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Risk of HLA antibody generation after receipt of Mirasol versus standard platelets in the MIPLATE randomized trial
Kaidarova Z, Di Germanio C, Custer B, Norris PJ
Transfusion. 2023
Abstract
BACKGROUND Human leukocyte antigen (HLA) alloimmunization can occur after platelet transfusion. These antibodies can complicate future platelet transfusions or organ transplantation. Animal data suggest that Mirasol pathogen reduction treatment (PRT) can prevent alloimmunization after transfusion. STUDY DESIGN AND METHODS The MIPLATE trial enrolled 330 of a planned 660 participants with hematological malignancies at risk for grade 2 or greater bleeding. The study was halted early for futility after a planned interim analysis. Participants were randomized to receive PRT versus standard control platelets. Serum samples were collected from participants at baseline (pretransfusion), weekly for the first 4 weeks, then at days 42 and 56. HLA antibody levels were determined using a commercial multianalyte bead-based assay. HLA antibody levels were analyzed using low, medium, and high cutoffs based on prior studies. RESULTS The rate of alloimmunization was low in both arms of the study, particularly at the high HLA antibody cutoff (total of 6 of 277 subjects at risk, or 2.2%). The risk of alloimmunization did not differ between study arms, nor did the risk of immune refractoriness to platelet transfusion. CONCLUSIONS The data do not support the conclusion that Mirasol exerted a protective effect against alloimmunization after platelet transfusion in the MIPLATE trial.
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Oral eltrombopag versus subcutaneous recombinant human thrombopoietin for promoting platelet engraftment after allogeneic stem cell transplantation: A PROSPECTIVE, NON-INFERIORITY, RANDOMIZED CONTROLLED TRIAL
Wen B, Zhang X, Chen S, Fan J, Yang S, Cai Y, Wang P, Zhang Q, Gu Q, Du X
Hematological oncology. 2022
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Abstract
Delayed platelet engraftment (DPE) is associated with poor survival and increased transplantation-related mortality after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Therefore, treatments are needed to improve platelet engraftment and prevent DPE. We performed a phase 3, non-inferior, randomized controlled study of eltrombopag or recombinant human thrombopoietin (rhTPO) to promot platelet engraftment after allo-HSCT. Candidates for allo-HSCT were randomly assigned to receive oral eltrombopag (50mg daily) or subcutaneous rhTPO (15000U daily ) from the first-day post-transplantation. The primary endpoint was the cumulative numbers of platelet engraftment (platelet recovery ≥ 20 × 10(9) /L, without transfusion, for seven consecutive days) on day 60 after transplantation. We performed intention-to-treat analyses with a non-inferior margin of -15%. A total of 92 participants underwent randomization. 44 and 48 patients were randomized to the eltrombopag and rhTPO groups, respectively. The median duration of follow-up was 360 days (range: 12-960 days). The cumulative incidence of platelet engraftment on day 60 after transplantation in eltrombopag group was 86.4% (38/44) compared with 85.4% (41/48) in the rhTPO group (absolute risk difference [ARD] 1%, one-sided lower limit of 95% confidence interval [CI] -13.28%, P(non-inferirioty) =0.014). The rate of DPE in the eltrombopag group was 6.8% (3/44) compared with 12.5% (6/ 48) in the rhTPO group (ARD -5.7%, one-sided higher limit of 95% CI 6.28%, P(non-inferirioty) =0.063). Approximately, 3/4 of non-haematologic adverse events were not observed in the eltrombopag group but three patients (3/48, 6%) experienecd them in the rhTPO group. In addtion, platelet transfusions unite from day 0 to day 21, or from day 22 to day 60, progression-free survival, overall survival were not significantly different between both groups. Eltrombopag was non-inferior to rhTPO in promoting platelet engraftment post allo-HSCT for patients with haematological malignancy. Oral eltrombopag was more convenient for patients than subcutaneous rhTPO (NCT03515096). This article is protected by copyright. All rights reserved.
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Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis
Rinaldi I, Sutandyo N, Winston K
Hematology (Amsterdam, Netherlands). 2022;27(1):141-149
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Editor's Choice
Abstract
OBJECTIVES One of the treatment modalities that can be used for hyperleukocytosis is leukapheresis. However, the result of studies showing the benefit of early mortality through the use of leukapheresis versus no leukapheresis is still inconclusive. Hence, we aimed to conduct a systematic review with meta-analysis to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis. METHODS We conducted a literature search on five databases (PubMed, EBSCOhost, Scopus, Clinicalkey, and JSTOR) up to October 2021 for studies comparing early mortality outcomes between hyperleukocytosis AML patients treated with leukapheresis versus no leukapheresis. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity tests were presented in I(2) value and publication bias was analyzed using a funnel plot. RESULTS Eleven retrospective cohort studies were eligible based on the inclusion and exclusion criteria. Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm(3) or 100,000/mm(3) (OR: 1.17; 95% CI: 0.74-1.86; p: 0.50; I(2): 0%). Similarly, studies using hyperleukocytosis cutoff of 50,000/mm(3) also showed no benefits of early mortality (OR: 0.67; 95% CI: 0.43-1.05; p: 0.08; I(2): 0%). Most of the studies used had a moderate risk of bias due to being observational studies. Funnel plot showed an indication of publication bias on studies using hyperleukocytosis cutoff of ≥50,000/mm(3). CONCLUSION The use of leukapheresis does not provide early mortality benefit in adult AML patients with hyperleukocytosis.
PICO Summary
Population
Adult acute myeloid leukemia patients (11 studies, n= 1,407).
Intervention
Leukapheresis intervention (n= 1,090).
Comparison
Not receiving leukapheresis (n= 317).
Outcome
Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm3 or 100,000/mm3. Studies using hyperleukocytosis cutoff of 50,000/mm3 showed no benefits of early mortality.
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Systemic therapy of necrobiotic xanthogranuloma: a systematic review
Steinhelfer L, Kühnel T, Jägle H, Mayer S, Karrer S, Haubner F, Schreml S
Orphanet journal of rare diseases. 2022;17(1):132
Abstract
BACKGROUND Even though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature. OBJECTIVE To review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies. METHODS All reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases. RESULTS The most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids. CONCLUSIONS Corticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.
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Efficacy of topical hemostatic agents in malignancy-related gastrointestinal bleeding: a systematic review and meta-analysis
Karna R, Deliwala S, Ramgopal B, Mohan BP, Kassab L, Becq A, Dhawan M, Adler DG
Gastrointestinal endoscopy. 2022
Abstract
BACKGROUND AND AIMS Despite advances in endoscopic therapies, malignancy-related gastrointestinal (GI) bleeding remains difficult to manage with high rates of treatment failure and rebleeding. Topical hemostatic agents (THA) are easier to apply to the wide bleeding surface of tumors. We conducted this systematic review and meta-analysis to evaluate the efficacy of THAs in malignancy-related GI bleed. METHODS We conducted a comprehensive search of multiple electronic databases to identify studies reporting on the use of THAs in malignancy-related GI bleeding. The primary outcome was the achievement of hemostasis; secondary outcomes were early rebleeding (≤ 3 days), delayed rebleeding (>3 days), aggregate rebleeding, all-cause mortality, and GI bleed related mortality. A meta-analysis of proportions was done for all outcomes. RESULTS Out of 355 citations, total 16 studies with 530 patients were included. Primary hemostasis was achieved in 94.1% (95% CI: 91.5 - 96.0%). Early rebleeding was seen in 13.9% (95% CI: 9.7 - 19.4%) while delayed rebleeding was seen in 11.4% (95% CI: 5.8 - 21.1%). Aggregate rebleeding was seen in 24.2% (95% CI:18.5 - 31.0%). All-cause mortality was 33.1% (95% CI: 23.7 - 44.0%) while GI bleed related mortality occurred in 5.9% (95% CI: 2.2% - 14.8%). CONCLUSIONS THAs are highly effective for achieving primary hemostasis in malignancy-related GI bleeding. It should be considered as an alternative to traditional endotherapy methods in malignancy-related GI bleeds. Future studies should be designed to evaluate its efficacy and safety as a primary method of hemostasis as compared to traditional endotherapy measures.
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Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Buchrits S, Itzhaki O, Avni T, Raanani P, Gafter-Gvili A
Journal of clinical medicine. 2022;11(14)
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Editor's Choice
Abstract
BACKGROUND The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. MATERIALS AND METHODS All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I(2) > 40%), in which we used a random effects model. RESULTS A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55-0.95) with a number needed to treat of 20 (95% CI 11-100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01-1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88-1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76-1.57; 8 trials). CONCLUSIONS IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.
PICO Summary
Population
People with chemotherapy induced anaemia enrolled in randomised controlled trials (RCTs), and identified by systematic review (n= 1,015, 8 RCTs).
Intervention
Intravenous [IV] iron (n= 553).
Comparison
Oral iron (n= 271), or no iron (n= 191).
Outcome
IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (Risk ratio [RR] 0.72; 95% confidence interval [CI] 0.55-0.95) with a number needed to treat of 20 (95% CI 11-100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01-1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88-1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76-1.57; 8 trials).
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Do liberal thresholds for red cell transfusion result in improved quality of life for patients undergoing intensive chemotherapy for acute myeloid leukemia? A randomized cross over feasibility study
Morton S, Sekhar M, Smethurst H, Mora A, Hodge RL, Hudson CL, Parsons J, Hopkins V, Stanworth SJ
Haematologica. 2022
Abstract
Not available.
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Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo controlled, randomized clinical trial
Gernsheimer TB, Brown SP, Triulzi DJ, Key NS, El Kassar N, Herren H, Poston JN, Boyiadzis M, Reeves BN, Selukar S, et al
Blood. 2022
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Editor's Choice
Abstract
Evidence of effectiveness of prophylactic use of tranexamic acid (TXA) in thrombocytopenia is lacking. To determine whether TXA safely reduces bleeding incidence in patients undergoing treatment for hematologic malignancies, a randomized double blind clinical trial was conducted June 2016 through June 2020. Of 3120 screened adults 356 patients were eligible and enrolled, and 337 patients (mean age, 53.9; 141 (41.8%) women), randomized to 1,300mg TXA orally or 1,000mg TXA intravenously (n=168) versus placebo (n=169) thrice daily for maximum 30 days. 330 patients were activated when their platelet counts fell below 30,000/µl; 279 (83%) had complete outcome ascertainment. WHO grade 2 or higher bleeding was observed in the 30 days following activation in 50.3% (73/145) and 54.2% (78/144) of patients in the TXA and placebo groups, adjusted odds ratio: 0.83 (95%CI:0.50,1.34; p=0.44). There was no statistically significant difference in mean number of platelet transfusions (0.1;95%CI:-1.9,2.0), mean days alive without grade 2 or higher bleeding (0.8;95%CI:-0.4,2.0), thrombotic events (6/163 (3.7%) TXA, 9/163 (5.5%) placebo), or deaths due to serious bleeding. Most common adverse events were: diarrhea [(116/164 (70.7%) TXA and 114/163 (69.9%) placebo)]; febrile neutropenia [111/164 (67.7%) TXA, 105/163 (64.4%) placebo]; fatigue [106/164 (64.6%) TXA, 109/163 (66.9%) placebo]; and nausea [104/164 (63.4%) TXA, 97/163 (59.5%) placebo]. Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with tranexamic acid compared with placebo did not significantly reduce the risk of WHO grade 2 or higher bleeding. Trial Registration: Clinicaltrials.gov Identifier: NCT02578901.
PICO Summary
Population
Patients who were thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy, and/or radiation therapy (n= 337).
Intervention
Tranexamic acid (TXA) orally or intravenously (n= 168).
Comparison
Placebo (n= 169).
Outcome
The primary outcome of WHO grade 2 or higher bleeding during the first 30 days after activation was observed for 73 out of 145 (50.3%) and 78 out of 144 (54.2%) patients in the TXA and placebo groups, respectively. There was no statistically significant difference in mean number of platelet transfusions (0.1), mean days alive without grade 2 or higher bleeding (0.8), thrombotic events (6/163 (3.7%) TXA, 9/163 (5.5%) placebo), or deaths due to serious bleeding.
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Outcomes and Clinical Characteristics of Intracranial Hemorrhage in Patients with Hematological Malignancies: A Systematic Literature Review
Raghavan A, Wright CH, Wright JM, Jensen K, Malloy P, Elder T, Burant C, Sajatovic M, Hoffer A
World Neurosurg. 2020
Abstract
BACKGROUND Many clinical and demographic factors can influence survival of patients with hematological malignancies who have intracranial hemorrhages. Understanding the influence of these factors on patient survival can guide treatment decisions and may inform prognostic discussions. We conducted a systematic literature review to determine survival of patients with intracranial hemorrhages and concomitant hematologic malignancy. METHODS A systematic literature review was conducted and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pubmed/MEDLINE, Web of Science, Ovid, SCOPUS, and Embase databases were queried with the following terms: ("intracranial hemorrhages" OR "brain hemorrhage" OR "cerebral hemorrhage" OR "subdural hematoma" OR "epidural hematoma" OR "intraparenchymal hemorrhage") AND ("Hematologic Neoplasms" OR "Myeloproliferative Disorders" OR "Myelofibrosis" OR "Essential thrombocythemia" OR "Leukemia"). Abstracts and articles were screened according to inclusion and exclusion criteria that were determined a priori. RESULTS Literature review yielded 975 abstracts from which a total of 68 full-text articles were reviewed. 12 articles capturing 634 unique patients were included in the final qualitative analysis. Median overall survival for all patients ranged from 20 days - 1.5 months while median overall survival for the subset of patients having ICH within 10 days of diagnosis of hematological malignancy was 5 days. Intraparenchymal hemorrhages, multiple foci of hemorrhage, transfusion-resistant low platelet counts, leukocytosis, low GCS scores at presentation, and ICH early in treatment course were associated with worse outcomes. CONCLUSIONS Survival for patients with hematological malignancies and concomitant ICHs remains poor. Early detection, recognition of poor prognostic and correction of hematological abnormalities appears essential to prevention and treatment of ICHs in this patient population.
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Exploring the components of bleeding outcomes in transfusion trials for patients with hematologic malignancy
Balitsky AK, Liu Y, Van der Meer PF, Heddle NM, Arnold DM
Transfusion. 2020
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Editor's Choice
Abstract
Clinically significant bleeding in patients with hematologic malignancies is a heterogeneous composite outcome currently defined as World Health Organization (WHO) bleeding Grades 2, 3, and 4. However, the clinical significance of some minor bleeds categorized as WHO Grades 1 and 2 remains controversial. We analyzed the number and frequency of individual signs and symptoms of WHO Grades 1 and 2 bleeds and explored their association with more severe incident bleeds graded as WHO Grades 3 and 4. STUDY DESIGN AND METHODS We aggregated daily bleeding assessment data from three randomized controlled trials conducted in patients with hematologic malignancies that used bleeding as an outcome. Cox proportional hazard regression analysis was used to identify signs and symptoms categorized as WHO Grades 1 and 2 bleeds that were associated with more severe bleeds (Grades 3 and 4). RESULTS We collected data from 315 patients (n = 5476 daily bleeding assessments; 3383 [61.8%] with a bleed documented). A total of 98.3% (3326/3383) were Grade 1 and 2 bleeds and 1.7% (57/3383) were Grades 3 and 4. Grade 1 and 2 bleeds were composed of 20 different bleeding signs and symptoms. Hematuria (hazard ratio, 16.1; 95% confidence interval, 4.4-59.2; P < .0001) was associated with incident Grade 3 or 4 bleeds. CONCLUSION In patients with hematologic malignancy, only hematuria (microscopic and/or macroscopic) was associated with more severe incident bleeds. This findings require validation in independent data sets.
PICO Summary
Population
Patients with haematologic malignancies and chemotherapy-induced thrombocytopenia (3 randomised controlled trials (RCTs), n= 315).
Intervention
Less severe bleeds (WHO Grades 1 and 2).
Comparison
More severe bleeds (WHO Grades 3 and 4).
Outcome
The total data aggregated from the 3 RCTs was 5,476 daily bleeding assessments, 61.8% with a bleed documented. A total of 98.3% were Grade 1 and 2 bleeds and 1.7% were Grades 3 and 4. Grade 1 and 2 bleeds were composed of 20 different bleeding signs and symptoms. Haematuria was associated with incident Grade 3 or 4 bleeds. In patients with haematologic malignancy, only haematuria was associated with more severe bleeds.
