Platelet Transfusion Research Articles

Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial

PurposeTo determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. Materials and MethodsThis was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician’s discretion. The primary outcome was periprocedural platelet transfusion in each arm. ResultsEighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26–43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9–31.7) compared with SOC group (100%; 95% CI, 88.1–100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9–31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2–27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1–17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. ConclusionsTEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates.

Cutibacterium acnes contamination does not enhance the proinflammatory profile of platelet concentrates.

Cutibacterium acnes, a common anaerobic platelet concentrate (PC) contaminant, has been associated with rare mild adverse transfusion reactions and is often considered a harmless commensal. Notably, C. acnes can cause chronic infections and has been shown to induce the release of proinflammatory cytokines by immune cells. Since elevated concentrations of proinflammatory factors in PCs have been linked to noninfectious adverse reactions, this study aimed to assess whether C. acnes could elicit the release and accumulation of proinflammatory factors during PC storage, thereby enhancing the risk of such reactions. Four ABO-matched buffy coat PCs were pooled and split into six units, each were inoculated with either saline (negative control), a Staphylococcus aureus isolate (positive control, 30 colony forming units [CFU]/unit), or four C. acnes PC isolates (10 CFU/mL) and stored at 20-24°C with agitation. Bacterial counts, platelet activation, and concentration of proinflammatory factors were assessed on days 0, 3, and 5. N = 3. C. acnes counts remained stable, while S. aureus proliferated reaching 108CFU/mL by the end of PC storage. By day 5, no significant differences in platelet activation or proinflammatory cytokine profiles were observed in C. acnes-contaminated PCs compared to the negative control (p > .05), while there was a significant increase (p ≤ .05) in sCD40L concentration (day 3), and platelet activation and IL-8 concentration (day 5) in S. aureus-contaminated units. C. acnes contamination does not promote the accumulation of proinflammatory factors in the absence of proliferation during storage and may not enhance the risk of inflammatory reactions when transfused to patients.

Perioperative Hyper-coagulation and Thrombosis: Cost Analysis After Congenital Heart Surgery.

Thrombosis, a major adverse event of congenital heart surgery, has been associated with poor outcomes. We hypothesized that in CHD patients undergoing cardiac surgery, increased perioperative use of pro-coagulant products may be associated with postoperative thrombosis in the setting of hyperfibrinogenemia, leading to greater hospital and blood product costs. Single-center retrospective study. Data from Boston Children's Hospital's electronic health record database was used in this study. All patients undergoing congenital heart surgery between 2015 and 2018 with postoperative fibrinogen levels above 400mg/dl were reviewed. Of 334 patients with high plasma fibrinogen levels, 28 (8.4%) developed postoperative thrombosis (median age: one year, 59% male). In our cohort, 25 (7%) demonstrated evidence of baseline hypercoagulability by one or more panel test results. Thrombosis was associated with greater hospital and blood product costs, longer ventilation times, and longer hospital and ICU length of stays. Preoperative hypercoagulable state (odds ratio: 2.58, 95% CI [1.07, 9.99], p = 0.002), postoperative red blood cell transfusion (odds ratio: 1.007, 95% CI [1.000, 1.015], p = 0.04), and single ventricle physiology (univariate odds ratio: 2.94, 95% CI [1.09, 7.89], p = 0.03) were predictors of postoperative thrombosis. Preoperative hypercoagulable state and intraoperative platelet transfusion were predictors of hospital cost. Thrombosis was associated with worse in-hospital outcomes and higher costs. Preoperative hypercoagulable state and postoperative red blood cell transfusion were significant predictors of thrombosis. Risk prediction models that can guide thrombosis prevention are needed to improve outcomes of patients undergoing congenital heart surgery.

Influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy

Objective: To evaluate the influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy. Methods: Clinical data of 38 children who underwent hemispherectomy from January 1, 2011 to October 31, 2023 at Xuanwu Hospital of Capital Medical University were retrospective collected. Patients were divided into study group (n=17) and control group (n=21) according to whether thromboelastography was employed to guide hemostatic algorithm. Demographic data and surgical data were recorded. The primary outcomes were allogeneic transfusion rates, including RBC transfusion rate, plasma transfusion rate, and platelets transfusion rate. The second outcomes were estimated blood loss, postoperative seizures during hospitalization, thromboembolic events, and length of hospital stay. Results: There were 13 boys and 4 girls with mean age of (5.7±3.3) years old in study group, and 16 boys and 5 girls with mean age of (7.4±3.4) years old in control group. The surgery duration, anesthesia duration and the proportion of prophylactic administration of tranexamic acid in study group were (424.5±98.5) min, (542.8±106.9) min, and 94.1% (16/17), which were higher than (353.1±85.3) min, (445.3±87.9) min, and 47.6% (10/21) in control group (all P<0.05). The rates of intra- and perioperative allogeneic plasma transfusion in study group were 52.9% (9/17) and 64.7% (11/17) respectively, which were lower than 90.5% (19/21) and 95.2% (20/21) in control group (all P<0.05). The ratio of fibrinogen concentrates administration in study group was 58.8% (10/17), which was higher than that in control group [4.8% (1/21), P=0.001]. There were no statistically differences in intra- and perioperative allogeneic RBC transfusion rates between the two groups (all P>0.05). No platelets were transfused in both groups. There were no statistically differences in estimated blood loss, postoperative seizures during hospitalization and the length of hospital stay between the two groups (all P>0.05). No postoperative thromboembolic events were observed. Conclusion: Thromboelastography-guided hemostatic algorithm can reduce allogeneic plasma transfusion requirements but not RBC transfusion requirements during pediatric hemispherectomy.

Lowering Platelet Threshold to 20,000/μL for Fluoroscopy-Guided Lumbar Puncture Does Not Result in Observed Clinical Adverse Outcomes.

Fluoroscopic-guided lumbar puncture (FG-LP) is a common neuroradiologic procedure. Traditionally, a minimum platelet count (MPC) of 50,000/μL for this procedure has been required; however, we recently adopted a lower MPC threshold of 20,000/μL. The purpose of this study was to compare adverse events in patients undergoing FG-LP with MPCs above to those below the conventional 50,000/μL threshold. This was an institutional review board-approved, retrospective study on adult patients with hematologic malignancy undergoing FG-LP in the neuroradiology division between May 2021 and December 2022, after lowering the minimal required MPC to 20,000/μL. Recorded data included indication for FG-LP, preprocedure and postprocedure MPC, need for and number of platelet transfusions within 24 hours of FG-LP, presence of traumatic tap, FG-LP-related complications, and any platelet transfusion-related adverse event. Patients were classified into 2 groups based on MPC: (1) those above 50,000/μL and (2) those below 50,000/μL. Descriptive statistics were used comparing these 2 groups. One hundred twenty-eight patients underwent FG-LP, with 46 having an MPC between 20,000 and 50,000/μL and 82 having an MPC above 50,000/μL. No postprocedural complications were encountered in either group. Traumatic taps occurred in 10/46 (22%)​ with MPC below 50,000/μL versus 10/82 (12%)​ in those with MPC above 50,000/μL. Forty of 46 patients (87%) were transfused with platelets within 24 hours prior to FG-LP. One patient developed a transfusion-related reaction. Lowering the MPC threshold from 50,000/μL to 20,000/μL for FG-LP did not result in a higher incidence of spinal hematoma.

Delayed cold-stored vs. room temperature stored platelet transfusions in bleeding adult cardiac surgery patients—a randomized multicentre pilot study (PLTS-1)

BackgroundPlatelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP.MethodsThis protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product).DiscussionDCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study.Trial registrationNCT 06147531 (clinicaltrials.gov).

Clinical and Laboratory Profile of Dengue Syndrome in Pediatric patients: Study in a Tertiary Care Hospital, Dhaka, Bangladesh

Introduction: Dengue fever is a mosquito-borne arboviral (arthropod-borne virus) disease which is of global concern. This fever is a benign syndrome caused by an arthropod-borne virus and is characterized by Biphasic fever, myalgia, arthralgia, rash, leukopenia, and lymphadenopathy. Aim of the study: This study aimed to evaluate the clinical and laboratory profile of dengue fever in children less than 15 years old admitted to an urban hospital. Methods: This retrospective study was conducted in the Department of Paediatrics of Anwer Khan Modern Medical College Hospital (AKMMCH), Dhaka, Bangladesh during the period from 4 April 2019 to 9 September 2019. They have followed up on the symptoms, platelet count and management of the patients. Data were analysed by using MS-Excel-2016. Result: In total 98 patients from both groups completed the study. In our study, we found a maximum of 54.08% were male, more than half 53(54.08%) patients were below five years of age, about 95(96.94%) of the patients had a fever. Maximum patients, 81(82.65%), were managed by I/V fluid, more than 72(73.47%) of the patients were managed by paracetamol. Others by antibiotics 16(16.33%), platelet transfusion 14(14.29%) and blood transfusion 12(12.24%). Other management also includes plasma, &amp; dopamine. Conclusion: These study children about 0-15 years of age more commonly suffer from dengue fever. As the vaccine is not available in Bangladesh, these patients need a timely diagnosis and critical monitoring during the disease course to prevent severity and mortality.

Advances in Human Leukocyte Antigen Testing Technologies and Management Strategies for Platelet Transfusion Refractoriness.

The blood bank is often consulted for transfusion support of patients with suspected platelet transfusion refractoriness (PTR). The workup is complex because testing includes specialized assays that are uncommonly ordered with limited availability. Add to this the variety of possible products-crossmatched platelets, human leukocyte antigen (HLA)-matched platelets, HLA antigen-negative platelets-and the approach to PTR can be overwhelming. Moreover, most literature on the subject is published in transfusion medicine journals aimed at transfusion medicine physicians and blood bank specialists in academic settings. Resources tailored to community hospital blood banks are lacking. To provide pathologists who may not have subspecialized training in transfusion medicine and who direct blood banks algorithmic workflows based on clinical scenario and test availability to provide appropriate transfusion support for patients with PTR. This review is a comprehensive overview of terminology, HLA testing procedures, interpretations, and practical recommendations for managing PTR in various scenarios based on expert opinion as well as relevant medical literature published from 2007 to 2022. Consultation on PTR is complicated and encompasses many clinical and laboratory aspects. The lack of guidelines derived from high-quality prospective studies poses challenges in the workup and management of PTR. Hindering the process further are limited test availability, unfamiliarity with the technical assays, and the various specialized platelet products. The clinical evaluation algorithm presented herein along with the workflow pathways offer pathologists user-friendly and best-practice guidelines with different options based on the clinical scenario and the tests available.

Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange

AbstractImmune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency. Caplacizumab, an anti–von Willebrand factor nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the 2 cohorts (3 and 4 days; P = .31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling, reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose, and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B virus coinfection, an ovarian teratoma with associated antiplatelet antibodies, and multiple platelet transfusions before the correct diagnosis may have impeded the immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.

The significant role of point-of-care coagulation studies: shorter cardiac surgery, better renal function and tranexamic acid cannot alone reduce early platelet transfusions

The significant role of point-of-care coagulation studies: shorter cardiac surgery, better renal function and tranexamic acid cannot alone reduce early platelet transfusions

Platelet-Rich Plasma in Fat Graft Type-1 Tympanoplasty - Should We or Should We Not?

Introduction Fat grafts have been in used since 1962 for small central perforations, with a success rate ranging from 86 to 100%. Platelet-rich plasma (PRP) containing platelet concentrations greater than 1 million platelets/μL assist the healing process by various means. Current data suggests improved healing when tympanoplasty is performed using temporalis fascia grafts if PRP is added during surgery. Objective To assess the effect of PRP on fat grafts in small and moderate-sized central perforations. Methods The present prospective observational study was conducted with 36 patients who underwent fat graft tympanoplasty with PRP under local anesthesia. Clinical and audiological observations were carried out after 4, 8, and 12 weeks, and a statistical analysis of the observations was performed. Results We assessed 23 patients with small central perforations and 11 patients with moderate central perforations. An overall success rate of 76.4% was observed, with an 82.6% success rate among patients with small central perforations and 63.6% among those with moderate central perforations. There was no statistically significant difference in the uptake regarding the location of the perforation, but a statistically significant difference was found in terms of hearing improvement following the procedure. Conclusion The morbidity of conventional tympanoplasty in cases of small-to-moderate central perforations in patients with chronic otitis media vis a vis the results of the procedure needs to be revisited, as in the present study fat grafts placed with PRP under local anesthesia could lead to surgical and audiological outcomes that are as good as those reported in the literature.

Comparison of the Effects of Apheresis and Pooled Platelet Transfusions on Platelet Count

Background: To compare the increase in platelet count after the transfusion of apheresis and pooled platelet suspensions among patients in the internal medicine intensive care unit. Methods Patients who received platelet suspension transfusions and were followed up at the internal medicine intensive care unit at Mehmet Akif Inan Training and Research Hospital were evaluated. The patient's platelet counts were administered apheresis, and pooled platelet suspensions were recorded before and after transfusion. The increase in platelet count was calculated. The two groups were statistically compared. Results: A total of 4,701 platelet suspension transfusions were performed at our hospital between January 1, 2020, and December 31, 2023. Of these transfusions, 2,990 belonged to pooled platelet suspensions and 1,711 to apheresis platelet suspensions. Conclusion: Platelet suspension transfusion is frequently used in patients receiving internal medicine intensive care. However, there is an ongoing debate concerning whether apheresis or pooled platelet transfusion is more effective in increasing platelet count. In this study, we found a significantly higher increase in platelet count among patients in the internal medicine intensive care unit after apheresis platelet suspension transfusion than pooled platelet suspension transfusion.

Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge.

6566 Background: In the IMerge trial (NCT02598661) of RBC transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory to or ineligible for erythropoiesis stimulating agents, imetelstat showed significant efficacy vs placebo (PBO) for 8-wk, 24-wk, and 1-y TI endpoints, with neutropenia and thrombocytopenia as the most common adverse events (Platzbecker. Lancet 2024). Supportive care was given to all pts as needed, per investigator discretion. Here we report RBC-TI rates in the absence of platelet transfusions or myeloid growth factor use. Separately, RBC-TI with mean central hemoglobin (Hb) rise of ≥1.5 g/d was assessed in all pts. Methods: Pts were randomized 2:1 to receive imetelstat (n=118) 7.5 mg/kg or PBO (n=60) Q4W IV until disease progression. Primary endpoint was 8-wk RBC-TI; 24-wk RBC-TI was a key secondary endpoint. Primary analysis cutoff was Oct 2022, with Oct 2023 cutoff for 1-y RBC-TI analyses. Results: Overall, 21/118 (18%) pts in the imetelstat group and 1/60 (2%) pts in the PBO group needed platelet transfusions; 41/118 (35%) and 2/60 (3%) pts received myeloid growth factors, respectively. Significantly higher percentages of pts achieved 8-wk, 24-wk, and 1-y RBC-TI with imetelstat vs PBO in the absence of either platelet transfusions or growth factor support (Table). In a separate analysis, 8-wk, 24-wk, and 1-y RBC-TI and concurrent Hb rise of ≥1.5 g/dL with imetelstat vs PBO occurred in 28% vs 2%, 23% vs 0%, and 17% vs 0% of pts, respectively (Table). Among responders, imetelstat increased median central Hb levels compared with PBO: 3.6 g/dL vs 0.8 g/dL for 8-wk, 4.2 g/dL vs 1.1 g/dL for 24-wk, and 5.2 g/dL vs 1.7 g/dL for 1-y RBC-TI. Conclusions: Results from this subanalysis confirm that pts who achieve RBC-TI with imetelstat do so without developing severe neutropenia and thrombocytopenia (functionally defined as needing myeloid growth factors or platelet transfusions, respectively), therefore not negating the clinical benefit of the drug. Imetelstat also led to significant rise in Hb levels in RBC-TI responders, particularly long-term responders. These data further support the efficacy of imetelstat in TD pts with LR-MDS. Clinical trial information: NCT02598661 . [Table: see text]

Role of Platelet Concentrates in Dental-Pulp Regeneration: A Systematic Review of Randomized Clinical Trials.

Treatment of immature necrotic teeth is a problematic situation. Conventional root canal therapy is challenging and leaves a weak, fragile, and undeveloped tooth for lifetime. This review was aimed to assess the outcome of available randomized clinical trials (RCTs) on the efficacy of platelet concentrates (PC) in dentine-pulp complex regeneration. In this systematic review, an electronic search was conducted on MEDLINE, EMBASE, Cochrane, and Google scholar databases. A further manual search was performed on the list of related articles in order to ensure inclusion of potentially missed articles in earlier electronic search. Those proved RCTs matched with the standard criteria were included following an initial assessment of abstracts and the text independently by the reviewers. From the total 602 harvested articles, only 13 met the criteria and were evaluated with 11 having parallel design and 2 split mouth. Only one study featured low risk of bias, while three had moderate risk and the rest were at high risk of bias. Six studies had used platelet rich plasma (PRP), 4 employed platelet rich fibrin (PRF), one utilized injectable platelet rich fibrin (I-PRF), and three used both PRF and PRP for their experimental groups while blood clot (BC) was used as the control group for all. The success rate was reported at 87.3% judged by the absence of pathologic signs and symptoms. Dentin wall thickening, root lengthening and apex closure were higher in PC groups, however, these differences were not statistically significant in reported studies. It can be concluded that PCs promote the pulp tissue revitalization and continuation of root development. However, a consensus on its potency for true pulp regeneration is yet to be reached.

Clinical observation study of recombinant human thrombopoietin in the prevention of chemotherapy-induced thrombocytopenia in patients with aggressive lymphoma.

e19056 Background: Recombinant human thrombopoietin (rhTPO) has demonstrated efficacy in elevating platelet counts in lymphoma patients suffering from chemotherapy-induced thrombocytopenia. However, the optimal timing for its administration remains to be established. Methods: This prospective, observational, non-randomized, multicenter study aimed to identify the optimal timing for rhTPO intervention in patients with aggressive lymphoma experiencing chemotherapy-induced thrombocytopenia. Participants aged between 18 and 70 years, diagnosed with aggressive lymphoma and chemotherapy-induced thrombocytopenia, were divided into three groups based on their baseline platelet counts. Group 1 received rhTPO when platelet counts fell below 50×109/L but remained above 25×109/L; Group 2 was treated with rhTPO at platelet counts ≥ 50×109/L and &lt; 75×109/L; and Group 3 received rhTPO treatment for platelet counts ≤ 25×109/L. Treatment was discontinued once platelet counts reached ≥ 100×109/L. The primary endpoint was the proportion of patients achieving normalization of platelet counts, the secondary outcomes including platelet nadir values, the incidence of platelet transfusions, and adverse events. Results: Eighty-eight patients were enrolled, with 36 in Group 1, 22 in Group 2, and 30 in Group 3. The groups were comparable in clinical manifestation of age, gender, comorbidities, lymphoma classification, and bone marrow involvement. Normalization of platelet counts was achieved in 69.44%, 81.82%, and 36.67% of patients in Groups 1, 2, and 3, respectively, with Groups 1 and 2 showing significantly higher rates than Group 3 (P&lt;0.05). The mean platelet nadir values were significantly higher in Groups 1 and 2 (28.39±10.19×109/L and 43.23±14.97×109/L, respectively) compared to Group 3 (11.13±6.21×109/L, P&lt;0.01). The incidence of platelet transfusions was notably lower in Groups 1 and 2 (19.44% and 13.64%, respectively) than in Group 3 (70.00%, P&lt;0.01). There were no significant differences in adverse event rates across the groups. Conclusions: Early administration of rhTPO significantly enhances platelet recovery and reduces the need for platelet transfusions in aggressive lymphoma patients with chemotherapy-induced thrombocytopenia.

Romiplostim for chemotherapy induced thrombocytopenia in solid tumors: A meta-analysis.

e24137 Background: Chemotherapy-induced thrombocytopenia (CIT), defined as platelets &lt; 100,000/mcL persisting for ≥3-4 weeks post-chemotherapy affects 20-25% of cases necessitating platelet transfusions or dose reductions leading to treatment delays and impacting patient outcomes. (1,2) Despite multiple studied agents, there are no established guidelines. Romiplostim, a thrombopoietin receptor agonist approved for immune thrombocytopenic purpura, stands out. NCCN suggests its use, but pooled analyses are lacking. Our meta-analysis addresses this gap, exploring romiplostim's efficacy in CIT management. Methods: We performed a systematic search of PUBMED, EMBASE, and COCHRANE databases for studies that evaluate the use of romiplostim in the setting of CIT for solid tumors. The primary endpoint was the proportion of patients that showed improvement in platelet counts in response to romiplostim. Secondary endpoints were the proportion of patients that continued full dose chemotherapy dose on romiplostim and incidence of thromboembolic events. Pooled proportions were calculated along with 95% confidence intervals (CI) using a random-effects model. I2 statistic was used to depict inter-study heterogeneity. Results: A total of 10 single arm studies - 3 prospective studies, 3 case series, and 4 retrospective studies were included. The pooled outcomes were: significant improvement of platelet count above 100K with response to romiplostim therapy in 80.53% patients [95 % CI 72.47 - 87.48, I2 = 69%], proportion of patients that continued full dose chemotherapy on romiplostim was 70.89% [95% CI 63.40 - 77.84, I2 = 0%], and incidence of thromboembolic events was 6.81% [ 95% CI 3.64 – 10.89, I2 = 35%]. Variables like platelet transfusions, bleeding events, type and stage of cancer were not reported uniformly and hence subgroup analyses could not be performed. Conclusions: Our analysis reveals that romiplostim improved the platelet counts in majority of patients with underlying CIT associated with solid tumors. It also shows that a majority of the patients were able to resume their full dose chemotherapy when maintained on romiplostim. The incidence rate of thromboembolic events with romiplostim believed to be consistent with what expected of this population with majority having advanced/high-risk malignancies. Given its efficacy, romiplostim may be used for routinely managing CIT in solid tumors. This analysis is limited by lack of comparative studies and warrant further randomized trials to confirm the safety and efficacy of romiplostim in this patient population.

Multicenter, randomized phase II study of epcoritamab for patients with large B-cell lymphomas achieving a partial response after CD19-directed CAR T-cell therapy (CAR-T).

TPS7100 Background: Despite the promising efficacy of CAR-T for patients with relapsed or refractory (R/R) large B-cell lymphomas (LBCL), more than 60% of patients will relapse, the majority of which occur in the first 6 months. Approximately 30% of patients with LBCL treated with CAR-T achieve a partial response (PR) on day 30 (D30) PET-CT assessment. Of patients in a D30 PR, 70% will eventually progress, yet the standard of care remains close observation. Early consolidative treatment strategies utilizing therapies with a different mechanism of action may improve outcomes, but there are currently no reliable biomarkers. Epcoritamab (Epco), a bispecific antibody directed against CD20 and CD3, has been approved by the FDA for LBCL patients who relapse after at least 2 lines of therapy. In the phase 2 study, Epco was associated with an overall response rate (ORR) of 63% and a complete response (CR) rate of 39%, including similar responses in a subset of patients who were relapsed 100 days post CAR-T. This study is a trial-in-progress that will evaluate the efficacy of epco compared to observation for patients with LBCLs achieving a PR on D30 post CAR-T PET-CT assessment. Methods: This is an investigator-initiated, randomized, phase II, multicenter, open-label study (NCT06238648) evaluating epco monotherapy for a fixed duration of 12 cycles compared to observation for LBCL patients with D30 PR after standard of care CAR-T. A maximum of 120 patients will be randomized 1:1 to epco or observation across 10 academic centers. Stratification factors include line of CAR-T (second vs third line) and costimulatory domain (CD28 vs 4-1BB). Key inclusion criteria include PET evidence of a D30 PR. non-bulky disease ( &lt;7.5cm), ANC of &gt;1000, hemoglobin &gt;7 g/dL if asymptomatic or &gt;8 if symptomatic, platelet count &gt;50,000. G-CSF, pRBCs and platelet transfusions are allowed. Key exclusion criteria include prior anti CD20xCD3 bispecific antibody therapy, ongoing or uncontrolled CRS or ICANS, and active or symptomatic CNS disease. Epco is administered subcutaneously at a dose of 0.16mg on day 1, 0.8mg on day 8, prior to full dose of 48mg on day 15. Epco is administered weekly in 28 day cycles (C) for C1-3, on day 1 and 15 of C4-9 and on day 1 of C10-12. PET-CT response is assessed by the 2014 Lugano criteria after 2 cycles, and then every 3 months during active treatment. The primary objective is efficacy, measured as conversion from D30 PR to CR. The secondary endpoints include frequency and severity of treatment emergent adverse events, ORR, duration of response, duration of complete response, progression free survival, event free survival, and overall survival. Peripheral blood samples will be collected pre-treatment and during treatment to assess for biomarkers of response and resistance. The study was activated in January 2024 and recruitment is ongoing. Clinical trial information: NCT06238648 .

A prospective study of all-trans retinoic acid plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia.

6545 Background: Over the decade, anthracycline and cytarabine-based intensive chemotherapy remains the standard of care for acute myeloid leukemia (AML) but is hampered by serious toxicities like myelosuppression, increased transfusion requirement and disappointing clinical outcomes among the so-called poor-prognosis AML subsets. BCL-2 inhibitor plus azacitidine (AZA) has become a preferred treatment for AML, but the remission rate and overall survival (OS) are suboptimal. Apart from hematologic toxicities, 70.0% of patients were RBC transfusion dependent and 58.6% were platelet transfusion dependent. At present, all-trans retinoic acid (ATRA) is used as a differentiation drug, and there is no combination regimen with BCL-2 inhibitor. This study aimed to assess the efficacy and safety of ATRA plus venetoclax and AZA for newly diagnosed AML. Methods: This study enrolled 35 patients (≥18 years) with newly diagnosed AML between 2022 and 2023. For induction, patients received AZA (75 mg/m²) from Day 1 to 7, venetoclax at a target dose of 400 mg/d from Day 2 to 10, and ATRA (45 mg/m²/d) from Day 12 to 28 of each 28-day cycle for up to 2 cycles or until disease progression. Patients who achieved complete remission (CR) after two cycles of induction therapy received bone marrow transplantation or consolidation at their own discretion. For consolidation, patients received ATRA (45 mg/m²/d) from Day 1 to 21 and AZA (75 mg/m²) from Day 1 to 7 of each 28-day cycle for up to 4 cycles or until disease progression. For maintenance, patients received ATRA (45 mg/m²/d) for 21 days per cycle plus AZA (75 mg/m²). Maintenance therapy was given every 3 months until disease progression and ATRA was provided during intermissions. The primary endpoint was the composite CR rate (CR and CR with incomplete hematologic recovery) at the end of cycle 1 of inductive therapy. Results: As of now, the composite CR rate reached 74% (26/35) and the objective response rate reached 91% (32/35). The composite CR was 73% (11/15) in the adverse risk group and 75% (15/20) in the favorable-intermediate risk group at the end of cycle 1. Thirty-three patients entered cycle 2. The cumulative composite CR rate reached 91%(30/33) after 2 cycles of induction therapy. The median event-free survival was 390 days, and the median OS was 573 days. Platelet transfusion independence occurred in 17% (6/35) patients in cycle 1 and 73% (24/33) in cycle 2. Furthermore, 20% (7/35) and 73% (24/33) patients were RBC transfusion independent in cycle 1 and 2, respectively. Any-grade infections occurred in 74% (26/35) patients, including 12 before admission. Conclusions: The treatment regimen achieved a high composite CR rate and was well tolerated, with reduced hematologic toxicities in cycle 2 of induction therapy. Both adverse risk and favorable-intermediate risk patients benefited from the regimen, which holds promise for treating AML in adult patients. Clinical trial information: NCT05654194 .

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]

Sex disparities in short-term outcomes among patients with diffuse large B cell lymphoma undergoing chimeric antigen receptor T-cell therapy in the United States.

e19062 Background: Chimeric Antigen Receptor (CAR) T-cell therapy, a promising immunotherapy used in various cancers, including Diffuse large B cell lymphoma (DLBCL), can involve multiple complications and the need for medical interventions. Our retrospective study strives to gain up-to-date insight into sex-based differences among DLBCL patients undergoing CAR T-cell therapy. Methods: We focussed on DLBCL patients undergoing CAR T-cell therapy via the 2017-2020 National Inpatient Sample(NIS). The events of complications between males and females were examined via multivariate regression models. Since the ICD-10 code for cytokine release syndrome (CRS) involved cases between October and December 2020, we used samples for that timeline while evaluating that particular complication. Results: Our study involved 3280 adult cases of DLBCL undergoing CAR T-cell therapy, with 1930 (58.8%) males and 1350(41.2%) females. Age differences were seen as females were older(mean age 61.93 vs. 60.40 years, p&lt;0.01). Females also had lower odds of atrial fibrillation (6.7% vs. 14.2%, aOR 0.440, p&lt;0.01) and acute kidney injury (AKI) (10.0% vs. 18.4%, aOR 0.458, p&lt;0.01), while having higher odds of use of invasive mechanical ventilation (5.6% vs. 5.2%, aOR 2.179, p&lt;0.01), events of sepsis (9.6% vs. 7.8%, aOR 1.575, p&lt;0.01), pancytopenia (69.6% vs. 64.0%, aOR 1.454, p&lt;0.01), and cryoprecipitate transfusion (2.2% vs. 1.8%, aOR 2.325, p=0.041) than males. We did not find any statistically significant differences for events of gastrointestinal bleeding (GIB)(aOR 0.866, p=0.636), tumor lysis syndrome(aOR 0.980, p=0.890), acute pulmonary embolism(aOR 1.133, p=0.719), toxic encephalopathy(aOR 1.009, p=0.935), platelet transfusion(aOR 0.994, p=0.976), RBC transfusion(aOR 0.828, p=0.192), or all-cause mortality(aOR 1.829, p=0.064). In addition, while 51.6% of males and 51.7% of females reported CRS, it was not statistically valid (aOR 0.923, p=0.850). Conclusions: The sex of DLBCL patients undergoing CAR T-cell therapy can influence multiple complications, as described in our study. Further research and endeavors aimed to deepen our understanding of our findings will help bring changes in protocols by physicians to improve the quality of care and outcomes of these patients.