Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis
Hematology (Amsterdam, Netherlands). 2022;27(1):141-149
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.
Adult acute myeloid leukemia patients (11 studies, n= 1,407).
Leukapheresis intervention (n= 1,090).
Not receiving leukapheresis (n= 317).
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.
Leukapheresis for the management of hyperleukocytosis in acute myeloid leukemia-A systematic review and meta-analysis
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.
Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta-analysis
International Journal of Clinical Pharmacology & Therapeutics. 2015;53((5):):391-7.
BACKGROUND/AIM: The clinical benefits of plasmapheresis in the management of multiple myeloma-induced acute renal failure remain controversial. In this study, we conducted a meta-analysis to quantitatively evaluate the clinical efficacy of chemotherapy with or without plasmapheresis in the treatment of multiple myeloma patients with renal failure. METHODS Randomized controlled trials evaluating clinical efficacy of plasmapheresis were identified by searching PubMed (from 1980 to November 2013) and EMBASE (from 1980 to November 2013). Outcomes subjected to meta-analysis were 6-month survival and dialysis-dependent rate. RESULTS Three randomized controlled studies were selected for meta-analysis. A total of 63 patients received chemotherapy only and 84 patients were given both chemotherapy and plasmapheresis. No difference was observed in 6-month survival rate between plasmapheresis and control group (75% vs. 66.7%; risk ratio, 0.92; 95% CI, 0.76 - 1.11; p = 0.39). 6-month dialysis-dependent ratio was significantly lower in patients treated with both chemotherapy and plasmapheresis than chemotherapy only (15.6% vs. 37.2%; risk ratio, 2.02; 95% CI, 1.03 - 3.96; p = 0.04). CONCLUSION Our meta-analysis results showed that plasmapheresis used as an adjunct to chemotherapy had a benefit in the management of dialysisdependent multiple myeloma patients with renal failure.
Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: A systematic review and meta-analysis
Leukemia Research. 2014;38((4):):460-8.
The role of leukapheresis and low-dose chemotherapy is unclear in decreasing early mortality in acute myeloid leukemia (AML) patients with hyperleukocytosis. This systematic review was conducted to describe early mortality (deaths during first induction) in patients with AML with an initial white blood count>100x10(9)L(-1) stratified by the approach to leukapheresis and hydroxyurea/low-dose chemotherapy. Twenty-one studies were included. Weighted mean early deaths rate (20 studies, 1354 patients) was 20.1% (95% confidence interval 15.0-25.1). Neither leukapheresis strategy (p=0.67) nor hydroxyurea/low-dose chemotherapy (p=0.23) influenced the early death rate. Early mortality related to hyperleukocytosis in AML is not influenced by universal or selected use of leukapheresis or hydroxyurea/low-dose chemotherapy. Copyright 2014 Elsevier Ltd. All rights reserved.
Role of plasmapheresis in the management of myeloma kidney: A systematic review
Hemodialysis International. 2010;14((4):):355-63.
Multiple myeloma complicated by acute renal failure is a diagnosis often encountered by the practicing nephrologist. The role of plasmapheresis in such patients has been of interest for decades. Three randomized controlled trials (RCTs) and multiple observational trials have evaluated the potential role of plasmapheresis in the management of this condition. This systematic review presents the results of these trials regarding survival benefits, recovery from dialysis, and improvement in renal function. A comprehensive search revealed 56 articles. Of these, only 8 articles met our inclusion criteria (3 RCTs, 1 correction of results, and 4 observational trials). Two of the 3 RCTs showed no difference in survival benefit. Two of the 3 RCTs showed a greater percentage of patients stopping dialysis in the intervention group; however, these results were not reproduced in the largest trial. All the studies showed an improvement in renal function for patients receiving plasmapheresis; however, only 2 RCTs and 1 retrospective study showed a statistically significant improvement in renal function among patients who received plasmapheresis in comparison with a control group. Our systematic review does not suggest a benefit of plasmapheresis independent of chemotherapy for multiple myeloma patients with acute renal failure in terms of overall survival, recovery from dialysis, or improvement in renal function.
A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease
Chronic graft-versus-host disease (cGVHD) is a major limitation of successful hematopoietic cell transplantation. The safety and efficacy of extracorporeal photopheresis (ECP) for 12 to 24 weeks together with standard therapy was compared with standard therapy alone in patients with cutaneous manifestations of cGVHD that could not be adequately controlled by corticosteroid treatment. The primary efficacy end point was a blinded quantitative comparison of percent change from baseline in Total Skin Score (TSS) of 10 body regions at week 12. Ninety-five patients were randomized to either ECP and standard therapy (n = 48) or standard therapy alone (n = 47). The median percentage improvement in TSS at week 12 was 14. 5% for the ECP arm and 8. 5% for the control arm (P = . 48). The proportion of patients who had at least a 50% reduction in steroid dose and at least a 25% decrease from baseline in TSS was 8. 3% in the ECP arm at week 12 and 0% in the control arm (P = . 04). The nonblinded investigator assessment of skin complete or partial responses revealed a significant improvement in favor of ECP (P < . 001). ECP was generally well tolerated. These results suggest that ECP may have a steroid-sparing effect in the treatment of cGVHD. Clinical trials registered at www. ClinicalTrials. gov as NCT00054613.
Prospective randomised comparison of the COBE spectra version 6 and haemonetics MCS(+) cell separators for hematopoietic progenitor cells leucapheresis in patients with multiple myeloma
Journal of Clinical Apheresis. 2006;21((2):):111-5.
A randomised crossover trial of two separators was undertaken to compare the mononuclear cell, CD34(+) cell and CFU-GM yield, in patients (<61 years) with previously untreated symptomatic multiple myeloma. After first-line therapy, all patients received mobilising chemotherapy (cyclophosphamide 4 g/m(2)) and daily G-CSF. The first leucapheresis was performed on the first day the peripheral blood absolute CD34(+) cell count was > 20 cells/microl. All patients underwent 2 leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra. The target duration of the procedure on the COBE Spectra was 2 total blood volumes, and for the Haemonetics MCS(+) it was 20 cycles with four recirculations. Between September 2003 and March 2005, 60 patients were entered in the study. COBE Spectra version 6 processed significantly larger volumes of blood than the Haemonetics MCS(+) (8,845 and 5,680 ml, respectively, P < 0. 01). The absolute yield of mononuclear cells (2. 1 vs. 1. 5 x 10(8)/kg, P = 0. 04), CFU-GM (11 vs. 3 x 10(4)/kg, P = 0. 01) and CD34(+) cells (3 vs. 1. 7 x 10(6)/kg, P = 0. 02) were all significantly higher with the COBE Spectra version 6, as were the yields per unit volume of blood processed. In conclusion, our study shows that COBE Spectra Version 6 is faster and has a better yield than the Haemonetics MCS(+), in patients with multiple myeloma.
Plasmapheresis in the treatment of renal failure associated with multiple myeloma
Blood. 2006;108((11):): Abstract No. 3585
Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trial
Annals of Internal Medicine. 2005;143((11):):777-84.
BACKGROUND Two small, randomized trials provide conflicting evidence about the benefits of plasma exchange for patients with acute renal failure at the onset of multiple myeloma. OBJECTIVE To assess the effect of 5 to 7 plasma exchanges on a composite outcome in patients with acute renal failure at the onset of multiple myeloma. DESIGN Randomized, open, controlled trial, stratified by chemotherapy and dialysis dependence, conducted from 1998 to 2004. SETTING Hospital plasma exchange units in 14 Canadian medical centers. PARTICIPANTS 104 patients between 18 and 81 years of age with acute renal failure at the onset of myeloma. INTERVENTION Study participants were randomly assigned to conventional therapy plus 5 to 7 plasma exchanges of 50 mL per kg of body weight of 5% human serum albumin for 10 days or conventional therapy alone. Ninety-seven participants completed the 6-month follow-up. MEASUREMENTS The primary outcome was a composite measure of death, dialysis dependence, or glomerular filtration rate less than 0. 29 mL x s(-2) x m(-2) (<30 mL/min per 1. 73 m2). RESULTS At enrollment, the plasma exchange and control groups were similar for dialysis dependence, chemotherapy, sex, age, hypercalcemia, serum albumin level, 24-hour urine protein level, serum creatinine level, and Durie-Salmon staging. The primary composite end point occurred in 33 of 57 (57. 9%) patients in the plasma exchange group and in 27 of 39 (69. 2%) patients in the control group (difference between groups, 11. 3% [95% CI, -8. 3% to 29. 1%]; P = 0. 36). One third of patients in each group died. LIMITATIONS The study was small, used a composite outcome, and did not use renal biopsy as an inclusion criterion. Recruiting physicians were blinded to treatment allocation but not to treatment thereafter. CONCLUSIONS In patients with acute renal failure at the onset of multiple myeloma, there is no conclusive evidence that 5 to 7 plasma exchanges substantially reduce a composite outcome of death, dialysis dependence, or glomerular filtration rate less than 0. 29 mL. s(-2). m(-2) (<30 mL/min per 1. 73 m2) at 6 months.
A randomised controlled trial of plasma exchange in rapidly progressive renal failure of myeloma
Blood. 2004;104((11, Pt 2):):307b.. Abstract No. 4899.