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Multicenter Study
. 2020 Dec;34(12):3149-3160.
doi: 10.1038/s41375-020-0783-3. Epub 2020 Mar 4.

Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study

Maximilian Stahl #  1 , Rory M Shallis #  1 , Wei Wei #  2 , Pau Montesinos  3 , Etienne Lengline  4 , Judith Neukirchen  5 , Vijaya R Bhatt  6 , Mikkael A Sekeres  7 , Amir T Fathi  8 , Heiko Konig  9 , Selina Luger  10 , Irum Khan  11 , Gail J Roboz  12 , Thomas Cluzeau  13 , David Martínez-Cuadron  3 , Emmanuel Raffoux  4 , Ulrich Germing  5 , Jayadev Manikkam Umakanthan  14 , Sudipto Mukherjee  7 , Andrew M Brunner  8 , Adam Miller  9 , Christine M McMahon  10 , Ellen K Ritchie  11 , Rebeca Rodríguez-Veiga  3 , Raphaël Itzykson  4 , Blanca Boluda  3 , Florence Rabian  3   4 , Mar Tormo  15 , Evelyn Acuña-Cruz  3 , Emma Rabinovich  11 , Brendan Yoo  10 , Isabel Cano  3 , Nikolai A Podoltsev  1 , Jan Philipp Bewersdorf  1 , Steven Gore  1 , Amer M Zeidan  16
Affiliations
Multicenter Study

Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study

Maximilian Stahl et al. Leukemia. 2020 Dec.

Abstract

Hyperleukocytosis in acute myeloid leukemia (AML) is associated with inferior outcomes. There is limited high quality evidence to support the benefits of leukapheresis. We retrospectively collected data from patients with newly-diagnosed AML who presented with a white cell count (WBC) >50 × 109/L to 12 centers in the United States and Europe from 2006 to 2017 and received intensive chemotherapy. Logistic regression models estimated odds ratios for 30-day mortality and achievement of composite complete remission (CRc). Cox proportional hazard models estimated hazard ratios for overall survival (OS). Among 779 patients, clinical leukostasis was reported in 27%, and leukapheresis was used in 113 patients (15%). Thirty-day mortality was 16.7% (95% CI: 13.9-19.3%). Median OS was 12.6 months (95% CI: 11.5-14.9) among all patients, and 4.5 months (95% CI: 2.7-7.1) among those ≥65 years. Use of leukapheresis did not significantly impact 30-day mortality, achievement of CRc, or OS in multivariate analysis based on available data or in analysis based on multiple imputation. Among patients with investigator-adjudicated clinical leukostasis, there were statistically significant improvements in 30-day mortality and OS with leukapheresis in unadjusted analysis, but not in multivariate analysis. Given the significant resource use, cost, and potential complications of leukapheresis, randomized studies are needed to evaluate its value.

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Figures

Figure 1:
Figure 1:. Overall Survival
A: Patients with WBC > 100.000 vs ≤ 100.000 B: Patients with and without evidence of leukostasis C: Patients receiving and not receiving leukapheresis D: Patients > 55 years vs. ≤ 55 years old
Figure 2:
Figure 2:. Forest plot of multivariable analysis.
The grey vertical line represents the odds ratio (Fig 2 A+C), and hazard ratio (Fig 2 B) of no effect. The box sizes are proportional to the precision of the estimates with large boxes indicating a great degree of precision. OR denotes odds ratio and HR denotes hazard ratio. A. Predictors of 30-day mortality by multivariable logistic regression analysis (N=619). B. Predictors of overall survival by multivariable Cox regression analysis (N=623). C. Predictors of CRc by multivariable logistic regression (N=531).
Figure 3:
Figure 3:. Forest plot of propensity score matched multivariate analysis
The grey vertical line represents the odds ratio (Fig 3 A+C), and hazard ratio (Fig 3 B) of no effect. The box sizes are proportional to the precision of the estimates with large boxes indicating a great degree of precision. OR denotes odds ratio and HR denotes hazard ratio. A: Predictors of 30-day mortality by multivariable logistic regression analysis (N=196). B: Predictors of overall survival by using multivariable Cox regression analysis (N=196). C: Predictors of CRc by multivariable logistic regression analysis (N=196).
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