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2.
Journal of Hypertension ; 40(10):2022-2036, 2022.
Article in English | EMBASE | ID: covidwho-2032197

ABSTRACT

Objective:Biomarkers have become important in the prognosis and diagnosis of various diseases. High-throughput methods, such as RNA sequencing facilitate the detection of differentially expressed genes (DEGs), hence potential biomarker candidates. Individual studies suggest long lists of DEGs, hampering the identification of clinically relevant ones. Concerning preeclampsia - a major obstetric burden with high risk for adverse maternal and/or neonatal outcomes - limitations in diagnosis and prediction are still important issues. We, therefore, developed a workflow to facilitate the screening for biomarkers.Methods:On the basis of the tool DESeq2, a comprehensive workflow for identifying DEGs was established, analyzing data from several publicly available RNA-sequencing studies. We applied it to four RNA-sequencing datasets (one blood, three placenta) analyzing patients with preeclampsia and normotensive controls. We compared our results with other published approaches and evaluated their performance.Results:We identified 110 genes that are dysregulated in preeclampsia, observed in at least three of the studies analyzed, six even in all four studies. These included FLT-1, TREM-1, and FN1, which either represent established biomarkers at protein level, or promising candidates based on recent studies. For comparison, using a published meta-analysis approach, 5240 DEGs were obtained.Conclusion:This study presents a data analysis workflow for preeclampsia biomarker screening, capable of identifying promising biomarker candidates, while drastically reducing the numbers of candidates. Moreover, we were also able to confirm its performance for heart failure. This approach can be applied to additional diseases for biomarker identification, and the set of DEGs identified in preeclampsia represents a resource for further studies.

3.
ASAIO Journal ; 68:146, 2022.
Article in English | EMBASE | ID: covidwho-2032192

ABSTRACT

Background: Revised guidelines clarify indications for extracorporeal membrane oxygenation (ECMO) support in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Commercially available ECMO analytics software records granular perfusion data continuously throughout the run. To date, electronic-medical record (EMR) clinical data has not been integrated with ECMO perfusion data and analyzed with machine learning-based algorithms to improve patient care. Methods: Retrospective chart review was performed on all SARS-CoV2 positive patients cannulated to veno-venous ECMO at an urban highvolume regional referral center from March 1st, 2020, through December 31st, 2021. Categorical data including patient demographics, clinical outcomes, and laboratory data (complete blood count, basic metabolic panel, arterial blood gas, lactate, anticoagulation assays) and vital signs (pulse, arterial line blood pressure, oxygen saturation) were collected for the entirety of the ECMO run. Time-series perfusion data (arterial flow normalized to body surface area (BSA), sweep gas, delta pressures normalized to arterial flow) were captured every 60-120 seconds. We constructed a predictive long-short term memory (LSTM) predictive model that integrated clinical and time-series data using an extended machine learning (ML) framework with neural network. Primary outcome was successful ECMO decannulation. Data were truncated to discrete and relative timepoints (7, 14, 21 days, or percent of the run). Receiver operating characteristic (ROC) curves show the model's diagnostic accuracy. Results: 42 patients were included in the analysis (30 male, 12 female). Mean age was 43.9 (SD=11.5) years old, and mean duration of ECMO run was 36.2 (SD=30.1) days. 24 patients were successfully decannulated and 4 are currently supported on ECMO. When provided the complete data, the LSTM model showed an area under the ROC curve >0.95, demonstrating strong diagnostic accuracy in predicting successful ECMO decannulation (Figure 1A). When data were truncated to only the first two weeks of the ECMO run, the area under the ROC curve was 0.93 (Fig. 1B). Patterns of arterial flow normalized to BSA and sweep gas normalized to flow also appear different in patients with divergent clinical outcomes (Fig 2). Conclusion: Characterizing key determinants of ECMO support may offer intensive care unit healthcare teams potentially lifesaving information in real-time. Our machine-learning model successfully integrates clinical and perfusion data from the mind's eye of a clinician managing the care of a patient supported with ECMO. We have identified critical variables with the most meaningful impact on the mechanics of ECMO support. Our model may also help predict patient outcomes into and offer clinicians opportunities for interventions to improve care. (Figure Presented).

4.
ASAIO Journal ; 68:140, 2022.
Article in English | EMBASE | ID: covidwho-2032190

ABSTRACT

Background: Timing of tracheostomy in COVID-19 patients supported with extracorporeal oxygenation membrane (ECMO) remains unclear. This study aims to compare the short-term outcomes in early (≤7 days from ECMO insertion) (ET) versus late (LT) tracheostomy. Methods: Charts of COVID-19 patients with tracheostomy from 2020 to 2021 were reviewed, retrospectively. Primary endpoint was in-hospital mortality. Secondary endpoints were analgesics/sedatives doses, length of treatment (LOT), and initiation of physiotherapy (PT). Results: Eight patients with ET were compared to six patients with LT. Mean age was 41.4±12.5 (ET) and 49.5±6.9 (LT) years. In both groups, 50% were male with comparable BMI. Twelve patients received venovenous (VV) and two received veno-arterial (VA) ECMO. Tracheostomy post ECMO cannulation was performed in 12 [ET:6(75%);LT:6(100%)] patients, whereas in the remaining two patients, it was performed immediately after initiation of ECMO support. Average duration of ECMO support was 48.0±21.3 (ET) than 42.2±27.0 (LT) days, P=0.34. Requirement of sedatives before [ET:6.4±4.6;LT:9.3±5.3;P=0.15] and after [ET:21.6±11.9;LT:12.2±14.0;P=0.11] along with analgesics before [ET:6.3±4.9;LT:7.0±6.5;P=0.41] and after [ET:19.0±6.9;LT:14.8±15.5;P=0.28] tracheostomy was comparable. No difference was observed in the LOT during sedatives/ analgesics dosing after tracheostomy. However, the LOT before tracheostomy was significantly longer in sedatives [ET:2.9±3.1;LT:11.8±6.2, P<0.01] and analgesics [ET:2.9±2.8;LT:9.8±3.5, P<0.01], explained by the longer interval between ECMO insertion and tracheostomy in LT group. Compared to LT, number of days from ECMO insertion to first PT session was significantly shorter in ET patients [ET:13.6±5.6;LT:26.5±4.5, P<0.01]. In-hospital mortality rate was 21.4% [ET:1(13%);LT:2(33%), P=0.33] patients with comparable ICU stay [ET:56.9±18.6;LT:50.2±26.4, P=0.30] between groups. Conclusion: Although the advantages of ET to reduce the requirement of analgesics and sedatives amongst COVID19 patients supported with ECMO were like LT group, ET was associated with early initiation of PT and improved survival.

5.
ASAIO Journal ; 68:66, 2022.
Article in English | EMBASE | ID: covidwho-2032185

ABSTRACT

Background: The COVID-19 pandemic has led to a significant increase in the use of Veno-venous extracorporeal membrane oxygenation (VV ECMO) as a bridge to various outcomes including transplantation or recovery. Unlike other etiologies of acute respiratory distress syndrome (ARDS), utilization of VV ECMO in COVID-19 has been associated with longer duration of ECMO support requirements. Our team sought to evaluate outcomes associated with prolonged duration of ECMO support in this patient population. Methods: Single-center retrospective review of patients who were placed on ECMO due to COVID-19 associated ARDS. Specifically examining outcomes-mortality, transplantation and discharge rates-of patients requiring VV ECMO support more than 50 days in duration. Data collected between February 15,2020 to February 15, 2022. Results: Reviewed outcomes in 18 patients who required VV support for >50 days. Twenty three percent (n=4) mortality rate within cohort. Three patients (16%) continue to require ECMO support at time of submission. Sixty-one percent (n=11) patients were discharged, of which sixteen percent (n=3) required a lung transplant (Table). Summary: Prolonged VV ECMO at our center was associated with comparable outcomes to the national ELSO pulmonary ECMO cohort. With availability of device and staffing, prolonged ECMO runs can potentially be justified in a highly selected patient population (Table Presented).

6.
ASAIO Journal ; 68:65, 2022.
Article in English | EMBASE | ID: covidwho-2032184

ABSTRACT

Objectives: The purpose of this study was to compare the outcomes of chest tubes (CT) inserted via three approaches in COVID-19 patients undergoing extracorporeal membrane oxygenation (ECMO): open thoracostomies (OT), percutaneously at bedside (PERC), and percutaneously by interventional radiology (PERC IR). Methods: We conducted an institutional review board - approved retrospective study of all COVID-19 patients who required CT placement while undergoing ECMO in our institution from February 2020 till February 2022. Insertions prior to ECMO cannulation or after decannulation, and those related to post-operative lung transplantation during ECMO were excluded from our analysis. Depending on the insertion approach, eligible CT insertion events were divided in three groups: OT, PERC and PERC IR. Data regarding patients' demographics and CT characteristics, clinical indications and associated complications for each group were collected and analyzed. Bleeding related to CT insertion was diagnosed based on requirement of blood transfusion, cessation of anticoagulation and/or ongoing bloody CT output. Results: Study criteria were met by 43 patients, with 35 (83.7%) of male sex. Mean age was 45 years. Mean BMI was 31.6 kg/m2. Forty patients (93.0%) had COVID-related acute respiratory distress syndrome as primary diagnosis. All patients but one had been receiving therapeutic anticoagulation which was held prior to CT insertion. Eighty-seven CT insertion events were recorded, of which 34 (39.1%) comprised the OT group, 20 (23.0%) the PERC group, and 33 (37.9%) the PERC IR group. Table 1 demonstrates a descriptive comparison of CT and insertion data among the three groups. Table 2 depicts the major outcomes among the three groups. Conclusions: For COVID-19 patients on ECMO, insertion of CTs percutaneously by IR is associated with significantly fewer bleeding episodes, transfusions, thoracic consults and explorations in the operating room compared to bedside OT or percutaneous CTs. One third of the percutaneously placed CTs by IR required tube upsizing in the IR suite, a rate still lower compared to the overall CT manipulations or repeat interventions required for CTs inserted via OT or percutaneously at bedside. (Table Presented).

7.
ASAIO Journal ; 68:62, 2022.
Article in English | EMBASE | ID: covidwho-2032180

ABSTRACT

Background: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is increasingly being utilized to manage critical COVID-19 associated ARDS (CCAA) in patients who fail medical optimization and mechanical ventilatory support. The aim of this study was to determine the probability of weaning patients from ECMO over time and whether a subset of patients should be considered for lung transplantation. Additionally, we investigated when lung transplant should be considered after VV ECMO support. Methods: 49 patients with CCAA who required ECMO between January 2020 and September 2021 were investigated. Baseline patient demographics, clinical, laboratory, and follow-up data were compared. The change in probability of ECMO weaning based on duration of ECMO support was studied using a univariate analysis. Additionally, patients who received lung transplantation following VV ECMO for COVID-19 during this same period were studied to compare outcomes to those of patients with only VV ECMO support. Cox proportion hazard analysis was performed to determine predictors of survival in patients who required greater than 28 days of ECMO support. Yuden index was used to determine change in probability of survival with time on ECMO. Results: Of 49 patients, 17 (35%) received lung transplants and 32 (65%) remained on ECMO for >28 days. The probability of weaning patients from ECMO was highest within the first 10 days (60%);beyond 40 days, it was 5.1% (Fig. A). The probability of successfully weaning patients from ECMO significantly decreased over time and ECMO support greater than 28 days (Yuden index, Hazard ratio: 1.09, 95% CI;1.00-1.03) was associated with a significantly increased risk of mortality. Additionally, both survival to hospital discharge (p<0.001, Fig. B) and post-discharge survival (p<0.001, Fig. C) were significantly greater in those who were weaned from ECMO prior to 28 days than those who were weaned after 28 days. In those who could not be weaned from ECMO, lung transplantation (HR:0.47, p<0.01, 95% CI 0.17-0.94), ECMO duration (HR:1.09, p=0.01, 95% CI 1.00-1.03) and higher BUN levels (HR:1.02, p<0.01, 95% CI 1.01- 1.46) prior to ECMO initiation were independent predictors of survival. ECMO support of greater than 8 days was associated with a statistically significant increase in mortality compared to those who received fewer than 8 days of support (Yuden index, HR 1.96, CI 1.06-5.51). Furthermore, the projected survival of patients on ECMO support for greater than 8 days was substantially worse than those requiring fewer than 8 days of support (Fig. C and D). Conclusion: This study suggests that survival and accompanying lung recovery is more probable in patients who require a short duration of ECMO support whereas those who require longer durations, particularly exceeding 28 days, is associated with a lower rate of survival. (Figure Presented).

8.
HemaSphere ; 6:3291-3292, 2022.
Article in English | EMBASE | ID: covidwho-2032172

ABSTRACT

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. Approximately 2% of patients with CLL develop immune thrombocytopenic purpura (ITP) during the course of the disease. When resistant to steroids, this constitutes as indication for treatment of the CLL. Here we report a patient with refractory ITP secondary to CLL successfully treated with venetoclax. Aims: To present an interesting case with CLL related refractory ITP treated successfully with novel agent venetoclax. Methods: Patient data was taken from the patient herself and Hospital records. Informed consent to publish the case is obtained from patient. Permission for off-label venetoclax and eltrombopag was obtained from Ministry of Health of Turkey. Results: 46-year-old female patient presented with lumps on her neck that were present for the last 9 months in November 2020. She has a history of frequent pneumonia and otitis but no constitutional symptoms. Her physical examination reveals multiple 2cm lymphadenopathies on her neck and no organomegaly or other pathological features. Blood work shows mild lymphocytosis (6800/mm3) with no serious cytopenias. Peripheral blood smear, flow cytometry and bone marrow biopsy were all compatible with CLL. She was classified as Binet A CLL and was followed up with no treatment after appropriate vaccinations against capsulated pathogens. In July and August 2021 she received two doses of mRNA vaccination against COVID-19. On 1st November 2021 she experienced excessive menstrual bleeding and blood work showed platelet count of 23000/mm3, she was started on steroids (1 mg/kg/day) and after 4 days platelet count has risen to 55000/mm3, she discontinued steroids on her own against medical advice. On 13th of November she presented with extensive petechiae and purpura and was again started on steroids and was given the courses of intravenous immunoglobulins (IVIG) without any sustained response. She was refractory to platelet transfusions too. She was transferred to our clinic. She was found to have del11q and del13q. She refused bone marrow examination. She was treated with rituximab, steroids, vincristine, IVIG and eltrombopag for ITP without success (Fig. 1). She had a minimal response to IVIG only. She received two courses of bendamustine (90 mg/kg for two days) also without success. Three courses of plasmapheresis yielded no response either. After mild success with immunadsorbtion apharesis she was started on venetoclax plus rituximab with ramp-up. Sustained response was achieved within the first week of venetoclax therapy. (Figure Presented ) Summary/Conclusion: Gordon et al. reported 2 CLL cases one with ITP and other with Evans syndrome successfully treated with venetoclax. We think, this treatment should be considered in patients with refractory immune cytopenias secondary to CLL and assessed with prospective clinical trials.

9.
HemaSphere ; 6:1647-1648, 2022.
Article in English | EMBASE | ID: covidwho-2032170

ABSTRACT

Background: Lenalidomide (LEN) maintenance and continuous LEN-based induction therapy until disease progression have become standard of care for frontline therapy of multiple myeloma (MM). As such, an increasing number of patients (pts) in need of 2nd line therapy have LEN-refractory disease. Optimal treatment in this setting has not been rigorously assessed in randomized studies. The phase I portion of Alliance A061202 demonstrated the safety of the ixazomib-pomalidomide-dexamethasone (IXA-POM-DEX) combination for the treatment of pts with LEN and proteasome inhibitor (PI)-refractory MM. Aims: In the randomized phase II portion, we evaluated the addition of IXA to POM-DEX for PI naïve / sensitive pts progressing on LEN as part of 1st line therapy. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), depth of response, survival and safety. Methods: Pts were randomized 1:1 to IXA-POM-DEX or POM-DEX and stratified by prior bortezomib exposure, International Staging System stage (1 and 2 vs 3) and the presence of high-risk cytogenetics. POM was administered at 4 mg on days 1-21;IXA 4 mg on days 1, 8 and 15;and DEX 20 mg (>75 years (yrs)) or 40 mg (≤75 yrs) on days 1, 8, 15 and 22 of a 28-day cycle. Treatment was continued until disease progression, the emergence of unacceptable side effects or withdrawal of treatment consent. Results: 38 and 39 eligible pts were assigned to IXA-POM-DEX and POM-DEX, respectively. The median age was 66 yrs (range 41-83) and 64 yrs (range 52-85). A planned first interim analysis was conducted after 43 out of 57 required events had occurred. PFS favored the IXA-POM-DEX arm (one-sided log rank test value = 4.6345, p=0.03134 [< p-value boundary of 0.058]), yielding a hazard ratio of 0.528 (upper 90% bound = 0.777). A stratified log-rank test found that PFS was superior for the triplet after adjusting for stratification factors (one-sided stratified log rank test value = 5.8371;p=0.0157), adjusted hazard ratio 0.451 (upper 90% bound = 0.694). The ORR favored IXA-POM-DEX (63.2% vs 43.6%, p=0.0853), and the ≥very good partial response was 26.3% vs 5.1%, respectively (p=0.01). The clinical benefit rate (ORR + minimal response rate) was 73.7% and 56.4%. The most common grade 3/4 adverse events included lymphopenia, neutropenia, anemia, and fatigue in 40%, 37%, 16% and 16% of IXAPOM-DEX-treated pts and 26%, 21%, 13%, and 15% of POM-DEX-treated pts. Therapy was discontinued for disease progression in 47.4% of pts on IXA-POM-DEX and 76.9% of pts on POM-DEX and for adverse events in 7.9% and 7.7% of pts, respectively. Summary/Conclusion: The addition of IXA to the POM-DEX backbone improved the depth of response and PFS for pts relapsing on LEN as part of 1st line therapy. Hematologic toxicity was increased with the addition of IXA, but side effects were manageable. The ease of administration of this all-oral combination allowed for safer, uninterrupted treatment during the COVID pandemic. Our results should be confirmed in phase III trials but lend support for this regimen as part of 2nd line therapy for this patient population.

10.
HemaSphere ; 6:1395-1396, 2022.
Article in English | EMBASE | ID: covidwho-2032168

ABSTRACT

Background: Persistent cytopenia due to poor graft function (PGF) is a life-threatening complication in patients undergoing allogeneic HSCT (allo-HSCT). Several therapeutic approaches have been tested in this subset of patients with poor clinical results. Aims: The objective of this multicenter open-label interventional prospective phase II Novartis study (ELTION, ClinicalTrials.gov id: NCT03718533), was to analyze efficacy and safety of EPAG in patients with post-allo-HSCT poor graft function. Methods: Adult patients diagnosed with PGF (defined as severe cytopenia after day +30 post-transplant, with two or more of the following: platelets <20000/μL-mandatory-, ANC <1000/μL, hemoglobin< 10 g/dL), and full donor chimerism, were eligible to enter the trial. Study treatment consisted of EPAG. at 150 mg/day administered up to 36 weeks;dose adjustments were contemplated as per protocol on an individual basis. The primary efficacy endpoint was the overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of EPAG. Results: Although the aim of the study was to include 33 patients, recruitment stopped prematurely due to the difficulties for hospital visits posed during COVID-19 pandemic, and eventually only 10 patients were included. The decision for this premature termination is not related to any safety concern related to the drug. Patient characteristics are shown in the table 1 attached below. At EPAG. initiation, all 10 patients showed thrombocytopenia (<20000/μcL), 5 presented with anemia (Hgb <10 g/dL), and 4 had neutropenia (ANC <1000/μcL). Four patients discontinued EPAG before week 12 due to: disease progression/relapse (2 patients), protocol deviation (1 patient), and CMV infection (1 patient). In none of the cases, the event was related to study drug. At week 16, 4 patients (4/10, 40%) and at week 24, 5 patients, showed improvement in at least one of the 3 hematologic cell lines (partial response), respectively. Counts pre-and post-EPAG and global response in patients who stayed on treatment > 12 weeks are displayed below: Image: Summary/Conclusion: In our experience, EPAG worked well in subjects with PGF, an otherwise life-threatening condition for patients, and its use at 150 mg/day is safe and well tolerated in this setting. Our data suggest that eltrombopag might improve hematologic cell counts in patients with PGF, especially in those patients who remained on treatment at week 24, however further research is warranted to extend its applicability for larger cohorts.

11.
HemaSphere ; 6:2000-2001, 2022.
Article in English | EMBASE | ID: covidwho-2032165

ABSTRACT

Background: Waldenström macroglobulinemia (WM) is an indolent lymphoma with a prolonged disease course which typically follows a remitting and relapsing trajectory, eventually leading to treatment resistance. Several treatment options exist including Bruton tyrosine kinase inhibitors (BTKi), rituximab-containing regimens, and bortezomibcontaining regimens. Treatment selection is based on patient performance status, disease characteristics, drug tolerability and availability. Aims: To assess the effectiveness and tolerability of bortezomib-based regimens in WM. Methods: Data for patients who had Bortezomib-containing regimens between 2010 and 2021 from 6 centres in the United Kingdom were retrospectively reviewed. Data was acquired from the WMUK Rory Morrison Registry. Research ethics approval was obtained. Results: Thirty-four patients were identified: 32/34 had Bortezomib-containing regimens once and 2/34 had >1 Bortezomib-containing regimens on separate occasions, giving a total of 38 subcutaneous Bortezomib-containing regimens administered at bi-weekly and weekly schedules. Median age was 62 years (37-87), with a median of 2 prior lines of therapy (0-7), at a median duration of 49.6 months from date of WM diagnosis (0.7-422). 5 patients received a prior BTKi, with the Bortezomib regimen prescribed following a median of 3 prior lines of therapy (2-5) in this group. Patients who were treated at first line had elected for non-chemotherapy regimens. Median performance status was 1 (0-2) in 23 evaluable patients. The median M-protein at initiation was 34.5g/l (8-60) with bone marrow infiltration 70%, and haemoglobin 94g/l (88-107). A median of 5 cycles (1-8) were delivered and 65% (13/20) received a dose of 1.6mg/m2 and 35% (7/20) received 1.3mg/m2. Grade (G) 1 to 2 neuropathy occurred in 19% (5/26) of evaluable patients but did not result in treatment cessation in any case. Six of 25 (24%) needed a dose reduction, the majority due to G1-2 neuropathy (67%;4/6). Gastrointestinal disturbance occurred in 12% (3/26) patients, 1 required admission with G4 diarrhoea and remaining cases were G1. Of 34 evaluable cases, major response rate (≥ PR) was 74% (5 CR, 6 VGPR, 14 PR). 62% (8/13) of patients receiving 1.6mg/m2 achieved a major response and 86% (6/7) of those who received 1.3mg/m2. Three of 5 patients who had prior BTKi achieved PR, 1 MR, 1 SD. Two patients had treatment discontinued due refractory disease. The overall median time to best response was 81 days from end of treatment. Six of 19 (26%) evaluable patients achieved best response during therapy. Two patients died during treatment due to infection (COVID;respiratory sepsis), not attributable to disease relapse. Eighteen patients (60%;18/30) had treatment after bortezomib regimens at a median of 5.3 months (0-75) and are alive. Median follow up was 30 months (1-111). Twenty-one evaluable patients (72%;21/29) were alive at the end of follow up. Image: Summary/Conclusion: This retrospective real-world analysis shows that bortezomib-containing regimens have utility in WM with effective major response rates even in those with multiple prior lines of therapy and heavy marrow infiltration including BTKi failures. Lower bortezomib doses are effective, and GI and neurotoxicity are manageable with dose reductions but no treatment discontinuations in this real-world cohort indicating an acceptable safety profile.

12.
HemaSphere ; 6:161, 2022.
Article in English | EMBASE | ID: covidwho-2032164

ABSTRACT

Background: High-risk (HR) cytogenetic is associated with poor outcome in transplant eligible (TE) newly diagnosed myeloma multiple myeloma (NDMM). The triplet combination carfilzomib lenalidomide and dexamethasone (KRD) plus transplantation demonstrated high efficacy with faorable safety profile in TE-NDMM patients (FORTE). The addition of daratumumab (Dara) to frontline therapy also improed response rate and progression free-surial in TE-NDMM patients (CASSIOPEIA, GRIFFIN). Double transplant also improed outcome of HR TE NDMM patients (EMN02, STAMINA). Aims: The phase 2 trial 2018-04 from the Intergroupe Francophone du Myelome (IFM) is ealuating an intensie strategy with Dara-KRD induction and consolidation plus double transplant in HR TE NDMM (NCT03606577). Methods: HR MM was defined by the presence of del17p, t(4;14) and/or t(14;16). Stategy includes Dara-KRD induction (6 cycles), autologous stem cell transplantation (ASCT), Dara-KRD consolidation (4 cycles), second ASCT, Dara-lenalidomide maintenance. The primary endpoint was the feasibility of this intensie strategy. Here, we report efficacy and safety analysis of Dara-KRD induction. Results: Fifty patients with preiously untreated NDMM were included from july 2019 to march 2021 in 11 IFM centers Median age was 57 (range 38 -65). ISS stage 3 was present in 12 (24%) patients. Based on inclusion criteria, all patients had HR cytogenetic, including 17p deletion (n=20, 40%), t(4;14) (n=26, 52%) or t(14;16) (n=10,20%). Forty-six patients completed Dara-KRD induction. Two patients discontinued treatment due to seere aderse eent (COVID-19 infection, n=1 ;drug-induced hepatitis, n=1) and 2 patients discontinued treatment due to disease progression. Grade 3-4 treatment related aderse eent (>5% of patients) were neutropenia (38%), anemia (14%), thrombocytopenia (8%), infection (6%), renal insufficiency (6%) and deep-ein thrombosis (6%). Two patients (6%) experienced stem-cell collection failure. Oerall response rate was 96%, including 92 % > ery good partial response. Among 37/46 ealuable patients post induction, Minimal Residual Disease negatiity rate (NGS, 10-5) was 62%. Summary/Conclusion: Dara-KRD as induction prior ASCT is safe and allows deep responses in TE NDMM patients with high-risk cytogenetic profile. IFM 2018-04 study is ongoing and longer follow-up is needed to ealuate safety and efficacy of the oerall strategy with Dara-KRD induction and consolidation plus double transplant in this subset of HR patients.

13.
HemaSphere ; 6:3515, 2022.
Article in English | EMBASE | ID: covidwho-2032161

ABSTRACT

Background: Diagnosis of AL amyloidosis requires demonstration of amyloid in affected tissues along with clonal plasma cells in bone marrow or presence of monoclonal light chains in blood. With increasing awareness among physicians and availability of proper diagnostics, more cases of AL amyloidosis are being diagnosed. Here we present our experience of AL amyloidosis diagnosis and treatment in the era of modern diagnostics and therapy with novel agents. Aims: We aimed to describe the clinical presentations, laboratory features and outcomes of patients with AL amyloidosis in a single center using standard diagnostic tests and treatment with novel agents. Methods: A retrospective analysis of AL amyloidosis patients, diagnosed in our hospital, a tertiary care center in India from January 2016 to December 2021. The data was collected from departmental database. All statistical analyses were done by SPSS version 17. Results: Diagnosis of AL amyloidosis was done in 27 patients. Median age of presentation was 59 years. 22 (81.5%) were males. Major symptoms were pedal edema (37%), shortness of breath (22.2%), frothy urine (11.1%) and fatigue (11.1%). Twenty two (81.5%) presented with ECOG PS ≥ 2. Most common system involved was renal in 16 (59.2%), followed by cardiac in 13 (48.1%) and gastro-intestinal in 9 (33.3%). Fifteen (55.6%) had two or more system involvement while 12 (44.4%) had single system involvement. Lambda monoclonal light chain was present in 22/27 (81.5%) and kappa monoclonal light chain was present in 5/27 (18.5%). Median Hb was 11.6 g/dl (range 6.7- 14.8 g/dl), median M-protein was 0.69 g/dL (range 0-2 g/dL) and median bone marrow plasma cells were 7% (range- 1-18%). Fourteen patients were treated;cyclophosphamide, bortezomib and dexamethasone (CyBORD) in 10/14 (71.4%) and bortezomib + dexamethasone in 4/14 (28.6%). Among 14 patients followed up with median follow up of 13 months (range 6-60 months), 5 expired;3 due to COVID, one due to cardiac arrhythmia (during first cycle) and one due to relapse and rest 9 were alive. Among the 9 patients who were alive 6 were in complete hematological response and 3 were in partial response after 6 cycles of therapy. Summary/Conclusion: Our study presents the spectrum of clinical manifestations, management and outcomes of primary amyloidosis in Indian context. There is a need to increase the awareness among the physicians about amyloidosis so that early diagnosis can be made and timely treatment can be done with novel agents to improve the dismal historical results.

14.
HemaSphere ; 6:4042-4043, 2022.
Article in English | EMBASE | ID: covidwho-2032160

ABSTRACT

Background: Special epidemiological measures aimed at suppressing SARS-CoV-2 outbreak were introduced in Croatia in March 2020, thus reducing regular work capacity in hematological outpatient and inpatient care. In our hospital, this included relocating the entire Hematology Department to a remote location, reduction of hospital beds in the Hematology Inpatient Unit by approximately 60%, Day Clinic operating at a reduced capacity, and a complete suspension of Hematology Polyclinic during first lockdown. Aims: Herein we report our observation of unusually high incidence of newly diagnosed malignant hematological diseases following first lockdown ease in May/June 2020. Methods: We collected data of patients hospitalized in Hematology Department for 4 periods: May 1 - June 15, 2020 for the test arm, and the same calendar period during previous 3 years (May 1 - June 15 of each of the calendar years 2017, 2018 and 2019), for the control arm. The rationale for such design was that a phenomenon of re-establishing regular work capacity, following temporary restriction, was only observed in the test arm. The study included patients of both sexes older than 18 who were diagnosed with either: Hodgkin lymphoma (C81.0 -C81.9 according to the 10th ICD Revision), different types of non-Hodgkin lymphoma (subsections C82.0 - C83.9 and C85.1-C85), as well as multiple myeloma and malignant plasma cell neoplasms (C90.0 - C90.3). Excluded from our study were diagnoses of T/NK cell lymphoma (C84.0- C84.9;C86.0 - C86.6), malignant immunoproliferative diseases (C88.0 - C88.9), leukemias and other specified malignant neoplasms of lymphatic, hematopoietic and related tissues (C91.0 - C96.9) as well as polycythemia vera and non-malignant hematological diseases (D45 and D50 - D89 in ICD-10). Results: In years 2017-2019, similar numbers of patients were diagnosed with a hematological malignancy in our Department (n=4 for 2017, n=8 for 2018, n=4 for 2019) whereas in 2020, a total of 28 patients were diagnosed during the same calendar period (Hodgkin lymphoma: n=5, NHL n=12, multiple myeloma n=7, CLL/SLL n=4). Statistical analysis revealed a significant increase (p ≤0.05) of newly diagnosed hematological malignancies in May and first half of June 2020, when compared to the same calendar periods during previous three years. Further statistical analysis has not established significant differences in outcome (difference in EFS statistically insignificant, p=0.86), as we had expected in the short follow-up period. (Table Presented) Summary/Conclusion: Facilitating treatment of patients affected by the novel coronavirus represented a welcome change in healthcare system in early 2020, in our country and abroad. At the same time, however, the reduction of tertiary health care capacity aimed at population with hematological diseases presented serious risks for successful diagnosis and treatment outcome, a subject that gained wide attention in literature. It has been reported that, also due to psychological reasons, a fraction of patients delayed seeking medical attention after noticing symptoms. In our study we aimed at analyzing the effects of lockdown ease on the number of newly diagnosed hematological malignancies. We were able to demonstrate the effect of pandemic-related measures on detecting new disease cases. It remains to be clarified if a sudden surge in new diagnoses was due to delayed first physician's appointments/hospitalizations, as is suggested by available literature. The results of our study suggest that longer follow-up period will be required in order to clarify the effects of possible late diagnoses on the treatment outcome.

15.
HemaSphere ; 6:2622-2623, 2022.
Article in English | EMBASE | ID: covidwho-2032155

ABSTRACT

Background: Etavopivat, an investigational, once-daily, selective, activator of erythrocyte pyruvate kinase (PKR) increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volunteers and patients (pts) with sickle cell disease (SCD).1,2 Aims: We report results of an open-label (OL) extension cohort from a Phase 1 study (NCT03815695) designed to characterize the safety and clinical activity of etavopivat at a maximal pharmacodynamic dose in pts with SCD. Methods: 15 pts were enrolled to receive etavopivat 400 mg once daily for 12 wks, followed by a 4-wk follow-up. Assessments included safety, pharmacokinetics, pharmacodynamics, RBC health parameters and systemic markers of SCD pathophysiology. Results: Of 15 pts (age 32.3 ±10.1 yr;HbSS/SC n=13/2), 14 completed 12-wks of treatment (tx);1 pt discontinued tx after ∼2 wks. Etavopivat 400 mg once daily was generally well tolerated. Adverse events (AEs) reported during tx and follow-up were commonly low grade (Gr) and consistent with pts' SCD. Gr1-2 AEs in >2 pts (n [%]) were sickle cell pain events (9 [60%]);headache (5 [33%]);and upper respiratory tract infection (3 [20%]). The Gr3-4 AE in >1 pt was sickle cell vaso-occlusion (VOC;4 [27%]). On-tx serious adverse events (SAEs;1 pt each) were Gr3 VOC post Gr3 COVID (not tx-related) and Gr3 left femoral deep vein thrombosis (possibly related, resulting in tx discontinuation as stated above). SAEs (1 pt each) during the 4-wk follow-up were Gr3 acute chest syndrome + Gr3 VOC, Gr3 non-cardiac chest pain and Gr3 syncope (all unrelated). Observed increases in ATP and decreases in 2,3-DPG were durable over 12 wks of etavopivat tx. Etavopivat tx normalized hemoglobin (Hb)S-oxygen affinity to that of HbA. Etavopivat tx over 12 wks improved overall sickle RBC health, demonstrated by a reduction in point of sickling as well as improved measures of deformability and hydration of sickle RBCs (all P<0.01;Figure). Etavopivat tx over 12 wks was associated with a sustained significant increase in Hb compared with baseline (BL;P<0.0001), with mean maximal increase of 1.5 (range 0.7-2.3) g/dL. Ontx increase in Hb >1g/dL was achieved in 11 (73%) pts, for whom the mean maximal Hb increase was 1.8 (1.2-2.3) g/dL. Absolute reticulocytes, indirect bilirubin and lactate dehydrogenase significantly decreased from BL and were sustained over the 12wk period (all P<0.05), indicative of increased RBC lifespan and decreased hemolysis. Several markers of disease activity significantly decreased from BL during daily etavopivat tx, including the inflammatory marker tumor necrosis factor-α , which decreased by 35% (P<0.001). Based on preliminary exploratory analysis with an aggregate duration of etavopivat exposure of 3.32 pt-yrs in the OL cohort, a decrease in the trend for VOC Hospitalizations was observed: annualized historical and on-tx VOC Hospitalization rates were 0.93 and 0.30, respectively;the 1 on-tx VOC Hospitalization was COVID-related. Summary/Conclusion: Etavopivat 400 mg once daily for up to 12 wks demonstrated a tolerable safety profile and showed improvements in various markers of RBC health in pts with SCD. Rapid and sustained increases in Hb were associated with decreases in reticulocyte counts and markers of hemolysis, supporting increased sickle RBC lifespan and improved anemia. Together, these results support further evaluation of etavopivat in the Phase 2/3 Hibiscus Study (NCT04624659) currently enrolling pts. (Figure Presented).

16.
HemaSphere ; 6:1910-1911, 2022.
Article in English | EMBASE | ID: covidwho-2032154

ABSTRACT

Background: Rituximab-based chemoimmunotherapy regimens are backbone treatment (Tmt) for both indolent (follicular [FL], marginal zone [MZL]) and aggressive (diffuse large B-cell [DLBCL], mantle cell [MCL]) B-cell lymphomas. Standard of care (SoC) for relapsed or refractory (R/R) disease includes anti-CD20 in combination with chemotherapy and targeted therapies, such as Bruton's tyrosine kinase inhibitors (eg, ibrutinib) and phosphoinositide 3-kinase (PI3K) inhibitors. Parsaclisib is a potent and highly selective next generation PI3Kδ inhibitor that is currently being investigated in hematological malignancies. Aims: CITADEL-112 (NCT03424122) is an open-label phase 1 study evaluating the safety and tolerability of adding parsaclisib to investigator choice SoC Tmt rituximab (RIT), RIT + bendamustine (BEN), or ibrutinib (IBR) in patients (pts) with R/R B-cell lymphoma. Methods: Enrolled pts were ≥18 years and had histologically confirmed DLBCL, FL, MCL, or MZL, ECOG PS 0-2, were R/R to ≥1 (≥2 for FL) prior systemic therapy, and ineligible for stem cell transplant. Pts received parsaclisib 20 mg orally once daily (QD) for 8 weeks then 20 mg once weekly (QW) in combination with either: RIT 375 mg/m2 IV QW for 4 doses in cycle 1 (± cycle 2) (Tmt A);RIT 375 mg/m2 IV on day 1 + BEN 90 mg/m2 on day 1 and day 2 of each 28-day cycle for ≤6 cycles (Tmt B);or IBR 560 mg QD (Tmt C). Pts received treatment until disease progression, unacceptable toxicity, or withdrawal. Results: At data cutoff (May 14, 2021), 50 pts were treated (16 pts each in Tmt A and C, 18 pts in Tmt B) and 13 pts were ongoing treatment (3 pts in Tmt A, 8 pts in Tmt B, 2 pts in Tmt C). Most pts had received ≥2 prior systemic treatments (81.3%, 61.1%, and 68.8% in Tmt A [range 1-4], B [range 1-4], and C [range 1-7], respectively). The most common reasons for discontinuation were progressive disease (56.3%, 38.9%, and 50.0%) and adverse events (AEs) (12.5%, 11.1%, and 6.3% in Tmt A, B, and C, respectively). One pt in Tmt B experienced a dose-limiting toxicity of grade 4 neutropenia for >14 days. All pts experienced at least 1 treatment-emergent AE (TEAE);in Tmt A, 75.0% had grade ≥3 and 37.5% had serious TEAEs;Tmt B, 83.3% had grade ≥3 and 27.8% had serious TEAEs;and Tmt C, 62.5% had grade ≥3 and 43.8% had serious TEAEs. Common any-grade TEAEs (≥30%) included neutropenia (62.5%), diarrhea (37.5%), and anemia (31.3%) in Tmt A;neutropenia (50.0%), abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Tmt B;neutropenia (50.0%) and increased ALT and increased AST (each 37.5%) in Tmt C. Most common grade ≥3 TEAEs (≥15%) were neutropenia (50.0%) and diarrhea (18.8%) in Tmt A, and neutropenia (38.9% and 25.0%) in Tmt B and Tmt C, respectively. Serious TEAEs occurring in >1 pt were COVID-19, diarrhea, and pneumonia (n = 2 each) in Tmt A, and atrial fibrillation (n = 2) in Tmt C. TEAEs with fatal outcome were reported in 2 pts in Tmt A (COVID-19 and COVID-19 pneumonia [n = 1], interstitial lung disease [n = 1]) and 1 pt in Tmt C (COVID-19, acute kidney injury). Parsaclisib dose interruption or dose reduction due to TEAEs occurred in 75.0% and 18.8% of pts, respectively, in Tmt A;66.7% and 27.8% of pts, respectively, in Tmt B;and 56.3% and 18.8% of pts, respectively, in Tmt C. Summary/Conclusion: Parsaclisib 20 mg QD for 8 weeks followed by 20 mg QW can be safely combined with RIT, RIT + BEN, or IBR in pts with R/R B-cell lymphomas. The tolerability profile of the combination regimens was manageable, with no unexpected safety concerns.

17.
HemaSphere ; 6:2558-2559, 2022.
Article in English | EMBASE | ID: covidwho-2032153

ABSTRACT

Background: We have previously described AUTO1, a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR T-cell immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL (Ghorashian S et al., Nat Med 2019;Roddie C et al., JCO 2021). This data confirms the intended function of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Aims: We have initiated testing of AUTO1 in the setting of B-NHL and CLL/SLL (NCT02935257). Methods: Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised patient leukapheresate. Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m x3) and cyclophosphamide (60mg/kg x1) prior to AUTO1 infusion, with the exception of the DLBCL cohort who additionally received a single dose of pembrolizumab (200mg) on day -1 to potentiate CAR-T expansion. AUTO1 dose varies based on the indication. Split dosing of 230 x106 CD19 CAR T-cells at day 0 and day 9 is employed in the CLL cohort. A single dose of 200 x106 CD19 CAR T-cells is delivered to patients with B-NHL. Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months. Results: As of 8th February 2022, we enrolled 23 patients: 11 low grade NHL (LG-NHL:7 with FL and 3 with MCL), 7 DLBCL and 5 CLL. Apheresis was successful in all 23 patients and product manufacture was successful in 22 (pending in the last). 19 patients were infused: 10 with LG-NHL, 6 with DLBCL and 3 with CLL. 1 CLL patient was pending infusion at time of data cut-off and 2 patients died pre-infusion: 1 MCL patient, from COVID-19 and 1 CLL patient, from intracerebral haemorrhage. Patients treated with AUTO1 had a median age of 60 years (range 39-79), had received a median of 3 prior lines of treatment (range 2-8). Grade 1 CRS was reported in 6/19 and Grade 2 CRS in 3/19. No ICANS was observed in the B-NHL and CLL cohorts. CAR engraftment was observed in 13/13 patients evaluated by qPCR with ongoing persistence in 12/13 patients at last follow-up. In the LG-NHL and DLBCL cohorts 10/10 and 4/5 evaluable patients respectively were in CMR by 18FDG PET-CT post-treatment. Responses were ongoing in 9/10 LG-NHL at 12 months and in 4/4 DLBCL at months 1, 3, 3 and 6. In the CLL cohort, 2/3 evaluable patients achieved MRD negative remission in the bone marrow with residual small volume lymph nodes by CT at 6 and 3 months of follow-up respectively. 1 CLL patient did not engraft and had SD at month 1. Summary/Conclusion: AUTO1 has a tolerable safety profile in patients with r/r B-NHL and CLL despite high disease burden. Early data shows excellent complete remission rates and excellent CAR engraftment/expansion. Additional patients, updated data and longer follow up will be presented.

18.
HemaSphere ; 6:3924, 2022.
Article in English | EMBASE | ID: covidwho-2032149

ABSTRACT

Background: Patients with hematological malignancies are at a higher risk of developing severe form and protracted course of COVID-19. Remdesivir, an inhibitor of RNA polymerase was identified early as a promising therapeutic regimen for COVID-19, while convalescent plasma (CP) therapy with anti-SARS-CoV-2 antibodies can aid the treatment of COVID-19 in B-cell depleted patients. Aims: Here we investigated whether the combination of externally administered immunoglobulins (Ig) via CP therapy and specific inhibition of viral replication might be sufficient to effectively treat B-cell depleted patients with COVID-19. Methods: We enrolled a series of 20 consecutive patients who suffered from various hematological malignancies with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. These patients demonstrated a profound B-cell lymphopenia based on flow cytometry analysis of peripheral blood lymphocyte subpopulations. Consequently, they showed undetectable baseline anti-SARS-CoV-2 Ig levels before CP therapy according to anti-SARS-CoV-2 nucleocapsid-and S1-RBD-specific total Ig tests. Each patient received a complete course of remdesivir and at least one unit (200 ml) of AB0 compatible convalescent plasma during their treatment for COVID-19. Results: Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of Bcell lymphopenia (p=0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p=0.017), length of hospital stay (p=0.007), and PCR positivity (p=0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p<0.001) and hospital stay (p<0.0001). In those cases where there were at least ten days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p<0.001). Summary/Conclusion: Via combined administration of remdesivir and CP, we experienced an overwhelming survival rate in COVID-19 patients with hematological malignancies. Inhibition of viral replication with passive immunization proved to be efficient and safe. Our results suggest the clear benefit of early administration of CP to avoid protracted COVID-19 disease in patients with B-cell lymphopenia.

19.
HemaSphere ; 6:2386-2387, 2022.
Article in English | EMBASE | ID: covidwho-2032147

ABSTRACT

Background: Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate Antibody is currently approved in combination with 7 + 3 in low- and intermediate risk acute myeloid leukaemia (AML). These patients are candidate for consolidation with autologous stem cell transplantation (ASCT) particularly when MRD- is obtained. GO can improve the rate of MRD negativity. There are limited data on the effect of its addition on the mobilization of Hemopoietic Stem Cells (HSC). Aims: To assess the feasibility of mobilization of HSC after re-introduction into market of GO at 3mg/m2 in 2019. Methods: We retrospectively studied AML patients undergoing 3+7 + GO induction and Ara-C + Daunorubicine + GO, consolidation (doses are derived from label instructions and ALFA0701 study) and mobilization on day +20 using GCSF 10μg/kg. CD34+ were monitored, and patients were harvested when a threshold of 20 cells/μL was reached in peripheral blood. Results: In 2020 and 2021, also considering constrains caused by COVID-19 pandemics, we attempted mobilization in our 3 Italian centres of 14 patients with a diagnosis of CD33+ de novo-AML. The median age was 52 years (range 29-65 yrs.), 4 were males and 10 females;11 patients carried a mutation of NPM1 and all had a normal karyotype except one with t(10p12;11q14) (Table 1). All received 3+7+GO induction and achieved a CR. Therefore, we started consolidation (total ARA-C 8g/m2) + GO as inpatient. Ten patients (71%) reached the established threshold of 20 CD34+ /μL and were successfully harvested, while 4 patients (29%) failed mobilization. The median day of apheresis was D+26 from the start to chemotherapy (range 22- 39). The median number of circulating CD34+ cells on the day of collection was 35.9 cells/μL (range 20-2153 cells/μL). The median CD34+ harvested was 4.65 x 106/kg (range 1.8- 44.6 x 106/kg). In our cohort, 4 patients (28% of the entire cohort and 40% of the harvested patients) underwent ASCT, 3 achieved favourable engraftment, while in the last patient ASCT is ongoing. Several reasons prevented ASCT in the remaining 6 patients: 3 patients underwent allogeneic SCT (2 had positive MRD on harvested apheresis;1 was reclassified as high-risk ELN2017 due to RUNX1 mutation resulting from NGS panel), 2 refused ASCT and one suffered early relapse. Summary/Conclusion: In our patients, the addition of GO did not impair HSC mobilization and harvesting that was reached in about 71% of cases, similarly to the AML-10 trial of the EORTC and GIMEMA Leukemia Groups where 70% of patients were successfully harvested. Our data are particularly interesting because in the pivotal ALFA0701 study, only one patient underwent Autologous- SCT, but in the control arm. An important limit of our case-series is that only 4 patients were auto-transplanted, so we have scant data on engraftment. In particular, evaluating day to engraftment of platelets would be interesting, given the known increase of thrombocytopaenia in patients treated with GO. In conclusion, mobilization with GO is feasible and further studies are warranted to evaluate the effects of fractioned doses of GO on HSC mobilization and ASCT outcome;the ongoing trial GIMEMA AML1819 - EudraCT number 2019-003871-20 - will prospectively assess the effect of GO, but with lower doses of ARA-C (total ARA-C 6 g/m2). (Table Presented).

20.
HemaSphere ; 6:523, 2022.
Article in English | EMBASE | ID: covidwho-2032145

ABSTRACT

Background: During the coronavirus pandemic, the risk of severe COVID-19 and mortality are higher in certain groups, in particular in patients with oncohematological diseases. Acute lymphoblastic leukemia (ALL) is a special group of oncohematological diseases in which mortality in the era of COVID-19 has increased 2-3 times. Currently, there is no consensus on the treatment of ALL during coronavirus infection. Aims: To determine the basic principles and features of the management of patients with ALL during COVID-19. Methods: 46 patients with ALL and COVID-19 (men 52.2%, women 47.8%) aged 18-74 years (median-44.5) were treated at the Moscow City Clinical Hospital 52 on 01.04.20-01.11.21. B-ALL was 58.7% (27 patients), T-ALL - 34.8% (16 patients), biphenotypic - 4.3% (2 patients), not defined - 2.2% (1 patient), Ph-positive ALL - 17.4% (8 patients). The status of the disease of patients upon admission to the Hospital differed: debut of ALL - 20 patients (43.5%), remission - 16 patients (34.8%), relapse and refractory course - 10 patients (21.7%). All patients were treated COVID-19 in accordance with the current guidelines for the prevention, diagnosis and treatment of COVID- 19 (interleukin 6 inhibitor, anticoagulant and antibacterial therapy, glucocorticoids (GCs), human immunoglobulin (IG) against COVID-19). According to vital indications and with stabilization of the patient's condition, 18 patients (39.1%) received chemotherapy (CT). Results: There were no deaths in the group of patients with remission of ALL. In patients with the debut of ALL, mortality was 45% (9 patients), in relapse and refractory course - 50% (5 patients) (p=0.005). Mortality in the group who did not receive CT was 35.7%, and in the group who received CT - 22.2%. 6 patients with Ph-positive ALL (75.0%) continued therapy with tyrosine kinase inhibitors (TKI). According to the protocol for the treatment of ALL, full doses of GCs (100%) and anthracyclines (ATC) (100%) were used, lumbar punctures (LP) and intrathecal (IT) injections of CT (100%) were continued. Due to the high risk of thrombotic complications in COVID-19 and asparaginase therapy, anticoagulant therapy was performed (100%). Prevention of pneumocystis pneumonia (PCP) (89.1%), antifungal (37.0%) and antibacterial (87.0%) therapy were carried out in the treatment of COVID-19. With the persistence of COVID-19 and the absence of antibodies to COVID-19, 2 patients received repeated transfusion of human IG against COVID-19. Summary/Conclusion: During the COVID-19 pandemic, patients in remission of ALL coronavirus infection are treated and controlled. Treatment of COVID-19 in patients with ALL is carried out according to general protocols for the treatment of COVID-19, taking into account the peculiarities of nosology (agranulocytosis, high risk of PCP and fungal infection with long-term therapy of GCs, persistence of COVID-19). When the patient's condition is stabilized, the issue of CT should be decided individually in each case, taking into account all the risks of ALL and COVID-19. During CT, use full doses of GCs, ATC. In patients with mild and moderate COVID-19, continue LP and IT injections of CT, therapy with TKI.

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