Received: 11 January 2017

| Revised: 6 February 2017

| Accepted: 27 February 2017
DOI 10.1002/jca.21534

CONCISE REVIEWS

Extracorporeal photopheresis in pediatric patients:

Practical and technical considerations

Robert A. DeSimone1 | Joseph Schwartz2 | Jennifer Schneiderman3

1
Department of Pathology and Laboratory
Abstract
Medicine, New York-Presbyterian
Hospital-Weill Cornell Medicine, In adults, extracorporeal photopheresis (ECP) is widely utilized for a variety of indi-
New York, New York cations, most commonly cutaneous T-cell lymphoma, acute or chronic graft-versus-
2
Department of Pathology and Cell host disease (GVHD), solid organ transplant rejection, and other autoimmune and T-
Biology, New York-Presbyterian Hospital- cell-mediated disorders. In pediatric patients, the majority of case series and reports
Columbia University Medical Center, have focused on its use in the management of acute and chronic GVHD. Currently
New York, New York utilized ECP technologies were designed for adult patients and there are several chal-
3
Department of Pediatrics, Division of lenges in adapting these technologies for use in children. In our review, we focus on
Hematology/Oncology/Stem Cell
practical considerations and procedural modifications for ECP use in pediatric
Transplantation, Ann & Robert H. Lurie
patients, with special attention to patient safety.
Children’s Hospital of Chicago, Feinberg
School of Medicine, Northwestern
University, Chicago, Illinois KEYWORDS
extracorporeal photopheresis (ECP), graft-versus-host disease (GVHD), pediatrics, therapeutic apheresis
Correspondence
Robert A. DeSimone, M.D., Weill
Cornell Department of Pathology and
Laboratory Medicine, 525 East 68th St.
Starr-1036, New York, NY 10065.
Email: rod9096@nyp.org

1 | INTRODUCTION 2 | ECP DEVICE SELECTION

Apheresis procedures performed on pediatric patients are
often challenging because of these patients’ small sizes and
blood volumes. When planning apheresis procedures in pedi-
atric patients, practitioners must adapt equipment designed
for adults to children, taking into account many details often
considered routine in adults, including placement of an
appropriately sized central line, fluid status, tolerance to
extracorporeal volume, procedure length, anticoagulant
selection and dosing, and overall safe modification of the
procedure.1 Data on the use of extracorporeal photopheresis
(ECP) in particular is limited in pediatric patients because
one of the more commonly used photopheresis systems is
FDA approved only for patients >40 kg.2 Of note, within
published case series to date, there are very few patients
weighing <15 kg. Here, we review ECP’s use in pediatric
patients, with special attention to technical considerations for
safe and efficacious procedures.
AND MODE
ECP is a type of leukocytopheresis. During the procedure, a
small percentage of the patient’s circulating white blood cells
(WBCs) are collected utilizing a centrifuge bowl, subse-
quently incubated with a psoralen compound, and finally,
exposed to ultraviolet A (UVA) light irradiation. The treated
cells are then reinfused into the patient.3 Approved by the
FDA in 1988 for the treatment of cutaneous T-cell lym-
phoma (CTCL), ECP is categorized by the American Society
for Apheresis (ASFA) as a primary, first-line adjunctive or
supportive therapy for CTCL. ASFA also acknowledges
ECP as a second-line therapy, either as a standalone treat-
ment or in conjunction with other therapies, for cellular/
recurrent rejection and rejection prophylaxis in cardiac trans-
plants, as well as acute and chronic graft-versus-host disease
(GVHD).4 Published retrospective experience utilizing ECP
in pediatric patients has focused on the management of acute

J Clin Apher. 2017;1–10 wileyonlinelibrary.com/journal/jca V

C 2017 Wiley Periodicals, Inc. | 1
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and chronic GVHD, most often when refractory to first-line
therapies.2,5–20 No randomized controlled trials investigating
ECP in pediatric patients have been published to-date.
ECP is commonly performed using the UVAR XTS or
CELLEX photopheresis systems (Therakos Inc., Exton, PA),
which are automated. Heparin or acid-citrate-dextrose can be
used as anticoagulants for either system, although both sys-
tems are only officially approved for heparin. For the UVAR
XTS, which is a discontinuous flow, single-needle proce-
dure, 125 mL or 225 mL of whole blood is collected into a
centrifuge bowl; the buffy coat is collected and the remaining
blood components (plasma, red blood cells [RBCs], and pla-
telets) are returned to the patient. Given the discontinuous
nature of procedures performed with this device, 6 cycles
(125 mL bowl) or 3 cycles (225 mL bowl) of whole blood
must be processed to produce a 270 mL mononuclear cell
(MNC) suspension. Following collection, the suspension is
incubated with methoxsalen and pumped through a photoac-
tivation chamber, at which time it is exposed to UVA light
and then reinfused to the patient.21 The general procedure for
the CELLEX is similar to the UVAR XTS, however the
CELLEX is a continuous flow procedure that has both
single-needle and double-needle modes and has only one
size centrifuge bowl; for most patients, 1500 mL of whole
blood is processed. As a result of these differences, the over-
all extracorporeal volume of the CELLEX is significantly
less than the UVAR XTS (216–266 mL for CELLEX
vs.220–620 mL for UVAR XTS), and is therefore better
suited for pediatric patients with less total blood volumes.21
In addition, for the CELLEX, the double-needle mode may
be safer for low-weight patients since this reduces extracor-
poreal volume by 63% relative to the single-needle mode.21
To reduce the risk of hypovolemia and hypotension, we rec-
ommend selecting and adapting ECP technologies to mini-
mize extracorporeal volume to <10–15% of total blood
volume, if possible.
ECP can also be performed in an off-line fashion using
two devices, with a standard cell separator for MNC collec-
tion followed by UVA irradiation, as is the practice in sev-
eral centers in Europe. Options for MNC collection include
the COBE Spectra Apheresis System (Terumo BCT, Lake-
wood, CO), COM.TEC (Fresenius SE & Co., Bad Homburg,
Germany), Amicus (Fenwal, Inc., Lake Zurich, IL), and Hae-
monetics MCS plus (Haemonetics Corp., Braintree, MA).
UVA irradiation can be performed with the UV-MATIC
(Vilber Lourmat, Eberhardzell, Germany), PIT System (Med
Tech Solutions, Modena, Italy), or Theraflex-ECP (Maco-
Pharma, Mouvaux, France). In the United States, this off-line
method has largely fallen out of favor following the develop-
ment of automated systems.22 Of note, many ECP case series
in pediatric patients utilized the COBE Spectra/UV-MATIC
technology (Tables 1 and 2).5–10,13,14,16–18
DESIMONE ET AL.
3 | ECP’S PROPOSED MECHANISM
OF ACTION IN GVHD
GVHD is a multisystem, potentially life-threatening com-
plication of allogeneic hematopoietic stem cell transplanta-
tion. ECP has been shown to be an effective therapy for
both acute and chronic GVHD, and its use has enabled clini-
cians to successfully wean, and in some cases even discon-
tinue, immunosuppressive medications in both adults and
children.19,23–25
ECP’s mechanism of action in GVHD has not been fully
elucidated, but it has been proposed to result in a shift from
an inflammatory (Th1) state to a tolerance (Th2) state, thus
inducing tolerance of donor T lymphocytes to host antigens.
A typical ECP treatment results in reinfusion of approxi-
mately 5 3 109 MNCs; during their photoactivation, mono-
functional and bifunctional DNA adducts form, leading to
MNC apoptosis within 24–48 hours. The apoptotic MNCs
are engulfed by antigen presenting cells, and their antigens
are presented in the context of major histocompatibility com-
plex class I and II.26,27 The downstream effects described in
both GVHD and cardiac transplant include reduced pro-
inflammatory cytokines (IL-2, TNF-a, IFN-g) and increased
anti-inflammatory cytokines (TGF-b) through arginine
metabolism pathways, as well as increased populations of
regulatory T-cells.28,29 The emergence of regulatory T-cell
populations during ECP treatments has been correlated with
clinical response.30 Other proposed mechanisms of action in
GVHD include expansion of memory CD81 T-cells31 and
differentiation of monocytes to immature dendritic cells,32
which then may acquire the ability to secrete IL-10.32,33 In
addition, decreased proportions of immature CD19 1 CD21-
lymphocytes have been correlated with ECP response in
chronic GVHD, highlighting dysregulation of B lymphocytes
as a potential contributing factor.34
4 | FLUID STATUS AND
TRANSFUSION SUPPORT
The majority of pediatric case series utilized a RBC prime
for their low-weight patients (Table 1), but weight cutoffs for
RBC priming varied greatly, ranging from <15 kg to
<40 kg. The manufacturer of UVAR XTS and CELLEX
systems recommends a RBC prime for patients weighing
<35 kg while utilizing the CELLEX to avoid symptomatic
hypovolemia.18 For patients >35 kg, the photopheresis cir-
cuit can be primed with heparinized normal saline. Accord-
ing to consensus recommendations published by the Italian
Society of Hemapheresis and Cell Manipulation and the Ital-
ian Group for Bone Marrow Transplantation, all patients
<20 kg should receive a RBC prime, irrespective of pre-
procedure hematocrit.35 In one retrospective study, fluid
TAB LE 1 Review of patients (indications for extracorporeal photopheresis [ECP], weight, age) blood prime criteria, venous access, and ECP schedule in published pediatric case series

Mean or Mean or Blood

DESIMONE

Total no. Total no. median weight median age in prime

Reference patients procedures Indication in kg (range) yr (range) (Y/N) Venous access Schedule
ET AL.

Halle5 8 254 cGVHD (n 5 8) 37 (18–49) 10 (5–15) N Tunnelized or double-lumen 2/wk for 2 wks, 1/wk or once
central catheter and/or every 2 wk for 3 mo
peripheral access

Salvaneschi6 23 NR aGVHD (n59), 35 (17–89) 10 (5–18) N Double-lumen central catheter aGVHD: 3/wk until
cGVHD (n514) (n 5 20); peripheral access improvement; cGVHD: 2
(n 5 3) consecutive days at 2 wk
interval for 3 mo

Messina7 77 NR aGVHD (n533), aGVHD: 30 9 (0.3–21) N Double-lumen central catheter 2 consecutive d/wk for 1 mo,
cGvHD (n544) (10–85), (n 5 50); peripheral access once every wks for 2 mo, then
cGVHD: 35 (n 5 27) monthly for 3 mo
(15–68)

Calore8 15 NR aGVHD (n515) NR 10 (1–18) Y NR 2 consecutive d/wk for 1 mo,

once every wks for 2 mo, then
monthly for 3 mo

Kanold9 23 750 aGVHD (n59), aGVHD: 48 14 (4–18) N Tunnelized or double-lumen 3/wk for 3 wks, then tapering
cGVHD (n514) (13–68), central catheter and/or
cGVHD: 43 peripheral access
(13–80)

Berger10 25 NR aGVHD (n515), 40 (17–72) aGVHD: 11 N NR 2 consecutive d/wk for 1 mo,

cGVHD (n510) (6–18), once every wks for 2 mo, then
cGVHD: monthly for 3 mo
12 (7–19)

Duzovali11 7 133 cGVHD (n57) 32 (16–89) 10 (8–17) Y, <40 kg Double-lumen central catheter 3-5 d/wk, then tapering

Landolfo12 8 157 GVHD 19 (7–35) NR Y, <20 kg Double-lumen central catheter 2 consecutive d/wk for 1 mo, 2
with or without peripheral consecutive d/wk every 2 wk
access for 2 mo, 2 consecutive d/wk
every mo for 6 mo

Linenberger13 7 287 GVHD median NR median NR Y, <25 kg NR NR

(11–38) (3–14)

Schneiderman14 11 334 cGVHD (n 5 9), 29 (19–39) NR N Single or double-lumen central Variable

GVHD catheter, peripheral access
prophylaxis (n 5 2)
|
3

(continues)
 4
|

TAB LE 1 (continued)

Mean or Mean or Blood

Total no. Total no. median weight median age in prime
Reference patients procedures Indication in kg (range) yr (range) (Y/N) Venous access Schedule
15
Perotti 73 2360 aGVHD (n 5 50), aGVHD: 32 aGVHD: 10 Y, <15 kg Double-lumen central catheter 2-3/wk until improvement, then
cGVHD (n 5 23) (SD 16), (SD 5), (n526); peripheral access tapering
cGVHD: 39 cGVHD 12 (n547)
(SD 17) (SD 4)

Merlin16 12 NR aGVHD (n 5 12) NR 11 (2–18) NR Tunnelized or double-lumen 3/wk for 3 wks, then tapering
central catheter

Gonzalez Vicent17 27 225 aGVHD (n521), 30 (9–77) 10 (1–17) Y, <15 kg Double-lumen central catheter aGVHD: 2 consecutive d/wk
cGVHD (n56) until improvement then
tapering; cGVHD: 2
consecutive d at 2-wk intervals,
then tapering

Rangarajan18 9 385 aGVHD (n 5 1), 49 (19–86) 14 (4–24) Y, <35 kg Double-lumen central catheter 2/wk until improvement, then
cGVHD (n 5 8) tapering

Uygun2 12 194 aGVHD (n 5 6), 28 (7–68) 12 (2–17) Y, <35 kg Double-lumen central catheter 2/wk for 2 mo, 2/wk every 2
cGVHD (n 5 62) (69%), single-lumen central wks for 2 mo, 2/wk every mo
catheter with peripheral access for at leat 1 yr
(10%), peripheral access only
(21%)

Kapadia19 10 440 aGVHD (n 5 5), 32 (22–65) 10 (8–27) Y, <30 kg Double-lumen central catheter, 2 consecutive sessions/wk, then
cGVHD (n 5 5) peripheral access, vortex port tapering

Nelson20 30 NR aGVHD (n 5 30) 26 (7–138) 10 (1–33) NR NR NR

Abbreviations: NR, not reported; cGVHD, chronic graft-versus-host disease; aGHVD, acute graft-versus-host disease; SD, standard deviation; kg, kilograms; yr, years; Y, yes; N, no; wk, weeks; d, days; mo, months.
DESIMONE
ET AL.
T AB L E 2 Review of extracorporeal photopheresis (ECP) procedure length, number and duration of procedures, ECP devices used, transfusion support, and complications in published pediatric
case series
DESIMONE

Median procedure Device used (COBE

ET AL.

length in hh:mm Median number of Median duration Spectra, UVAR

Reference (range) procedures (range) of ECP (range) XTS, CELLEX) RBC transfusions PLT transfusions Complications

Halle5 02:20 (01:00–04:00) 29 (10–66) 9 mo (2–20) COBE Spectra 6/8 patients (23 units total) 2/8 patients Catheter-related
(4 units total) infections (n 5 2, 25%)

Salvaneschi6 NR NR aGVHD: 5 mo COBE Spectra aGVHD 7/9 patients, NR Hypotension (number of

(0.5-13), cGVHD: cGVHD 1/14 patients patients NR)
17 mo (1-32)

Messina7 03:30 aGVHD: 8 cycles aGVHD: 74 d COBE Spectra Threshold to transfuse: Hb All aGVHD patients Mild hypotension
(03:00-04:00) (2–20), cGVHD: NR (8–467); cGVHD: (n 5 44) and UVAR <12 (if <15 kg), all required for first 8 (n 5 21, 27%),
NR XTS (n 5 33) patients with aGVHD; all procedures abdominal pain (n 5 8,
aGVHD patients required 10%)
RBC transfusions for first 8
procedures

Calore8 03:30 NR 171 d (35-311) COBE Spectra Threshold to transfuse: Hb NR Catheter related
(03:00-04:00) <12 (if <15 kg) infection (n 5 1, 7%)

Kanold9 aGVHD: 02:02 24 (10-68) NR COBE Spectra aGVHD 16% required, aGHVD 15% re- Overall (n52, 8%);
(01:01-04:10); cGVHD 7% required; quired, cGVHD stress/unwillingness,
cGVHD: 01:59 <25 kg 16% required, 1.5% paresthesia, pain at site
(01:12-03:40) >25 kg 8% required required; < 25 kg 7% of line placement,
required, >25kg 7% nausea/vomiting,
required general complaints,
fever and/or sepsis,
interrupted sessions

Berger10 03:30 aGVHD: 12 (4-21), COBE Spectra Threshold to transfuse: NR Abdominal pain (20%),
(03:00-04:00) cGVHD: 22 (10-98) (<40kg), UVAR Hb < 9 2 required de novo
XTS (>40 kg) catheter placement (8%)

Duzovali11 03:30 21 (3-31) 3 mo (4 d–6 mo) UVAR XTS Threshold to transfuse: Hb Threshold to Catheter-related
(03:00-04:00) <9; no additional transfuse: infections (n 5 3, 42%),
transfusions required with <20,000/mL; 2 catheters replaced
blood priming 3/7 patients (29%)
12
Landolfo 2:03 (1:55-2:10) NR NR COBE Spectra NR NR NR
(continues)
|
5
 6
|

T AB L E 2 (continued)

Median procedure Device used (COBE

length in hh:mm Median number of Median duration Spectra, UVAR
Reference (range) procedures (range) of ECP (range) XTS, CELLEX) RBC transfusions PLT transfusions Complications

Linenberger13 NR median NR (19–72) median NR (5–16 COBE Spectra (col- 2 RBC units for every 212 total PLT Fever (5%), hypotension
mo) lection) and UVAR/ patient requiring blood transfusions (5%), hypocalcemia
XTS (photoactiva- prime (1 in COBE Spectra, (5%), nausea (4%),
tion) 1 in UVAR/XTS) (40 units catheter occlusion (4%),
total) catheter-related
infections (0.7%)

Schneiderman14 2:58 (1:30-5:03) 15 (7–113) NR UVAR/XTS Median of 5 RBCs/patient
(range 0-14), 9/11 patients
required RBCs; threshold to
transfuse: Hct < 30
(if 25-40 kg), Hct < 35 (if
<25 kg)
2/11 patients Overall in 31% of
(aGVHD); procedure days:
Threshold > 50,000/ tachycardia, dizziness,
mL nausea, vomiting,
hypotension, headache,

Perotti15 NR aGVHD: 18 (12– 24 mo (2–145) COBE Spectra Threshold to transfuse: Threshold to Catheter-related
24), cGVHD: 34 Hb  8 transfuse: 20,000/ infections (n 5 10,
(16–43) mL 14%); chills (n 5 12,
0.5%), abdominal pain
(n 5 7, 0.2%), headache
(n 5 22, 0.9%), fever
(11, 0.4%)

Merlin16 NR 22 (10–56) 4 mo (0.7–9) COBE Spectra NR NR NR

17
Gonzalez Vicent 03:00 (average) 6 (2-25) 30 d (2-442) COBE Spectra NR NR Hypotension (n 5 3,
11%), catheter-related
infections (n 5 3, 11%)

Rangarajan18 1:46 (1:00–3:25) 47 (10–85) 10 mo (1–18) CELLEX Threshold to transfuse:
Hct < 27; 2 patients re-
quired blood prime (1 pa-
tient received 53 RBCs, 1
patient received 10 RBCs);
excluding blood prime, 10
RBCs were given pre-ECP
and 4 RBCs post-ECP
Threshold to Catheter-associated
transfuse: <20,000/ thrombosis (n 5 1,
mL; 3 platelet doses 0.2%), delayed bleeding
given pre-ECP (n 5 1, 0.2%), catheter-
related infections (n 5 4,
1%); 15 (3.9%)
procedures cancelled
(continues)
DESIMONE
ET AL.
 DESIMONE
ET AL.

T AB L E 2 (continued)

Median procedure Device used (COBE

length in hh:mm Median number of Median duration Spectra, UVAR
Reference (range) procedures (range) of ECP (range) XTS, CELLEX) RBC transfusions PLT transfusions Complications
2
Uygun NR 16 (4-36) NR CELLEX Threshold to transfuse: Threshold to Hypotension (n57, 4%),
initially Hct < 27, revised to transfuse: initially palpitation and
Hct <24 <50,000/mL, revised tachycardia (n56, 3%),
to <30,000/mL or increase in purpuric
<50,000/mL with lesions (n54, 2%),
bleeding gastrointestinal bleeding
(n52, 1%), pruritus
(n51, 0.5%),
catheter-related infection
(n51, 0.5%)

Kapadia19 UVAR/XTS: 3:09 UVAR/XTS: 14 8 mo (1-30) UVAR/XTS (n5225 Threshold to Threshold to Line occlusions (n523,
(average), CELLEX: (2-66), CELLEX: 17 procedures) or transfuse: Hct <30 transfuse: <30,000/ 5.2%), alarms (n529,
1:58 (average) (4-71) CELLEX (n5215 mL 7%), hypotension
procedures) (n518, 4%),
hypertension (n56, 2%),
blood products required
(n559, 13%), citrate
toxicity (n56, 1%)

Nelson20 NR NR NR CELLEX NR NR None

Abbreviations: NR, not reported; cGVHD, chronic graft-versus-host disease; aGHVD, acute graft-versus-host disease; hh, hours; mm, minutes; mo, months; d, days; kg, kilograms; RBC, red blood cells; Hb, hemoglobin;
Hct, hematocrit; PLT, platelets.
|
7
8 |
boluses with 5% albumin (for patients <20 kg) or normal
saline (for patients >20 kg) were utilized during the proce-
dures utilizing the UVAR XTS without RBC priming, how-
ever many patients in this study required peri-procedural
transfusion support.14
Published pediatric case series2,5–20 vary widely in their
recommendations for pre-procedural transfusions (Table 2).
For the UVAR XTS and CELLEX systems, the patient’s
hematocrit (Hct) must be >27% in order to program the
machines for effective buffy coat collection. In line with
practices described in these published case series, we recom-
mend a Hct >27% and a platelet count >20,000/mL in non-
bleeding patients or >50,000/mL in bleeding patients prior to
the start of the procedure. Many of the patients described in
these case series required pre- and post-procedural blood
product support, and patients with acute gastrointestinal
GVHD were more likely to require blood products, presum-
ably due to their increased ongoing bleeding. The lowest
weight patients were also more likely to require blood
products.
5 | ACCESS
As with other apheresis procedures, the placement of an
adequately sized, functional line is essential for successful
completion of the procedure. Central line placement and
maintenance are especially challenging in pediatric patients.
Successful ECP procedures have been performed in pediatric
patients using single-or double-lumen central catheters,
peripheral access, and vortex ports (Table 1). Line sizes
should be based on institutional recommendations regarding
patients’ age and weight, as well as ECP manufacturer rec-
ommendations. In our pediatric patients undergoing ECP,
lines with an internal diameter of at least 1.3 mm have been
well-tolerated and successfully used.
6 | ANTICOAGULANT SELECTION
AND DOSING
There are no standardized or evidence-based protocols for
anticoagulant selection and dosing in pediatric patients
undergoing ECP, and practices vary widely among ECP
practitioners. The manufacturer user manuals for the UVAR
XTS and CELLEX only describe the use of heparin as an
anticoagulant solution, without mention of other anticoagu-
lants. At our institution using CELLEX for pediatric patients,
heparin is always selected as the anticoagulant at a dose of
250 units/kg diluted in 500 mL of normal saline, and is
infused at a whole blood:anticoagulant (AC) ratio set at 10:1.
Rutella et al. also published their anticoagulant protocol
for CELLEX use in pediatric patients.22 For patients at a low
risk of bleeding, they select heparin as the anticoagulant at a
DESIMONE ET AL.
dose of 12,500 units in 500 mL normal saline, which is
infused at an AC ratio ranging from 8:1 to 16:1, based on
the platelet count. During the procedures, they adjust their
AC ratio based on the activated clotting time (ACT), which
is maintained at >180 seconds. In their patients at a high
risk of bleeding, the authors use citrate anticoagulation,
infused at an AC ratio ranging from 12:1 to 16:1. In patients
<10 kg, the authors use 5,000 units of heparin, adjusting its
dose based on the ACT. When citrate is used, ionized cal-
cium is checked before and at multiple time points during
the procedure. To correct for hypocalcemia, a 100 mg/mL
calcium gluconate drip is administered at a dose of 0.5–
1 mL/kg. Bleeding risk assessment in pediatric patients is
largely based on clinical judgement as no formally validated
scoring systems exist at this time to predict bleeding.
7 | SCHEDULE AND DURATION
OF ECP TREATMENTS FOR GVHD
The ideal schedule and duration of ECP for management of
GVHD has not been definitively established, and again, there
is great variation in practice. There is some degree of consen-
sus for treatment schedules, especially for acute GVHD, with
a single-day treatment 2–3 times a week (in some practices
performed as consecutive days, and in others with 1–2 day
breaks in between ECP treatments) until clinical improve-
ment, followed by progressive tapering (Table 1). Patients
with chronic GVHD often require treatment for a year or
more. ECP can has been completely discontinued without a
rebound in symptoms,36 but tapering decisions must be indi-
vidualized to patients’ symptoms. In addition, more intensive
schedules consisting of 3–5 treatments per week for chronic
GVHD have not been shown to provide additional benefit.11
To date, clinical trials comparing different treatment sched-
ules have not been performed.
8 | ECP COMPLICATIONS
IN PEDIATRIC PATIENTS
In general, ECP is well-tolerated with few acute side effects.
The most commonly reported adverse effects include hypo-
tensive episodes, mild fever during reinfusion, and lethargy
following the procedure for 1–2 days.37 In the reviewed
pediatric literature,2,5–20 the most commonly reported
adverse events include hypotension (range 0–27%), catheter-
related infections (range 0–42%), and abdominal pain (range
0–20%) (Table 2). In addition, smaller patients (<20 kg)
seemed to be at a greater risk of developing adverse events,
most commonly hypotension, likely related to their extracor-
poreal volume constituting a greater fraction of total blood
volume. We also recently reported an episode of acute
mechanical hemolysis in a 10.6 kg patient, which is a rare
DESIMONE ET AL.
but potentially fatal adverse event.38 The benefits and risks
of ECP, and of having a central line if necessary, must be
carefully weighed and discussed in an interdisciplinary fash-
ion before starting ECP procedures in pediatric patients.
Although this has not been reported, we hypothesize that
centers performing ECP more routinely in pediatric and low-
weight patients with established protocols will have lower
adverse event rates.
9 | CONCLUSIONS
Although case series in pediatric patients have focused on
ECP’s use in GVHD, ECP is a widely-used modality, with
many centers exploring its use in diseases not mentioned or
currently listed as category III indications in the ASFA guide-
lines, including inflammatory bowel diseases, scleroderma,
and pemphigus vulgaris, to name a few.39 Even in adult
patients, health care practitioners are using ECP without fully
understanding its mechanism of action, how to adequately
dose and schedule it, or an appropriate treatment and tapering
schedule. Given these uncertainties with adult patients, even
less is known with regards to pediatric patients. Researchers
must continue to investigate ECP’s mechanism of action to
close the gap in knowledge of these areas, with the ultimate
goal of helping both adult and pediatric practitioners develop
standardized treatment protocols. Further investigation of
ECP’s mechanism of action in various diseases may also lead
to modification of the procedure to further enhance its efficacy
and safety in low-weight patients.
R EF ERE NC ES
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[3] Zic JA, Miller JL, Stricklin GP, et al. The North American expe-
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How to cite this article: DeSimone RA, Schwartz J,
Schneiderman J. Extracorporeal photopheresis in pedi-
atric patients: Practical and technical considerations.
J Clin Apher. 2017;00:1–10. https://doi.org/10.1002/
jca.21534