Hyperleukocytosis and Leukostasis in Hematologic Malignancies

Hyperleukocytosis and leukostasis in hematologic malignancies
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Author
Charles A Schiffer, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Rebecca F Connor, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2016. | This topic last updated: Mar 22, 2016.
INTRODUCTION Hyperleukocytosis refers to a laboratory abnormality that has been variably defined as a
total leukemia blood cell count greater than 50 x 109/L (50,000/microL) or 100 x 109/L (100,000/microL). In
contrast, leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen
in patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) in blast crisis. It is
characterized by an extremely elevated blast cell count and symptoms of decreased tissue perfusion.
Leukostasis is a pathologic diagnosis in which white cell plugs are seen in the microvasculature. Clinically,
leukostasis is typically diagnosed empirically when a patient with leukemia and hyperleukocytosis presents with
respiratory or neurological distress. Prompt treatment is indicated since, if left untreated, the one-week mortality
rate is approximately 20 to 40 percent.
The epidemiology, clinical presentation, diagnosis, and management of hyperleukocytosis and leukostasis in
hematologic malignancies will be reviewed here. Other complications of leukemia are presented separately. (See
"Overview of the complications of acute myeloid leukemia" and "Overview of the complications of chronic
lymphocytic leukemia".)
EPIDEMIOLOGY The incidence of hyperleukocytosis and leukostasis vary by leukemia type and patient
population. In general, symptoms of leukostasis are more common in leukemias with large, poorly deformable
blasts, such as acute myeloid leukemia.
Acute myeloid leukemia Hyperleukocytosis is present in 10 to 20 percent of patients with newly

diagnosed acute myeloid leukemia (AML). It is more common in patients with myelomonocytic (FAB-M4)
leukemia, monocytic (FAB-M5) leukemia, or the microgranular variant of acute promyelocytic leukemia
(FAB-M3) [1,2]. Symptoms of leukostasis occur less frequently and typically affect patients with white blood
cell (WBC) counts over 100 x 109/L (100,000/microL).
Acute lymphoblastic leukemia Hyperleukocytosis is seen in 10 to 30 percent of patients with newly
diagnosed acute lymphoblastic leukemia (ALL) [3]. The incidence appears to be highest in infants, patients
between the ages of 10 and 20 years, males, and those with a T cell phenotype [3,4]. Symptoms of
leukostasis are rarely seen in patients with ALL and hyperleukocytosis. Tumor lysis syndrome and
disseminated intravascular coagulation are more common complications related to the elevated WBC
count.
Chronic lymphocytic leukemia A significant proportion of patients with chronic lymphocytic leukemia (CLL)
present with hyperleukocytosis. Symptoms of leukostasis are rare unless the WBC count exceeds 400 x
109/L (400,000/microL).
Chronic myeloid leukemia Patients with chronic myeloid leukemia (CML) typically present with
leukocytosis and a median WBC count of approximately 100 x 109/L (100,000/microL). Most often, these
are segmented neutrophils, metamyelocytes, and myelocytes. Symptoms of leukostasis are very
uncommon in patients in chronic phase but can be seen occasionally in patients with myeloid blast crisis
and very elevated blast counts.
PATHOPHYSIOLOGY OF LEUKOSTASIS The pathophysiology of leukostasis is not well understood. There

are two main theories, which are not mutually exclusive:
Leukostasis may be due to increased blood viscosity as a direct complication of a large population of
leukemic blasts that are considerably less deformable than mature leukocytes [5,6]. With increasing blast
counts, plugs of these more rigid cells can develop in the microcirculation, thereby impeding blood flow
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(leukostasis) [1,7]. This situation can be worsened by red blood cell transfusions or the use of diuretics,
both of which can increase whole blood viscosity.
Local hypoxemia may be exacerbated by the high metabolic activity of the dividing blasts and the
associated production of various cytokines [8,9]. These cytokines can result in endothelial damage and
subsequent hemorrhage that add to the hypoxic damage already present from reduced blood flow [8,9].
Leukemic blasts can migrate into the surrounding tissues, causing additional damage [10]. Thus, the lower
incidence of clinically significant leukostasis and vascular injury in patients with chronic lymphocytic
leukemia (CLL) and acute lymphoblastic leukemia (ALL) may be related to the lower metabolic and mitotic
rate in the former and the lack of catabolic enzymes and cytokines in both.
It is likely that both of these mechanisms, and additional yet unidentified mechanisms, are involved in the
development of leukostasis. In vitro studies have demonstrated a dramatic rise in viscosity when leukocyte
suspensions exceed a fractional volume of leukocytes (ie, leukocrit) of 12 to 15 mL/dL [11]. Attainment of such a
high leukocrit requires an acute myeloid leukemia (AML) blast count of approximately 300 x 109/L
(300,000/microL) or an ALL blast count of approximately 600 x 109/L (600,000/microL). This observation is
consistent with the increased incidence of leukostasis in AML compared with ALL. It also suggests that factors
other than white blood cell count are important in the pathogenesis of leukostasis, since symptoms of leukostasis
commonly occur at blast concentrations below these predicted thresholds.
SIGNS AND SYMPTOMS Although pathologic evidence of leukostasis can be found in most organs in
patients with extremely high white blood cell (WBC) counts, the main clinical symptoms of leukostasis and
causes of early death are related to involvement of the central nervous system (approximately 40 percent) and
lungs (approximately 30 percent) [1,3,7].
Pulmonary signs and symptoms include dyspnea and hypoxia with or without diffuse interstitial or alveolar
infiltrates on imaging studies. Measurement of the arterial pO2 can be falsely decreased in patients with
hyperleukocytosis, since the WBCs in the test tube utilize oxygen. Pulse oximetry provides a more accurate
assessment of O2 saturation in this setting. (See 'Laboratory abnormalities' below.)
Neurological signs and symptoms include visual changes, headache, dizziness, tinnitus, gait instability,
confusion, somnolence, and, occasionally, coma. In addition, patients who present with hyperleukocytosis
have an increased risk of intracranial hemorrhage that persists for at least a week after the reduction of
white cell count, perhaps from a reperfusion injury as areas of the brain that were ischemic from leukostasis
regain blood flow. Because there can be other structural causes of central nervous system (CNS)
symptoms, brain imaging with noncontrasted CT or MRI is indicated in patients with neurologic
abnormalities. Clinicians must be cautious about using intravenous contrast dye at a time when renal
function may be compromised by leukostasis or tumor lysis syndrome, and dehydration.
Approximately 80 percent of patients with leukostasis are febrile, which may be due to inflammation
associated with leukostasis or concurrent infection. Since an infectious cause cannot be easily excluded,
we treat empirically for infection in all such patients. (See "Overview of neutropenic fever syndromes" and
"Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell
transplant recipients (high-risk patients)" and "Treatment and prevention of neutropenic fever syndromes in
adult cancer patients at low risk for complications".)
Less common signs or symptoms of leukostasis include electrocardiographic signs of myocardial ischemia
or right ventricular overload, worsening renal insufficiency, priapism, acute limb ischemia, or bowel
infarction [3].
Occasionally, patients develop dyspnea and worsening hypoxemia following the initiation of chemotherapy due to
the lysis of leukemic cells trapped in the lungs (eg, acute lysis pneumopathy) [12-15].
LABORATORY ABNORMALITIES Hyperleukocytosis may result in laboratory abnormalities, which can be
due to interference with laboratory assays or may be a consequence of the high number of circulating blasts.
Arterial pO2 can be falsely decreased because of the enhanced metabolic activity of the malignant cells,
even when the specimen is appropriately placed on ice during transport to the laboratory. Pulse oximetry
provides a more accurate assessment of O2 saturation.
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The platelet count may be overestimated by automated blood cell counters because fragments of blasts on
blood smear can be mistakenly counted as platelets. A manual platelet count and careful review of the
peripheral smear is appropriate in such settings. (See "Approach to the patient with thrombocytosis",
section on 'Spurious thrombocytosis'.)
Serum potassium can be spuriously elevated due to its release from leukemic blasts during the in vitro
clotting process. Potassium levels measured from heparinized plasma samples, rather than serum, can
circumvent this effect. (See "Causes and evaluation of hyperkalemia in adults", section on
'Pseudohyperkalemia'.)
Disseminated intravascular coagulation (DIC) occurs in up to 40 percent of patients [3]. DIC presents with
various degrees of thrombin generation (eg, decreased fibrinogen) and increased fibrinolysis (eg, elevated
fibrin degradation products and D-dimer). DIC may develop or worsen following chemotherapy. (See
"Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults".)
Spontaneous tumor lysis syndrome (TLS) is present in up to 10 percent of patients with leukostasis [3].
Laboratory evidence of tumor lysis syndrome includes increased elevated serum concentrations of uric
acid, potassium, and phosphate, often accompanied by hypocalcemia. TLS may develop or worsen
following chemotherapy. (See "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations,
etiology and risk factors".)
DIAGNOSIS Leukostasis (symptomatic hyperleukocytosis) is diagnosed empirically when a patient with

leukemia and a white blood cell (WBC) count over 100 x 109/L (100,000/microL) presents with symptoms thought
to be due to tissue hypoxia, most commonly respiratory or neurological distress. The diagnosis requires a high
degree of suspicion, and some patients have pathologically proven leukostasis at WBC counts below this level.
Pathologically, leukostasis is diagnosed when a biopsy of involved tissue demonstrates white cell plugs in the
microvasculature [1,5-7]. A pathologic diagnosis of leukostasis is rarely obtained because of the risks associated
with biopsy of affected tissues.
MANAGEMENT Leukostasis (symptomatic hyperleukocytosis) constitutes a medical emergency, and efforts

should be made to rapidly stabilize the patient and lower the white blood cell count. In most cases, rapid
cytoreduction can be achieved with induction chemotherapy, which should be administered in conjunction with
prophylaxis for tumor lysis syndrome. Because clinical deterioration can sometimes occur rapidly, most clinicians
also advocate prompt initiation of cytoreductive therapy in patients with asymptomatic hyperleukocytosis.
Adequate fluid resuscitation to prevent dehydration and ensure good urine output is important. (See "Tumor lysis
syndrome: Prevention and treatment", section on 'Clinical impact of TLS'.)
Cytoreduction Twenty to 40 percent of patients with symptomatic hyperleukocytosis die within the first week
of presentation [16-22]. The mortality rate appears to be unrelated to the level of the white blood cell count, but
patients with symptoms (eg, respiratory distress or neurological compromise) have a significantly worse
prognosis when compared with patients who have hyperleukocytosis alone.
Cytoreduction can be achieved through the use of chemotherapy (hydroxyurea or remission induction
chemotherapy) or leukapheresis. While both modalities rapidly decrease the circulating white blood cell count,
chemotherapy also destroys leukemia cells in the bone marrow and is the only treatment proven to improve
survival. There have been no prospective trials or large observational studies comparing these two options for
the treatment of hyperleukocytosis and leukostasis.
In general, we propose the following approach to patients with hyperleukocytosis:
For patients with symptomatic or asymptomatic hyperleukocytosis, we suggest initial treatment with
induction chemotherapy rather than hydroxyurea or leukapheresis. This should be accompanied by tumor
lysis syndrome prophylaxis with aggressive hydration and allopurinol. (See 'Induction chemotherapy' below
and "Tumor lysis syndrome: Prevention and treatment", section on 'Clinical impact of TLS'.)
Our preference for induction chemotherapy is primarily based upon the knowledge that such therapy is also
a necessary step toward the successful treatment of patients with leukemia. There is little evidence to
confirm that decreasing the white blood cell (WBC) count alone will reduce the early mortality rate [23]. In
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addition, clinical deterioration may occur even after the WBC count has been significantly reduced.
An exception to this approach may occur in patients who cannot start induction chemotherapy immediately.
Such patients include those who have poor venous access, renal insufficiency, or other severe metabolic
disturbances, and those with delays in initiating prophylaxis for tumor lysis syndrome (TLS). If induction
chemotherapy must be delayed, our approach to hyperleukocytosis depends upon whether or not the
patient is having symptoms of hyperleukocytosis (ie, leukostasis):
For patients without symptoms of leukostasis who must have induction chemotherapy delayed, we suggest
cytoreduction with hydroxyurea rather than leukapheresis. Cytoreduction with hydroxyurea can precipitate
or exacerbate hyperuricemia and occasionally precipitate TLS, therefore such patients also need
intravenous hydration and TLS prophylaxis. (See 'Hydroxyurea' below.)
For patients with symptoms of leukostasis who must have induction chemotherapy delayed, we suggest
initial cytoreduction with leukapheresis in combination with hydroxyurea to lower or stabilize the WBC
count. (See 'Leukapheresis' below.)
The use of these three approaches to cytoreduction is presented in more detail in the following sections.
Induction chemotherapy Induction chemotherapy is an essential component of the successful treatment

of patients with leukemia. In the setting of hyperleukocytosis, induction chemotherapy serves to both rapidly
decrease the circulating WBC count and target the leukemia cells in the bone marrow. Induction therapy typically
substantially reduces the WBC count within 24 hours. Details regarding the administration of induction therapy
are presented separately. (See "Induction therapy for acute myeloid leukemia in younger adults" and "Treatment
of acute myeloid leukemia in older adults" and "Induction therapy for Philadelphia chromosome negative acute
lymphoblastic leukemia in adults".)
Patients with hyperleukocytosis are at higher risk of developing tumor lysis syndrome with induction
chemotherapy. This syndrome is best prevented via appropriate treatment with intravenous hydration to ensure
adequate urine flow, allopurinol or rasburicase to reduce serum uric acid levels, and correction of any electrolyte
disturbances or causes of reversible renal failure. (See "Tumor lysis syndrome: Prevention and treatment",
section on 'Clinical impact of TLS'.)
Hydroxyurea We typically reserve hydroxyurea for patients with asymptomatic hyperleukocytosis who are
unable to receive immediate induction chemotherapy. Hydroxyurea, given at a total dose of 50 to 100 mg/kg per
day orally, reduces the WBC count by 50 to 80 percent within 24 to 48 hours [24]. The usual hydroxyurea dose is
2 to 4 grams orally every 12 hours, which is continued until the WBC count is below 50 x 109/L (50,000/microL).
Side effects of hydroxyurea are usually minimal and are typically limited to patients who are exposed to
hydroxyurea for a prolonged period. Rare complications include fever and abnormal liver function tests.
Hydroxyurea should not be used in pregnancy or in women who are breastfeeding.
Leukapheresis The role of leukapheresis as an adjunct to the treatment of all patients with
hyperleukocytosis is controversial. It is not clear whether survival is improved in patients treated with
leukapheresis when compared with patients who receive cytoreductive chemotherapy promptly.
Although intensive leukapheresis, with procedure times often lasting many hours, has been reported to produce
improvement in pulmonary and central nervous system symptoms, there are theoretical and practical limitations
to its benefits. It is precisely the patient in whom leukostasis is most likely to occur, that is, the patient with a high
and rapidly rising blast count, in whom the technical limitations of leukapheresis are relevant. It is often difficult,
even with highly efficient cell separators, to reduce the rapidly rising count. Cycle-specific chemotherapeutic
agents (eg, induction chemotherapy) are more likely to be the most rapidly effective.
Although some clinicians advocate its use for patients with asymptomatic hyperleukocytosis, we typically reserve
leukapheresis for patients with symptomatic hyperleukocytosis who must have induction chemotherapy
postponed. Our preference to reserve leukapheresis for this selected patient population is primarily based upon
the known risks associated with leukapheresis described below and an unclear benefit. Anecdotal reports have
claimed dramatic responses [25-29], but larger retrospective analyses have demonstrated conflicting effects on
early mortality rates [19,22,30]. Given the paucity of data concerning the efficacy of leukapheresis in reducing
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early mortality and/or improving overall survival, leukapheresis cannot be recommended for routine therapy as a
form of tumor "debulking" in patients with high blast counts.
However, patients with symptomatic leukocytosis have an extremely high mortality rate without immediate
therapy [16-22]. When both respiratory failure and neurologic compromise are present, the death rate at one
week reaches 90 percent [22]. Therefore, if facilities are available, we suggest leukapheresis for patients with
leukemic blast counts greater than 50 to 100 x 109/L (50 to 100,000/microL) and associated symptoms as a
temporizing measure until chemotherapy can be initiated. It is difficult to predict the percent leukocyte count
reduction in individual patients, but sessions are usually planned for four- to five-hour collections with repeat
sessions as needed.
It is generally agreed that leukapheresis should not be used for patients with acute promyelocytic leukemia
because it may worsen the intrinsic coagulopathy associated with this subtype of leukemia [2]. Placement of
large intravenous leukapheresis catheters in these patients has been associated with venous thrombosis or
hemorrhage. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in
adults", section on 'Disseminated intravascular coagulation'.)
Additional considerations include:
Leukapheresis usually requires the placement of a large bore, central venous catheter, is only available at
select medical centers, and lacks standardization. The procedure can also be done using antecubital veins
if they are adequate for placement of large bore needles bilaterally.
A small number of platelets are inevitably removed with the leukemic blasts, resulting in worsening
thrombocytopenia.
Some patients require multiple sessions to control their white blood cell (WBC) count, while many others,
presumably those with the most rapidly proliferating acute myeloid leukemia (AML), do not respond to
multiple sessions of leukapheresis [31].
The effect is generally transient with WBC counts typically rebounding after leukapheresis is discontinued
unless chemotherapy is begun.
It is unclear whether leukapheresis can reverse vascular damage already sustained from leukostasis. In
addition, symptomatic leukostasis can still develop after the WBC count has been lowered by
leukapheresis.
Supportive care The following supportive care measures should be considered for all patients with
hyperleukocytosis:
Symptomatic leukostasis can be precipitated by increases in whole blood viscosity following red blood cell
transfusions. Such transfusions should be withheld, if possible, until the blast count is reduced. If a
transfusion is necessary, it should be given slowly, administering a single unit of red blood cells over a few
hours, or during the leukapheresis procedure. Hydration is encouraged and diuretics are discouraged.
Patients with hyperleukocytosis are at risk of tumor lysis syndrome (TLS), although this syndrome is less
common in patients with AML than in those with acute lymphoblastic leukemia (ALL) or Burkitt
leukemia/lymphoma. TLS is best prevented with intravenous hydration to ensure adequate urine flow,
allopurinol to reduce serum uric acid levels, and the correction of any electrolyte disturbances or causes of
reversible renal failure. (See "Tumor lysis syndrome: Prevention and treatment", section on 'Clinical impact
of TLS'.)
Although intravenous hydration is recommended for the management and prevention of tumor lysis
syndrome, care should be taken to avoid overhydration and hypervolemia which could exacerbate
pulmonary symptoms.
Coagulation abnormalities, including disseminated intravascular coagulation (DIC), further increase the risk
of local hemorrhage. Specific treatment aimed at the DIC should be considered. (See "Clinical features,
diagnosis, and treatment of disseminated intravascular coagulation in adults" and "Initial treatment of acute
promyelocytic leukemia in adults", section on 'Control of coagulopathy'.)
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Patients should also receive prophylactic platelet transfusions to maintain a count of greater than 20 to
30,000/microL until the WBC count has been reduced and the clinical situation has been stabilized. The
risk of intracranial hemorrhage is greatest after the WBC count has been markedly reduced, suggesting
that a reperfusion injury may occur when the circulation is restored to previously hypoxemic or ischemic
capillary beds. Thus, aggressive platelet support and correction of coagulopathy should continue for
several weeks during the remission induction period.
In addition, patients with leukostasis often require specialized, symptom-directed supportive care including
mechanical ventilation for respiratory failure and/or stroke. (See "Initial assessment and management of acute
stroke" and "Overview of mechanical ventilation".)
Is there a role for cranial irradiation? Some centers advocate low dose cranial irradiation (eg, 400 cGy in a
single fraction), including treatment of the retina, in order to prevent further proliferation of leukemic cells in
central nervous system sites where drug delivery may theoretically be compromised. However, there are no
comparative studies to determine whether the results with cranial irradiation are superior to those with
chemotherapy alone, and we do not advocate the routine use of cranial irradiation in this setting. Nevertheless, it
could be considered for patients with serious central nervous system symptoms related to leukostasis.
PROGNOSIS The prognostic impact of hyperleukocytosis and leukostasis (symptomatic hyperleukocytosis)
depends upon the type of leukemia (acute myeloid leukemia or acute lymphoblastic leukemia) and the presence
of symptoms.
The initial mortality rate for patients with acute myeloid leukemia (AML) and leukostasis has been estimated at
20 to 40 percent and appears to be unrelated to the severity of the hyperleukocytosis [16-19,22]. If patients
survive the initial period, they tend to have somewhat lower remission rates. Remission durations are also
shorter, possibly because of a larger initial tumor mass, but more likely related to the biology and intrinsic
chemotherapy resistance of the leukemia [16,18].
Risk factors for mortality in patients with AML and hyperleukocytosis were identified in a retrospective analysis
[22]. When compared with patients who lived more than one week after presentation, patients who died within
the first week of presentation had significantly higher rates of coagulopathy (64 versus 18 percent), respiratory
distress (100 versus 15 percent), renal failure (43 versus 29 percent), and neurologic symptoms (64 versus 12
percent) [22].
In patients with acute lymphoblastic leukemia (ALL), hyperleukocytosis is rarely complicated by leukostasis and
the early death rate is less than 5 percent in childhood ALL [4]. The challenge of leukostasis management in ALL
involves preventing tumor lysis syndrome, disseminated intravascular coagulation, and the higher risk of relapse
(approximately 50 percent by four years) [3]. (See "Risk group stratification and prognosis for acute
lymphoblastic leukemia in children and adolescents" and "Clinical features, diagnosis, and treatment of
disseminated intravascular coagulation in adults" and "Tumor lysis syndrome: Prevention and treatment", section
on 'Clinical impact of TLS'.)
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SUMMARY AND RECOMMENDATIONS
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Hyperleukocytosis is a laboratory abnormality that has been variably defined as a total white blood cell
(WBC) count greater than 50 x 109/L (50,000/microL) or 100 x 109/L (100,000/microL). In contrast,
leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency that is most commonly
seen in patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) in blast crisis and is
characterized by an extremely elevated WBC count and symptoms of decreased tissue perfusion.
The main clinical symptoms of leukostasis and causes of early death are related to involvement of the
central nervous system and lungs. (See 'Signs and symptoms' above.)
Clinically, leukostasis is diagnosed empirically when a patient with leukemia and a blast cell count over 50
to 100 x 109/L (100,000/microL) presents with respiratory or neurological distress. (See 'Diagnosis' above.)
The initial management of a patient with hyperleukocytosis is directed at rapid lowering of the WBC count.
(See 'Management' above.)
For patients with symptomatic or asymptomatic hyperleukocytosis, we suggest initial cytoreduction
with induction chemotherapy rather than hydroxyurea or leukapheresis (Grade 2B). (See "Induction
therapy for acute myeloid leukemia in younger adults" and "Treatment of acute myeloid leukemia in
older adults" and "Induction therapy for Philadelphia chromosome negative acute lymphoblastic
leukemia in adults".)
For patients with asymptomatic hyperleukocytosis who must have induction chemotherapy delayed,
we suggest cytoreduction with hydroxyurea rather than leukapheresis (Grade 2C).
For patients with symptoms of leukostasis who must have induction chemotherapy delayed, we
suggest initial leukapheresis in addition to hydroxyurea (if possible) to lower or stabilize the WBC
count (Grade 2C).
The following supportive care measures should be considered for all patients with hyperleukocytosis (see
'Supportive care' above):
Red blood cell transfusions should be withheld, if possible, until the blast count is reduced. If a
transfusion is necessary, it should be administered slowly.
Most patients with hyperleukocytosis are candidates for tumor lysis syndrome prophylaxis with
aggressive intravenous hydration and allopurinol or rasburicase to decrease serum uric acid levels.
(See "Tumor lysis syndrome: Prevention and treatment", section on 'Clinical impact of TLS'.)
Coagulation abnormalities require aggressive treatment with platelet transfusions and coagulation
factors. (See "Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in
adults" and "Initial treatment of acute promyelocytic leukemia in adults", section on 'Control of
coagulopathy'.)
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myeloid leukemia with high white cell counts but does not improve long- term survival. Leuk Lymphoma
2001; 42:67.
31. Thibaut A, Thomas X, Belhabri A, et al. Impact of pre-induction therapy leukapheresis on treatment
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outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis. Ann Hematol 2000;
79:501.
Topic 4522 Version 10.0
Contributor Disclosures
Charles A Schiffer, MD Grant/Research/Clinical Trial Support: Celgene [CLL, myeloma (pomalidomide,

thalidomide)]; Novartis [CML (imatinib, nilotinib)]; Bristol Myers [CML (dasatinib)]; Ariad [CML (ponatinib)];
Cephiad (PCR analytic machine). Data Safety Monitoring Boards: Teva [CML (omacetaxine)]; Ambit [AML
(AC220)]; Pfizer [CML (bosutinib)]; Takeda (MLN4924). Consultant/Advisory Boards: Celgene [CLL, myeloma
(pomalidomide, thalidomide)]; Onconova [MDS (rigosertib)]. Richard A Larson, MD Grant/Research/Clinical
Trial Support: Amgen [leukemia (blinatumomab)]; Astellas [leukemia (gilteritinib)]; Erytech [leukemia
(GRASPALL)]; Ariad [leukemia (ponatinib)]; Novartis [leukemia (nilotinib)]; Ambit Bioscience [leukemia
(quizartinib)]; Daiichi Sankyo [leukemia (quizartinib)]; Celgene [leukemia (AG-221)]. Consultant/Advisory Boards:
Novartis [leukemia (imatinib, nilotinib)]; Ariad [leukemia (ponatinib)]; CVS/Caremark [leukemia (drug prior
authorization program)]; Pfizer [leukemia (gemtuzumab ozogamicin)]; Celgene Data Safety Monitoring Board
[leukemia (azacitidine)]; Bristol Meyers Squibb Data Safety Monitoring Board [leukemia (dasatinib)]; Amgen
[leukemia (blinatumomab)]; Astellas [leukemia (gilteritinib)]; Bayer [leukemia (copanlisib)]; Incyte [leukemia].
Rebecca F Connor, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy
24-May-16 12:01 AM

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