Therapeutic Apheresis and Dialysis 11(2):146–149
doi: 10.1111/j.1744-9987.2007.00417.x
© 2007 International Society for Apheresis
A Case Report of Therapeutic Leukapheresis in an Adult
With Chronic Myelogenous Leukemia Presenting With
Hyperleukocytosis and Leukostasis
Shahzad Shafique,1 Robert Bona,2 and Andre A Kaplan3
1
Department of Internal Medicine, 2Department of Medicine/Division of Hematology-Oncology, and
3
Department of Medicine/Division of Nephrology, University of Connecticut Health Center, Farmington,
CT, USA
Abstract: Hyperleukocytosis (>100 ¥ 109/L) is an uncom-
mon presentation of chronic leukemias. It can present with
a variety of symptoms secondary to leukostasis, a syndrome
caused by the sludging of circulating leukemic blasts in the
microvasculature. The management includes hydration,
cytoreduction, prevention of tumor lysis and, rarely, leuka-
Premature deaths in chronic myeloid leukemia
(CML) can be directly attributed to hyperleukocyto-
sis and its resultant microcirculatory dysfunction, a
phenomenon known as leukostasis, where the sludg-
ing of leukemic blasts in capillary vessels and their
adhesive interactions give rise to deleterious effects.
CASE REPORT
A previously healthy 22 years-old Hispanic male
presented to the emergency department because of
fatigue, blurry vision, decreased hearing and weight
loss.
The patient reported excellent health until eight
weeks before admission when he noticed decreased
hearing in the left ear with no associated headache,
nausea, vomiting or tinnitus. Six weeks later, two
weeks before admission, he also noticed some blurry
vision, difficulty focusing on distant objects and
decrease in exercise tolerance. The patient denied
Received January 2006; revised March 2006.
Address correspondence and reprint requests to Dr Shahzad
Shafique, University of Connecticut, Department of Medicine,
263 Farmington Avenue, Farmington, CT 06030, USA. Email:
drshahzi@yahoo.com
146
pheresis in cases complicated by leukostasis and hypervis-
cosity syndrome. We present a case of severe leukocytosis
complicated by leukostasis in which leukapheresis was
utilized to bring about a rapid reversal of microvascular
sludging. Key Words: Chronic myeloid leukemia, Hyper-
leukocytosis, Leukapheresis, Leukostasis, Roth spot.
any fever, chills or night sweats. Review of systems
was only significant for a 20 pound weight loss over a
period of two months. The patient was not taking any
medications. He had no known drug allergies. He had
a 5 year history of cigarette smoking and reported
drinking approximately 8 beers each weekend night
and several beers each night during the week. He had
a history of cocaine, marijuana and heroin use, but
not recently. His family history was notable for hyper-
tension in the father. On physical examination, he
appeared well and was afebrile with blood pressure
110/70 mm Hg, pulse 82 beats per minute, respiratory
rate 14 per minute and oxygen saturation 98% while
breathing ambient air. His visual fields were intact
and there was no jugular venous distension. His lungs
were clear and cardiac examination revealed a
regular rate and rhythm, and the absence of a
murmur, rub or gallop. His abdomen was diffusely
tender on deep palpation with hepatosplenomegaly.
The bowel sounds were normal and the central
nervous system was intact.
Initial laboratory studies revealed a white blood
cell (WBC) count of 540 ¥ 109/L and differential
count showed 15% neutrophils, 2% lymphocytes,
1% monocytes, 5% eosinophils, 2% basophils, 25%
bands, 28% metamyelocytes, 13% myelocytes, 5%
 Leukapheresis in an Adult with CML
FIG. 1. Roth spots (A), intraretinal hemorrhages (B), blot hemorrhages (C), and disk edema (D) consistent with hyperviscosity syndrome
(courtesy of Jeanine Suchecki, MD).
promyelocytes and 4% blasts. Hematocrit was 21%
and platelet count was 192 ¥ 109/L. Measurements
of his electrolytes, liver-function tests, coagulation
indices, and the level of amylase and lipase were
normal. Uric acid was 10.5 mg/dL. Computed tomog-
raphy of the abdomen revealed hepatomegaly
(20 ¥ 21 cm) and splenomegaly (16 ¥ 21 cm) with no
other abnormalities.
The patient was admitted to the hospital with a
provisional diagnosis of leukemia and a bone
marrow biopsy was planned on the same day. The
patient was started on hydroxyurea, allopurinol and
intravenous fluids to avoid tumor lysis syndrome. A
bone marrow biopsy showed a markedly hypercel-
lular bone marrow with complete replacement by
proliferating granulocytes consistent with chronic
myeloid leukemia. Erythroid precursors were mark-
edly reduced, reticulin was within normal limits and
blast forms were 10%. On the next day, the patient
was started on imatinib 400 mg daily (Gleevec,
Novartis Pharmaceuticals, Basel, Switzerland). Oph-
thalmologic evaluation revealed Roth spots and
© 2007 International Society for Apheresis
147
intraretinal hemorrhages, optic disk edema and blot
hemorrhages consistent with hyperviscosity syn-
drome (Fig. 1). Ear, nose and throat consultation
revealed left sensorineural hearing loss, probably
secondary to ischemia brought on by leukostasis. On
admission day four, the patient developed priapism
when his WBC count was 297 ¥ 109/L and was seen
by urology whose opinion was that, it, too, was likely
secondary to leukostasis. Emergency leukapheresis
was performed on the same day and the priapism
improved quickly. Leukapheresis was performed a
total of six times over the subsequent eight days
resulting in a decrease in his WBC count from
297 ¥ 109/L to 35 ¥ 109/L (Table 1). The hydroxyurea
was stopped two weeks after admission and, after
three weeks, the patient was discharged home on
imatinib 400 mg daily (Gleevec) with a WBC count
of 4.6 ¥ 109/L. On his one month follow up with the
hematology–oncology clinic, he was doing well with
a WBC count of 4.7 ¥ 109/L. On his two month
follow up, his WBC count was 7 ¥ 109/L and he con-
tinued to tolerate the imatinib.
Ther Apher Dial, Vol. 11, No. 2, 2007
148
TABLE 1. Effects of leukapheresis on WBC counts
Leukapheresis Hospital
cycles day
1 4
2 5
3 6
4 7
5 8
6 11
†
¥ 109/L. N/A, not available; WBC, white blood cell.
METHODS
All six leukapheresis treatments were performed
with a Cobe Spectra centrifuge (Gambro BCT, Lake-
wood, CO, USA). Estimated blood volume was 4.2 L
and estimated plasma volume was 3.15 L. Vascular
access was achieved with a subclavian double lumen
catheter. Blood flows were set at 69–90 mL/min and
the total blood volume processed was about 9.7 L per
treatment. The total volume of leukocyte-rich plasma
removed was approximately 750 mL per treatment.
Anticoagulation was provided with Anticoagulant
Citrate Dextrose Formula A (ACD-A; Gambro BCT,
Lakewood, CO, USA), with whole blood ratios
ranging from 12:1 to 18:1. ACD-A solution contains:
dextrose 2.45 g/dL, sodium citrate 2.2 g/dL, citric acid
730 mg/dL, total citrate 21.3 mg/mL and sodium
252 mEq/L. Each treatment took around 2.5 h.
DISCUSSION
Leukostasis associated with large numbers of cir-
culating blasts can be associated with headache,
dizziness, altered mental status and pulmonary insuf-
ficiency. Blasts of the monocytic, myelocytic or
myelomonocytic cell lines are considered the ‘sticki-
est’ (1) resulting in leukostasis, vascular occlusion
and perivascular leukemic infiltration. Release of
lysosomal contents can initiate the coagulation
cascade causing catastrophic microvascular coagula-
tion (1). Involvement of the pulmonary circulation
resulting in acute lung injury is a major complica-
tion. Given that chemotherapy may require a pro-
longed period before becoming effective, peripheral
leukocytosis of 100 ¥ 109/L may be temporarily
managed with high volume leukapheresis. Daily
treatments may be necessary until production of
white blood cells can be controlled. An erythrocyte
sedimentation agent such as hydroxyethyl starch is
recommended to improve WBC harvest and return
of red cells (2).
Ther Apher Dial, Vol. 11, No. 2, 2007
S Shafique et al.
WBC counts† Volume of blood
Pre-apheresis Post-apheresis processed (L)
296.5 195.0 9.7
173.0 N/A 9.7
164.4 N/A 9.7
167.8 N/A 9.7
105.2 92.8 9.7
73.0 35.4 (Day 12) 9.7
In the pediatric population leukapheresis has been
shown to be effective as a cytoreductive procedure
prior to the initiation of chemotherapy and as a treat-
ment for pulmonary symptoms felt to be secondary
to leukostasis (3). Nonetheless, childhood hyper-
leukocytosis has been successfully managed with
intravenous hydration, urinary alkalinization and
allopurinol, providing a median reduction in WBC
count of 81% (range: 66–98.8%) within a median
period of 36 h (range: 12–60 h) (4).
A retrospective review has demonstrated a lack
of correlation between the degree of leukoreduction
and early mortality (5). In 48 procedures, leukapher-
esis reduced pretreatment leukocyte counts by more
than 50% and resulted in post-apheresis WBC
counts of less than 100 ¥ 109/L in 65% of patients
treated. Unfortunately, those patients presenting
with neurological, respiratory or renal complications
had higher early mortality rates than those without
such complications, despite similar initial leukocyte
counts and comparable leukoreductions. In the case
presented here, we document a rapid reversal of
leukostasis-mediated symptoms soon after initiation
of leukapheresis-mediated leukoreduction.
CONCLUSION
Leukapheresis is an effective treatment modality
for the treatment of the hyperviscosity syndrome
associated with leukostasis, for the management of
chronic myeloid leukemia complicated by priapism
and for chronic lymphoid leukemia if conventional
therapy has failed or is contraindicated (1,6).
REFERENCES
1. Kaplan AA. A Practical Guide to Therapeutic Plasma
Exchange. Malden, MA: Blackwell Science, 1999.
2. McLeod BC, Strauss RG, Ciavarella D et al. Management of
hematologic disorders and cancer. J Clin Apher 1993;8:211–30.
© 2007 International Society for Apheresis
 Leukapheresis in an Adult with CML 149

3. Bunin NJ, Kunkel K, Callihan TR. Cytoreductive procedures in
the early management in cases of leukemia and hyperleukocy-
tosis in children. Med Pediatr Oncol 1987;15:232–5.
4. Basade M, Dhar AK, Kulkarni SS et al. Rapid cytoreduction in
childhood leukemic hyperleukocytosis by conservative therapy.
Med Pediatr Oncol 1995;25:204–7.
5. Porcu P, Danielson CF, Orazi A, Heerema NA, Gabig TG,
McCarthy LJ. Therapeutic leukapheresis in hyperleucocytic
leukaemias: lack of correlation between degree of cytoreduc-
tion and early mortality rate. Br J Haematol 1997;98:433–6.
6. Isbister JP. Cytapheresis: the first 25 years. Ther Apher 1997;1:
17–21.

© 2007 International Society for Apheresis Ther Apher Dial, Vol. 11, No. 2, 2007