ORIGINAL ARTICLE
Leukapheresis in Management of Hyperleukocytosis in
Children’s Leukemias
Victoria Gre`ze, MD,* Fanny Chambon, MD,*wz Etienne Merlin, MD,*w
Emmanuelle Rochette, MSc,*w Florentina Isfan, MD,*
Franc¸ois Deme´ocq, MD,*wz and Justyna Kanold, MD*wz
Summary: We describe 16 leukapheresis (LK) procedures per-
formed in 7 children with different types of leukemia and hyper-
leukocytosis. We also provide an analysis of previously published
experiences of pediatric LK. Median age and body weight of
patients were 12.3 years (range, 0.2 to 16.7 y) and 49 kg (range, 5 to
61 kg). Immediate pre-first-LK median white blood cell count was
478 109/L (108 109/L to 988 109/L). All cytoreduction were
performed on Cobe Spectra cell separator. Sixty-eight percent of
procedures were performed with peripheral veins. Extracorporeal
line had been primed with red blood cell for 31% of LK. The
median decrease in white blood cell count after each LK was 33%
(0% to 69%), and overall decrease after completion of LK pro-
cedures was 62% (11% to 94%). Only minor clinical adverse events
and no metabolic complication were attributable to LK. No more
clinical symptom of hyperleukocytosis was observed after com-
pletion of LK procedures. Our findings are consistent with reported
results in other pediatric series: LK is a well-tolerated procedure
that can be safely performed with an experienced pediatric team
even on the smallest children.
Key Words: leukapheresis, hyperleukocytosis, leukostasis, leuke-
mia, children
(J Pediatr Hematol Oncol 2014;36:e513–e517)
A t diagnosis time, 5% to 25% of children with acute
leukemia present with hyperleukocytosis, arbitrarily
defined as a white blood cell (WBC) count >100109/L
and often associated with increased morbidity and mor-
tality.1,2 Leukostasis is one of the predominant manifes-
tations of hyperleukocytosis: high leukocytes level leads to
vascular obstruction and tissue hypoxia. It results from 2
mechanisms: the overcrowding of leukemic blasts in the
microcirculation increasing blood viscosity and the adhe-
sive interactions between blasts and endothelium.3 Leuko-
stasis is a medical emergency because it can lead to organ
damages and it is associated with increased mortality (up to
40% in adult patients).4 Although leukostasis can affect any
organ system, symptoms usually arise from involvement
of pulmonary and cerebral microvasculature leading to
Received for publication February 28, 2014; accepted May 15, 2014.
From the *CHU de Clermont-Ferrand, Centre Régional de Cancér-
ologie et Thérapie Cellulaire Pédiatrique, Hôpital Estaing; wCIC
Inserm 501; and zClermont Université, Université Clermont1,
Faculté de Médecine, Clermont-Ferrand, France.
The authors declare no conflict of interest.
Reprints: Justyna Kanold, MD, CHU de Clermont-Ferrand, Centre
Régional de Cancérologie et Thérapie Cellulaire Pédiatrique, CHU
Estaing, 1 place Lucie-Aubrac, 63003 Clermont-Ferrand Cedex 1,
France (e-mail: jkanold@chu-clermontferrand.fr).
Copyright r 2014 by Lippincott Williams & Wilkins
J Pediatr Hematol Oncol  Volume 36, Number 8, November 2014
respiratory distress and neurological and ophthalmological
disorders.4
Because of risk of organ damage, therapy must be
started quickly to decrease the WBC count. However, early
chemotherapy can worsen lysis syndrome in first place
despite supportive care (aggressive hydratation, rasburi-
case). Therefore, leukapheresis (LK) (apheresis stems from
the Greek to take away or remove) which consists in the
withdrawal of whole blood from the body, WBC being then
concentrated and removed from the blood and the other
constituents being infused back into the patient, allows
reducing mechanically the peripheral WBC count and to
decrease or prevent leukostasis symptoms, limiting tumor
lysis syndrome or disseminated intravascular coagulation.
Because of relatively rare occurrence of major hyper-
leukocytosis in pediatric patients and because of potential
apheresis problems which are specific to children (vascular
access, flow rate difficulties, and metabolic or hemodynamic
problems due to high proportion of patient’s total blood
volume extracted from the intravascular circuit), pediatric
LK reports are anecdotal2,5–8 and most of reports about
LK in hyperleukocytosis concern adult patients.9,10 Here,
we report our monocentric experience in LK on children to
analyze efficiency and tolerance of the method in pediatric
population. We also provide an analysis of previously
published experiences of pediatric LK.
MATERIALS AND METHODS
Patients
All patients with leukemia younger than 18 years who
underwent LK in Clermont-Ferrand University Hospital
Pediatric Department between March 2000 and March
2013 were included in analysis.
LK
All LK procedures were conducted by 2 experienced
pediatric nurses and a pediatrician in a LK room installed
in the pediatric ward. We used a Cobe Spectra separator
(Gambro BcT Inc., Lakewood, CO), under manual control
of the standard MNC program (Program 4.7). Minimal
hemoglobin (Hb) values before starting LK and transfusion
or red blood cell (RBC) priming were according to pre-
viously published algorithm.11 Briefly, the priming of the
extracorporal line with 150 mL of irradiated, CytoMega-
loVirus negative, RBC was reserved for patients with blood
volume of <1 L and/or a Hb level of <100 g/L, but the
decision to prime or not was made on a case by case basis,
the child’s general condition and the anticipated duration of
procedure being of importance. Platelets transfusion was
considered when the preapheresis platelets count was
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Gre`ze et al J Pediatr Hematol Oncol  Volume 36, Number 8, November 2014

ALL indicates acute lymphoblastic leukemia; AML, acute myeloblastic leukemia; B, broviac catheter; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; DIC, disseminated
WBC Extraction
<15 109/L. Citrate glucose formula A (ACD-A) was used

3.1 (1.2-5.8)
as anticoagulant, at a ratio of between 1:12 and 1:15. To
prevent hypocalcemia, 0.5 g/10 kg of calcium gluconate was

(%)
74

69
26
37
22
42
systematically administered 12 hours and 1 hour before LK
starts and every 60 minutes during collection (orally or in
bolus intravenous dose). Hypothermia was prevented in all
patients with woollen blankets and hot-water bottles. Body
WBC Platelets
After Last LK

temperature and diuresis were carefully monitored. As in

Blood Count

323

229
35

39
44

59
—
most patients, a central line was not yet inserted for che-
109/L

motherapy, peripheral access (18- or 22-G intravenous

catheter with wings and injection port; Surflo-W, Terumo,
174

445
407

223
78

39
—
Leuven, Belgium) was privileged. Local anesthesia with
lidocaine-prilocaine (5% EMLA crème; Astra, Paris,
France) was systematically used for peripheral venous
Duration

100; 110;

120; 135

147; 132
125 (95-
(min)

access, together with inhalation of equimolar mixture of

150)
150

160
95
90

nitrous oxide and oxygen (Entonox; Aga Medical, Tou-

louse, France). A temporary femoral or jugular catheter
was used if it was deemed impossible to ensure adequate
Blood Volumes

blood flow with peripheral veins. The femoral/jugular

1.9 (1.4-2.4)
Processed
1.5; 1.4; 1

catheter was not removed until the last LK and continuous

1.7; 1.7

2.0; 1.8

infusion of heparin solution was used to prevent occlusion

1.9

1.9
1.1

of the line. At the start of the procedure the blood flow rate
LK

used was 1 mL/kg/min and was subsequently gradually

adjusted (manual control) to the maximum rate tolerated.
The rate of blood withdrawal that was maintained for the
No.
3

1
2
1
1
2
6

longest duration per LK was considered the procedure flow

rate. Complications related to LK were assessed up to 2
pv20 G/22 G

pv18 G/20 G
pv18 G/20 G

pv22 G/22 G
pv18 G/18 G

hours post-LK with clinical examination and full blood

Venous
Access

pv18 G/B

F/B

F/F

count (1 h post-LK).

RESULTS
Before First LK
WBC Platelets
Blood Count

476

516
26

67
33

14
83

Patients
109/L

Seven children with newly diagnosed different types of

leukemia were concerned, 3 acute lymphoblastic leukemias,
690

255
988
460
108
500
680

1 acute myeloblastic leukemia, 1 chronic myelomonocytic

intravascular coagulation; F, femoral line; G, gauge; LK, leukapheresis; pv, peripheral veins.

leukemia, and 2 chronic myelogenous leukemias. Median

Chemotherapy

age, body weight, and blood volume of the patients were

First LK/

12.3 years (range, 0.2 to 16.7 y), 49 kg (range, 5 to 61 kg),

Interval

 144w
24

24
24
24

24
0
(h)

and 3083 mL (range, 836 to 3799 mL), respectively. At the

time of diagnosis, 4 patients (57%) suffered from symptoms
imputable to hyperleukocytosis (dyspnea, priapism, papil-
TABLE 1. Patients’ Characteristics and Leukaphereses Outcome

ledema, and headache). Immediate pre-first-LK median

WBC, platelet count, and Hb level were 478  109/L (range,
Dyspnea, ocularz
Manifestation*

108 109/L to 988 109/L), 75 109/L (range, 14 109/L to

Priapism, DCI
Clinical

wLeukapheresis performed 144 hours after chemotherapy.

—
—
—
Headache
Dyspnea

zBilateral papillary edema, retinal hemorrhage.

Diagnosis

CMML
AML

CML

CML
ALL

ALL

ALL

*Imputable to leukostasis.
Age (y)/Body
Weight (kg)

0.2/5.0
6.8/23

4.4/20
13.1/61
12.3/50
10.9/27

16.6/49

FIGURE 1. Peripheral blood WBC count during course of leuka-

Patient

pheresis in 3 patients with acute lymphoblastic leukemia and

hyperleukocytosis. LK indicates leukapheresis; WBC, white blood
cells.
1

2
3
4
5
6
7

e514 | www.jpho-online.com r 2014 Lippincott Williams & Wilkins

 r
TABLE 2. Results From Published Cases of Pediatric LK
WBC (109/L)*
J Pediatr Hematol Oncol

No. of Age (y)/ Vascular Blood Volumes



References Patients Weight (kg) Diagnosis Device Access Processed /LK No. LK Before LK After LK Author’s Comments
Haase et al2 2 14/531 AML Cobe Spectra Sheldon 1 patient’s BV 4 302 102 LK together with conservative
5/57 ALL 2.3 patient’s BV 527 312 management and specific oncological
therapy may contribute to rapid
leukocyte reduction with acceptable
risk. There were no procedure-related

2014 Lippincott Williams & Wilkins

adverse events. Symptoms due to
hyperleukocytosis markedly improved
after cytoreduction.
Woloskie et al8 1 0.08/4.5 ALL Cobe Spectra 8 Fr 1 551 116 LK can be safely performed on even the
Quinton smallest children with forethought,
jugular planning, and a multidisciplinary effort
(in a neonatal intensive care unit)
Buba"a et al5 2 15/— CML — — 3250 mL 4 366 140 Rapid cytoreduction, no clinical
17/— 4600 mL 353 180 complications
Veljković et al7 2 16/– CML Cobe Spectra pv 1 patient’s BV 3 320 100 LK is safe and effective (a single LK can
17/— 435 150 reduce the WBC count by 30%-60%)
therapeutic option for patients with:
Volume 36, Number 8, November 2014

WBC count of >300 109/L or

leukostasis (confusion, visual
disturbances, hearing disturbances,
respiratory symptoms, priapism).
Discontinue the LK when the WBC is
<50 109/L-100 109/L and clinical
manifestations are resolved.
Lowe et al6 68 — ALL — 416 (202-1512) WBC reduction: LK may be reserved for patients with
244 (37-1342) extremely high leukocyte counts
(> 400 109/L) and patients who have
leukostasis-related complications at
presentation
This study 7 12.3 (0.2-16.7)/ AML Cobe Spectra pv or F 1.7 patient’s BV 2 (1-6) 500 (108-980) 198 (39-445)
49 (5-61) ALL (1-2.5)
CML

*Before the 1st and after the last LK.

ALL indicates acute lymphoblastic leukemia; AML, acute myeloblastic leukemia; BV, blood volume; CML, chronic myelogenous leukemia; F, femoral line; FR, French; HB, hemoglobin; LK, leukapheresis; pv,
peripheral vein; WBC, white blood cells.

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Pediatric Leukapheresis
Gre`ze et al
554 109/L), and 95 g/L (range, 39 to 118 g/L), respectively.
Patient’s clinical and biological characteristics are detailed
in Table 1.
LK
A total of 16 LK: 1 to 6 for each patient (median 2
LK/patient) were performed. Most of procedures (68%)
were performed with peripheral veins. Extracorporeal line
had been primed with RBC for 5 of 16 LK (31%). Median
duration of LK was 125 minutes (range, 90 to 160 min),
median collection rate 2.25 mL/min (range, 1 to 3.66 mL/
min), and median blood volumes processed 1.7 (range, 1.0
to 2.5). Median collection volume was 8.2 mL/kg (range,
3.4 to 20 mL/kg). Chemotherapy started the day after the
first LK in 6 patients. For the remaining patients (#2),
chemotherapy started first but without any efficiency so LK
began on the sixth day of chemotherapy to initiate the
WBC decrease.
Efficiency
The median decrease in WBC count after each LK was
33% (range, 0% to 69%), and overall decrease in WBC
after completion of LK procedures was 62% (11% to
94%). No more clinical symptoms of hyperleukocytosis
were observed after completion of LK procedures.
Peripheral blood WBC count modifications during course
of LK in 3 patients with acute lymphoblastic leukemia are
shown in Figure 1.
Tolerance
Only minor clinical adverse events: hypotension and
tachycardia, rapidly resolute with symptomatic treatment
were noted in patient #1 during the second LK. The median
platelets drop was 15.4% (range, 0% to 57%) and the
median Hb drop was 2.0 g/L (range,  50 to 20 g/L) (neg-
ative values in patients for whom priming of extracorporeal
volume was performed). Platelets transfusions were per-
formed before or after 5 of 16 LK procedures (31%). RBC
transfusions were performed during or the day before 5 of
16 LK procedures (31%) (Table 1). There was no metabolic
complication attributable to LK.
Long-term Outcome
Two patients (patient #1 and patient #2) are still alive:
6 and 12 months after diagnosis, respectively. Five patients
died: patient #5 from uncontrolled multiorgan failure 1
week after LK and the 4 other patients from relapse or
postbone marrow transplantation complications between
6 and 39 months after LK.
DISCUSSION
Here, we report one of the largest experiences in
pediatric LK in children with leukemia and hyper-
leukocytosis. Because of the small number of pediatric
patients eligible for LK there are only anecdotal reports,
which suggests that this cytoreductive procedure may be
helpful in preventing serious early complications of hyper-
leukocytosis in childhood leukemia.2,5–8
Although there are no clearly formulated guidelines
concerning LK indication in pediatric wards, all authors
agree that patients who have leukostasis-related complica-
tions at diagnosis time are eligible for this procedure. Lowe
et al6 suggest that cytoreduction may be reserved for
patients with extremely high WBC count (> 400  109/L),
whereas Veljković et al7 propose to use LK in patients with
e516 | www.jpho-online.com
J Pediatr Hematol Oncol  Volume 36, Number 8, November 2014
WBC count of >300 109/L. In our experience, LK is
discussed for all patients with WBC count of >100109/L
for preventing complications of stasis. One to 4 LK pro-
cedures per patient are performed in published reports,
however, there is no universally accepted criterion as to a
discontinuation of the LK. Generally, the aim is a marked
reduction of leukocytes, to a “safe” count of <100109/L.
We agree with Veljković et al’s7 recommendation to dis-
continue LK when the total cell count is <50–100109/L
and clinical manifestations are resolved.
In our study, as in Lowe et al’s6 experience, chemo-
therapy was delayed (no more than 24 h) in children who
had LK as compared with those who did not need
cytoreduction.
LK procedures are more difficult in very young and
small (< 15 kg) children due to the technical requirements
of blood cell separators that had been designed for appli-
cation in adults. However, the ability of Cobe Spectra and
more recently of Optia separator to pediatric LK is con-
firmed.2,7,8 Woloskie et al8 showed that these devices allow
safe LK even in the smallest patients (< 8 kg).
Because of the small calibers of peripheral veins, cen-
tral venous access is systematically used by some
authors.2,5,8 This remains a valuable option in very young
children. However, as Veljković et al,7 we recommend to
use peripheral veins whenever possible.
Here, after each of the 16 LK, the median decrease in
WBC count was 33%. The achieved reduction in leukocyte
counts is consistent with reported results in other pediatric
series (20% to 50%).
Tolerance is a crucial issue in a pediatric context. Most
authors agree that LK is well tolerated, with minimal acute
side effects, even in children with a body weight as low as
4.5 kg.8 Given that the main LK-related difficulties
encountered in the smallest patients (vascular access and
metabolic or hemodynamic problems) are strongly
dependent on the experience of the care team, we stress the
importance of having a dedicated pediatric environment
with an experienced team specifically dedicated to pediatric
care, and we recommended to carry out LK in neonatal
intensive care unit with reinforced experienced collection
team.
In summary, although LK has restricted indications
and seems to be obsolete, it is an effective and helpful
technique of cytoreduction that we must not forget, espe-
cially in some circumstances such as clinical leukostasis or
high blood viscosity associated with severe anemia. In
children diagnosed with hyperleukocytic leukemia, LK for
cytoreduction is a well-tolerated procedure that can be
safely performed with an experienced pediatric team even in
the smallest children. Although there is consensus that in
children with leukostasis-related complications LK may be
useful on preventing serious complications, there are no
universally accepted criteria as to the WBC count that
would initiate leukocyte depletion in children without
clinical symptomes of leukostasis (Table 2).
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