The impact of leukapheresis on clinical outcomes in patients with AML and hyperleukocytosis, results from a large, retrospective, study

Hyperleukocytosis (HL) is defined by a white blood cell (WBC) count of > 50 × 10⁹/L or > 100 × 10⁹/L.¹ HL is associated with poor outcome in patients with acute myeloid leukemia (AML) because of complications, such as leukostasis, tumor lysis syndrome (TLS) and disseminated intravascular coagulopathy (DIC).¹ HL associated with leukostasis requires immediate treatment, with options such as leukapheresis, intensive chemotherapy (IC), and hydroxyurea.²

Limited data are available on short- and long-term outcomes of patients with HL, and the impact of leukapheresis on clinical outcomes is not well defined. In this large, international, retrospective study recently published in Leukemia, Maximilian Stahl and colleagues aimed to evaluate the impact of hyperleukocytosis, leukostasis, and leukapheresis on short- and long-term clinical outcomes in newly diagnosed patients with AML.³

Study design and patient characteristics³

• Data were retrospectively collected from 998 patients with AML and hyperleukocytosis (WBC > 50 × 10⁹/L), of these 779 received IC and were selected for this study
• Patient characteristics are reported in Table 1
• Hyperleukocytosis was managed by:
  • Leukapheresis in 113 patients, with
    • immediate induction of IC (n = 68)
    • delayed induction of IC (n = 41)
  • immediate initiation of IC (n = 340)
  • administration of hydroxyurea followed by IC (n = 301)

Table 1. Patient characteristics

DIC, disseminated intravascular coagulopathy; IQR, interquartile range; TLS, tumor lysis syndrome
Characteristics	All (N = 779)	No leukapheresis (n = 666)	Leukapheresis (n = 113)	p value
Median age, years (IQR)	55 (41–66)	55 (42–66)	55 (38–65)	0.459
Median WBC (IQR)	110 × 109/L (77–170)	103 × 109/L (73–152)	175 × 109/L (127─246)	< 0.001
Favorable cytogenetic risk	23.6%	27.6%	2%	< 0.001
Intermediate cytogenetic risk	59.8%	56.5%	77.2%	< 0.001
Unfavorable cytogenetic risk	16.6%	15.9%	20.8%	< 0.001
Leukostasis	27.2%	22.1%,	55.9%	< 0.001
TLS	28.2%	29.3%	20.8%	0.09
DIC	18.2%	17.8%	20.4%	0.566

Results³

• Short- and long-term outcomes were analyzed in the entire population and by treatment groups. The results are reported in Table 2
• For patients without clinical leukostasis vs patients with leukostasis, median OS was 15.1 months (95% CI, 13.4–17.4) vs 7.4 months (95% CI, 3.9–9.8; p < 0.0001)
• The median OS
  • for patients > 55 vs ≤ 55 years was 6.6 months (95% CI, 5.4–8.6) vs 23 months (95% CI, 17.8–32.8, p < 0.0001), respectively
  • for patients > 65 years with hyperleukocytosis was only 4.5 months (95% CI, 2.7–7.1) vs 16.2 months (95% CI, 14.1–20.6; p < 0.0001) for patients ≤ 65 years with hyperleukocytosis
• 30-day survival probability:
  • 0.745 vs 0.918 (p < 0.0001) in patients > 55 vs ≤ 55 years, respectively
  • 0.692 vs 0.885 (p < 0.0001) in patients > 65 vs ≤ 65 years, respectively

 Table 2. Clinical outcomes

CI, confidence interval; CR, complete response; CRi, complete response with incomplete count recovery; IQR, interquartile range; PR, partial response; OS, overall survival
Outcomes	All	No leukapheresis	Leukapheresis	p value
Death in the first 30 days	16.7%	17.3%	13.2%	0.329
Response CR CRi PR No response	50.4% 13.7% 3.8% 32.1%	51.5% 12.8% 3.2% 32.5%	43.5% 19.4% 7.4% 29.6%	0.036
Median duration of CR, days (IQR)	202 (114─363)	208 (133─368)	171 (78─280)	0.192
Relapse	42.6%	38.8%	63.8%	< 0.001
Median OS, months (95% CI)	12.6 (11.5─14.9)	12 (10.4─13.9)	18.8 (13.3─32.5)	0.07

• Predictors of 30-day mortality
  • age ≥ 55 years (odds ratios [OR] = 4.37; p < 0.001)
  • presence of clinical leukostasis (OR = 3.59; p < 0.001)
• Predictors of OS
  • age ≥ 55 years (HR = 2.67; p < 0.001)
  • presence of clinical leukostasis (HR = 1.59; p < 0.001)
• Predictors of CR/CRi
  • age ≥ 55 years (OR = 0.24; p <0.001)
  • poor cytogenetics (OR = 0.48; p = 0.004)
  • leukostasis (OR = 0.37; p < 0.001)
• A subgroup of patients with clinical evidence of leukostasis (investigator adjudicated), showed better outcomes with leukapheresis vs no leukapheresis:
  • 30-day mortality, 19.3% vs 36.1% (p = 0.026)
  • median OS, 12 months vs 4.4 months (p = 0.044)

Conclusions³

The results of this study, from one of the largest cohorts of patients with AML and hyperleukocytosis, showed that

• leukostasis was associated with poor outcomes
• older patients had worse OS and 30-days survival probability
• non-significant impact of leukapheresis on 30-day mortality, achievement of CR, or OS
  • a subgroup of patients with leukostasis showed significant improvement in 30-day mortality and OS with leukapheresis

The definition of leukostasis is one limitation of this study. Due to the absence of diagnostic tests, leukostasis was defined by the investigators based on clinical symptoms, thus patients might have been incorrectly assigned to this group. Because of this issue, plus the small number of patients with leukostasis, the benefit of leukapheresis on the short and long-term clinical outcomes of this sub-population was not well defined. Randomized studies are needed to define the impact of leukapheresis on the outcome of patients with AML and hyperleukocytosis.