High Incidence Of Relapse Research Articles

Evaluating Outcomes Using Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil As Gvhd Prophylaxis Compared with Methotrexate/Tacrolimus in Matched-Related and Matched-Unrelated Hematopoietic Stem Cell Transplant in Relation to the Haploidentical Setting in Acute Lymphoblastic Leukemia: A Single Center Experience

Intro: Acute and chronic graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (allo-HSCT). Post-transplant cyclophosphamide (PTCy), alongside mycophenolate mofetil (MMF) and tacrolimus (TAC), is known to be effective in reducing cGVHD in haploidentical (HI) transplant recipients. Results of the prospective randomized HOVON-96 trial in recipients of matched related (MRD) and unrelated donors (MUD) showed that PTCy leads to a reduction in risk of severe cGVHD. However, the role of PTCy in HSCT with acute lymphoblastic leukemia (ALL) remains controversial. The purpose of this study is to evaluate outcomes using PTCy, TAC, and MMF for GVHD prophylaxis in MRD and MUD stem cell recipients who have ALL.Methods: This study is a retrospective analysis of adult patients (aged 19 and up) with ALL who received MRD, MUD, and HI HSCT at USC Norris Cancer Hospital from 2018 to 2020. The primary end-points were to compare incidence of aGVHD and cGVHD within the first year post-transplant after receiving MRD, MUD, and HI donor transplants. Secondary end-points were day +100 mortality, 1-year overall survival (OS), relapse free survival (RFS), transplant-related mortality (TRM), and GRFS within the same subgroups. Kaplan-Meier curves and Log Rank tests were used to evaluate a difference in outcomes.Results: A total of 46 patients with ALL who received HSCTs were identified and separated based on type of GVHD prophylaxis received: 7 (15.1%), 16 (34.8%), and 23 (50.0%) in the PT-Cy, HI and standard groups respectively. Demographic data can be found on Table 1 attached. Baseline characteristics among all groups were similar with the exception of the more Human Leukocyte Antigen (HLA) mismatch (p<0.01), higher number of patients receiving stem cells from bone marrow (p=0.02) and the increased proportion of patients receiving less than 5.0 x 10^6 CD34+ cells/kg (p=0.02) in the PTCy group. With regards to the primary end-points as seen on Table 2, there was a non-significant trend toward less frequent severe aGVHD and severe cGVHD in the PTCy group compared to the standard and HI cohorts (p=0.13). The rates of severe aGVHD were 0%, 6.2%, and 8.7% in the PT-Cy, HI and standard groups respectively. The rates of severe cGVHD were 0%, 6.2%, and 21.8% in the PT-Cy, HI and standard groups respectively. With regards to the secondary end-points in our study, as seen on Tables 2 and 3, patients receiving standard GVHD prophylaxis had a 95.7% 1-year OS, a 91.1% 1-year RFS, and 87.0% 1-year GRFS. Moreover, MRD/MUD recipients receiving PTCy for GVHD prophylaxis had worse outcomes with an 40.0% 1-year OS, a 62.5% 1-year RFS, and 62.5% 1-year GRFS. Comparatively, patients receiving HI transplants exhibited a 100% 1-year OS, a 100% 1-year RFS, and 91.7% 1-year GRFS. This was statistically significant across all outcome measures: OS (p=<0.01), RFS (p=0.0038), and GRFS (p=0.048). Kaplan-Meier curves for OS, GRFS, and RFS are attached.Discussion: In this single institution analysis, we observed that patients with ALL who underwent HI transplant had the best outcomes. Moreover, patients receiving MUD/MRD HSCT with use of PTCy had a non-significant reduced incidence of aGVHD and cGVHD, though had significantly worse 1-year OS, RFS, and GRFS when compared to standard GVHD prophylaxis or patients receiving HI transplants. We believe this is likely a multifactorial process. However, the increased percentage of mismatched antigens in the MUD transplants (p=0.19) and higher proportion of patients receiving less than 5.0 x 10^6 CD34+ cells/kg (p=0.02) in the PTCy group is important to acknowledge and can also be contributing to their poorer outcomes. We pose the idea that the use of PTCy may also lead to a reduced graft vs. leukemia effect in this population and thus a higher incidence of relapse and worse outcomes overall. A larger, prospective study should be considered to take into account these factors to better determine if patients with ALL could benefit from PTCy for GVHD prophylaxis. [Display omitted] DisclosuresChaudhary: Celldex: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Pancella: Consultancy; Oncotartis: Consultancy; Athelas: Consultancy, Current holder of stock options in a privately-held company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Yaghmour: Takeda: Consultancy, Speakers Bureau; Astellas: Speakers Bureau; Alexion: Speakers Bureau; BMS: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Jazz: Speakers Bureau.

Long-Term Outcome of Peripheral Blood Autologous Stem Cell Transplantation (AutoSCT) for De Novo Acute Myeloid Leukemia in Patients Achieving First Complete Remission after One Vs Two Induction Courses: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Background: Achieving a first complete remission (CR1) is the primary goal in the treatment of AML and is an important prognostic factor for transplantation outcome in general and even more so for autologous transplantation (AutoSCT). However, there are no data for AutoSCT indicating whether the number of chemotherapy courses (1 vs 2) needed to achieve CR1 is of prognostic significance for transplantation outcome.Methods: Using the EBMT/ALWP registry, we compared transplantation outcomes of adult patients (pts) aged ≥18 years with de novo AML that underwent a peripheral blood AutoSCT in 2000-2019 in CR1 achieved following one vs two chemotherapy courses. The primary outcome was the Leukemia Free Survival (LFS). Multivariate analysis (MVA) adjusting for differences between the groups and knowns factors were performed using Cox's proportional- hazards regression model for outcomes.Results: 1825 pts were included: 1532 (84%) with one and 293 (16%) with two induction chemotherapies courses. Time from diagnosis to AutoSCT was 4.7 (3.9-5.8) vs 5.7 (4.7-7.1) months, respectively (p<0.001). Median follow-up was 7.9 (95% CI: 7.4-8.4) and 7.7 (95% CI: 7.0-8.6) years, respectively (p=0.8). Median year of transplant was 2005 (2002-2009) and 2004 (2002-2007), respectively (p<0.001). Median age was 49 (38-57) and 47 (36 -56) years (p=0.06); 54% and 57 % of both groups were male, (p=0.35). Cytogenetic risk as defined by the Medical Research Council (MRC) classification, differed significantly between the two induction groups (p<0.001). Patients with one induction had a higher percentage of favorable-risk than those with two inductions (18% vs 14%), and a lower percentage of adverse-risk cytogenetics (6% vs 13%), while 76% and 73%, respectively, had intermediate-risk cytogenetics (missing data-11percentage). Karnofsky performance score (KPS) > 90 was higher in pts receiving 1 vs 2 inductions, 71% and 58% of pts, respectively (p<0.001). The most frequent conditioning regimen for both groups was Busulfan (Bu) /Cytoxan (Cy) 50% vs 45% and Bu / Melphalan (Mel) 17% and 19%, respectively, for induction groups 1 and 2, respectively.Day 30 neutrophil engraftment incidence was 96% and 96.5%.Five -year non-relapse mortality (NRM) was 6.2% vs 6.0% for pts achieving CR1 with 2 vs 1 chemotherapy courses, respectively, and did not differ significantly (HR=1.31 (95% CI: 0.81-2.10), p=0.27). Five -year relapse incidence (RI) was higher :67.2% vs 52.3%, (HR=1.46 (95% CI: 1.25-1.72), p<0.001), while LFS and overall survival (OS) were lower for pts achieving CR1 with 2 vs 1 course of chemotherapy: 26.6% vs 41.7% (HR= 1.42 (95% CI: 1.22-1.66), p<0.001) and 36.2% vs 53.3%, (HR=1.48 (95% CI: 1.25-1.75), p<0.001), respectively (Figure). Other significant prognostic factors in MVA were adverse- compared to good risk cytogenetics and older age (per 10 years) for all AutoSCT outcome parameters including RI, NRM, LFS and OS; intermediate compared to good risk cytogenetics for RI, LFS and OS; female gender for RI and LFS ;and year of transplant for RI and OS.Conclusions: The five -year RI was higher and transplantation outcomes significantly inferior in pts with AML undergoing AutoSCT but who received two lines of chemotherapy to achieve CR1. Such pts may benefit from additional novel therapies in the conditioning or post-AutoSCT or be considered for allogeneic transplantation in an attempt to reduce their high RI and improve outcomes. [Display omitted] DisclosuresLabopin: Jazz Pharmaceuticals: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Huynh: Jazz Pharmaceuticals: Honoraria. Mohty: Takeda: Honoraria; Jazz: Honoraria, Research Funding; Astellas: Honoraria; Janssen: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Gilead: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

The Omission of High-Dose Cytarabine during Consolidation Therapy of Ph-Positive ALL Patients Treated with Nilotinib and Low-Intensity Chemotherapy Results in an Increased Risk of Relapses Despite Non-Inferior Levels of Late BCR-ABL1 MRD Response. First Results of the Randomized Graaph-2014 Study

The Omission of High-Dose Cytarabine during Consolidation Therapy of Ph-Positive ALL Patients Treated with Nilotinib and Low-Intensity Chemotherapy Results in an Increased Risk of Relapses Despite Non-Inferior Levels of Late BCR-ABL1 MRD Response. First Results of the Randomized Graaph-2014 Study

Comparative Study of Unrelated and Haploidentical Donor Hematopoietic Cell Transplant for Chronic Myeloid Leukemia with Post Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis: A Study from the Chronic Malignancies Working Party of EBMT

Comparative Study of Unrelated and Haploidentical Donor Hematopoietic Cell Transplant for Chronic Myeloid Leukemia with Post Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis: A Study from the Chronic Malignancies Working Party of EBMT

The Importance of Disease Burden after Induction and Prior to Transplantation in Patients with Acute Myeloid Leukaemia Receiving Allogeneic Transplantation

Introduction: Response to chemotherapy treatment both by cytology and by more sensitive techniques such as cytometry is one of the most influential parameters in the survival of patients with Acute Myeloid Leukaemia (AML). Patients with detectable minimal residual disease (MRD) or those with active disease (AD) after induction or prior to allogeneic transplantation (HCST) represent a high-risk group.Objectives: to analyse the impact of disease burden before HSCT in terms of Overall Survival (OS) and Event Free Survival (EFS) in a group of patients who received HSCT in a single institution. We also analysed the influence of disease burden at the end of induction (considering best response after 1 or 2 cycles) and its impact on those patients in Cytological Remission (CR) with MRD <0.1% prior to transplantation.Methods: We analysed 103 patients who received HSCT in one centre between 2008 and 2020 in whom we knew disease status after induction and before HSCT. We divided the cohort into three groups according to preHSCT disease: Group 1) Patients in CR with MRD <0.1% by cytometry, Group 2) CR with MRD ≥0.1% and Group 3) patients with AD (≥5% blasts by cytology). We analysed post-transplant EFS and OS using the Kaplan Meier method and the Cumulative Incidence of Relapse (CIR) using Gray's test.Results: The baseline characteristics of the population are reflected in table 1. Median follow-up was 13 months (0-140). One-year EFS (1y-EFS) was 49%. One-year OS (1y-OS) was 57.5%, with a 1y-IAR of 27%. We first analysed the impact on post-transplant survival according to the different groups. Group 1 had significantly better EFS than Group 2 (p=0.04) and Group 3 (p<0.001) (Figure 1A). Regarding OS there was no difference between Group 1 and Group 2 (p=0.2) although it was significantly better than Group 3 (p<0.001) (Image 1B). IAR-1 was 14% vs 48% vs 50% (p<0.001) respectively. We subsequently analysed the impact on post-transplant survival according to the response to induction. Post-transplant EFS and OS were better in those in CR MRD- after induction compared to patients in CR with MRD+ (p=0.05 and p=0.002) as well as in patients with AD at the end of induction (p=0.002 and p=0.008). We stratified Group 1 according to the best response to induction (MRD- or MRD+/EA) and we performed an analysis according to the following groups: A) Patients with MRD- after induction and also before HSCT, B) Patients with MRD+/EA after induction achieving MRD- before HSCT. Comparing both groups there were no differences in either EFS (1y-EFS Group A 69% vs Group B 54%, p=0.5) or OS ( Group A 69% vs Group B 61%, p=0.8).Conclusions: Patients with pre-transplant AD or MRD+ are a high-risk group due to a high incidence of post-HSCT relapse. Although patients with AD or CR with MRD+ after induction have a worse prognosis, those who achieve MRD- before HSCT have a similar survival to the MRD- group from the start of chemotherapy. [Display omitted] DisclosuresGarcia-Gutiérrez: Pfizer: Research Funding; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Novartis: Consultancy.

Allogeneic blood or marrow transplantation with haploidentical donor and post-transplantation cyclophosphamide in patients with myelofibrosis: a multicenter study.

We report the results from a multicenter retrospective study of 69 adult patients who underwent haploidentical blood or marrow transplantation (haplo-BMT) with post-transplantation cyclophosphamide (PTCy) for chronic phase myelofibrosis. The median age at BMT was 63 years (range, 41-74). Conditioning regimens were reduced intensity in 54% and nonmyeloablative in 39%. Peripheral blood grafts were used in 86%. The median follow-up was 23.1 months (range, 1.6-75.7). At 3 years, the overall survival, relapse-free survival (RFS), and graft-versus-host-disease (GVHD)-free-RFS were 72% (95% CI 59-81), 44% (95% CI 29-59), and 30% (95% CI 17-43). Cumulative incidences of non-relapse mortality and relapse were 23% (95% CI 14-34) and 31% (95% CI 17-47) at 3 years. Spleen size ≥22 cm or prior splenectomy (HR 6.37, 95% CI 2.02-20.1, P = 0.002), and bone marrow grafts (HR 4.92, 95% CI 1.68-14.4, P = 0.004) were associated with increased incidence of relapse. Cumulative incidence of acute GVHD grade 3-4 was 10% at 3 months and extensive chronic GVHD was 8%. Neutrophil engraftment was reported in 94% patients, at a median of 20 days (range, 14-70). In conclusion, haplo-BMT with PTCy is feasible in patients with myelofibrosis. Splenomegaly ≥22 cm and bone marrow grafts were associated with a higher incidence of relapse in this study.

Germline CEBPA mutation in familial acute myeloid leukemia.

Myeloid Neoplasms with germline predisposition become part of 2016 World Health Organization (WHO) classification of hematological malignancies since 2016. CCAAT/enhancer binding protein-alpha (CEBPA) is a myeloid transcription factor located in chromosome 19q. Acute myeloid leukemia (AML) with biallelic mutations of CEBPA AML with recurrent genetic abnormalities according to WHO classification. The inheritance of a germline CEBPA mutation predisposes to the development of AML with autosomal dominant inheritance. Familial CEBPA AML share characteristics with somatic CEBPA AML. However, a higher relapse incidence is reported. We present the case of a 46-years-old male with family history of acute leukemia who was diagnosed with single mutated CEBPA acute myeloid leukemia. The same mutation was found in two of his siblings. The clinical suspicion and proper diagnosis of familial cases is necessary, especially when a related allogenic transplant is indicated in order to select an adequate donor.

Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before surgery in patients with locally advanced rectal cancer (A phase II study)

Abstract Background Locally advanced rectal cancer (LARC) has a high incidence of local and distant relapse even after adequate treatment. The emerging role of neoadjuvant induction chemotherapy may allow initial down staging of the primary tumor, less toxicity profile and early treatment of micrometastatic disease followed by chemoradiation, and optimum local control may be attained, with the hope of increased complete response rates Objectives to identify the effect of induction chemotherapy with oxaliplatin and capecitabine (CapeOx) before concurrent chemoradiation in locally advanced rectal cancer in terms of response and toxicity. Primary end point is assessment of complete pathological response rate. Patient and Methods patients with MRI based criteria of high-risk LARC (T4 tumors, tumors within 2 mm of mesorectal fascia, T3 tumors at or below levators and T2-4N+ve tumors) were included. Patients received 12 weeks of induction capecitabine/oxaliplatin followed by concomitant capecitabine and conventional three dimensional conformal radiotherapy. Surgery was done at least 6 weeks after CCRTH. Results Thirty five patients with LARC were recruited during the period from December 2017 till January 2019. Five patients (20.8%) had a pathological complete response (TRG 0) (ypT0N0). Another three patients (12.5%) had near complete pathological response (TRG 1). While unfortunately 29.2% and 37.5% had partial response and poor response respectively. Conclusion Induction chemotherapy could be a promising option for better response rates either clinical or pathological for high risk LARC patients with acceptable toxicity profile.

Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic Population

Chronic myelomonocytic leukemia (CMML) is an aggressive disease in which survival after allogeneic hematopoietic stem cell transplantation (HCT) remains relatively poor. An assessment of prognostic factors is an important part of treatment decision making and has the potential to be greatly improved by the inclusion of molecular genetics. However, there is a significant knowledge gap in the interpretation of mutational patterns. This study aimed to describe outcomes of allogeneic HCT in patients with CMML in relation to clinical and molecular genetic risk factors. This retrospective study included 64 patients with CMML who underwent allogeneic HCT between 2008 and 2018, with a median follow-up of 5.4 years. Next-generation sequencing using targeted myeloid panels was carried out on saved material from 51 patients from the time of transplantation. Kaplan-Meier and Cox regression were used for analysis of overall survival (OS), and cumulative incidence with competing risks and Fine and Gray models were used for analysis of relapse and nonrelapse mortality (NRM). Mutations were detected in 48 patients (94%), indicating high levels of minimal residual disease (MRD) positivity at transplantation, even among those in complete remission (CR) (n=14), 86% of whom had detectable mutations. The most frequently mutated genes were ASXL1 (37%), TET2 (37%), RUNX1 (33%), SRSF2 (26%), and NRAS (20%). Risk stratification using the CMML-specific Prognostic Scoring System molecular score (CPSS-Mol) resulted in 45% of patients moving to a higher risk-group compared with risk stratification using the CPSS. High leucocyte count (≥13×109/L), transfusion requirement, and previous intensive chemotherapy were associated with higher incidence of relapse. Being in CR was not linked to better outcomes. Neither ASXL1 nor RUNX1 mutation was associated with a difference in OS, relapse, or NRM, despite being high risk in the nontransplantation setting. TET2 mutations were associated with a significantly higher 3-year OS (73% versus 40%; P=.039). Achieving MRD-negative CR was rare in this CMML cohort, which may explain why we did not observe better outcomes for those in CR. This merits further investigation. Our analyses suggest that the negative impact of ASXL1 and RUNX1 mutations can be overcome by allogeneic HCT; however, risk stratification is complex in CMML and requires larger cohorts and multivariate models, presenting an ongoing challenge in this rare disease.

Impact of Cell of Origin on Outcomes After Autologous Hematopoietic Cell Transplant in Diffuse Large B-Cell Lymphoma

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

Inhibition of the MAP2K7-JNK pathway with 5Z-7-oxozeaenol induces apoptosis in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric leukemia with a worse prognosis than most frequent B-cell ALL due to a high incidence of treatment failures and relapse. Our previous work showed that loss of the pioneer factor KLF4 in a NOTCH1-induced T-ALL mouse model accelerated the development of leukemia through expansion of leukemia-initiating cells and activation of the MAP2K7 pathway. Similarly, epigenetic silencing of the KLF4 gene in children with T-ALL was associated with MAP2K7 activation. Here, we showed the small molecule 5Z-7-oxozeaenol (5Z7O) induces dose-dependent cytotoxicity in a panel of T-ALL cell lines mainly through inhibition of the MAP2K7-JNK pathway, which further validates MAP2K7 as a therapeutic target. Mechanistically, 5Z7O-mediated apoptosis was caused by the downregulation of regulators of the G2/M checkpoint and the inhibition of survival pathways. The anti-leukemic capacity of 5Z7O was evaluated using leukemic cells from two mouse models of T-ALL and patient-derived xenograft cells generated using lymphoblasts from pediatric T-ALL patients. Finally, a combination of 5Z7O with dexamethasone, a drug used in frontline therapy, showed synergistic induction of cytotoxicity. In sum, we report here that MAP2K7 inhibition thwarts survival mechanisms in T-ALL cells and warrants future pre-clinical studies for high-risk and relapsed patients.

AML-322: Third Time Lucky: A Case Report of Relapsing Blastic Plasmacytoid Dendritic Cell Neoplasm

This is a case report about a case of blastic plasmacytoid dendritic cell neoplasm (BPDCN), which relapsed twice and is currently in third remission. We describe the presentation and management of this case. We aim to illustrate the management of BPDCN, which is a rare disorder, and the development and characteristics for coping with changes in care, especially in a relapsed setting. This is a descriptive case report of a BPDCN from November 2017 until May 2021. Our facility is an academic referral center. Our patient is a married 37-year-old fisherman living in a fishing village in a nearby coastal district. The patient is a moderate cigarette smoker with no previous medical history. The patient presented to us in September 2017 with a history of having a scalp lesion for three months, with toxic symptoms in the form of night sweats and fever. A biopsy of the scalp lesion showed rounded cell tumor, positive LCA, negative CK and HMB 45, and CBC showing mild leukopenia. BMA showed hypercellular BM and 58% blasts, suggestive of AML. M5 for IPT and BMB hypercellular BM were suggestive of acute leukemia. On examination, he had bilateral bulky cervical LNs, approximately 3×3 cm, and bilateral parotid swellings with an unpalpable spleen. We repeated BMA, which showed hypercellular, 0 blasts, and was confirmed by BMB. Revision of the scalp lesion biopsy IHC was positive for LCA, CD4, CD56, and S100. The case was diagnosed as BPDCN. The patient started the hyperCVAD protocol in January 2018 with a good response and the disappearance of the scalp lesions. He was referred for HLA matching, but his siblings refused; therefore, he continued up to eight hyperCVAD courses and was prepared for the ninth in October 2018, when he was lost to follow-up. The patient presented five months later with a recurrent swelling in the left forearm, showing recurrence after medullary clearance. He started the HAM protocol in June 2019 and received a 2nd cycle, followed by four cycles of the HDA protocol in January 2020, after which PET/CT showed negative. In April 2020, he had a recurrent forearm lesion, showing recurrence. His PET/CT was negative, and he received steroids with local irradiation. OS of 44 months, DFS of 13, 9, and 9 months (31 months total). Treating BPDCN using chemotherapy only has a higher incidence of relapse.

Prognostic significance of TIM-3 expression pattern at diagnosis in patients with t(8;21) acute myeloid leukemia

Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease and needs to be stratified. Both, cancer cells and immune cells participate in tumor initiation, growth and progression and might affect clinical outcomes. TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3), an immune checkpoint molecule, is expressed not only on immune cells but also on leukemic stem cells (LSCs) in AML. This prompted us to investigate the prognostic significance of TIM-3 in t(8;21) AML. A total of 47 t(8;21) AML patients were tested for TIM-3 expression by multi-parameter flow cytometry at diagnosis. 35 of these, who received chemotherapy alone or along with allogeneic hematopoietic stem cell transplantation were followed up. The expression pattern of TIM-3 on T-cells and NK (natural killer) cells as a whole (T + NK) and LSCs were evaluated independently. High percentage of T + NK − TIM-3+ and CD34+CD38−TIM-3+ cells were significantly associated with a high 2-year cumulative incidence of relapse (CIR) (p = 0.028, 0.016). Further, concurrent high frequencies of T + NK-TIM-3+ and CD34+CD38-TIM-3+ cells at diagnosis were significantly associated with a high 2-year CIR (p < 0.0001) and this together with c-KIT D816 mutation were the independent adverse prognostic factors for relapse (hazard ratio (HR)=2.5, [95% confidence interval (CI), 1.1–6.0], p = 0.04; HR = 46.5, [95% CI, 2.7–811.5], p = 0.009). In conclusion, the expression pattern of TIM-3 on both T and NK cells and LSCs at diagnosis had prognostic significance in t (8;21) AML.

The Prognostic Value of Early Detection of Minimal Residual Disease as Defined by Flow Cytometry and Gene Mutation Clearance for Myelodysplastic Syndrome Patients After Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation.

High relapse incidence remains a major problem for myelodysplastic syndrome (MDS) patients who have received an allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We retrospectively analyzed the correlations between clinical outcomes and minimal residual disease (MRD) by using mutations (MUT) and flow cytometry (FCM) analysis of 115 MDS patients with allo-HSCT. We divided 115 MDS patients into four groups based on molecular genetics and FCM MRD results at day 30 post-HSCT. There were significant differences in the 2-year progression-free survival (PFS) between the FCMhigh MUTpos and FCMlow MUTneg groups (20% vs 79%, P < 0.001). In addition, by univariate analysis, we found that an IPSS-R score ≥4 pre-HSCT (HR, 5.061; P=0.007), DNMT3A mutations (HR, 2.291; P=0.052), TP53 mutations (HR, 3.946; P=0.011), and poor and very poor revised International Prognostic Scoring System (IPSS-R) cytogenetic risk (HR, 4.906; P < 0.001) were poor risk factors for PFS. In multivariate analysis, we found that an IPSS-R score ≥ 4 pre-HSCT (HR, 4.488; P=0.015), DNMT3A mutations (HR, 2.385; P=0.049), positive FCM MRD combined with persistence gene mutations at day 30 (HR, 5.198; P=0.013) were independent risk factors for disease progression. In conclusion, our data indicated that monitoring MRD by FCM combined with gene mutation clearance at day 30 could help in the prediction of disease progression for MDS patients after transplantation.

APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients

Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100-200IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1-3months at the minimum until 12months.

Pathological N3 Stage (pN3/ypN3) Gastric Cancer: Outcomes, Prognostic Factors and Pattern of Recurrences After Curative Treatment.

pN3 or ypN3 stage gastric cancers (GCs) are known to have aggressive clinical behaviour. This study aimed to investigate factors affecting survival and pattern of recurrences of N3 stage GCs, treated with curative intent. A total of 196 GC patients, operated on at the Tata Memorial Centre from 2003 to 2017 and reported as pN3 or ypN3 status on histopathology after D2 gastrectomy were included in this retrospective analysis. On multivariate analysis, use of NACT (neoadjuvant chemotherapy) and LN ratio (≤ 0.5/> 0.5) emerged as significant predictors for long-term survival. Patients who received NACT but were still harbouring N3 nodes (ypN3; n = 102) had a worse prognosis than those operated on upfront (pN3; n = 94), with a median survival of 19 months versus 24months respectively (p = 0.003). The 5-year overall survival of the entire cohort was 16.3% (95% CI 12.8-19.8%), while 5-year disease-free survival (DFS) was 14.6% (95% CI 12.6-20%). Adjuvant chemoradiotherapy, though offered in a small number of patients (n = 38) resulted in improvement in DFS. Median DFS of adjuvant CT versus adjuvant CRT was 13months versus 23 months (p = 0.020). The commonest site of relapse was the peritoneum (49.18%) and incidence of isolatedloco-regional failure was 10.7%. In GCs with N3 stage determined after radical D2 gastrectomy, LN ratio of > 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.

CMV Status Predicts Survival in Refractory/Relapsed Myeloid Patients after a Clofarabine-Based Sequential Regimen: A Retrospective Study on Behalf of the SFGM-TC

Background: Recently, we have published the prospective results of a sequential regimen using a clofarabine (clo), cytosine arabinoside and reduced-intensity conditioning (RIC) regimen in 24 cases with primary refractory acute myeloid leukemia (AML) showing encouraging results with a very low non relapse mortality (Mohty, 2017). Here we report the outcomes after such sequential regimen in a larger cohort of patients.Methods: This was a retrospective study including all patients reported within the SFGM-TC registry having received a clo-based sequential conditioning regimen before allotransplant for active myeloid disease. Data were obtained through PROMISE, an internet-based system shared by all European transplantation centers. All patients gave informed consent allowing to collect their personal data from this data base.The sequential regimen consisted of clo (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by RIC combining cyclophosphamide (60 mg/kg), iv busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days.The primary objective of the study was to report the main outcomes at 1 year: overall survival (OS), disease free survival (DFS), relapse incidence (RI), NRM and GVHD Relapse free survival (GRFS). Secondary objectives were to identify prognostic factors for patient's survival.Results: Between January 2007 and December 2016, 131 patients (males n=75, median age: 52.6 years, range: 18-71) met the inclusion criteria. There were 111 AML patients, including 9 secondary AML, and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was as follows: primary refractory n=81, relapse 1 or 2 n=46, missing n=4. The majority of patients received peripheral blood stem cell as source of graft (n=127, bone marrow n=4). All patients received a graft from a matched donor (sibling n=64, unrelated n=67). Donor (D)/recipient (R) CMV status was as follows: D-/R-: n=55, D+/R-: n=14, D-/R+: 24, D+/R+: 38.Engraftment was observed in 105/122 assessable cases (86%) and patients achieving complete remission (CR) after transplant were 63% (n=72/114 evaluable cases). With a median follow-up of 12 months (range: 2.7-74.3) for alive patients, 1-year OS, DFS, RI, NRM and GRFS were 39.2% [30.2-48.2], 28.1% [19.8-36.5], 41% [32.1-49.8], 30.8% [22.7-39.3], and 22.2% [14.3-30], respectively.In univariate analysis, the only factor associated with lower survivals and GRFS and higher RI was unexpectedly a D-/R- CMV status at transplant: 1-year OS: 30% vs others status: 46.1%, =0.009; 1-year DFS: 18.1% vs 35.7%, p=0.015; 1-year GRFS: 11.9% vs 29.9%, p=0.009; 1-year RI: 53.2% vs 31.9%, p=0.004. In multivariate analysis, D/R CMV negative status remained independently associated with lower OS (HR: 1.74, 95%CI: 1.10-2.76, p=0.016), DFS (HR: 1.70; 95%CI: 1.09-2.66, p=0.018) and GRFS (HR: 1.76; 95%CI: 1.15-2.71, p=0.009) and higher RI (HR: 2.48; 95%CI: 1.37-4.50, p=0.002). D/R CMV status was not associated with NRM.Conclusion: Despite high CR achievement, this large cohort of patients confirmed the relatively poor outcome of patients with active myeloid disease at transplant and receiving a clofarabine-based sequential regimen. Post-transplant strategies should be proposed early to improve results and decrease incidence of relapse. The favorable impact on survivals of positive D or R CMV status may be related to a potential graft-vs-leukemia effect of CMV reactivation (thanks to NK or T cells stimulation) after transplant. The validation of this hypothesis is on-going. DisclosuresPeffault De Latour:Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Mohty:Sanofi: Honoraria, Speakers Bureau.

Clofarabine-Based Reduced Intensity Conditioning Regimen with Post-Transplant Cyclophosphamide and Peripheral Stem Cell Graft in Adults with Myeloid Malignancies: Results of the Clo-Baltimore Regimen

Backgound: The Baltimore reduced-intensity conditioning (RIC) regimen using high-dose post-transplant cyclophosphamide (PTCY) is considered as a standard of care for haplo-transplant. However, it is associated with relatively low survivals (OS 46% and EFS 34% at 1 year) and high incidence of relapse (51% at 1 year), especially when considering myeloid malignancies (Luznik, 2008). Here, we have replaced fludarabine by clofarabine, a second-generation purine analogue with high anti-myeloid leukemic activity, as part of the Baltimore regimen (Clo-Baltimore regimen) and we report the results of such an approach in 36 patients with myeloid malignancies.Methods: This retrospective study included 36 adults with a median age of 60.5 (range: 31-70) years who received an allotransplant between March 2014 and March 2017. They were 18 males. Seventeen cases had acute myeloid leukemia (AML), 13 myelodysplastic syndrome (MDS), 3 myelofibrosis (MF), 1 chronic myeloid leukemia (CML), 1 mixed MDS/myeloproliferative syndrome (MPS), and 1 plasmacytoid dendritic cell neoplasm. The status at transplant was as follows: first complete remission (CR) n=16, second CR n=4, third CR n=1, active disease n=15 (MDS n=10, MF n=3; CML n=1, MDS/MPS n=1). Seven patients had already received a first allograft. Twenty-seven patients received a graft from an haploidentical donor (son n=10; daughter n=2; sister n=7; brother n=4; father n=2; nephew n=2) while 8 cases (AML n=1; MDS n=4, myelofibrosis n=2; mixed syndrome n=1) had a matched donor (sibling n=2, mud n=6) and 1 a 9/10 mis-matched unrelated donor. The Clo-Baltimore regimen consisted of Clofarabine 30 mg/m²/day days -6 to -2, cyclophosphamide 14.5 mg/kg day -6, low dose total body irradiation 2 Grays day-1, and PTCY 50 mg/kg/day days +3 and +4. All patients received PBSC as stem cell source at day 0. All patients provided informed consent for data collection before the graft.Results: Except one patient who died during aplasia of multiple organ failure (MOF), all patients engrafted. The median time of neutrophils (>1x109/L) and platelets (>50 x109/L) recoveries were 18 (range: 8-27) and 28.5 (range: 11-111) days, respectively. With a median follow-up of 12.3 months for alive patients (range: 3-39.5), 1-year and 18-month OS were both 74% (0.55-0.86), while 1-year and 18-month DFS were 74% (0.55-0.86) and 62% (0.38-0.78), respectively. At 100 days and 1 year, NRM was 5.5% and 8.3%, respectively. Seven patients have relapsed so far with a median time between graft and relapse of 90 days (range: 66-125). The 1-year relapse incidence was 19.4%. Incidences of grade 2-4 and 3-4 acute GVHD were 48% and 11.4%, respectively, while the incidence of chronic GVHD was 20% (limited 6%, extensive 14%). 1-year and 18-month GRFS were 55% (36-71) and 46% (27-64), respectively. At last follow-up, only 9 patients have died, the causes of death being relapse in 5, dermatomyositis in 1, MOF in 1, sepsis in 1 and grade 4 acute GVHD in 1.In univariate analysis, there were no differences regarding 18-month survivals between patients allografted: 1) in CR vs active disease (OS 65% vs 86%, p=0.13; DFS 56% vs 69%, p=0.18), 2)for AML vs MDS (OS 70% vs 85%, p=0.72; DFS 58% vs 85%, p=0.49), or 3) between haplo-identical vs matched+9/10 mis-matched donors (OS: 69% vs 88%, p=0.29; DFS 59% vs 61%, p=0.57).Conclusion: The Clo-Baltimore regimen has shown very encouraging results in this series for patients with myeloid malignancies, improving OS and DFS at 1 year compared to the Baltimore regimen. A low rate of relapse was observed even although using a RIC regimen, which is suitable for older patients and cases with co-morbidities. An update of the follow up will be provided at the meeting. These data have to be validated prospectively. DisclosuresTouzeau:AbbVie: Research Funding. Moreau:Onyx Pharmaceutical: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria; Takeda: Honoraria; Millennium: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria.

Haplo-Identical Stem Cell Transplantation for Patients with Multiple Myeloma Who Relapsed after Autografting. a Study from the Cmwp of EBMT

IntroductionHaploidentical stem cells are becoming an alternative stem cell source for patients lacking an HLA-identical sibling or 10/10 HLA-matched donor. While an increasing number of studies for patients with acute leukemia, malignant lymphoma, and MDS are reported there are only very few results of haploidentical stem cell transplants in myeloma patients.Method and patientsIn EBMT registry 50 MMpatients with a median age of 55 y (r: 37 - 73) with relapse after autograft who received a mismatched related stem cell graft after myeloablative (n = 12, 25%) or reduced intensity conditioning (n = 37, 75%) between 2004 and 2014 were reported. The median time to relapse after single (n = 28, 56%) or tandem (n = 18, 36%) autologous stem cell transplantation was 6.2 months (r: 0.1 - 30.5) and the median time between last autograft and allograft was 17.4 months (r: 2 = 74 months).At time of allograft 4 (8%) of the patients were in CR, 21 (42%) in PR, 9 (18%) had stable disease or minor response, and 15 (30%) had progressive disease. The majority (84%) received peripheral blood stem cells as graft source and GvHD prophylaxis with ex- or in-vivo T-cell depletion (CD34 selection or ATG) (Cyclophosphamide post transplant) was performed in 37% of the patients while 63% did not receive any in-vivo or ex-vivo T-cell depletion.ResultsAfter a median follow-up of 52 months (95% CI: 12-112) the cumulative incidence of non-relapse mortality at 1 year was 20% (95% CI: 9 - 31%) and the cumulative incidence of relapse at 3 years was 56% (95% CI: 42 - 70%) resulting in an estimated 3-year PFS and OS of 15% (95% CI: 5 - 26%) 31% (95% CI: 7 - 45%), respectively. Significant factor for improved OS in a univariate analysis was only the use of BM (3 y OS: 71% (95% CI: 38 -100%) vs. 24% (95% CI: 11 - 38%), p = 0.02) and for relapse a higher but not significant incidence for ex-vivo T-cell depletion was observed (p = 0.07). The use of cyclophosphamide post transplantation as GvHD prophylaxis did not influence NRM, relapse incidence, PFS, OS, or chronic GvHD.ConclusionHaploidentical stem cell transplantation after relapse to an autograft is feasible for MMpatients. Major treatment failure is the high incidence of relapse. Post-transplant cyclophosphamide had no major impact on outcome in this limited number of patients. DisclosuresDreger:medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Jansen: Consultancy; medac: Other; medac: Other: Travel grants; medac: Other: Travel grants; medac: Other; Gilead: Consultancy, Speakers Bureau; medac: Other; medac: Other; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Jansen: Consultancy; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau. Corradini:Amgen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Gilead: Honoraria. Zuckerman:BioSight Ltd.: Consultancy. Ciceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Petersen:Sanofi: Membership on an entity's Board of Directors or advisory committees. Schönland:Sanofi: Research Funding; prothena: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Speakers Bureau. Garderet:Amgen: Honoraria; Takeda: Honoraria.

Applicability and Prognostic Significance of Flow Cytometric Cerebrospinal Fluid Investigation in Children with Acute Lymphoblastic Leukemia

Conventionally central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is found by blasts detection in cerebrospinal fluid (CSF) via cytospin slides microscopy. It was shown earlier, that low levels of tumor cells, undetectable by cytomorphology (CM), could be found in several ALL cases using more sensitive techniques such as multicolor flow cytometry (MFC) (A. Popov et al, ASH-2011). Nevertheless prognostic value of these low levels of blasts in CSF is still unclear. The aim of present study was to evaluate the clinical significance of MFC application for initial diagnostics of leukemic cells in CSF of children with ALL.Patients and methods. Since December 2008 till November 2014 in 155 consecutive children older than 1 year with ALL initial CNS involvement was investigated by CSF flow cytometry. Study group included 65 girls and 90 boys aged from 1 to 16 years (median age 4 years) treated according to ALL MB-2008 protocol. 134 patients (86.5%) suffered from various types of B-cell precursor ALL (BCP-ALL), while remaining 21 cases (23.5%) were T-lineage ALL. According to the protocol stratification system 59 patients belonged to standard risk group (SRG), 87 - to intermediate risk group (ImRG) and 9 - to high risk group. CSF lesion was studied in parallel by microscopy of cytospin slides and by MFC. CNS status was classified as CNS1 (no blast cells in CSF), CNS2 (<5 WBC/ul CSF with blast cells), or CNS3 (≥5 WBC/ul CSF with blast cells, or other signs of CNS involvement). Antibodies' combinations for cytometric CSF assessment were developed on the basis of leukemic cells immunophenotype defined by initial diagnostic bone marrow investigation. Treatment outcome was estimated by cumulative incidence of relapse (CIR). Median of follow up was 5 years.Results. In 5 patients CNS3 status was defined. These patients were excluded from the further analysis due to obvious neuroleukemia signs. CNS2 was found in 23 of 150 remaining cases (15.3%) while 127 (84.7) had CNS1. Totally 53 out of 150 studied children (35.3%) had MFC-detectable CSF lesion. In 32 CNS1-patients leukemic blasts were found only by MFC. Absolute blast count in 1 ml in CSF samples, positive by both methods was significantly higher than in samples, positive only by MFC (median = 418, range 8-158171 and median = 34, range 5-2762 respectively, p<0.001). Thus MFC allows detecting tumor cells in CSF much more frequently (p<0.001) than conventional CM. This difference could be explained mainly by higher MFC sensitivity. Both CM and MFC presented results, valuable for outcome prediction. Children with CNS2 (n=23) had higher relapse incidence that patients with CNS1 (n=127): CIR 0.38(0.11) and 0.16(0.05) respectively, p=0.005. 53 MFC-positive patients displayed higher CIR compared to 97 MFC-negative ones: 0.26(0.06) and 0.15(0.05) respectively, p=0.019. Nevertheless MFC lacked prognostic impact in clinically relevant patients' groups. Among CNS1 cases the CIR difference between MFC-positive (n=32) and MFC-negative (n=95) groups was not significant: 0.19(0.07) and 0.15(0.05) respectively, p=0.148. SRG patients, who could be restratified according to the results of CSF inspection, also haven't displayed any difference in relapse incidence between 51 MFC-negative patients (CIR 0.18(0.07)) and 8 MFC-positive ones (CIR 0.27(0.17), p=0.313). In ImRG after exclusion of T-ALL cases cytometric CSF assessment also lacked its prognostic impact: MFC-negative group (n=33) had similar outcome to MFC-positive patients (n=33): CIR 0.08(0.06) and 0.17(0.07) respectively, p=0.239. In 37 initially MFC-positive cases follow-up CSF samples were also studied. Patients with fast clearance of CNS burden (n=24) displayed better outcome compared to children who remained MFC-positive (n=13), although these differences didn't achieve statistical significance: CIR 0.32(0.10) and 0.54(0.14) respectively, p=0.116.Conclusions. Our data shows that MFC is able to find in CSF even small number of leukemic blasts, which are undetectable by conventional cytospin slides microscopy. Despite of this advantage of cytometric CSF inspection, the prognostic value of MFC data remains controversial. In contrast, larger tumor cells populations that could be detected in CSF also by cytomorpology are more strictly associated with high incidence of relapse. Nevertheless this data should be confirmed on larger patients' cohort in multicenter trial. DisclosuresNo relevant conflicts of interest to declare.