Patients Required Platelet Transfusions Research Articles

Effect of platelet storage duration on platelet increment and clinical outcomes in critically ill patients – A randomised controlled trial

Background and objectivesPlatelet storage duration may influence transfusion effectiveness and patient outcomes.The present study aimed to evaluate the effect of platelet storage duration on platelet increment and clinical outcomes in patients admitted to the intensive care unit (ICU). Material and methodsThis prospective, open-label, randomized controlled trial, conducted at a single centre, enrolled ICU patients requiring platelet transfusion. Patients were randomly assigned to receive platelet concentrates aged ≤ 3 days (Group 1) or 4–5 days (Group 2). Platelet increments were assessed by Absolute Platelet Count Increment (ACI), Corrected Count Increment (CCI), and Percentage Platelet Recovery (PPR). Clinical outcomes including bleeding, infection rates, ICU stay, red cell transfusion requirements, and mortality were also monitored. ResultsPatients transfused fresher platelets (Group 1) had higher median ACI, CCI and PPR at 1 h compared to those transfused older platelets (Group 2) though the difference was not statistically significant. At 24 h, Group 1 patients had a median ACI of 28,000/µl compared to 14,000/µl in Group 2(p = 0.001). The median CCI was 16,800 in Group 1 versus 8,200 in Group 2(p = 0.001). Group 1 also had a higher median PPR of 45.7% compared to 23.6% in Group 2(p = 0.011).There was no significant difference in clinical outcomes such as bleeding, infection rates, ICU stay, or mortality between the groups. Multivariate analysis indicated that co-morbidities and higher APACHE-III score were associated with increased mortality. ConclusionTransfusion of fresher platelets resulted in higher increments and transfusion effectiveness but did not affect clinical outcomes or mortality. Trial registration detailsClinical Trials Registry of India (CTRI/2023/03/050676).

A retrospective comparison of abbreviated course “7+7” vs standard hypomethylating agent plus venetoclax doublets in older/unfit patients with newly diagnosed acute myeloid leukemia.

6507 Background: Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in older/chemotherapy ineligible patients with acute myeloid leukemia (AML). While the VEN label recommends continuous 28-day cycles, shortened VEN durations may mitigate cytopenias and improve tolerability. It is unknown how shorter VEN cycles compare to standard HMA+VEN in terms of efficacy/safety. Methods: We performed a retrospective comparison of patients with newly diagnosed (ND) AML treated with azacitidine (AZA) x 7 days plus VEN x 7 days (“7+7” regimen) at 7 French centers (n=82, Willekens, ASH 2022) vs patients treated with standard dose HMA+VEN (s-HMA/VEN) at a US center (n=173), generally consisting of 21-28 days of VEN. We compared composite complete remission rate (CRc, consisting of CR + CRi), overall survival (OS), event-free survival (EFS), and myelosuppression between regimens. Results: Baseline characteristics are shown in the table. The s-HMA-VEN group consisted of 10-day decitabine (DAC) in 59% with the remaining patients receiving 5-day DAC or 7-day AZA. The CRc rate was similar; 72% with “7+7” vs 71% with s-HMA/VEN (p=0.89). The CR rate was 57% with “7+7” vs 55% with s-HMA/VEN (p=0.72). Median cycles to first response was 1 in both groups, however 42% of responders on “7+7” required more than 1 cycle for first response whereas almost all responders on s-HMA-VEN (99%) had a first response after cycle 1. Median cycles to best response was 2 with “7+7” vs 1 with s-HMA-VEN (p=0.02). 4-week mortality was similar (2% with “7+7”, 6% with s-HMA-VEN; p=0.24). 8-week mortality was higher with s-HMA-VEN (17%) compared to “7+7” (6%) (p=0.02). The median OS was 11.2 months (2-year 28%) with “7+7” vs 10.1 months (2-year 33%) with s-HMA/VEN (p=0.93). Outcomes stratified by molecular groups will be updated at the meeting. Fewer patients required platelet transfusions during cycle 1 with “7+7” compared to s-HMA/VEN (62% vs 77%, p=0.01). The cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar. Conclusions: Acknowledging the limitations of a retrospective comparison across multiple centers, we did not observe a signal for a difference in efficacy between "7+7" vs standard VEN-based HMA doublets in ND-AML. The “7+7” regimen was associated with lower platelet transfusion requirements and lower 8-week mortality. [Table: see text]

Multi-Institutional Phase I Feasibility Trial of Vertebral Body Sparing CSI for Pediatric Brain Tumors

Craniospinal irradiation (CSI) is an essential part of curative treatment for several pediatric brain tumors. Proton CSI allows for sparing of the organs anterior to the vertebral bodies (VBs), but this technique still includes the entire VB in the target for growing children. providing no advantage in marrow sparing or adverse effects on growth. Advances in proton therapy including Proton Beam Scanning (PBS) allow for delivery of proton CSI with substantial vertebral body sparing (VBS). We sought to determine the feasibility of VBS CSI using PBS based on the effects on tumor control and growth, and the occurrence of grade III/IV hematologic toxicity. Clinical and treatment characteristics were recorded for 20 pediatric patients with medulloblastoma (n = 14) or germ cell tumor (GCT) (n = 6) who received proton VBS CSI without concurrent chemotherapy or with concurrent single-agent vincristine in a multi-institutional clinical trial. The following standard variables were extracted for each patient: age, histology, radiation dose, chemotherapy regimen, and growth hormone replacement status. Complete blood counts (CBC) with differential and data on height/weight were recorded at baseline pre-RT, weekly during RT, and after completion of cancer treatment. Hematologic toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). Median age of 13 male and 7 female patients receiving proton VBS CSI was 10 years (range: 5.1 - 15.1). All GCT patients (n = 6, 30%) received pre-RT chemo. Median CSI dose was 23.4 Gy (range: 21.0 - 37.8), and total dose to tumor bed was 54 Gy in 18 patients (90%) while 2 patients with pure germinoma received a total dose of 36 and 37.5 Gy, respectively. 11 patients (55%) did not receive concurrent vincristine. At a median follow up of 26.4 months (range: 12.5 - 56.3) from the start of RT, no patients relapsed. 17 patients (85%) developed grade ≥3 hematologic toxicity including grade 3 lymphopenia (n = 16), leukopenia (n = 9), neutropenia (n = 8), anemia (n = 1), and grade 4 neutropenia (n = 1). The patient who developed grade 4 neutropenia had low white blood counts prior to RT. 14 patients (70%) received post-RT chemo. No patients required platelet transfusion during RT. Those findings are similar to historical controls. 4 patients started growth hormone replacement therapy after RT. No patients developed spine deformities after the completion of treatment. Proton VBS CSI is a feasible and well tolerated treatment for children with brain tumors. Longer follow up is needed to assess for late effects on tumor control. It is too early to assess for height in this cohort but for the patients that had longer follow up, normal height was achieved.

Omics markers of platelet transfusion in trauma patients.

Even in the era of the COVID-19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma-induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life-saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion. To bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post-hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post-hospitalization. Longitudinal plasma samples were subjected to mass spectrometry-based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions. Higher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non-recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post-PLT transfusion). The present study provides the first multi-omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry-based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

Impact of Post-Transplantation Cyclophosphamide on Transfusion Requirements in HLA-Matched Sibling Peripheral Blood Stem Cell Transplantation

Post-transplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis is progressively being used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors (MRD). However, information regarding the transfusion needs in this setting is lacking. to compare red blood cell (RBC) and platelet units transfused and time to transfusion independence according to the GVHD prophylaxis in MRD HSCT. We performed a matched-pair analysis comparing the transfusion requirements and the clinical outcomes of patients who received a MRD peripheral blood HSCT using PT-Cy from January 2017 until June 2021 (n = 100) with historical MRD transplants using standard cyclosporine A-based prophylaxis (n = 100). Neutrophil engraftment was significantly delayed in the PT-Cy group as compared with the CsA group (16 days vs. 13 days; P = 0.003). PT-Cy was associated with increased RBC (median, 5 units vs. 4; P = 0.04) and platelet transfusion requirements (median, 6 units vs. 3; P = 0.01) during the first 30 days after transplant. The proportion of patients requiring platelet transfusion during days 31 to 90 after transplant was also higher in the PT-Cy cohort (55% vs. 25%; P < 0.0001). In multivariate analysis, PT-Cy was associated with delayed RBC and platelet transfusion independence ([Hazard ratio [HR] = 0.61; P = 0.007 and HR = 0.51; P < 0.0001, respectively). Cumulative incidence at 100 days of BK polyomavirus (BKPyV)-associated haemorrhagic cystitis grade ≥ 2 was higher in the PT-Cy cohort (34% vs. 12%; P < 0.0001). However, PT-Cy resulted in lower rates of acute GVHD grade II-IV (100-days cumulative incidence 57% vs. 23%; P < 0.0001) and moderate to severe chronic GVHD (1-year cumulative incidence 49% vs. 28%; P = 0.003), as well as improved 2-year overall survival (74% vs. 56%; P = 0.01). Our study shows that PT-Cy increases transfusion burden in MRD HSCT. However, it results in a low incidence of severe GVHD, with encouraging survival outcomes.

QLTI-07. IDENTIFYING RISK FACTORS FOR PROLONGED TRANSFUSION-DEPENDENT TEMOZOLOMIDE-INDUCED THROMBOCYTOPAENIA IN PATIENTS RECEIVING CONCURRENT CHEMO-RADIOTHERAPY FOR GLIOBLASTOMA (GBM)

Abstract BACKGROUND Temozolomide-induced thrombocytopaenia is a well-recognised clinical issue with significant inter-patient variation. However, knowledge of the extent of the problem and its potential risk factors remains limited. Our aim was to determine the incidence of patients requiring platelet transfusion and ascertain associated risk factors using real-world data. METHODS Data from patients with GBM receiving concurrent temozolomide-chemo-radiotherapy (CRT) from 01/01/18-31/12/2019 retrospectively reviewed. Patients receiving platelet transfusion identified (Local policy: transfusion for platelet count ≤ 30x109/L). Logistic regression and chi-squared tests used to compare variables in patients requiring platelet transfusion and those not. RESULTS 111 patients with GBM received TMZ-CRT (60Gy/30#; 75mg/m2 temozolomide). 12/111 patients received platelet transfusion: 10 during concurrent-CRT and 2 during adjuvant-treatment. Numbers of transfusions: 1-2: 7 patients; 3-4: 2 patients; ≥ 5 transfusions: 3 patients. Median time from platelet count ≥ G3 to ≥ 100 in 11/12 patients: 38 days (range 6-72). 1 did not recover, patient died 84 days following start of TMZ-CRT with thrombocytopaenia. Comparison of the transfused vs the non-transfused cohort shows: transfused: 50% female; non-transfused: 36% female. Mean BSA: transfused: 1.73, SD0.21; non-transfused:1.96, SD0.22 (OR 0.01; 95% CI:0.0003 – 0.16). Mean age: transfused: 57, SD15.8; non-transfused: 58, SD10.7 . Mean baseline platelet count: transfused: 329, SD185; non-transfused: 319, SD117. Mean PTV: transfused: 400, SD115; non-transfused: 414, SD123. There were no statistically significant associations with demographics, age, blood parameters or planning target volume. CONCLUSION This study demonstrates a subset of patients who experience severe and prolonged thrombocytopaenia. Risk factors elucidated are female sex and lower BSA. Large-scale prospective trials evaluating a panel of predictors including concomitant medications, patient MGMT variants and temozolomide-metabolite concentrations would be valuable. Precise stratification of this vulnerable subgroup may permit consideration of temozolomide dose-capping in the future. Careful informed consent with all patients and caution with intensifying treatment under trials is vital presently.

Prolonged Transfusion-Dependent Temozolomide-Induced Thrombocytopaenia in Glioblastoma: Risk Factors Remain Elusive

Abstract AIMS Temozolomide-induced thrombocytopaenia is well-recognised; clinical-course varies widely. Aims: To identify risk factors for prolonged thrombocytopaenia; improve patient-care; inform trial design. METHOD Glioblastoma (GBM) patients requiring platelet transfusion were identified. (Local policy: transfuse when plt count ≤ 30 x 109/L). Inclusion criteria: First-line-standard-of-care temozolomide-chemo-radiotherapy (TMZ-CRT). Case-notes reviewed for demographics, blood-counts, radiotherapy and treatment parameters. Thrombocytopaenia grading: CTCAE V5. Date of onset measured from start of TMZ-CRT to date of platelets &amp;lt; 100 x 109/L, and to date of first instance of ≥ grade 3 thrombocytopaenia. Thrombocytopaenia duration: time to platelet count recovery to ≥ 100x109/L. RESULTS Between 2017-2021, 69 patients required platelet transfusion; 68/69 identified on routine monitoring. 49 patients were analysed (6:no CRT; 5:trial study drug; 7:≥ 2nd line treatment; 2:inadequate data). Median age: 59 (range 25-73); 61% female. First incidence of thrombocytopaenia during concurrent TMZ-CRT: 27/49 patients; during adjuvant TMZ in 22/49 (13/22 following 6-week-TMZ-CRT, 9/22 following 3-week-TMZ-CRT). In concurrent patients, median time to thrombocytopaenia: 33 days (range 23-38); median duration: 44 days (range 20-105; 5 not recovered); number of transfusions: 1-2:9 pts; 3-4:6pts; 5-7:3pts; 8-10:7pts; &amp;gt;10:2pts. Of 22 adjuvant patients transfused, 8/22 developed ≥G3 thrombocytopaenia post-cycle-2; 19/22 resolved after 1 or 2 transfusions. Thrombocyopaenia was associated with ≥G3 neutropaenia in 11% of patients requiring &amp;lt;5 transfusions vs 75% requiring ≥ 5. Comparison of &amp;lt; 5 vs ≥ 5 transfusion-patients did not identify differences in any demographic or treatment parameters. CONCLUSION Risk factors for prolonged TMZ-induced thrombocytopenia vs swiftly-resolving thrombocytopaenia remain elusive. This needs to be reflected in consent processes and in design of clinical trials.

Pretransplant Splenic Irradiation in Patients With Myeloproliferative Neoplasms

PurposeAllogeneic hematopoietic cell transplantation (HCT) serves as the only curative treatment option for patients with myelofibrosis and other myeloproliferative neoplasms. Splenomegaly commonly manifests in patients with myeloproliferative neoplasms and can lead to delayed or poor engraftment, increased transfusion burden, and worse survival. Methods to decrease the effect of splenomegaly include splenectomy and splenic irradiation. We sought to report on clinical outcomes for patients treated with splenic irradiation as part of their transplant conditioning. Methods and MaterialsPatients with splenomegaly measuring greater than 22 cm were referred for splenic irradiation. They received radiation to the entire spleen to 10 Gy in 5 fractions using 3-dimensional conformal radiation with anteroposterior/posteroanterior or opposed tangent fields. Blood counts were monitored closely on treatment. Changes in splenic size were measured using first and last treatment image guided radiation therapy and pre- and posttransplant diagnostic imaging. ResultsSeventeen patients completed pretransplant splenic irradiation between 2012 and 2021. Median platelet, white blood cell, and hemoglobin levels decreased on treatment. One patient required platelet transfusion and 3 required packed red blood cell transfusions. Mean decrease in spleen size during radiation was -8.5% in the craniocaudal dimension. Prolonged decreases, measured 2 to 12 months after transplant, averaged 14.64%. All patients engrafted. Fourteen (82.4%) were alive at time of analysis with median follow-up of 4.2 years from hematopoietic cell transplantation. ConclusionsSplenic irradiation offers a safe method of managing significant splenomegaly as part of transplant conditioning. Transplant outcomes in this series were excellent. Prospective data may be beneficial to determine the absolute benefit of this addition to pretransplant conditioning in this patient population.

Analysis of Outcome of Patients Treated with Anti PD-1/Pdl-1 Therapy According to the Degree of Lymphopenia

Introduction: Immunotherapy directed against the PD-1/PDL-1 pathway has shown activity across a wide range of malignancies and is currently being investigated in several others. Attia et al. showed that autoimmune toxicity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). Grade ¾ lymphopenia has been reported in up to 9% of patients receiving anti PD-1/PDL-1 treatment. The aim of this study was to examine if severe lymphopenia (Grade ¾) correlates with outcome in patients treated with anti PD-1/PDL-1 therapy.Methods: We looked at a sample of 154 patients aged 18 years or older, treated at the University of Oklahoma Health Sciences Center between 2014 and 2016. Total white blood cell (WBC) count at baseline as well as peak and nadir WBC count were examined. Similarly, absolute lymphocyte count (ALC) at nadir was examined as well. We also looked at the hemoglobin at baseline and number of packed red blood cell and platelet transfusions. Simple descriptive statistics were created for all covariates. The primary objective of this study was to examine the association between grade ¾ lymphopenia and progression free survival (PFS),defined as disease progression or death. Our secondary objectives were to examine if the choice of a particular anti PD-1/PDL-1 treatment or the line of treatment correlate with PFS. Kaplan Meier Survival analysis and plots were created for categorical outcomes and cox proportional hazards model was used to assess the association of each continuous covariate with survival.Results: The majority of patients were females (57%). The median age was 63 years. Lung cancer was the most common diagnosis (20.8%) followed by melanoma (20.1%) and ovarian cancer (12.3%). Nivolumab was the most commonly used agent (47.4%) followed by Pembrolizumab (22.7%), other investigational agents (22.7%) and Atezolizumab (7.2%). Median number of treatments received was 5. Median WBC count at baseline was 6.87 K/mm3. Median peak and nadir WBC counts were 10.5 k/mm3 and 5 k/mm3 respectively. Median hemoglobin at baseline was 11.8 g/dL. 19.5% patients required PRBC transfusion with a median number of 3 transfusions. Only 3.3% patients required platelet transfusion with a median number of 4 transfusions. Grade ¾ lymphopenia (less than 500/mm3 ) was observed in 20.3% of patients. Among those patients, lung cancer was the most common diagnosis (23.3%) followed by cervical cancer (20%), urothelial cancer (13.3%) and head and neck cancer (10%). On a univariate analysis, there was a trend towards worse PFS in patients with grade ¾ lymphopenia but it was not statistically significant (p= 0.0829) . Similarly, one anti PD-1/PDL-1 agent was not found to be superior over another (p=0.099). Not surprisingly, patients who received anti PD-1/PDL-1 treatment as first line had a better PFSand overall survival (OS) than those who received it as second line, third line or higher and this was statistically significant (p=0.0001).Conclusion: In our patients treated with anti PD-1/PDL-1 therapy, we noticed a higher incidence of grade ¾ lymphopenia than previously reported in literature. Grade ¾ lymphopenia was associated with a trend towards worse PFS but this was not statistically significant. DisclosuresNo relevant conflicts of interest to declare.

Chimeric Antigen Receptor Induced Cytopenia Differs from Chemotherapy Induced Myelosuppression

▪Background: Cytopenias are a potential complication of chimeric antigen receptor (CAR) therapy. The specific degree, duration, or implication of these cytopenias is not well established, and is further confounded by baseline cytopenias in heavily pre-treated patients with active leukemia. Preclinical models suggest that these cytopenias may be due to a cytokine rich milieu which may contribute to nonspecific suppression of marrow progenitors-independent of the CAR target (Sauter, ASH 2016, abstract 3357); which differs from standard cytotoxic chemotherapy based myelosuppression. We systematically analyzed CAR-related cytopenias on our phase I dose-escalation study of CD22 CAR.Design: Children and young adults with relapsed/refractory CD22+ acute lymphoblastic leukemia (ALL) treated on our phase I dose escalation anti-CD22 CAR therapy protocol (NCT02315612) were evaluated for time to neutrophil and platelet recovery (defined by absolute neutrophil count (ANC) of > 500 k/mcL x 3 days and achievement of transfusion independent platelet count > 20 k/mcL, respectively). All patients had bone marrow evaluations by morphology and flow cytometry at baseline, prior to lymphodepleting chemotherapy (Fludarabine 25 mg/m2 x 3 days and Cyclophosphamide 900 mg/m2 x 1 day) and again at day 28 (+/- 4 days) post-CAR. Infections were closely monitored for. All patients were on anti-fungal prophylaxis and were empirically treated for fever during periods of neutropenia.Results: From December 2014 to July 2017, 30 patients with ALL were treated on study at 3 dose levels. All patients had active bone marrow involvement at baseline with the majority (n=21) having an M2 marrow (>5% blasts) or higher. Twenty-six patients had prior transplants, and 21 patients had prior CD19-directed CAR therapy. Cytokine release syndrome (CRS) was seen in 24/30 (80%), with most patients having grade 1-2 CRS. 18/30 patients (60%) attained a complete remission following CD22 CAR therapy. Baseline hematologic parameters for responders prior to lymphodepletion included grade 2-4 neutropenia and grade 2 and 3 thrombocytopenia, with five patients requiring platelet transfusions (Table 1). Amongst complete responders, the bone marrow at day 28 demonstrated a median cellularity of 28% with trilineage hematopoiesis noted in 16/18 patients. The median CAR T cell % in bone marrow at 1 month was 30%. The median time to ANC nadir was 15 days post CAR infusion (range:10-23 days).17/18 patients had ANC recovery >500 k/mcL, at a median of 22 days post-infusion (range: 15-44 days). One patient had ANC recovery to 260 k/mcL but subsequently developed disease relapse. Eight patients received intermittent GCSF, with clinically relevant responses seen in seven of these patients with a median increase in ANC of 2,180 k/mcL (range: 850-4,100 k/mcL) with limited dosing. The median number of days of GCSF administration to time of ANC recovery was 4, with 3 patients requiring only 1 injection to achieve robust ANC response. Interestingly, only 1/18 patient (6%) had a new onset of infection (clostridium difficile colitis) during the period of CAR associated neutropenia, which was confounded by administration of intravenous antibiotic therapy for fevers that was initiated 24 hours prior to onset of diarrhea. There was no new development of fungal infections or worsening of any pre-existing infections. Platelet recovery to > 20 k/mcL was at a median of 36 days (range: 21-55) post-CAR and was seen in 16 of 18 responders. Two patients who remained platelet transfusion dependent post-CAR included one patient who was later found to have donor-cell monosomy 7 MDS and another patient whose disease relapsed prior to recovery.Conclusion: In contrast to chemotherapy associated myelosuppression, CAR-therapy associated peripheral blood cytopenias existed despite evidence for trilineage hematopoiesis on the bone marrow. Although the period of CAR associated neutropenia is substantial, with prophylactic antifungals and intermittent growth factor support, this heavily pre-treated population was not at an increased risk of developing serious bacterial or fungal infections over baseline. The rapid response to G-CSF is suggestive of an alternative modality of bone marrow inhibition distinct from chemotherapy induced cytotoxicity. Further evaluation in the context of multiple CAR targets and constructs are needed to further explore this complication. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Epidemiology of Platelet Transfusions: An Analysis of Platelet Use at 12 U.S. Hospitals

Background: Platelet transfusions in the United States are increasing in sharp contrast to the marked decrease in red cell and plasma use. Understanding the epidemiology and clinical practice for patients requiring platelet transfusions, particularly in the non-oncologic setting, is needed to identify clinical needs or significant change in practice. Such information can be used to focus the design of evidence based studies to assess platelet transfusion practice and efficacy to areas of high clinical need.Methods: Patient demographics, laboratory and clinical data were extracted from 2013 - 2015 from blood bank information systems and medical records from 12 REDS-III hospitals (both academic and community) located in four states across the U.S. A patient encounter was defined as any inpatient admission or outpatient visit documented with a unique visit date and discharge date. A transfusion episode was defined as all platelets transfused within an 8 hour interval beginning with the first platelet dose transfused within any encounter. Pre-platelet counts are defined as the nearest count up to 24 hours prior to the first transfusion for inpatients, and up to 48 hours before for outpatients. Post-platelet counts are defined as the first count up to 24 hours after completing the last transfusion for inpatients, and up to 48 hours after for outpatients.Results: A total of 122,298 platelet doses were issued for transfusion: 74,721 (61%) were apheresis platelets; 47,577 (39%) were pooled whole blood derived platelets; 103,759 (85%) were for inpatients, 18,539 (15%) were for outpatients. For inpatient transfusions 54% were issued to the General Ward, 29% to ICU, 12% to OR, 3% to ER. One platelet dose was issued per episode 78% of the time, 2 doses in 17%, 3 doses in 3%, and 4 doses in 1%. ABO donor-recipient identical platelets were transfused 37% of the time. For selected ABO mis-matched transfusions, type O platelets were given to non-type O patients 8%, and non-type O platelets to type O patients 19% of the time. Cardiovascular, Hematology-Oncology and Gastrointestinal were the most common broad diagnostic categories for encounters. The top three primary ICD 9-10 codes for each of these categories were: Cardiovascular: coronary atherosclerosis of the native coronary artery, aortic valve disorder and intracerebral hemorrhage; Hematology-Oncology: acute myeloid leukemia without achieving remission, neutropenia NOS, and multiple myeloma with achieving remission; Gastrointestinal: alcohol cirrhosis of the liver, cirrhosis of the liver NOS and hepatic encephalopathy.For inpatients a platelet count between >20,000/µL and 50,000/µL was the most common pre-transfusion count (28% of all episodes) with similar results for general ward (29%) and ICU patients (35%). In the ED and OR a platelet count >100,000/µL was most common - found in 38% and 37% of all episodes. For outpatient transfusions a count of >10,000/µL to 20,000/µL was most common (25%). For inpatients post-platelet count increment ranged from a median of 12,000/µL to 23,000/µL with progressively larger increments seen with progressively higher starting counts (Table 1). For outpatients post-platelet count increments ranged from 21,000/µL to 27,000/µL (Table 1).Conclusion: The REDS-III data base provides a wealth of information to assess platelet transfusion therapy in the U.S. Transfusion of more than 1 dose of platelets per episode is uncommon. Transfusion of ABO mismatched platelets is a common practice. Cardiovascular and Hematology -Oncology patients are prominent users of platelet products. General Ward and ICU dominate the location for platelet transfusion therapy and have similar transfusion practice patterns. The common pre-transfusion platelet count of 20,000-50,000/µL is surprising (as this exceeds evidence based recommendations for prophylactic transfusions in hematology-oncology patients) with reasons unclear. Platelet count increments were also surprisingly low. These findings, particularly the high pre-transfusion platelet count, the poor platelet increments and the high number ABO mis-matched transfusions, highlight differences in real world versus controlled studies and provide epidemiologic and laboratory data to develop future research to improve platelet transfusion practice. [Display omitted] DisclosuresNess:Terumo BCT: Consultancy.

PMU11 Economic Evaluation of Avatrombopag for Elective Diagnostic Procedure or Surgery of Thrombocytopenia in Adult Patients with Chronic LIVER Disease (CLD) in China

To perform a cost-minimization analysis (CMA) comparing Avatrombopag with platelet transfusion for the treatment of prerioperative thrombocytopenia in patients with chronic liver disease (CLD) based on a health system perspective in China. The target patients were adults with CLD complicated with thrombocytopenia who required elective diagnostic procedures or surgery. A decision tree model was developed. Both intervention and control groups distinguished between a lower and a higher baseline platelet count cohorts, and patients requiring platelet transfusions were separated into a single and a double transfusion groups. The model considered patient proportions, Avatrombopag cost, number, cost and medical expenses of platelet transfusion, cost of treatment of post-transfusion adverse events, and cost of rescue procedure for bleeding, which were obtained from ADAPT-1 and ADAPT-2 phase III clinical trials and clinician interviews. Scenario analyses of the drug cost changes and the Asian subgroup, and a one-way sensitivity analysis were conducted. The average cost of the Avatrombopag group and the platelet transfusion group were ￥13,235 and ￥11,054 respectively ($2181 difference). The incremental cost was zero when the price of Avatrombopag decreased to $788 (18.6% decrease). The incremental cost in the Asian subgroup was $621 higher compared with the whole population group. Sensitivity analysis results indicated that the drug cost of Avatrombopag had the greatest effect on the model results. The average cost of the Avatrombopag group was higher than that of the platelet transfusion group, but the result may have been overestimated due to poor platelet accessibility in some areas of the country resulting in higher platelet acquisition costs, or the possibility of performing the surgery despite lower platelet counts, thereby increasing the risk of bleeding. Other therapeutic values would be further evaluated in the future in the context of the real-world situation of the Chinese population.

Ehl Factors at Lower Than Standard Dose Achieve Satisfactory Surgical Haemostatsis in Haemophilia

Patients and methods All patients with haemophilia A or B who underwent major surgery, either as elective or as emergency, with rFVIIIFc or rFIXFc as the clotting factor concentrate (CFC) for hemostasis were included in this study. None of them were positive for inhibitors before. The factor was administered once daily or once every 36-48 hours depending on the product. The factor assays were done with a one stage APTT method. The CFC support was continued till suture removal, usually 10 days. Other supportive measures included tranexamic acid,at physician discretion. Results A total of 57 patients underwent surgery. There were 45 patients with haemophilia A and 12 with haemophilia B. Of those with haemophilia A, - 37 (82.2%) had severe, 3 (11.1%) moderate and 5 (6.7%) mild disease. Of those with haemophilia B, 7 (58.3%) had severe,3 (25 %) moderate and 2 (16.7%) mild disease. The median age was 30 years (range: 1-70). Among those with haemophilia A, there were 4 with inhibitor titre &amp;lt;5 BU, 3 more developed inhibitor 3-7 days following surgery, 1 of &amp;gt;5 BU, requiring bypassing agents. None with haemophilia B had inhibitor. The surgical procedures included 40 (70.1%) orthopaedic, 6 (10.5%) abdomino-perineal, 4(7%) urological and 3(5.2%) neurosurgical and 1(1.7%) each - venricular septal defect repair, skin graft, tympanoplasty and coronary angioplasty. The orthopaedic surgeries included pseudotumour excision (n=9), bilateral total knee replacement (bilateral n=4, unilateral n=1), total hip replacement (n=3), open reduction and internal fixation of fracture (n=11), corrective osteotomies/soft tissue release (n=6), amputation (n=1), arthrodesis (n=1), laminectomy (n=1), implant removal (n=1),intra articular repair(n=1)and curettage (n=1). For those with haemophilia A, the median recovery assay pre-op was 108% (range: 50-200).The median trough levels for post- operative days +1,+3,+5 ,+7 were 40% (11-138), 36.5% (13-94), 36.4% (1.4-118), and 27%(1.6-77) respectively. Among 35 patients with severe haemophilia undergoing major surgery, the median total factor used was 305 (125-563)IU/kg. The median recovery assay for those with haemophilia B prior to surgery was 70.1%(50-165).The median trough levels for post operative days+1,+3,+5 ,+7 were 49.8% (28-70.7), 40.7%(31.6-56.2), 42.3%(11.6-58.2), and 40.5%(24.5-59.4) respectively. The median total factor used was 400 (134-1000)IU/kg. Seventeen of those with haemophilia A (37.8%) required transfusion of at least 1 packed red cell each as per expected blood loss in those surgeries. Two patients required FFP and 1 patient required platelet transfusion as well for DIC. One patient had sustained injury to axillary artery during surgery and the other one had undergone resection of extensive pseudotumour. There was no unexpected post-operative bleeding. In those with haemophilia B, 2(16.7%) patients required transfusion of packed red cell as per expected blood loss in those surgeries. No other blood product was required. There was no excessive bleed during the perioperative period. Conclusions Modest doses of rFVIIIFc and rFIXFc can be used safely for major surgery in haemophilia with effective haemostasis and monitored with one stage APTT based assays. The less frequent administration makes these agents a more convenient option. Disclosures No relevant conflicts of interest to declare.

Combined Use of Rotational Thromboelastometry (Rotem) and Platelet Impedance Aggregometry (Multiplate Analyzer) in Cyanotic and Acyanotic Infants and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass: Subgroup Analysis of a Randomized Clinical Trial

Few studies have investigated the Multiplate platelet function analyzer in pediatrics. The authors evaluated Multiplate combined with Rotem in terms of guiding platelet transfusion after pediatric cardiac surgery with cardiopulmonary bypass (CPB). The authors further compared coagulation parameters between cyanotic and acyanotic patients. Subgroup analysis of a randomized clinical trial. Tertiary hospital. Patients weighing between seven and 15 kg. None. Rotem and Multiplate tests were performed (1) after anesthesia induction, (2) upon CPB separation, and (3) upon intensive care unit arrival. Among a total of 59 subjects, 9 patients required platelet transfusion. In multivariate linear regression, analysis EXTEM maximum clot firmness upon CPB separation was associated with the volume of transfused platelets (regression coefficient = -0.348 [95% confidence interval -1.006 to -0.028]; p = 0.039). No such association was found for the Multiplate test. Acyanotic and cyanotic heart disease were present in 32 and 27 children, respectively. There were no significant differences between these two groups in terms of platelet count and function. Postoperative blood loss was significantly higher in the cyanotic group compared with the acyanotic arm (p = 0.015; difference [95% confidence interval -2.40 {-4.20 to -0.60}]). There were no differences between groups regarding transfusion of allogeneic blood products. This study showed that Rotem, but not Multiplate results, were associated with platelet transfusion in pediatric cardiac surgery with no intake of platelet inhibitors. The usefulness of combining these tests in platelet transfusion decision-making needs to be evaluated in larger populations.

Hematologic Toxicities of CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Chimeric Antigen Receptor T-Cell (CART) therapy remains a novel approach for the treatment of relapsed, refractory B-cell Lymphoma. Complications of CAR T-cell therapy including cytopenias, infections, cytokine release syndrome (CRS) and neurotoxicity require aggressive supportive care. The objective of this study was to characterize the incidence of cytopenias and the utilization of growth factor and transfusion support following CAR T-cell therapy. This retrospective, single center study included 38 patients with relapsed, refractory non-Hodgkin lymphoma (NHL), who received CD19 directed CAR T-cell therapy, axicabtagene ciloleucel, as standard of care for the treatment relapsed NHL between January, 2018 and October, 2019. Cytopenias included 34% grade 4 thrombocytopenia (13/38), 76% grade ≥3 anemia (29/38), and 92% grade 4 neutropenia (35/38). Thirty-four percent (13/38) of patients required platelet transfusion support, 76% of patients (29/38) required RBC transfusions, 92% (35/38) of patients became neutropenic and 81.6% (31/38) received growth factor support. Twenty-nine percent of patients were found to have recurrent neutropenia status post recovery of their initial onset. The median initial onset occurred on day +8 (0-+14) and lasted a median of 5 days (0-85 days) with a median ANC nadir of too few cells to count (0-490). The median onset for a 2nd occurrence of neutropenia occurred on day +21 (D+12- D+28) which lasted 1 day (1-11 days) with a nadir of 430 cells/mm³ (0-480). Sixteen percent of patients experienced a 3rd occurrence on day +35 (D+25-+52), lasting a median of 3.5 days (1-19 days) with a median nadir of 335 cells/mm³ (270-440). One patient had a 4th occurrence on day +28 with a nadir of 220 cells/mm³. The etiology of recurrent neutropenia described is unclear. Multiple factors may contribute including bridging therapy, infection, steroids, CRS, and growth factor support. More is data is needed to identify risk factors for recurrent neutropenia.

Dengue in pregnancy

Background: Dengue is a viral fever commonly seen in the Southeast Asia. It is spread by Aedes mosquito and is health menace, in our country. Dengue during pregnancy can affect the mother and the fetus. This study was done to study the effect of dengue fever on the fetomaternal outcome. Aim and Objectives:The aim was to study the effect of dengue during pregnancy on fetomaternal outcome. Materials and Methods: A prospective observational study was done to include the patients who were diagnosed with dengue using enzyme-linked immunosorbent assay based test, for a period of 2 years. Results: A total of 31 cases of dengue were diagnosed during a period of 2 years. Nine patients required platelet transfusions. Five patients were admitted to the intensive care unit (ICU) and nine newborns were admitted to neonatal ICU (NICU). Conclusion: Dengue during pregnancy leads to obstetric complications such as preterm labor, oligohydramnios, and NICU admissions.

Real-World Rates and Management of Thrombocytopenia Due to Cancer Treatment in Advanced/Metastatic Female Genitourinary Malignancies

OBJECTIVES Thrombocytopenia is a common, potentially treatment-limiting hematologic side effect in cancer treatment (Kuter DJ, 2018). This is particularly true for female genitourinary (fGU) cancers, such as ovarian and endometrial, where treatment involves agents such as platinum-based agents, taxanes, PARP inhibitors, and gemcitabine (Lord R et al., 2018; Berek JS et al., 2018; Cassidy CA et al., 2001; Ten Berg MJ et al., 2001; Mahner S., 2015). Evidence has shown that dose reduction can be an effective way to address thrombocytopenia and avoid discontinuation of treatment (Lord R et al., 2018; Berek JS et al., 2018). In this study, we explore the use of RWD to understand real-world rates of thrombocytopenia in fGU cancer, including rates of occurrence, management and impacts on chemotherapy treatment, dose reduction, and discontinuation. METHODS Analyses were conducted on nationally representative insurance claims database and Electronic Medical Records (EMR). Inclusion criteria of adult fGU cancer patients with prior exposures to gemcitabine, platinum-based agents, taxanes, or PARP inhibitor with 1-month continuous enrollment (or activity, for EMR) were applied. Thrombocytopenia post-treatment exposure was identified using ICD codes. Baseline descriptive characteristics and subsequent dosing changes were assessed. Results were also stratified for the top 2 fGU malignancies present in the data, ovarian and endometrial cancer (approximately two-fifths and one-third respectively). Factors associated with thrombocytopenia were assessed using logistic regression modeling and ensemble predictive model approaches (e.g., XG Boost). Covariates for regression modeling included patient demographics, pre-existing medical conditions, drug exposures and lab test procedures. Model performance was assessed using Receiver-Operating Characteristic (ROC) scores). RESULTS Thrombocytopenia incidence ranged from 10-15%, with approximately 6% of cases diagnosed within the first 60 days of therapy. Early onset of thrombocytopenia (within 30 days of initiating therapy) occurred in less than 5% of patients and increased to 13% after more than 90 days. A significant proportion of patients with thrombocytopenia showed evidence of treatment discontinuation, with relatively few showing evidence of dose reduction in chemotherapy. Of patients with TCP, up to 15% of patients were prescribed corticosteroids and less than 10% of patients required platelet transfusion. ROC scores for ensemble model approaches were on the order of 85-90%. Factors associated with development of TCP included age, history of arterial disease, and concomitant GI malignancy. CONCLUSION Thrombocytopenia is a common condition in ovarian and endometrial cancer, leading to treatment discontinuation in a high proportion of patients. Given relatively low rates of chemotherapy dose titration in TCP patients, there is an opportunity to improve management of this hematologic complication and enable patients to remain on chemotherapy. Predictive model findings, while preliminary, also suggest opportunity to proactively identify patients with high risk of developing TCP, thereby facilitating earlier identification and pre-emptive treatment modification. Disclosures Ransom: Medidata Solutions: Employment. Galaznik:Medidata Solutions: Employment. Rusli:Medidata Solutions: Employment. Lempernesse:Medidata Solutions: Employment. Berger:Medidata Solutions: Consultancy.

Efficacy of repeat doses of avatrombopag: a case series

Thrombocytopenia is a common hematologic complication in patients with chronic liver disease. Thrombocytopenia places these patients at risk who undergo invasive procedures. Patients with cirrhosis often require repeat procedures. Patients with chronic liver disease and platelet counts below 50,000/µL who underwent repeat doses of avatrombopag (AVA) prior to multiple invasive procedures. Changes in platelet count were measured with each course of AVA. The need for platelet transfusion and adverse events from AVA were noted. Four patients underwent repeat AVA dosing. The mean [± standard deviation (SD)] age of the patients who underwent repeat dosing was 65 (±29) years. The mean (± SD) platelet count prior to the procedure was 38,250 (±5,679)/µL, and the mean increase of platelets was 52,000 (±33,000)/µL. Similarly, the mean (± SD) increase after the repeat administration was 51,000 (±31,000)/µL. No patient required platelet transfusion or rescue therapy. No adverse effects were reported. Repeat use of AVA continues to be an effective tool to minimize the use of platelet transfusions in patients undergoing invasive procedures who have chronic liver disease. Repeat dosing does not appear to reduce AVA efficacy.

Efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation in patients with recurrent hepatocellular carcinoma and thrombocytopenia.

AimsThrombocytopenia is often associated with chronic liver disease. Lusutrombopag is a small molecule thrombopoietin receptor agonist designed to temporarily increase the platelet count in patients with chronic liver disease for whom elective invasive procedures are planned. In the present study, the efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma were examined.MethodsEight patients with hepatocellular carcinoma who had a platelet count <50 000/μL prior to both initial and repeat RFA at the time of recurrence received lusutrombopag (3 mg/day) orally for 7 days between March 2016 and August 2018. The following were compared: the effect of lusutrombopag to increase the platelet count as determined by the platelet count after the initial and repeated use of lusutrombopag, the rate of avoiding platelet transfusion, and the presence of any complications.ResultsThe platelet count increased to 103 100 ± 22 800/μL 14 days after the first treatment and to 110 700 ± 17 800/μL 14 days after the repeated use. None of the patients required platelet transfusion. None of the patients developed clinical symptoms such as thrombosis, fever, rash, portal vein thrombosis, bleeding, or any other serious adverse events.ConclusionsRepeated use of lusutrombopag increased the platelet count. It did not cause any serious adverse events and led to avoidance of platelet transfusion. Radiofrequency ablation was carried out safely in all patients. Future studies with more cases of repeated use are needed to examine the long‐term efficacy and safety of lusutrombopag.

Alloimmunogenicity of an isolated MHC allele is affected by the context of MHC mismatch in a murine model.

Humoral alloimmunization to human leukocyte antigen (HLA) can represent a barrier to solid-organ transplantation, can lead to a refractory state in patients requiring platelet transfusion, and can also contribute to transfusion-related acute lung injury (TRALI). While exposure to HLA-mismatched cells/tissues are generally required for HLA alloimmunization, the effect of the extent of major histocompatibility complex (MHC) mismatch between donor and recipient is poorly understood. A novel mouse was generated that allows the expression of a single MHC Class I alloantigen, Kd . Alloimmune responses to Kd were studied in C57BL/6 mice transfused with splenocytes from different donor mice, allowing the analysis of responses to Kd as an isolated alloantigen, or in the context of additional mismatched MHC molecules. Advanced tools were utilized to study responses to Kd , including T-cell receptor transgenic mice that recognize the immunodominant Kd peptide presented by C57BL/6 mice to CD4+ T cells. A single MHC Class I alloantigen mismatch is less immunogenic than when the same alloantigen is encountered in the context of additional mismatched MHC alloantigens. This difference is due, at least in part, to induction of CD4+ helper T cells, as the effect is overcome by increasing either mature CD4+ T-cell help through immunization or by increasing the precursor frequency of naïve CD4+ T cells by adoptive transfer from T-cell receptor transgenic donors. These findings indicate that the immunogenicity of a single alloantigen can be affected by the context in which it is encountered, demonstrating the potential for cooperative effects between different mismatched MHC alloantigens.