Leukapheresis for the management of hyperleukocytosis in acute myeloid leukemia—A systematic review and meta‐analysis

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 (Cochranʼs 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.

Leukapheresis Does Not Improve Early Survival Outcome of Acute Myeloid Leukemia with Leukostasis Patients – A Dual-Center Retrospective Cohort Study

“…38 However, due to all studies used being retrospective in design and including pediatric patients, there was mild heterogeneity in the pooled analysis. 38 Given the rarity of AML patients with hyperleukocytosis, ethical issues, and preferences of clinicians in deciding which patients receive leukapheresis or not, it is theoretically very difficult for a randomized controlled study to be conducted. 12 In Indonesia itself, leukapheresis was only introduced around the year 2002 and was only implemented as a means of therapy much later on.…”

“…Our results are in line with several studies. 10,[19][20][21]36,38 Despite similar conclusion, there were major differences in those studies that should be noted. For example, the study by Stahl et al used inclusion criteria of WBC > 50 x 10 9 /L and also included patients without leukostasis, while all patients in this study had leukostasis symptoms.…”

Oncogenic Kinase Cascades Induce Molecular Mechanisms That Protect Leukemic Cell Models from Lethal Effects of De Novo dNTP Synthesis Inhibition

“…Chemotherapeutics eliminate transformed cells through the induction of replication stress and DNA damage [1][2][3]. Hydroxyurea is used as cytoreductive therapy for leukemic disorders and brain tumors [4][5][6][7]. This drug specifically inhibits ribonucleotide reductase (RNR) and thereby depletes the cellular dNTP pool [8].…”

Indolent Presentations of Leukemic Lung Disease in Acute Myeloid Leukemia

“…However, it is considered the rarest etiology in this population and therefore may be overlooked. 17 Three manifestations of leukemic lung disease have been defined in the literature: (i) leukostasis, an emergent medical condition characterized by intravascular accumulation of blasts, increased blood viscosity, vascular inflammation, and multi-organ dysfunction; [18][19][20] (ii) leukemic infiltration (LI) of blasts into the lung parenchyma;…”

“…1,8,21,22 Leukostasis is well-described, with clearly defined diagnostic criteria that facilitate prompt recognition and treatment. [18][19][20] However, the clinical features of LI and ATLP in patients with AML have not been fully characterized.…”