Leukapheresis and cranial irradiation in patients with hyperleukocytic acute myeloid leukemia: No impact on early mortality and intracranial hemorrhage

Abstract

To assess the role of leukapheresis and cranial irradiation in reducing the incidence of intracranial hemorrhage (ICH) and early death in patients with hyperleukocytic acute myeloid leukemia (AML) and the impact of such treatment on survival. This study retrospectively analyzed the records of 75 patients with hyperleukocytic AML who had a white cell count over 100,000/lL. All patients had de novo AML except for two with therapy-related AML. Various factors were assessed for their impact on morbidity and mortality, particularly the role of pre-induction leukapharesis and cranial irradiation. The most significant risk factors for ICH were the presence of two or more symptoms of leukostasis (odds ratios [OR] 10.6, 95% CI: 2.67-42.02; P 5 0.001) and respiratory distress (OR 5.41, 95% CI: 1.44-20.32, P 5 0.012). The most significant risk factors for early death were age ‡ 65 (OR 4.21, 95% CI: 1.45-12.21, P 5 0.008), respiratory failure (OR 3.34, 95% CI: 1.24-9.50, P 5 0.018), and two or more symptoms (OR 3.50 95% CI: 1.16-10.52, P 5 0.026). Neither leukapheresis nor cranial irradiation were significantly associated with a decreased incidence of ICH (P 5 0.349 and 0.378, respectively). Leukapheresis had no significant influence on early death (P 5 0.367). The median survival patients receiving no pretreatment was 10.50 months (range 2.58-18.42) and for those receiving pretreatment 1.50 months (range 0.10-3.16; log-rank test, P 5 0.062). Leukapheresis and cranial irradiation do not improve survival or decrease the incidence of ICH in adults with hyperleukocytic AML. Am. J. Hematol. 82:976-980, 2007. V

Prognostic factors and treatment outcome in 1,516 adult patients with de novo and secondary acute myeloid leukemia in 1999–2009 in 5 hematology intensive care centers in the Czech Republic

“…Firstly, patients with APL in whom WBC count at diagnosis is part of a scoring system assessing the risks of both early mortality and relapse (30). Secondly, patients with hyperleukocytosis (>100x10 9 /L), have a higher risk of early death, leukostasis, tumor lysis syndrome, infection and the leukemic CNS involvement (31)(32)(33)(34)(35). The results of the other analyses of the prognostic value of the initial WBC count in AML patients are inconsistent.…”

Leukocytapheresis for the treatment of hyperleukocytosis secondary to acute leukemia

“…7,11 Additional leukocytapheresis procedures may be undertaken if clinically indicated to improve symptoms of leukostasis. 16,17 Adverse reactions Citrate (acid citrate dextrose) is the anticoagulant most commonly used to prevent clotting of the apheresis circuit. The advantage of using citrate over heparin is that it is rapidly metabolized and thus avoids prolonged anticoagulation.…”

“…21 Several studies have evaluated the impact on morbidity and mortality of the use of leukocytapheresis in the treatment of acute leukemias, but have yielded conflicting results. 1,17,[22][23][24][25] For example, Giles et al 22 published a retrospective study of 146 patients with newly diagnosed AML, of whom 71 underwent leukocytapheresis. Although the 2-week mortality rate was reduced in leukocytapheresis patients, there was no effect on long-term survival.…”

Clinical Reasoning: A 69-year-old man with leukocytosis and hemorrhagic brain lesions

“…[3][4][5] Patients with respiratory distress or neurologic compromise have a poorer prognosis. 2,4 In 1 study, the presence of both respiratory and neurologic symptoms had an early mortality rate approaching 90%. 6 Prompt cytoreduction can be achieved with hydroxyurea, induction chemotherapy, or leukapheresis.…”

“…Although leukapheresis can effectively reduce the leukocyte count, treatment may not change patients' overall mortality or reverse the clinical consequences of leukostasis. 2,4 Leukapheresis may lower the risk of early death in patients with AML and hyperleukocytosis. 5 In this case, the presence of intracranial hemorrhage in the setting of hyperleukocytosis was suggestive of leukostatic ischemic infarcts with hemorrhagic transformation, but the patient continued to deteriorate despite successful cytoreduction.…”