Multiple myeloma (MM) is a disease characterized by spatiotemporal heterogeneity of tumor clones. Different genetic aberrations can be observed simultaneously in tumor cells from different loci, and as the disease progresses, new subclones may appear. The role of liquid biopsy, which is based on the analysis of tumor DNA circulating in the blood plasma, continues to be explored in MM. Here, we present an analysis of the STR profiles and mutation status of the KRAS, NRAS, and BRAF genes, evaluated in plasma free circulating tumor DNA (ctDNA), CD138+ bone marrow cells, and plasmacytomas. The prospective single-center study included 97 patients, with a median age of 55 years. Of these, 94 had newly diagnosed symptomatic MM, and three had primary plasma cell leukemia. It should be noted that if mutations were detected only in ctDNA, “non-classical” codons were more often affected. A variety of adverse laboratory and clinical factors have been associated with the detection of rare KRAS or NRAS gene mutations in bone marrow or ctDNA, suggesting that these mutations may be factors of an unfavorable prognosis for MM. Liquid biopsy studies provide undeniable fundamental information about tumor heterogeneity and clonal evolution in MM. Moreover, we focus on using liquid biopsy to identify new high-risk factors for MM.

Background The Russian ALL (RALL) group conducted 3 consecutive trials in Ph+ ALL to evaluate chemotherapy approaches combined with continuous imatinib. Patients From January 2010 to May 2024, 78 new Ph+ ALL cases were diagnosed in 4 RALL centers. From 2010 to 2012, 15 pts were treated according to RALL-2009 protocol (clinicaltrials.gov; NCT01193933) with concurrent administration of imatinib. From 2012 to 2018, 32 patients were included in the RALL-2012 protocol based on the de-escalation chemotherapy approach in the RALL-2009 + TKI study. From 2018 until now, 31 pts were included in RALL–2012m protocol. All protocols suggested the shift to dasatinib for patients who did not achieve complete molecular response (CMR) on day 70 of treatment. CMR was stated if BCR/ABL chimeric transcript was <0.01% by PCR with 10-4 sensitivity. All patients were considered candidates for allogeneic HSCT if an HLA-identical donor was available. 32 pts (40%) underwent allo-HSCT as the first-line therapy. Results CMR on day 70 was achieved in 36%, 43%, and 33% on RALL-2009 (4 of 11), RALL-2012 (14) and RALL-2012m (9 of 27), respectively. Death on therapy within 2 months of induction/consolidation was registered in 2 (6%) cases on less intensive RALL-2012, 3 (20%) cases on RALL-2009, and no cases on RALL-2012m. Hematological CR was achieved in 71 of 78 pts (91%), except for 4 early deaths and 2 refractory cases. Allo-HSCT in 1 CR was carried out in 5 pts on RALL-2009, 16 pts on RALL-2012, and 11 pts on RALL-2012m. The long-term outcomes were similar across protocols. For RALL-2009, RALL-2012, and RALL-201m, respectively: 5-year OS, 53% vs 48% vs 76% (P=.08), 5-year RFS, 40% vs 47% vs 50% (P=.43). In order to evaluate the impact of allogeneic HSCT we performed a comparison of transplanted and non-transplanted patients by a landmark analysis. The landmark was the median time from CR to allo-HSCT (4.3 months, range: 3-16). The 5-year RFS from the landmark was 45% for non-transplanted patients, and from the day of HSCT, 65% in transplanted (P=.48). Conclusion De-intensification of chemotherapy does not alter the effectiveness of therapy for Ph+ acute lymphocytic leukemia in the era of tyrosine kinase inhibitors.

Tumor cells of acute lymphoblastic leukemia (ALL) may have various genetic abnormalities. Some of them lead to a complete loss of certain genes. Our aim was to reveal biallelic deletions of genes in Ph–negative T-ALL. Chromosomal microarray analysis (CMA) was performed for 47 patients with de novo Ph–negative T-ALL, who received treatment according to RALL-2016m clinical protocol at the National Medical Research Center for Hematology (Moscow, Russia) from 2017 to 2023. Out of forty-seven patients, only three had normal molecular karyotype. The other 44 patients had multiple gains, losses, and copy neutral losses of heterozygosity. Biallelic losses were found in 14 patients (30%). In ten patients (21%), a biallelic deletion of 9p21.3 involved a different number of genes, however CDKN2A gene loss was noted in all ten cases. For seven patients (15%), a biallelic deletion of 7q34 was found, including two genes—PRSS1, PRSS2 located within the T-cell receptor beta (TRB) locus. A clonal rearrangement of the TRB gene was revealed in 6 out of 7 cases with 7q34 biallelic loss. Both biallelic deletions can be considered favorable prognostic factors, with an association with 9p21 being statistically significant (p = 0.01) and a trend for 7q34 (p = 0.12) being observed.

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities—104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort.

APL is the rarest form of acute myelogenous leukemia.Advances in the treatment of APL have transformed this disease from a condition associated with significant morbidity and mortality to one with an excellent outcome.We present a case of a 68-year-old male who presented with delirium at the Saint Louis Hospital in July 2016.He was diagnosed with AML and achieved complete remission on day 10 of the first consolidation by ATRA/ATO.A neurologic examination revealed fluctuating delirium with temporospatial disorientation.During exploration, he was unable to focus.Cranial nerves were fully intact, and muscle strength was 5/5 throughout.He was hyper-reflexive on the right side compared with the left, and his toes were curled bilaterally, with no tremors or dysmetria.After a few hours, the patient experienced a sudden neurological deterioration with coma Glasgow 3.He was transferred to the intensive care unit.Consolidation therapy was discontinued due to neurological degradation.A Total CT scan was normal, and MRI showed no T2 signal changes.A lumbar puncture showed a WBC count 1, glucose 4.46 mmol/l, and protein 0.54.CSF cultures were negative, and a normal EEG.Investigations revealed a WBC of 6.64/mm 3 , hemoglobin 8.6 g/l, blasts 0%, normal electrolytes, bacteriology, and virology were negatives.The level of arsenic in the urine was 11394 ug/L (N 0 -50 ug/L).The results of CNS investigations were normal.Thus, the focus of the differential diagnosis shifted towards a primary psychiatric disorder.Based on consultation with the psychiatrist, there was no basis for a psychiatric decompression of thymic origin.The patient was diagnosed with an iatrogenic confusional syndrome caused by arsenic toxicity.The patient was treated with succimer 600 mg TID for 10 days with monitoring of the level of arsenic in the urine.On day 4 of treatment with succimer, the patient had a slow favorable resolution of symptoms with a clear improvement of temporal-spatial disorientation and nocturnal agitation.Arsenic trioxide is not known to cause encephalopathic side effects in leukemia patients.However, the side effect observed in this patient were reversible.The patient was treated with idarubicin + ATRA per guidelines and achieved complete remission.

Measurable residual disease (MRD) is a well-known independent prognostic factor in acute leukemias, and multicolor flow cytometry (MFC) is widely used to detect MRD. MFC is able not only to enumerate MRD accurately but also to describe an antigen expression profile of residual blast cells. However, the relationship between MRD immunophenotype and patient survival probability has not yet been studied. We determined the prognostic impact of MRD immunophenotype in adults with B-cell acute lymphoblastic leukemia (B-ALL). In a multicenter study RALL-2016 (NCT03462095), 267 patients were enrolled from 2016 to 2022. MRD was assessed at the end of induction (day 70) in 94 patients with B-ALL by six- or 10-color flow cytometry in the bone marrow specimens. The 4 year relapse-free survival (RFS) was lower in MRD-positive B-ALL patients [37% vs. 78% (p < 0.0001)]. The absence of CD10, positive expression of CD38, and high expression of CD58 on MRD cells worsened the 4 year RFS [19% vs. 51% (p = 0.004), 0% vs. 51% (p < 0.0001), and 21% vs. 40% (p = 0.02), respectively]. The MRD immunophenotype is associated with RFS and could be an additional prognostic factor for B-ALL patients.

Thrombosis is an extremely dangerous complication in elderly patients with COVID-19. Since the first months of the pandemic, anticoagulants have been mandatory in treatment protocols for patients with COVID-19, unless there are serious contraindications. We set out to discover if genetic thrombophilia factors continue to play a triggering role in the occurrence of thrombosis in patients with COVID-19 with prophylactic or therapeutic anticoagulants. We considered the following genetic markers as risk factors for thrombophilia: G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A and C494T in the FII gene, and (-675) 4G/5G in the PAI-I gene. In a cohort of 176 patients, we did not obtain a reliable result indicating a higher risk of thrombotic complications when taking therapeutic doses of anticoagulants in carriers of genetic markers for thrombophilia except the C494T mutation in the FII gene. However, there was still a pronounced tendency to a higher incidence of thrombosis in patients with markers of hereditary thrombophilia, such as FV G1691A and FII G20210A mutations. The presence of the C494T (Thr165Met) allele in the FII gene in this group of patients showed a statistically significant effect of the mutation on the risk of thrombotic complications despite anticoagulant therapy.

Background: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adult pts, including pregnant. AML accounts for two-thirds of all cases of acute leukemia diagnosed during pregnancy. Formulated more than 25 years ago, the postulate about the neсessity for “saving two lives” formed the basis of a systematic approach to the treatment of acute leukemia in pregnant pts with AML, and allowed to develop appropriate clinical protocols. Aims: To assess prognostic impact of allo-HSCT conducted in CR1 in pregnant pts with AML. Methods: In total 45 pregnant pts with AML were included in the multicenter research. All pts were divided into two groups: the 1st group included 20 pts (a set of pts from 1997 to 2014), who were scheduled to undergo allo-HSCT in the first complete remission (CR1) only in the presence of an unfavorable karyotype, the 2nd group - 25 pts (a set of pts from 2015 to 2021), who were scheduled to undergo allo-HSCT in CR1, regardless of the karyotype. The control group consisted of non-pregnant fertile women who received treatment at the National Medical Research Center for Hematology from 2015 to 2021 (n=55). Landmark analysis was performed in group of pregnant pts with CR1 of AML (n = 35) and in the control group (n = 49). The landmark point for pts who underwent allo-HSCT was the date of allo-HSCT, and for the rest – the date of CR plus the median time to allo-HSCT, which in pregnant pts was 190 days (6.3 months) (17-270 days). Results: CR was achieved in 78% of pregnant pts in total (n=35): in 75% of pts from 1st group (n=15) and in 80% of pts from 2nd group (n=20). In the control group the frequency of CR was 89% (n=49). The percent of pts who underwent allo-HSCT was 2.5 times greater in group 2 than in group 1: 68% and 30%, respectively (p = 0.029). In the control group, this indicator was 60%. It was found that performing allo-HSCT in CR1 significantly improved RFS in pregnant women with AML compared to those who did not underwent allo-HSCT (Fig. 1A). In order to assess the combined prognostic impact of various factors on RFS for groups of pts treated under a single program (group 2 and comparison group), a multifactorial analysis of RFS with step-by-step selection of factors was carried out. The following factors were included in the model as candidates: pregnancy, ELN risk group, time when CR was achieved (after the 1st course of induction, or after the 2nd course of induction) and the performance of allo-HSCT in CR1 as a time-dependent factor (the factor does not act until the time of transplantation). The only factor selected for the final model was the performance of allo–HSCT (p = 0.0108). Thus, this factor neutralized impact of other factors, including pregnancy. Figure 1B shows the OS estimated for three subgroups of pts: pregnant women with AML who were treated before 2015 (1st group), pregnant women with AML who were treated after 2015 (2nd Group), and non-pregnant fertile women with AML (control group). The median follow-up time was 17.5 months. Although there were no statistically significant differences between the subgroups, the OS in 2nd group was higher than in 1st group. This difference is observed due to the performance of allo-HSCT in CR1. Summary/Conclusion: It was found that pregnancy is an unfavorable prognostic factor in pts with AML. However, the implementation of allo-HSCT in CR1 allows to neutralize the negative influence of this factor. Thus, women who are diagnosed with AML during pregnancy are candidates for performing allo-HSCT in CR1.Keywords: Chemotherapy, Pregnancy, Acute myeloid leukemia

BACKGROUND:Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and nonmalignant hematologic diseases and COVID-19.PATIENTS AND METHODS:Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-days all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic.RESULTS:Thirty-days all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-months overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients.CONCLUSION:Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed.

Background: Beginning in April 2009 the Russian Research Group for the Study of Ph-negative ALL in Adults conducted multicenter studies ALL-2009(NCT01193933) and ALL-2016(NCT03462095) based on a de-escalated but non-interruptive treatment approach with low numbers of allo-HSCT. The ALL-2009 study provided the cornerstone for further de-escalation of the consolidation phase in a new RALL-2016 study with centralized MRD-monitoring. Aims: To compare long-term (5-year) results of two studies and detect the factors of unfavorable prognosis for adult patients with Ph-negative ALL. Methods: The studies were performed from Apr 2009 to Dec 2016 (ALL-2009) and from Dec 2016 till to Jan 2023 (ALL-2016), with 642 patients included: 330 in ALL-2009 and 312 in ALL -2016. The analysis was completed in Jan 2023. The median age of patients in ALL-2009 was 28 years (15-55), ALL-2016 - 32.5 years (18-55), f/m 147/182 were recruited in ALL-2009 and 117/195 – in ALL-2016. In the ALL-2009 protocol the 6-pts phenotype was unknown. Biphenotypic AL was diagnosed in – 1,2% (n=4), T-ALL/lymphoma – in 38,7% (n=125), and BCP-ALL - in 59,1% (n=194) of the enrolled patients. In the ALL-2016 protocol biphenotypic AL was diagnosed in – 4% (n=13), T-ALL/lymphoma – in 39% (n=123), and BCP-ALL - in 57% (n=176) of patients. Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3%) and 287 patients in ALL-2016 (92%). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by flow cytometry on protocol day +70 (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7% of patients in ALL-2009 and 9% in ALL-2016. Results: The 5 year overall, disease-free survival (OS, DFS) and the probability of relapse were 59%, 63%, 23% for ALL-2009 patients, and for ALL- 2016 patients - 67%, 59%, 22%, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates significantly differed: the standard group (hyperploid set of chromosomes and normal karyotype) - OS 63%, RFS 70% - and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) - OS 49%, DFS 52% (p=0.001, p=0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of ETP T-ALL turned out to be an important predictor of poor prognosis (the probability of relapse was 52% compared with 15% for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the significant negative factors were the high cytogenetic risk group and positive MRD status at +70 days, and for T-cells, the early immunophenotype and positive MRD status at +133 days. Summary/Conclusion: The results of the ALL-2009 and ALL-2016 studies show that the effectiveness of the two Russian protocols is absolutely the same and MRD persistence after induction is the main factor for poor prognosis for Ph-negative ALL.Keywords: Adult, Multicenter, Chemotherapy, Acute lymphoblastic leukemia

The obtained results indicate that the cytostatic treatment used in the RALL-2016 protocol had a minimal effect on differentiated B cells. In this way, a stable number of the most differentiated B cells can contribute to the maintenance of humoral immunity. BCP were more sensitive to cytostatic effects and were not recovered for more than a year after the end of treatment. The absence of changes in PC count may indicate the resistance of this cell population to ongoing chemotherapy.

MRD at the end of induction impaired RFS in patients in the RALL-2016 study. The immunophenotype of MRD cells is associated with RFS and could be an additional prognostic factor.

Background: NHL-BFM-90 chemotherapy is highly effective in pediatric aggressive B-cell lymphomas. Purpose: To evaluate the efficacy and toxicity of the R-mNHL-BFM-90 and R-DAEPOCH-21 programs in adult patients with de novo DLBCL. Patients and methods: Inclusion criteria: newly diagnosed DLBCL (NOS), no previous chemotherapy, 2 or more signs of poor prognosis, age 18-60. The protocol included 140 patients from 13 medical centers in Russia: R-DA-EPOCH-21 – 33; R-DAEPOCH-21+auto-HSCT - 29; R-mNHL-BFM-90 - 33; R-mNHL-BFM-90+ auto-HSCT -35 patients. R-DA-EPOCH-21 branch: 6 courses were performed. If CR was not achieved, 2 courses of R-DHAP were performed ± auto-HSCT. Branch R-mNHL-BFM-90 included 6 cycles: RA-RB-RA-RB-RA-RB. If CR was not achieved, 2 courses of R-DHAP ± auto-HSCTResults: Of 62 patients on R-DA-EPOCH-21±auto-HSCT, CR was achieved in 36 (58.1%) patients, PR was achieved in 14 (22.6%) patients, progression was reported in 6 (9.7%) patients, 3 (4.8%) patients had died, and treatment continued in 3 (4.8%) patients. Of 68 patients on R-mNHL-BFM-90±autoHSCT CR was achieved in 63 (92.7%) patients, PR was achieved in 2 (2.9%) patients, progression was not reported, 2 (2.9%) patients had died, and treatment continued in 1 (1.5%) patient. The 4-year OS of patients in the high-risk group 94% on R-mNHL-BFM-90 therapy, 81% on R-DA-EPOCH-21 therapy;. the 4-year EFS of patients in the high-risk group was 78% and 43%, respectively (p = 0.0004). Conclusion: R-mNHL-BFM-90 program is highly effective in de novo DLBCL NOS adult patients; toxicity is acceptable.

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]

Aim. To analyze the results of treatment in patients with acute myeloid leukemia (AML) within protocols AML-17 and modified AML-17 (mOML-17) as part of two consecutive pilot studies in order to develop the best treatment strategy for AML patients aged below 60 years. Materials and methods. The study included 89 AML patients who were aged below 60 years and received treatment within the AML-17 and mOML-17 protocols. Cytogenetic and molecular genetic studies were performed in all patients. The presence of mutations in the FLT3, NPM1, CEBPa genes was assessed by fragment analysis. 35 patients underwent a study for mutTP53, mutRUNX1 using next generation sequencing (NGS). The minimum residual population of tumor cells was evaluated by multicolor flow cytometry. Statistical analysis was performed using the procedures of the SAS 9.3 package. Results. Complete remission (CR) was achieved in 89.7% of patients treated with intensive chemotherapy (CT) courses and in 52.4% of patients treated with low-dose CT courses. 8.8% of intensively treated patients were refractory to therapy, and 38% did not respond to low-dose exposure. The early mortality rate was 3%. The overall survival and disease-free 3-year survival for patients included in 2 consecutive studies was were 60% and 67%, respectively. The level of minimal residual disease (MRD) after the first course of induction CT was an important prognostic indicator. The three-year relapse-free survival for patients in whom CR was achieved after the first course of induction CT and in whom MRD was not detected (MRD-negative status was obtained) was 90% compared to 43% for patients who were MRD positive after the first course of induction CT (p=0.00001). Conclusion. The key factor that significantly affects the long-term results of therapy is the rate of MRD after the first course of induction CT.

Background: Patients (pts) with acute leukemia (AL) are at high risk of COVID-19 severe and lethal course. Intensive chemotherapy and immunosuppression in these patients are the possible causes of high mortality. Emerging data on risk factors and outcomes in this vulnerable patient population is aimed to support strategies of their medical care. Aims: To evaluate treatment outcomes and risk factors in pts with AL and COVID-19 in a real-world setting. Methods: CHRONOS19 [NCT04422470] is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hematologic disease (both malignant and non-malignant) and lab-confirmed or suspected (based on clinical and/or CT findings) COVID-19. We performed a subgroup analysis of pts with AL and COVID-19. Primary objective was to evaluate treatment outcomes and identify risk factors associated with higher mortality in this group of pts. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web-based platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 132 of them with AL were eligible for primary endpoint assessment n(%): AML - 86(65%), ALL - 37(28%), APL - 9(7%);M/F 55(42%)/77(58%), median age 45 [18-79] years, induction phase/R/R/ treatment in remission 49(37%)/27(21%)/ 54(42%), agranulocytosis in 55(42%) pts, 68(53%) pts were transfusion dependent, comorbidities - in 58(45%) pts. Complications developed in 98(74%) pts: pneumonia (71%), sepsis (9%), CRS (8%), ARDS (6%). One-third of pts had severe COVID-19, 30% were admitted to ICU, 26% required mechanical ventilation. We performed comparative analysis of characteristics between a group of pts with AL and other hematologic diseases (lymphomas, chronic leukemia, multiple myeloma, and other malignant and non-malignant diseases): pts with AL had significantly more frequent agranulocytosis (42% vs 20%, p 60 years HR, 3.340 (1.08-10.9) were the most significant risk factors of death. Overall, AL were associated with a higher risk of death, HR, 2.40 (1.28-4.51), compared to less aggressive diseases (CML, CLL, MM, lymphomas, non-malignant), HR, 0.54 (0.37-0.80). COVID-19 affected treatment of AL in 65% of pts, 58% experienced treatment delay for a median of 4 [1-10] weeks. In 11 of 103 (10,7%) pts with AL early relapse/refractory disease was detected, but the association of relapses with affected treatment is unknown. COVID-19 re-infection was described in 2 patients. Summary/Conclusion: Thirty-day all-cause mortality was significantly higher in SARS-CoV-2-infected pts with AL than in those with other hematologic diseases. Longer-term follow-up (180 days) for AL outcomes and OS will be presented.

Background: Patients (pts) with lymphoproliferative diseases (LPD) are at high risk of COVID-19 severe and lethal course.Objective: To evaluate treatment outcomes and risk factors in pts with LPD and COVID-19 in a real-world setting.Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (18 y) pts with hematologic disease and COVID-19.Data from 15 centers were collected on a web-based platform and managed in a de-identifi ed manner.We performed a subgroup analysis of pts with LPD and COVID-19.Primary endpoint was 30-day all-cause mortality.Long-term follow-up was at 90 and 180 days.Results: As of data cutoff on April 14, 2021, 626 pts were included, 170 of them with LPD were eligible for primary endpoint assessment n(%): CLL -64 (38%), Hodgkin lymphoma -18 (10%), B-cell lymphomas aggressive/indolent -49(29%) / 19(11%); M/F 96 (56%) / 74(44%), median age 56 [19-90] years, induction phase/ R/R/remission 62(36%) / 68(40%) / 40(24%); comorbidities in 86 (51%) pts.Complications occurred in 126 (74%) pts; one-third had severe COVID-19, 25% were admitted to ICU, and 20% required mechanical ventilation.Comparative analysis of basic characteristics between pts with LPD and all other hematologic diseases did not reveal any signifi cant clinical differences.All-cause mortality at 30 days was 14% in pts with LPD vs 15% in pts with other hematologic diseases (p=0.87);86% of deaths were due to COVID-19 complications.Eight additional deaths due to COVID-19 at 90 days and 5 deaths due to LPD progression at 180 days occurred.In multivariate analysis, ICU + mechanical ventilation (HR,), and age >60 years (HR, were the most signifi cant risk factors of death.COVID-19 affected treatment of LPD in 55% of pts, and 52% experienced treatment delay for a median of 4[1-10] weeks.Early relapsed/refractory disease occurred in 5 of 170 (2.9%) pts; the association of relapses with impaired treatment is unknown.COVID-19 re-infection occurred in 1 patient.Data on antibodies after SARS-CoV-2 infection are available for 65 patients with LPD: anti-SARS-CoV-2 IgG was detected in 44 (66%) pts and only in 60% of pts with CD20-positive LPD vs 100% of pts with T-cell and Hodgkin lymphomas (p=0.004).Conclusions: Thirtyday all-cause mortality in SARS-CoV-2-infected pts with LPD was comparable with other hematological diseases and higher than in the general population.Lower frequency of anti-SARS-CoV-2 IgG in CD20-positive patients is probably due to anti-CD20 therapy.

We report the data on 15 women who presented with Ph-negative acute lymphoblastic leukemia (ALL) between Jan 2009 until Dec 2016 and who were treated on the prospective multicenter RALL-2009 clinical trial. A comparison of their outcome was made with 129 non-pregnant females who entered the study and were treated by the same schedule. 10-years OS for pregnant and non-pregnant women was 58.6 % (29.6 %-85.0 %) and 43.3 % (32.1 %-58.8 %), DFS was 46 % (15.2 %-78.8 %) and 51 % (39.7 %-64.6 %); probability of relapse was 49 % (16.6 %-83.3 %) and 40.3 % (27.3 %-53.4 %), respectively. Twelve born during the study children are well and alive with a median age 5 years 2 months (2 years - 9 years). Though small, our study has shown some specific features of ALL diagnosed during pregnancy (more T-cell ALL, higher initial WBC, later responses) and has shown that the long-term outcome of women with ALL treated while pregnant is equivalent to female control patients treated on the same protocol.