Leukapheresis in acute myeloid leukemia patients with hyperleukocytosis: A single center experience

doi:10.1016/j.transci.2015.03.015

Transfusion and Apheresis Science

Volume 53, Issue 2, October 2015, Pages 185-190

https://doi.org/10.1016/j.transci.2015.03.015 Get rights and content

Abstract

Hyperleukocytosis is defined as WBC count above 100,000/mm³ in peripheral blood. Increased WBC count leads to leukocyte aggregation, increased blood viscosity, and consequently results in stasis in small blood vessels. Ultimate neurological, pulmonary, gastrointestinal complications, coagulopathy, and tumor lysis syndrome cause increase in morbidity and mortality. Leukapheresis is a treatment modality used for hyperleukocytosis. In patients presenting with hyperleukocytosis the indications for leukapheresis were accepted as having symptoms of leukostasis and prophylactic. Indications for leukapheresis in prophylactic group evaluated according to WBC count. We report a single center experience about leukapheresis in managing 31 AML patients with hyperleukocytosis. In addition to demographic characteristics, disease-related clinical and laboratory findings of the patients were recorded. Survival rates were also calculated. Ten patients were female. The most common of AML subtype was AML-M2. The median number of leukapheresis per patient was 2 and totally 60 leukapheresis cycles were performed in all patients. There was a significant decrease in WBC count and LDH level after leukapheresis as compared with the baseline values (p < 0.05). Early and total mortality were 16.1% and 58.0%, respectively. Alive and died patients were evaluated according to baseline WBC, LDH; increased WBC count and LDH level were found in died patients (p < 0.05). According to leukapheresis indications, patients were divided into two groups: 14 patients in symptomatic leukostasis, 17 patients in prophylaxis. No statistically significant differences were noted between both groups in leukapheresis effectiveness, mean survival time, early and total mortality rate (p > 0.05). None of our patients suffered serious side effects and tumor lysis syndrome during or after apheresis. Leukapheresis is an effective and safe approach to reduce WBC counts in patients with AML with hyperleukocytosis. Further evidence-based data obtained from larger sample sizes are required to better understand the impact of prophylaxis leukapheresis on early and total mortality of AML patients with hyperleukocytosis.

Introduction

Hyperleukocytosis, which is among the medical emergencies, is defined as a peripheral blood leukocyte count higher than 100,000/mm³ [1]. Increased leukocyte count leads to leukocyte aggregation, increased blood viscosity, and consequently results in stasis in small blood vessels. Ultimate neurological, pulmonary, and gastrointestinal complications, coagulopathy, and tumor lysis syndrome cause increase in morbidity and mortality [2]. Tumor lysis syndrome, which occurs due to rapid cellular destruction, manifests with fever, hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia. Renal insufficiency, cardiac arrhythmias, disseminated intravascular coagulopathy, hemorrhage, multi-organ failure, and early deaths may also be seen [2], [3].

In hematological malignancies, hyperleukocytosis is encountered at a rate of between 5% and 30%. Leukostasis can occur with a leukocyte count of less than 50,000/mm³ in certain leukemia subtypes [2], [3]. In patients presenting with hyperleukocytosis the indications for leukapheresis were accepted as having symptoms of leukostasis (headache, dizziness, stupor, blurred vision, papilledema, tachypnea, dyspnea, lung hypoxia) and prophylactic. It has been reported that critical white blood cell (WBC) count varies according to the type of leukemia in prophylactic group. Serious symptoms can be encountered with a WBC count of 50,000/mm³ in a patient with acute myeloid leukemia (AML-M4, M5), a WBC count of 100,000/mm³ for AMLs other than M3, M4, and M5 [2].

Initial approach for the treatment of hyperleukocytosis includes hydration, allopurinol use to prevent tumor lysis syndrome, and correction of metabolic, coagulation, and electrolyte abnormalities. In addition to these primary treatments, leukapheresis and high-dose chemotherapy are the treatments of choice to reduce the number of circulating leukocytes. Leukapheresis efficiency is defined as the decrease in the leukocyte count after the leukapheresis procedure [3], [4].

In the present study, it was aimed to evaluate characteristics and outcomes of patients with hyperleukocytosis who were diagnosed acute myeloid leukemia and underwent leukapheresis in our hospital from 2006 through 2014.

Section snippets

Methods

Records of 31 patients who were diagnosed acute myeloid leukemia and underwent leukapheresis in our clinic from 2006 through 2014 were evaluated retrospectively. The diagnosis of hyperleukocytosis and AML was made with a peripheral smear, flow cytometry, and bone marrow examination. According to 2014 National Comprehensive Cancer Network (NCCN) Guidelines [5], one patient who had MLL (11q23) translocation was accepted poor risk cytogenetic group, the others in intermediate risk cytogenetic

Results

Apheresis is extraction of a specific component from donated blood, with the remainder returned to the donor. The study included 31 patients. Median age of all patients was 60 (18–83) years old. Ten patients were female. The median number of leukapheresis per patient was 2; totally 60 leukapheresis cycles were performed in 31 patients. Respiratory tract symptoms (n = 6) were the most common presenting symptoms of the patients. There was a significant decrease in WBC count and LDH level after

Discussion

Therapeutic leukapheresis is recommended by the American Society for Apheresis in patients with symptoms of leukostasis and WBC count of >100,000/mm³ [6]. The role of prophylactic leukapheresis before appearance of clinical symptoms is debatable. Pastore et al. [7] retrospectively evaluated leukapheresis in 52 patients (median age 60 years) with hyperleukocytic AML with and without clinical signs of leukostasis. Twenty patients received leukapheresis in combination to chemotherapy compared to

Conclusion

Leukapheresis is an effective and safe approach to reduce WBC counts in patients with AML and hyperleukocytosis. Further evidence-based data obtained from larger sample sizes are required to better understand the impact of prophylaxis leukapheresis on early and total mortality of AML patients with hyperleukocytosis.

Contributions

This report reflects the opinion of the authors and does not represent the official position of any institution or sponsor. IB was responsible for reviewing previous research, journal hand searching, and drafting the report. MK, IN, MO, SB were responsible for provision of published trial bibliographies, and preparing photographs. MAE, HG, EK, IK contributed to the final draft of the manuscript and analysis of relevant data. IB were responsible for project coordination. All authors read and

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The management of hyperleukocytosis or thrombocytosis by therapeutic cytapheresis in the early 21 st century is far from codified (universal). Therapeutic cytapheresis have been proposed to achieve more rapid cytoreduction in peripheral blood than old universal support in order to quickly prevent potential complications. But, there are no randomized studies demonstrating the superiority of cytapheresis over other treatments alone. In this short review, based on our own experience (since 1980), we will give the indications and the role of cytapheresis procedures and we will try to answer the questions: when is therapeutic cytapheresis appropriate and do they still have a place in 2020, especially as a medical emergency?
Leukapheresis do not improve early death rates in acute myeloid leukemia patients with hyperleukocytosis
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Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm [3] in peripheral blood [1].
Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm³ in peripheral blood. It has been already shown in the literature that leukapheresis, a conventional technique to decrease the serum WBC level, is ineffective for long-term survival in cases of hyperleukocytotic acute myeloid leukemia (AML) with leukostasis. However, the effect of leukapheresis on early mortality is still unclear. In this study, we aimed to evaluate the effect of leukapheresis on early mortality of patients with AML who have HL. Twenty-eight de novo patients with AML, diagnosed with HL between 2002 and 2015 at the Hacettepe Hematology Department, were analyzed retrospectively. Leukapheresis was performed in 10 patients, and the mean WBC decrease with leukapheresis was 57.4 × 10³/μl which accounts for 31% of the initial WBC count. The indications for leukapheresis were hyperviscosity and prophylaxis in four and six patients, respectively. In the group of patients who received leukapheresis, three of four patients who had hyperviscosity symptoms died, and three of six patients died who did not have symptoms. In our study, we observed that the leukapheresis procedure is highly effective in reducing plasma WBC levels. However, although it is statistically insignificant, our findings also revealed that there is a much higher rate of death in patients who were treated with leukapheresis. Therefore we conclude that leukapheresis does not lower rates of early death; nevertheless, this finding should be confirmed by prospective studies with larger cohorts.
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No significant changes in the coagulating parameters were observed. The efficacy of leukapheresis to reduce the number of WBC and peripheral blasts has been shown in several studies [3–7,17]. As the majority of leukemia burden is located in the bone marrow, these cells can be mobilized in the peripheral blood after leukapheresis.
Hyperleukocytosis is present in 5 to 20 percent of patients with newly diagnosed acute myeloid leukemia (AML). The management of hyperleukocytosis, when symptoms of leukostasis occur, includes intensive supportive care and interventions for rapid cytoreduction. Leukapheresis is a rapid and effective means of cytoreduction and has been used in AML patients. In the current study, we evaluated the outcomes of 68 newly diagnosed AML patients that underwent leukapheresis and the effects of leukapheresis on various laboratory parameters. A total of 127 leukapheresis cycles were performed. The median number of leukapheresis cycles was 2 (range, 1–8). The overall survival for all patients was 4.2 months (95% CI 1.2–9.7 months). The median overall survival for patients who achieved complete remission after induction chemotherapy was significantly higher (19.1 months [95% CI 12.1–41.8 months]) than patients that did not achieve complete remission (0.46 months [95% CI 0.33–0.99 months]). Stepwise logistic regression demonstrated that elevated number of peripheral blasts, low platelet count and elevated bilirubin at AML diagnosis were predictive of death within a week. Leukapheresis was effective in reducing the peripheral blood leukocytes and leukemia blasts and was a safe procedure with regard to organ function, coagulation parameters, red blood cells and platelet count. The high initial response rates in newly diagnosed AML patients fit to receive intensive chemotherapy suggest that leukapheresis could be beneficial in reducing the complications associated with hyperleukocytosis until systemic intensive chemotherapy commences.
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Leukapheresis in acute myeloid leukemia patients with hyperleukocytosis: A single center experience

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Contributions

Blood Rev

Transfus Apher Sci

Leuk Res

Hyperleukocytosis: emergency management

Indian J Pediatr

Acute leukemia with a very high leukocyte count: confronting a medical emergency

Cleve Clin J Med

Leukocytoreduction for acute leukemia

Ther Apher

According to 2014 National Comprehensive Cancer Network (NCCN) guidelines

Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue

J Clin Apher

The role of therapeutic leukapheresis in hyperleukocytotic AML

PLoS ONE

Therapeutic and prophylactic leukapheresis in hyperleukocytositic leukaemias; our experiences

İnönü Üniversitesi Tıp Fakültesi Dergisi

Hyperleukocytosis and leukocytapheresis in acute leukaemias: experience from a single centre and review of the literature of leukocytapheresis in acute myeloid leukaemia

Transfus Med

Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis

Ann Hematol