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1.
Extracorporeal photopheresis as graft-versus-host disease prophylaxis: a randomized controlled trial
Ali MM, Gedde-Dahl T, Osnes LT, Perrier F, Veierød MB, Tjønnfjord GE, Iversen PO
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for many patients diagnosed with hematological malignancies. A major obstacle is graft-versus-host disease (GvHD) causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied GvHD treatment, partly due to its favourable safety profile. In contrast, the use of ECP in preventing GvHD is sparse, and randomized controlled trials (RCTs) are lacking. OBJECTIVE We therefore conducted a RCT to assess if ECP applied post-transplant, could prevent the development of GvHD within the first year of transplantation. STUDY DESIGN We enrolled 157 patients (18-74 years) with a hematological malignancy receiving first allo-HSCT: 76 randomized to the intervention group and 81 to the control group. ECP was initiated directly upon engraftment and was planned twice weekly for two weeks, then once weekly for four weeks. GvHD, relapse, and death were analyzed with Cox regression analysis. RESULTS During the first year, 45 patients in the intervention and 52 control patients developed GvHD (HR=0.82, 95% CI 0.55-1.22, P=0.32). There were no differences in acute or chronic GvHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GvHD between the intervention (per-protocol; n=39 of 76) and the control group (n=77), 46% vs 68%, respectively, (HR 0.47, 95% CI 0.27-0.80, P=0.006). Relapse occurred in 15 patients in the intervention group and in 11 patients among the controls (HR=1.38, 95% CI 0.64-3.01, P=0.42). GvHD-free relapse-free (GRFS) survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. No significant difference in immune reconstitution between the two study groups was revealed. CONCLUSION This first intention-to-treat RCT, investigating ECP as GvHD prophylaxis in allo-HSCT for hematological malignancy does not support the use of ECP as adjunct to standard drug-based GvHD-prophylaxis. This trial was registered at www. CLINICALTRIALS gov as #NCT03204721.
PICO Summary
Population
Adult patients with a haematological malignancy receiving first allogeneic haematopoietic stem cell transplantation (n= 157).
Intervention
Prophylactic extracorporeal photopheresis (ECP), (intervention group, n= 76).
Comparison
No ECP (control group, n= 81).
Outcome
During the first year, 45 patients in the intervention and 52 control patients developed graft-versus-host disease (GVHD), (HR= 0.82, 95% CI [0.55, 1.22]). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat randomised controlled trial. A per-protocol analysis revealed a significant difference in GVHD between the intervention (per-protocol; n= 39 of 76) and the control group (n= 77), 46% vs. 68%, respectively, (HR 0.47, 95% CI [0.27, 0.80]). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR= 1.38, 95% CI [0.64, 3.01]). GVHD-free relapse-free survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. There also was no significant difference in immune reconstitution between the two groups.
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2.
Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial
Seed, P. T., Brien, S. B., Oakley, L. L., Robinson, V., Sharif, J., Thompson, H., Joseph, J., Oteng-Ntim, E.
Trials. 2023;24(1):225
Abstract
BACKGROUND There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study. METHODS AND DESIGN TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes. RESULTS Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update. CONCLUSION The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias. TRIAL REGISTRATION NIH registry ( www. CLINICALTRIALS gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
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3.
Therapeutic plasma exchange-free treatment for first-episode TTP: A systematic review
Wang J, Cheng F, Niu Y, Yan L, Li J, Tan B, Qin L
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103661
Abstract
OBJECTIVE Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE sometimes cannot be implemented. The aim of this study was to systematically review patients with a first TTP episode who were treated without TPE. METHOD The PubMed, Embase, Web of Science and Cochrane Library databases were searched by two investigators independently to collect case reports and clinical studies on TTP patients treated without TPE. After removing duplicate records and records that did not meet the inclusion criteria, the patients' data of eligible studies, including the basic characteristics, treatment regimens, and outcomes were extracted for further analysis. RESULTS A total of 5338 potentially relevant original studies were identified, from which 21 studies, including 14 cases, 3 case series and 4 retrospective studies, met eligibility requirements and were included. Treatment regimens in the absence of TPE were found to vary based on individual information. Most patients recovered, with normal platelet counts and ADAMT13 activity at discharge. In the meta-analysis of retrospective studies, the TPE-free group had no higher mortality than the TPE-treated group. CONCLUSION Our study shows that TPE-free treatment may not increase the mortality of TTP patients, which provides a new treatment concept for patients with first episodes of TTP. However, the current evidence is not high due to the lack of randomized controlled trials, so more well-designed prospective clinical trials are warranted to investigate the safety and efficacy of TPE-free treatment regimens in TTP patients.
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Comparative evaluation of efficacy and safety of automated versus manual red cell exchange in sickle cell disease: A systematic review and meta-analysis
Mukherjee S, Sahu A, Ray GK, Maiti R, Prakash S
Vox sanguinis. 2022
Abstract
BACKGROUND AND OBJECTIVES Exchange transfusion is a valuable treatment option in sickle cell disease (SCD) and is preferred over simple transfusion as it removes abnormal haemoglobin S (HbS) levels and reduces complications. This meta-analysis aims to evaluate the efficacy and safety profile of automated red cell exchange (aRBX) procedure over manual red cell exchange transfusion (MET) in SCD patients. MATERIALS AND METHODS A standard meta-analysis protocol was developed, and after performing a comprehensive literature search in PubMed/MEDLINE, Cochrane and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from nine relevant studies. A random effects model was used to estimate the pooled effect size calculated from the mean difference in HbS percentage, serum ferritin level and risk ratio for the adverse events. Quality assessment was done using the risk-of-bias assessment tool, and a summary of observations was prepared using standard Cochrane methodology with GradePro GDT. RESULTS The random-model analysis revealed a mean difference of 4.10 (95% CI: -3.29-11.49; Z = 1.09; p = 0.28) for HbS percentage, mean difference of 435.29 (95% CI: -73.74-944.32; Z = 1.68; p = 0.09) for serum ferritin and pooled risk ratio of 1.35 (95% CI: 0.63-2.87; Z = 0.77; p = 0.44) for adverse events. CONCLUSION This meta-analysis did not reveal any significant benefit of aRBX in reducing HbS percentage and attenuating the serum ferritin level when compared with MET. There was also no significant increased risk of adverse events detected in association with aRBX.
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5.
Efficacy of plasma exchange in children with severe hemophagocytic syndrome: a prospective randomized controlled trial
Yuan, Y. H., Zhang, H., Xiao, Z. H., Zhang, X. P., Lu, X. L., Xu, Z. Y., He, J., Zhu, L. F.
Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. 2022;24(3):249-254
Abstract
OBJECTIVES To investigate the efficacy and application value of plasma exchange as an adjuvant therapy in children with hemophagocytic syndrome (HPS). METHODS A prospective randomized controlled trial was designed. Forty children with severe HPS were enrolled, who were treated in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 2018 to October 2020. The children were randomly divided into a plasma exchange group and a conventional treatment group using a random number table, with 20 children in each group. The children in the conventional treatment group received etiological treatment and conventional symptomatic supportive treatment, and those in the plasma exchange group received plasma exchange in addition to the treatment in the conventional treatment group. The two groups were compared in terms of general information, clinical symptoms and signs before and after treatment, main laboratory markers, treatment outcome, and prognosis. RESULTS Before treatment, there were no significant differences between the two groups in gender, age, course of the disease before admission, etiological composition, pediatric critical illness score, involvement of organ or system functions, and laboratory markers (P>0.05). After 7 days of treatment, both groups had remission and improvement in clinical symptoms and signs. After treatment, the plasma exchange group had significantly lower levels of C-reactive protein, procalcitonin, and serum protein levels than the conventional treatment group (P<0.05). The plasma exchange group also had significantly lower levels of alanine aminotransferase and total bilirubin than the conventional treatment group (P<0.05). The length of stay in the PICU in the plasma exchange group was significantly shorter than that in the conventional treatment group (P<0.05). The plasma exchange group had a significantly higher treatment response rate than the conventional treatment group (P<0.05). There were no significant differences between the two groups in the total length of hospital stay and 3-month mortality rate (P>0.05). CONCLUSIONS Plasma exchange as an adjuvant therapy is effective for children with severe HPS. It can improve clinical symptoms and signs and some laboratory markers and shorten the length of stay in the PICU, and therefore, it may become an optional adjuvant therapy for children with severe HPS.
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6.
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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Immunoadsorption for the Treatment of Acquired Hemophilia: New Observational Data, Systematic Review, and Meta-Analysis
Esteves Pereira M, Bocksrucker C, Kremer Hovinga JA, Mueller M, Daskalakis M, Mansouri Taleghani B, Nagler M
Transfusion medicine reviews. 2021
Abstract
The treatment of patients with acquired hemophilia is challenging due to life-threatening hemorrhages, delayed response, and adverse effects to immunosuppressive agents. Even though immunoadsorption (IA) rapidly removes autoantibodies against factor VIII, this intervention's effectiveness is still a matter of debate. We aimed to study important outcomes of IA as adjunctive treatment in patients with acquired hemophilia. We performed comprehensive literature searches in MEDLINE and EMBASE databases. Clinical and laboratory data of all patients treated in our institution were additionally included. Literature searching yielded 498 records, of which 10 studies describing 106 patients were finally included. The number of patients varied from 1 to 65, and patients' ages ranged between 14 and 89. Treatment criteria in most patients were (1) failed response to immunosuppressive treatment alone, and/or (2) uncontrollable bleeding episodes, and/or (3) high inhibitor titer. Methodological quality was moderate. The number of IA sessions varied from 1 to 24. Within our institution, 12 patients have been treated since 2002; median age was 76 years (range 34-86); median titer of factor VIII inhibitor was 20 Bethesda units (range 3-214). Pooled estimates, modeling a random-effect binominal distribution incorporating the Freeman-Tukey double arcsine transformation, were 86% in case of factor VIII recovery (95% confidence interval 76%-94%), 95% for reduction of factor VIII inhibitor (83%, 100%), and 7% in case of death (0%, 18%). Our data suggest that IA might be a beneficial adjunctive treatment in patients with high-risk acquired hemophilia, but future studies shall confirm this observation.
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8.
Clinical hemocompatibility of double filtration lipoprotein apheresis comparing polyethersulfone and ethylene-vinyl alcohol copolymer membranes
Krieter DH, Jeyaseelan J, Rüth M, Lemke HD, Wanner C, Drechsler C
Artificial organs. 2021
Abstract
INTRODUCTION Activation of the complement system and leukocytes by blood-membrane interactions may further promote arteriosclerosis typically present in patients on lipoprotein apheresis. As clinical data on the hemocompatibility of lipoprotein apheresis are scarce, a controlled clinical study comparing two different types of plasma separation and fractionation membranes used in double filtration lipoprotein apheresis was urgently needed, as its outcome may influence clinical decision-making. METHODS In a prospective, randomized, crossover controlled trial, eight patients on double filtration lipoprotein apheresis were subjected to one treatment with recent polyethersulfone (PES) plasma separation and fractionation membranes and one control treatment using a set of ethylene-vinyl alcohol copolymer (EVAL) membranes. White blood cell (WBC) and platelet (PC) counts, complement factor C5a and thrombin-anti-thrombin III (TAT) concentrations were determined in samples drawn at defined times from different sites of the extracorporeal blood and plasma circuit. RESULTS With a nadir at 25 min, WBC in EVAL decreased to 33.5 ± 10.7 % of baseline compared to 63.8 ± 22.0 % at 20 min in PES (P < 0.001). The maximum C5a levels in venous blood re-entering the patients were measured at 30 min, being 30.0 ± 11.2 µg/L with EVAL and 12.3 ± 9.0 µg/L with PES (P < 0.05). The highest C5a concentrations were found in plasma after the plasma filters (EVAL 56.1 ± 22.0 µg/L at 15 min vs. PES 23.3 ± 15.2 µg/L at 10 min; P < 0.001). PC did not significantly decrease over time with both membrane types, while TAT levels did not rise until the end of the treatment without differences between membranes. Regarding lipoprotein(a) and LDL cholesterol removal, both membrane sets performed equally. CONCLUSION Compared to EVAL, PES membranes cause less leukocyte and complement system activation, the classical parameters of hemocompatibility of extracorporeal treatment procedures, at identical treatment efficacy. Better hemocompatibility may avoid inflammation-promoting effects through blood-material interactions in patients requiring double-filtration lipoprotein apheresis.
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9.
Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta-analysis
Paydary K, Banwell E, Tong J, Chen Y, Cuker A
Transfusion. 2020
Abstract
BACKGROUND The PLASMIC score was developed to identify patients with thrombotic microangiopathy who are most likely to have immune thrombotic thrombocytopenic purpura (TTP) and benefit from therapeutic plasma exchange (TPE). PLASMIC scores of 0-4, 5, and 6-7 are said to correspond to low, intermediate, and high probability of TTP, respectively. STUDY DESIGN AND METHODS We conducted a systematic review and meta-analysis on the diagnostic accuracy of the PLASMIC score in adults with suspected TTP. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of PLASMIC score thresholds of ≥5 and ≥6. Study quality was appraised using the QUADAS-2 tool. RESULTS We identified 13 eligible studies, which collectively enrolled 970 patients. The median prevalence of TTP among eligible studies was 35%. The sensitivity and specificity of a PLASMIC score ≥5 was 0.99 (95% confidence interval [CI], 0.91-1.00) and 0.57 (95% CI, 0.41-0.72), respectively. At a prevalence of 35%, the NPV of a PLASMIC score ≥5 was 0.99 (95% CI, 0.92-1.00). A PLASMIC score ≥6 was associated with a sensitivity and specificity of 0.85 (95% CI, 0.67-0.94) and 0.89 (95% CI, 0.81-0.94), respectively. The NPV of a PLASMIC score ≥6 at a prevalence of 35% was 0.92 (95% CI, 0.82-0.97). CONCLUSION A PLASMIC score threshold of ≥5 is associated with high sensitivity and NPV and may be a useful screening tool for identifying patients who are unlikely to have TTP and do not require TPE, though prospective assessment is required. A PLASMIC score <6 appears to have insufficient sensitivity to rule out TTP and the need for TPE.
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10.
Leukapheresis for the management of hyperleukocytosis in acute myeloid leukemia-A systematic review and meta-analysis
Bewersdorf JP, Giri S, Tallman MS, Zeidan AM, Stahl M
Transfusion. 2020
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Abstract
BACKGROUND Up to 20% of patients with acute myeloid leukemia (AML) present with hyperleukocytosis, usually defined as a white blood cell (WBC) count greater than 100 × 10(9) /L. Given the high early mortality rate, emergent cytoreduction with either leukapheresis, hydroxyurea, or chemotherapy is indicated, but the optimal strategy is unknown. STUDY DESIGN AND METHODS For this systematic review and meta-analysis we searched MEDLINE and EMBASE via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception through March 2020 for multiarm studies comparing early mortality rates of patients with AML treated with leukapheresis and those who were not. The risk ratio (RR) of early death for patients who received leukapheresis vs patients who did not was estimated using a sum of the log-ratio of individual study estimates weighted by sample size. RESULTS Among 13 two-arm, retrospective studies with 1743 patients (486 leukapheresis and 1257 nonleukapheresis patients), leukapheresis did not improve the primary outcome of early mortality compared to treatment strategies in which leukapheresis was not used (RR, 0.88; 95% confidence interval [CI], 0.69-1.13; P = .321) without statistically significant heterogeneity between studies (Cochran's Q, 18; P = .115; I(2) , 33.4%). Patients presenting with clinical leukostasis tended to be more likely to undergo leukapheresis (odds ratio, 2.01; 95% CI, 0.99-4.08; P = .052). CONCLUSION As we did not find evidence of a short-term mortality benefit and considering the associated complications and logistic burden, our results argue against the routine use of leukapheresis for hyperleukocytosis among patients with AML.