Search

We retrospectively compared the outcomes of 20 patients receiving Venetoclax + low-dose Cytarabine + Actinomycin D (ACTIVE) with 29 patients receiving FLAG-Ida as salvage therapy for relapsed or refractory AML (R/R AML) after alloSCT. The groups were statistically balanced according to age, performance status, cytogenetics, and previous treatment. The overall response rate (CR + CRp + MLFS) of ACTIVE was 75% (15/20) in comparison to 66% (19/29) in the FLAG-Ida group (p = 0.542). The cumulative CR + CRp rate was significantly higher in the ACTIVE group compared to FLAG-Ida (70% (14/20) vs. 34% (10/29), respectively, p = 0.02). All three patients failing previous Venetoclax therapy and five out of seven patients with previous FLAG-Ida exposure achieved a CR/CRp after ACTIVE induction. ACTIVE patients survived longer compared to FLAG-Ida patients (13.1 vs. 5.1 months, respectively, p = 0.032). The treatment-related mortality was 0% in the ACTIVE group and 34% (10/29) in the FLAG-Ida patients (p = 0.003). The cumulative incidence of relapse did not differ between the two treatment groups. ACTIVE appears to have comparable antileukemic activity and lower toxicity compared to FLAG-Ida resulting in improved survival. Patients with Venetoclax or FLAG-Ida exposure responded to ACTIVE.

BACKGROUND: Haematological malignancies and their treatments are likely to affect SARS-CoV-2 vaccine efficacy. We aimed to evaluate serological response to BNT162b2 vaccine in patients with haematological malignancies by type of treatment. METHODS: Our national prospective cohort study was done in Lithuania and assessed serological response to one and two BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine doses in healthy health-care workers and in patients with haematological malignancies. Eligible participants were aged 18 years or older, had received both vaccine doses, and had available biobanked blood samples from before vaccination and after the second dose. Biobanked samples and health data were obtained from Vilnius University Hospital Santaros Klinikos Biobank. Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG antibody) concentrations 0-10 days before the first BNT162b2 vaccine, on the day of second immunisation (around day 21), and 7 to 21 days after the second immunisation. Adverse events were assessed by a standardised questionnaire. Breakthrough infections were characterised clinically and by SARS-CoV-2 genotyping whenever possible. This study is registered with ClinicalTrials.gov, NCT04871165. FINDINGS: Between Jan 8 and April 21, 2021, 885 participants with haematological malignancies were included in the study. 857 patients were anti-S1 IgG seronegative at timepoint 0 and constituted the main analysis cohort. The age-matched comparison was made between 315 patients with haematological malignancies who were aged 18-60 years and 67 healthy health-care workers in the same age group. Patients aged 18-60 years with haematological malignancies had lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses than did health-care workers of the same age group (median 6961 AU/mL [IQR 1292-20 672] vs 21 395 AU/mL [14 831-33 553]; p

We retrospectively collected clinical data on 31 relapsed or refractory acute myeloid leukemia (R/R AML) patients who were treated with outpatient glasdegib and low-dose Cytarabine (LDAraC) at our institution. The median age was 67 years (45-86). The median Eastern Cooperative Oncology Group performance status was 2 (1-3). The patients had previously received a median number of 2 (1-4) treatment lines, 61% (19/31) had been treated with intensive chemotherapy, 29% (9/31) had relapsed after allogeneic stem cell transplantation, and 45% (14/31) had had venetoclax exposure. Adverse cytogenetics were identified in 45% (14/31) of the cases. The CR + CRp rate was 21% (6/29) among evaluable patients. The median overall survival was 3.9 months for all patients. Different median overall survival times were observed in responders, patients achieving stable disease and those diagnosed with progressive disease: not reached vs 3.9 months vs 0.8 months, respectively (p < 0.001). The most common adverse events were pneumonia (29%, 9/31), sepsis (23%, 7/31), and febrile neutropenia (16%, 5/31). Glasdegib + LDAraC is a fairly safe, non-intensive, outpatient regimen inducing complete remission and resulting in prolonged survival in some R/R AML patients.

Background: Patients with active haematological malignancies (HM) have been excluded from clinical trials evaluating vaccines against SARS-CoV-2. Both HM and their treatments are commonly immunosuppressive and are likely to impact COVID-19 vaccine efficacy. Methods: We performed a study assessing serological response to one and two BNT162b2 vaccine doses in healthy healthcare workers (HCWs) and in patients with HM. Peripheral blood samples were collected at three time points: 0-10 days before the first BNT162b2 vaccine jab, on the day of second jab (around day 21) and 7 to 21 days after the second jab. Abbott Architect SARS-CoV-2 IgG Quant II assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG) levels. HM individuals were stratified into groups by current or most recent treatment, latency since treatment and anti-S1 IgG seroconversion status before the first jab. Results: 653 anti-S1 IgG negative participants with HM (median age 64 years, IQR 53 - 72, 52% female) and 69 healthy HCWs (40 [32 - 53] years, 83% female) were included in the study. 18-60 year-old HM patients had lower median anti-S1 IgG response (median 6810 [IQR 635 - 20574] vs 21394 [14289 - 33322], p

Background: Hydroxychloroquine and Azithromycin use is associated with QT interval prolongation and arrhythmias. Despite ongoing multiple clinical trials for treatment of COVID19 infection, no definite cardiac safety protocols were proposed. The aim of our study was to assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using close monitoring and arrhythmia risk management plan.Methods and results: We retrospectively examined arrhythmia safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined cardiac arrhythmia risk management plan. 81 patients were included from March 23rd to May 10th 2020. The median age was 59 years, 58.0% were female. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia. 7 patients (8.6%) had QTc prolongation of ≥500 ms. The treatment was discontinued in 4 patients (4.9%). 14 patients (17.3%) experienced QTc≥480 ms and 16 patients (19.8%) had an increase of QTc≥60 ms. None of the patients developed ventricular tachycardia. The risk factors significantly associated with QTc≥500 ms were hypokalemia (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients had a lethal outcome; none of them associated with ventricular arrhythmias.Conclusion: We recorded a low incidence of QTc prolongation ≥500 ms and no ventricular tachycardia events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia risk management plan.

OBJECTIVES AND METHODS We conducted a retrospective analysis to evaluate the outcomes of 28 heavily pretreated (median 3 (2-6) treatment lines, sixteen (57%) allotransplanted) relapsed/refractory acute myeloid leukemia patients who had failed salvage venetoclax-based therapies. RESULTS The median age was 59 years (20-80), 20 patients (71%) had ECOG 2-4 status, and 18 patients (64%) were stratified to European Leukemia Network 2017 adverse risk group. The most common mutations were ASXL1 (21%), RUNX1 (18%), FLT3 ITD/TKD (18%), PTPN11 (15%), NRAS/KRAS (15%), and WT1 (15%). Twenty-two patients (79%) received different post-venetoclax salvage therapies with the overall response rate of 23% (complete remission + morphological leukemia-free state). Three of six (50%) patients achieved complete remissions after therapy with venetoclax + actinomycin D ± low-dose cytarabine. The remaining 6 patients did not receive any further salvage treatment mainly due to poor general condition. The median overall survival was 3.9 months for all patients (4.3 for those receiving post-venetoclax salvage vs 1.3 months receiving palliative care alone, P

Endoscopic submucosal dissection (ESD) is a standard treatment option for early gastric cancer (EGC) in Asia; however, data about ESD efficacy in Western populations are limited. Furthermore, outcomes of EGC treatment after ESD or surgery have not been compared in Western cohorts. This study aimed to compare short-term and long-term results of ESD and surgery for EGC. This retrospective case–control study included patients with EGC treated in two largest cancer centers in Eastern Lithuania between 2005 and 2016. Propensity score nearest-neighbor 1:1 matching, based on clinicopathologic characteristics, was performed between patients who underwent ESD and surgery. The primary endpoint of the study was 5-year disease-free survival (DFS). Of 260 eligible patients, 42 (16.1%) underwent ESD. After matching, two well-balanced groups consisting of 42 patients in each were analyzed. The operation time (83 vs. 151 min., p = 0.001) and postoperative hospitalization stay (5.4 vs. 13.4 days, p = 0.001) was significantly shorter in the ESD group. 5-year DFS rate was significantly higher in the surgery group (97.6% vs. 77.5%, p = 0.002). However, this difference was reduced after exclusion of non-curative ESD cases (97.6% vs. 89.7%, p = 0.099). There was no significant difference in 5-year OS rate between the study groups (73.8% vs. 69.0%, p = 0.599). ESD might be an excellent alternative to surgery for EGC if curative resection is achieved. Non-curative ESD is associated with poor DFS and high rate of recurrence. Additional surgery should be recommended after non-curative ESD whenever treatment-associated risk is acceptable.

Background Endoscopic resection is widely accepted treatment option for early gastric cancer if tumors meet the standard or expanded indications. However, the safety of expanded criteria is still under investigation. Furthermore, discussion, if any additional treatment is necessary for patients who underwent endoscopic resection but exceeded expanded criteria, is rising. This study aimed to evaluate the safety of extended indications for endoscopic resection of early gastric cancer in a Western cohort. Also, we aimed to analyze the lymph node metastasis rate in tumors which exceeds the extended criteria. Methods Two hundred eighteen patients who underwent surgery for early gastric cancer at National Cancer Institute, Vilnius, Lithuania between 2005 and 2015 were identified from a prospective database. Lymph node status was examined in 197 patients who met or exceeded extended indications for endoscopic resection. Results Lymph node metastasis was detected in 1.7% of cancers who met extended indications and in 30.2% of cancers who exceeded expanded indications. Lymphovascular invasion and deeper tumor invasion is associated with lymph node metastasis in cancers exceeding expanded indications. Conclusions Expanded criteria for endoscopic resection of early gastric cancer in Western settings is not entirely safe because these tumors carry the risk of lymph node metastasis.

Background The proportion of early gastric cancer stages is increasing, as is the incidence of gastric cancer among the elderly population. Therefore, this study was designed to analyze surgical treatment outcomes of T1-T2 gastric cancer in elderly patients. Methods A total of 457 patients with T1-T2 gastric cancer who underwent gastrectomy between 2005 and 2015 were enrolled in this retrospective study. Patients were classified into two groups according to age (

Background Venetoclax based therapies have produced varying results in the relapsed or refractory acute myeloid leukemia (R/R AML) setting. Highest response rates were demonstrated after Venetoclax in combination with high dose chemotherapy. However, this approach is feasible mainly in fit, younger patients. Herein, we present a lower intensity combination therapy consisting of Venetoclax, low dose Cytarabine and Actinomycin D (ACTIVE) in patients with R/R AML administered in real-life clinical practice setting. Methods We performed an observational, retrospective, single centre study. The patients were at least 18 years of age and had R/R AML. All patients provided informed consent for treatment as well as data collection. Venetoclax ramp-up was administered over either 3 or 5 days until the daily dose of 600mg/d was reached. The ACTIVE regimen consisted of Venetoclax 600mg/d p/o on days 1-28, Cytarabine 20mg/m 2 s/c on days 1-10, Actinomycin D 12.5 µg/kg i/v on days 1, 2 and 3 (on days 1 and 2 for patients ≥65 years). Strong/moderate CYP3A inhibitors/inducers or Venetoclax dose reductions were not allowed. Indications for stopping Venetoclax before Day 28 were life threatening infectious complications or faster hematological recovery with the addition of G-CSF in responders. A second ACTIVE cycle was administered in non-responders without evidence of progressive disease after Cycle 1 or in responders with positive minimal residual disease (MRD). We evaluated baseline characteristics, composite CR (CRc = CR + CRi + CRp), overall response (ORR = CRc + MLFS), MRD negativity rates, overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), Grade 3-5 non-hematological toxicities and Day 30 and Day 60 mortality rates. Results Fifty R/R AML patients were treated with ACTIVE and 56% (28/50) were male. The median age was 65 years (20-84). The median Eastern Cooperative Oncology Group (ECOG) status was 1 (0-3) and 40% (20/50) had ECOG status of 2 or 3. Secondary AML was confirmed in 48% (24/50) of cases. Adverse cytogenetics were identified in 28% (14/50) of patients whereas 60% (30/50) were stratified to adverse risk group in accordance with ELN 2017 guidelines. The most common gene mutations were IDH1/2 30% (15/50), FLT3 28% (14/50), ASXL1 22% (11/50), NPM1 14% (7/50), N/KRAS 12% (6/50) and RUNX1 12% (6/50). The median number of prior therapies was 2 (1-5). Intensive chemotherapy was administered in 80% (40/50) of whom 38% (15/40) had primary refractory disease and 48% (19/40) had previously received Fludarabine + Cytarabine + Idarubicin (FLAG-Ida) or Cytarabine + Mitoxantrone (HAM). Eight percent (4/50) had had prior Venetoclax exposure. Thirty-six percent (18/50) had relapsed after allogeneic stem cell transplantation (alloSCT) with a median time of 7.4 months (1.6-37.3) from transplant to relapse. One cycle of ACTIVE therapy was administered in 76% (38/50) of cases, whereas 24% (12/50) received 2 cycles. The median number of Venetoclax 600mg/d days per cycle was 18 (8-28). Additional FLT3/RAS/BCR-ABL1 inhibitors Gilteritinib, Trametinib or Dasatinib were administered in 12% (6/50). Forty-nine patients were evaluable for response and one patient died of sepsis before response evaluation (Table 1). The ORR was 73% (36/49) and the CRc rate was 67% (31/46). MRD negativity was confirmed in 61% (19/31) of CRc patients. Sixteen patients had undergone additional early bone marrow evaluations. Blast count reduction to Half of the ACTIVE responders (18/36) continued maintenance therapy with Venetoclax + low dose Cytarabine and optional DLI, whereas 36% (13/36) proceeded to either first or second alloSCT. After 16.4 months of median follow-up, the median OS, RFS and EFS were 13.1, 7.2 and 4.5 months, respectively (Figure 1A). Median OS was not reached in MRD negative patients (Figure 1B). In multivariable Cox regression analysis, adverse cytogenetics (HR 3.48, 95% CI 1.39 -8.55) and primary refractory disease (HR 2.54, 95% CI 1.05-6.12) were associated with worse OS. The most common grade 3-5 non-hematological adverse events were febrile neutropenia (54%, 27/50) and bacteremia/sepsis (34%, 17/50). Day 30 and Day 60 mortality rates were 8% (4/50) and 16% (8/50), respectively. Conclusions ACTIVE was effective and well tolerated in this unselected prognostically unfavourable older R/R AML patient population. Figure 1 Figure 1. Disclosures Zucenka: Jannsen: Honoraria, Other: Travel-expenses; Takeda: Other: Travel Expenses; Novartis: Honoraria, Other: Travel Expenses; Pfizer: Honoraria, Other: Travel Expenses; Astellas: Honoraria; Abbvie: Honoraria, Other: Travel Expenses. Maneikis: Abbvie: Honoraria. Pileckytė: Abbvie: Honoraria, Other: Travel Expenses. Griškevičius: Abbvie: Other: Travel Expenses. OffLabel Disclosure: Venetoclax has been used off-label for the treatment of R/R AML

Background Current risk factors for lymph node metastasis in early gastric cancer have been primarily determined in Asian countries; however their applicability to Western nations is under discussion. The aim of our study was to identify risk factors associated with lymph node metastasis in Western cohort patients from the Eastern European country - Lithuania. Methods A total of 218 patients who underwent open gastrectomy for early gastric cancer were included in this retrospective study. After histolopathological examination, risk factors for lymph node metastasis were evaluated. Overall survival was evaluated and factors associated with long-term outcomes were analyzed. Results Lymph node metastases were present in 19.7% of early gastric cancer cases. The rates were 5/99 (4.95%) for pT1a tumors and 38/119 (31.9%) for pT1b tumors. Submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation were identified as independent risk factors for lymph node metastasis. Submucosal tumor invasion and lymphovascular invasion were also associated with worse 5-year survival results. Conclusion Our study established submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation as risk factors for lymph node metastasis.