CMR), in 19 cases disease progression was documented. The data on response was available for 71 patients in TKI group. Among patients with BC 36 (59%) patients did not respond to therapy, while complete hematological response (CHR), complete cytogenetic response (CCR) and CMR were achieved in 22 (34%), 1 (2%) and 2 (3%) cases, respectively. Nine patients (90%) without BC history achieved response to therapy (CHR 5, CCR 2, CMR 2), while 1 patient failed to respond. Sixty-nine patients died; all deaths were CML-related. Four-year OS was 58% in allo-HSCT+TKIs versus 33% in TKI group (p=0.032) (Figure 1A). However, there was no significant difference in 4-year EFS between groups: 35% vs. 17% (p=0.5), accordingly. BC at the moment of allo-HSCT significantly worsened 4-year OS: 23% vs. 63% (p=0.007). The 4-year OS in patients transplanted in BC (n=10) was comparable to one in TKI group: 23% vs. 33% (p=0.3) (figure 1B). Conclusions: Allo-HSCT still has an advantage as potentially curative treatment for part of advanced phase CML patients even in the presence of new generation TKIs. Allo-HSCT in BC is associated with worse outcome. An earlier referral of these patients to the transplant center can improve the outcome of allo-HSCT and prognosis.. Disclosures No relevant conflicts of interest to declare.