Pediatr Blood Cancer
Paroxysmal Nocturnal Hemoglobinuria in Pediatric Patients
Kevin J. Curran, MD,1 Nancy A. Kernan, MD,1 Susan E. Prockop, MD,1 Andromachi Scaradavou, MD,1
Trudy N. Small, MD,1 Rachel Kobos, MD,1 Hugo Castro-Malaspina, MD,2 David Araten, MD,3
Donna DiMichele, MD,4 Richard J. O’Reilly, MD,1 and Farid Boulad, MD1*
Background. Paroxysmal nocturnal hemoglobinuria (PNH) is a
rare disease in children. The most significant clinical features of
PNH include: bone marrow failure, intravascular hemolysis, and
thrombosis. To further characterize the clinical presentation and
outcome to treatment we performed a retrospective analysis of
pediatric patients with PNH. Procedure. We reviewed the medical
records of 12 consecutive pediatric patients with PNH diagnosed at
our institution from 1992 to 2010. Results. Presenting clinical symp-
toms included: bone marrow failure (N ¼ 10); gross hemoglobin-
uria with isolated red cell anemia (N ¼ 1); and jaundice, hepatitis,
and isolated thrombocytopenia (N ¼ 1). Immunosuppressive
therapy was the initial treatment for 8 patients. Five patients had
myelodysplastic features without developing excessive blasts or
leukemic transformation. Thrombosis occurred in 6 patients. Five
patients underwent hematopoietic stem cell transplant (HSCT) of
Key words: aplastic anemia; hematopoietic stem cell transplantation; myelodysplastic syndrome; paroxysmal nocturnal
hemoglobinuria; pediatric
INTRODUCTION
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired
clonal hematopoietic stem cell disorder characterized by comple-
ment-mediated hemolysis, thrombosis, and bone marrow failure
[1–3]. Other clinical symptoms include increased susceptibility
to infection, fatigue, headache, dysphagia/esophageal spasms,
abdominal pain, back pain, and male erectile dysfunction [4].
PNH develops subsequent to a mutation in the phosphatidylino-
sitol glycan anchor biosynthesis class A (PIG-A) gene. PIG-A
gene mutation results in the inability of hematopoietic cells to
synthesize glycosyl phosphatidylinositol (GPI), a required anchor
for several cell surface proteins. Lack of GPI-Associated Proteins
(GPI-APs) translates into many of the clinical manifestation found
in PNH.
Pediatric cases of PNH (presentation <18 years) are rare,
accounting for approximately 10% of reported cases [1,5]. Most
reports of pediatric patients with PNH are case reports (1–2
patients) with only two series published in the literature [1,5].
To further define the clinical spectrum and prognosis for children
with PNH we performed a retrospective analysis of 12 pediatric
patients diagnosed with PNH from a single center. This analysis
demonstrates pediatric patients with PNH present with a high
rate of bone marrow failure and without hemoglobinuria. Further-
more, the rate of thrombotic events in pediatric patients with
PNH is similar to the rate seen in adult patients with PNH.
Additionally, pediatric patients with PNH may develop bone
marrow cytogenetic abnormalities, including monosomy 7, but
surprisingly the rate of spontaneous regression is high and
leukemic transformation or formation of excessive blasts is a
rare event. This analysis verifies our understanding of pediatric
PNH, underscores the need for timely diagnosis, and reviews
options for therapeutic treatment including hematopoietic stem
cell transplant (HSCT) and eculizumab, a monoclonal antibody
directed against the complement protein C5.
ß 2011 Wiley Periodicals, Inc.
DOI 10.1002/pbc.23410
Published online in Wiley Online Library
(wileyonlinelibrary.com).
whom 3 patients are alive and disease-free. Three patients received
anti-complement therapy with eculizumab. Two patients died
following complications related to thrombosis and 2 patients
are transfusion independent with stable disease. Conclusion. This
report highlights a high rate of bone marrow failure along with
a low rate of hemoglobinuria at presentation, a high rate of throm-
bosis, and for some patients the spontaneous resolution of myelo-
dysplastic features. Delay in diagnosis is common and we
recommend appropriate PNH testing in all patients with AA,
MDS, unexplained Coombs-negative hemolysis, or thrombosis.
While HSCT remains the only curative option the high prevalence
of hemolysis and thrombosis should warrant the consideration
of early treatment with anti-complement therapy. Pediatr Blood
Cancer ß 2011 Wiley Periodicals, Inc.
METHODS
We reviewed the medical records of pediatric patients with
PNH diagnosed, referred to, or treated at our institution from 1992
to 2010. We restricted our search to patients diagnosed with PNH
before the age of 18. Patient data collected from the medical
record included age, gender, presenting signs and symptoms,
diagnostic work-up, clinical course, laboratory data, treatments
received, and treatment responses. Cases were reviewed with
the approval of the institutional review board at Memorial
Sloan-Kettering Cancer Center (MSKCC).
RESULTS
Clinical Features at Presentation
Twelve patients with PNH diagnosed before the age of 18
were identified (Table I). Year of initial presentation ranged
from 1992 to 2008. There were 8 males and 4 females with a
Additional Supporting Information may be found in the online version
of this article.
1
Department of Pediatrics, Memorial Sloan-Kettering Cancer
Center—Bone Marrow Transplant Service, New York, New York;
2
Department of Medicine, Memorial Sloan-Kettering Cancer
Center—Bone Marrow Transplant Service, New York, New York;
3
Division of Hematology, NYU School of Medicine, and the New
York VA Medical Center, New York, New York; 4Department of
Pediatrics, Weill Cornell Medical College, New York, New York
Conflict of interest: nothing to report.
Donna DiMichele present address is National Heart, Lung and Blood
Institute, National Institutes of Health.
*Correspondence to: Farid Boulad, MD, 1275 York Avenue, New
York, NY 10065. E-mail: bouladf@mskcc.org
Received 2 August 2011; Accepted 30 September 2011
 2 Curran et al.
depletion Eculizumab Outcome

Pt, patient; Pres., presentation; Dx, diagnosis; N/A, not available; AA, aplastic anemia; MDS, myelodysplastic syndrome; Tx, treatment; HSCT, hematopoietic stem cell transplant; ATG,
antithymocyte globulin; PDN, prednisone; CSA, cyclosporine; Dex, dexamethasone; TBI, total body irradiation; Thio, thiotepa; Cy, cyclophosphamide; Bu, busulfan; Mel, melphalan, Flu,
fludarabine; M-URD, matched unrelated donor; MRD, matched-related donor; MM-URD, mismatched unrelated donor; Ecu, eculizumab. Location of patient thrombosis: a—portal vein
thrombosis; b—left hepatic vein thrombosis, portal vein thrombosis; c—IVC/renal vein thrombosis, transverse/sigmoid sinus thrombosis; d—sagittal sinus thrombosis, IVC thrombosis,
mesenteric vein thrombosis; e—left upper lobe pulmonary embolus, right caudate infarct; f—hepatic vein thrombosis, IVC thrombosis, portal vein thrombosis, right subclavian vein thrombosis,
median age at presentation of 13 years (range 3–17 years). PNH

Alive

Alive

Alive
Alive

Alive
Alive
Alive
Alive
Dead
Dead
Dead

Dead
was diagnosed at presentation in 2 patients (Pt 5 and Pt 8); within
3 months of presentation for 3 patients (Pt 3, Pt 6, and Pt 7); and
delayed >3 months (range 10–55 months) for the remaining
Yes 7 patients. Acidified serum lysis (Ham Test) and sucrose lysis

Yes

Yes
was the initial method of diagnosis for 2 patients (Pt 2 and
Pt 3; confirmation with flow cytometry) while flow cytometry
was the initial method for diagnosis in the remaining 10 patients.
#1: Bu/Mel/Flu, MM-URD #1: Yes,
MM-URD #2: No
T-cell

During follow up (median 40 months; range 3–174 months), clone

Yes

Yes

Yes

Yes
size did not change significantly (<10% variation) unless the
patient underwent HSCT which resulted in successful eradication
MM-URD of the PNH clone.
M-URD

M-URD
donor

MRD
BMT

Pancytopenia and bone marrow failure was the presenting

clinical findings in 10 patients including 9 with aplastic anemia
(AA) and 1 patient with hypoplastic myelodysplastic syndrome
TBI/Thio/Flu

Mel/Thio/Flu
Conditioning
TBI/Thio/Cy

TBI/Thio/Cy

(MDS; RCMD) with monosomy 7 (Pt 4). One patient (Pt 11)
#2: Thio/Cy

presented with gross hemoglobinuria and isolated red cell anemia.

One patient (Pt 12) presented with jaundice, hepatitis, and isolated
thrombocytopenia. This patient was initially diagnosed as possi-
ble hemophagocytic lymphohistiocytosis (HLH) but subsequent
testing revealed PNH.
Thrombosis HSCT
Yes

Yes

Yes

Yes

Yes

Nine of the 12 patients exhibited signs and symptoms of

anemia including weakness, fatigue, pallor, or shortness of
breath. Five of the 12 patients had signs and symptoms of throm-
Yes (b)

Yes (d)
Yes (a)

Yes (c)

Yes (e)

Yes (f)
No

No
No

No
No
No

bocytopenia including bruising, epistaxis, or subconjunctival

hemorrhage. One patient (Pt 3), who presented with AA, had
thrombosis of the hepatic and portal vein associated with abdom-
ATG/PDN/CSA

ATG/PDN/CSA

ATG/PDN/CSA

ATG/PDN/CSA

AA/MDS Monosomy 7 ATG/PDN/CSA

ATG/PSN/CSA

inal pain and vomiting at presentation.

Observation
(pre-HSCT)

PDN/CSA
ATG/CSA

ATG/CSA
Unknown
Initial Tx

None

Treatment and Clinical Course

The clinical course of the 12 patients is shown in Figure 1.
Immunosuppressive therapy (IST) with equine antithymocyte
AA/MDS Monosomy 7;
AA/MDS Monosomy 7
Cytogenetics
abnormality

AA/MDS Deletion 5q
deletion 7q

globulin (ATG) and cyclosporine (CSA) was the initial treatment

Normal

for 8 of the 10 patients presenting with pancytopenia and bone

marrow failure. Six of these patients also received oral steroids
TABLE I. Characteristics and Treatment of the MSKCC PNH Patients

along with ATG/CSA. Patient 11 presented with gross hemoglo-

binuria and has not required treatment. Patient 12 presented with
AA/MDS
marrow
failure

hepatitis, jaundice, and isolated thrombocytopenia. He was

Bone

AA
AA
AA

AA

AA

AA
No

initially started on dexamethasone and subsequently developed

pancytopenia for which he was started on CSA. Partial response
Gender (months) (%) at Dx.
in Dx. Clone size

with an improvement in all three lineages and a period of trans-

N/A
N/A

N/A

fusion independence was seen in all patients who received IST.

35

85

57

92
90

85
90
65
73

Initial treatment of pancytopenia for 1 patient was unavailable and

1 patient proceeded directly to HSCT.
Evidence of myelodysplasia on bone marrow examination was
Delay

55
12

30

25
29
10
26
2

0
2

3
0

found in 5 patients, all of whom presented with bone marrow

failure and received IST. Briefly, patient 4 presented with hypo-
plastic MDS with monosomy 7, which resolved 4 months after
Female
Female
Female

Female
Male
Male

Male

Male
Male

Male
Male
Male

diagnosis and 2 months following IST. Patient 6 developed mono-

somy 7 and deletion 7q (del 7q) 48 months after presentation and
Age at Pres.

erythroid dysplasia 74 months after diagnosis. Fourteen months

(age at Dx.,

right pulmonary embolus.

12 (17)
15 (16)
13 (13)
12 (15)
12 (12)
16 (17)

11 (11)
13 (13)

16 (18)
17 (20)
16 (17)
years)

following detection of these findings and 70 months following

3 (5)

IST his marrow morphology and cytogenetics reverted to normal.

Patient 8 developed erythroid dysplasia (nuclear/cytoplasmic
asynchrony; dysplastic changes) and megakaryocytic dysplasia
Pt # Yr Pres.
1992
1993
1994
1994
1996
2001

2001
2002

2004
2006
2007
2008

(hypolobulated megakaryocytes) with normal cytogenetics

21 months after initial presentation of AA and underwent
HSCT. Patient 9 developed monosomy 7 thirty-four months after
10
11
12

presentation and erythroid dysplasia 42 months after presentation.

1
2
3
4
5
6

7
8

Pediatr Blood Cancer DOI 10.1002/pbc


1 *
2 *
3 *
4 *
5 *
6 *
Patient
7 *
8 *
* BMF at presentation
9 * PNH diagnosis
Thrombosis
10 *
HSCT
MDS features present
11
MDS features resolved
Eculizumab
12
Death
0 24 48 72 96 120 144 168
Months post presentation
Fig. 1. Clinical course of the MSKCC PNH patients.
Twelve months following detection of these findings and
46 months following IST her marrow morphology and cytogenet-
ics reverted to normal. Patient 10 developed deletion 5q (del 5q)
with a hypocellular marrow 32 months after presentation and
underwent HSCT. The remaining 7 patients did not exhibit any
marrow dysplasia or abnormal cytogenetics on bone marrow
examination over their clinical course. No patient in this cohort
developed excess blast or leukemic transformation.
All patients in this series showed evidence of intravascular
hemolysis (elevated LDH, total bilirubin, and/or reticulocytosis)
during their clinical course. All patients required transfusions
of red blood cells and platelets during their clinical course.
Four patients (Pt 1, Pt 4, Pt 9, and Pt 12) developed significant
red blood cell (RBC) and platelet transfusion requirements
(>12 units/year).
Thrombosis occurred in 6 patients including 4 patients with
multiple sites and/or episodes of thrombosis (Table I). Thrombo-
sis occurred at the time of presentation for 1 patient and subse-
quent to the diagnosis of PNH in an additional 5 patients. In this
latter group, median time to thrombosis following diagnosis of
PNH was 30 months (range 5–88). All 6 patients who developed
thrombosis presented with bone marrow failure of which 5 were
initially treated with IST. Initial therapy is unknown for the
final patient (Pt 5) who presented with bone marrow failure and
subsequent to diagnosis of PNH developed thrombosis.
Flow cytometry data was available in 4 of the 6 patients with
thrombosis. The PNH clone (defined by deficiency of 2 GPI-APs
or 1 GPI-APs þ FLAER analysis), ranged from 58% to 98% in
these four patients. The mean PNH clone for the 6 patients
without thrombosis ranged from 35% to 93% which was
not statistically different (P ¼ 0.9148; Supplemental Appendix).
Median age at diagnosis of first thrombosis was 15 years (range
13–24 years). Four of the 6 patients with thrombosis were of
Pediatr Blood Cancer DOI 10.1002/pbc
Pediatric PNH: MSKCC Single Center Review 3
African-American decent (Pt 2, Pt 4, Pt 5, and Pt 9), 1 patient
was Hispanic (Pt 3), and 1 patient was Caucasian (Pt 6). Throm-
bosis occurred in all 4 female patients, of whom 2 (Pt 4 and Pt 9)
were taking estrogen containing hormonal contraceptives at
time of initial thrombotic event. Thrombosis occurred in 2 out
of 8 male patients with PNH. Transient myelodysplastic features
occurred in 3 out of 6 of the patients with thrombosis (Pt 4, Pt 6,
and Pt 9). All 6 patients were treated with anticoagulation
(heparin or low-molecular weight heparin, and warfarin) follow-
ing thrombosis. Thrombolytic therapy was initiated in 2 patients
(Pt 4 and Pt 9) following thrombosis.
Serious infections complicated the clinical course in 4 of
12 patients. Patient 3 developed fungemia and bacteremia prior
to HSCT. Patient 4 required a tracheostomy following severe
necrotic tonsillar abscess requiring surgical debridement,
recurrent soft tissue infections, and multiple episodes of
bacteremia. Patient 8 developed recurrent cellulitis and peri-rectal
abscesses. Patient 9 developed septic shock along with a history
of recurrent cellulitis and polymicrobial bacteremia.
Five patients received HSCT following diagnosis with PNH.
Indications for HSCT were transfusion dependent AA (N ¼ 2;
192 Pt 1 and Pt 12), MDS (N ¼ 2; Pt 8 and Pt 10), and AA with
life-threatening thrombosis (N ¼ 1; Pt 3). Briefly, Pt 1 underwent
a T-cell-depleted (TCD) HSCT from a matched unrelated
donor (URD) after he became transfusion-dependent following
initial response to IST. His transplant course was complicated
by graft failure requiring a TCD marrow boost 3 months
after initial transplant. He ultimately died of a fungal infection
involving the lung and brain 8 months after his transplant.
Patient 3 underwent a TCD HSCT from a matched-related
donor after several thromboembolic events. Prior to transplant
her condition was complicated by hepatic and portal vein
thrombosis and pulmonary tuberculosis. She ultimately died
from complications related to her infection and thrombosis.
Patient 8 underwent a TCD HSCT from a mismatched URD
after developing MDS features. His post-transplant course was
complicated by late graft failure. He underwent an unmodified
HSCT from a second mismatched unrelated transplant donor.
He is currently alive and disease-free. Patient 10 underwent a
TCD HSCT from a mismatched URD after development of
MDS. He is currently alive and disease-free. Patient 12 underwent
a TCD HSCT from a matched URD after he became transfusion
dependent. He is also currently alive and disease-free post-
transplant.
Three patients were started on anti-complement therapy with
eculizumab. Patient 4 started eculizumab at age 24. Her clinical
course after initiation of eculizumab has been complicated by one
episode of acute hemolysis, renal insufficiency, pericardial effu-
sion with tamponade, and cardiac arrhythmia following a Medi-
Port placement. Pharmacokinetic studies of eculizumab showed a
subtherapeutic level 14 days following her maintenance dose
indicating rapid drug metabolism. Her dosing interval was
decreased to every 12 days and she has since remained
complication free. Patient 7 started eculizumab at age 18. He
has completed over 3 years of therapy without any complications.
Patient 9 started eculizumab at age 20 following development of
an infra-hepatic/IVC clot. During the first year of treatment she
had poor adherence to therapy. However, following progression of
her thrombotic disease, her treatment adherence improved and she
has since been complication free.
4 Curran et al.
Of the remaining four patients, 2 died following complications
related to thrombosis (Pt 2 and Pt 5), and 2 patients (Pt 6 and
Pt 11) remain transfusion independent with stable disease. Follow
up in this cohort of patients was 40 months (median) with range
of 3–174 months.
DISCUSSION
This report highlights several key distinctions between the
presentation of adult and pediatric patients with PNH. In contrast
to adults, pediatric patients with PNH appear to rarely present
with isolated hemoglobinuria. In this series only 1 of 12 patients
had evidence of hemoglobinuria at presentation compared to the
reported rate of 26–50% in adults [6,7]. More significantly, bone
marrow failure at presentation was found in 10 of 12 patients
(83%). In comparison, the reported rate of bone marrow failure in
adults with PNH is 24–33% [1–3]. During our review period
(1992–2010) 60 cases of AA/MDS were evaluated at our pediatric
institution of whom 12 (20%) were eventually diagnosed with
PNH. This high incidence again confirms that all pediatric
patients with bone marrow failure (AA/MDS) should be tested
for PNH.
Myelodysplastic features occurred in 5 of 12 patients
(42%). One patient was diagnosed with hypoplastic MDS
(RCMD þ monosomy 7) at presentation while an additional
4 patients developed myelodysplastic features (abnormal cyto-
genetics and marrow dysplasia) at a median time of 33 months
(range 21–48 months) following presentation. Two patients
received HSCT following development of myelodysplastic
features. In the 3 patients who did not receive HSCT, the myelo-
dysplastic features were transient and bone marrow morphology
and cytogenetics (including monosomy 7) reverted to normal
within 4–14 months. Spontaneous resolution of MDS has been
reported in adults with PNH but not pediatrics [8]. Significantly,
the resolution of monosomy 7 was unexpected considering the
poor prognosis of this feature in patients with AA [9]. In our
series, 2 patients with MDS received HSCT; however, their indi-
cation for transplantation was not the MDS per se, but other
features of aplasia and transfusion dependence. Our findings
may suggest a conservative approach of observation, supportive
care, and aggressive monitoring for pediatric PNH patients with
MDS features, without proceeding to transplant, if the patients are
transfusion-independent and have low-risk features.
While both our cohort and the series published by van den
Heuvel-Eibrink et al. [5] are small, we demonstrated a higher
incidence of thrombosis (6 of 12 patients vs. 2 of 11 patients).
Significantly, thrombotic complications resulted in mortality for
3 of our patients. While the mechanism of thrombosis in PNH is
multifactorial, a correlation between clone size and thrombotic
risk has been established in adults [10]. However, as seen in our
series, demonstrating this correlation in pediatrics has been diffi-
cult due to a small sample population. African-American and
Latin-American ethnicity has also been implicated in thrombotic
risk for patients with PNH [11]. The ethnicity of the 6 patients
with thrombosis in this series included African-American (4),
Caucasian (1), and Hispanic (1), while the ethnicity of the
6 patients without thrombosis was African-American (3) and
Caucasian (3).
The use of prophylactic anticoagulation in pediatric patients
with PNH is still debated. In adults, prophylactic anticoagulation
Pediatr Blood Cancer DOI 10.1002/pbc
is recommended for patients with granulocyte clone size >50%,
platelet counts >100
109/L, and without a known contraindi-
cation to anticoagulation [10]. For pediatric patients current
data is insufficient to guide the routine use of prophylactic
therapy. Furthermore, a significant reduction in the thrombotic
rate has been seen in adult patients treated with eculizumab
[12]. However, given the high rate of thrombosis, consideration
between prophylactic anticoagulation prior to initiating anti-
complement therapy must be balanced against the risk of
hemorrhage in pediatric patients with PNH. Management
of thrombotic events include anticoagulation, and, in cases of
hepatic vein occlusion (Budd–Chiari syndrome), thrombolytic
therapy.
Delay in diagnosis is common in patients with PNH.
Historically, this delay has been attributed to the use of less
sensitive methods of detecting PNH clones (e.g., Ham test or
Sucrose lysis test). In this cohort, flow cytometry was the initial
method of diagnosis in 10 of the patients and was used as a
confirmatory test in the remaining 2 patients. Despite this, delay
of >3 months (range 10–55 months) occurred in a majority
(n ¼ 7) of patients. Critical to decreasing this delay is the aware-
ness of presenting signs/symptoms which will then lead to the
appropriate testing by flow cytometry and FLAER analysis. As
this series highlights, pediatric patients with PNH are likely to
present with bone marrow failure and therefore we suggest testing
all patients with AA or MDS for PNH. In addition children with
unexplained Coombs-negative hemolysis or thrombosis warrant
testing for PNH.
Serious infection in patients with PNH is typically related
to the underlying bone marrow failure and subsequent
neutropenia. Serious infections can result in significant complica-
tions which occurred in 4 out of 12 patients (33%) in our
cohort. Supportive care including appropriate antimicrobial
treatment and in select cases, antimicrobial prophylaxis is
warranted for PNH patients with significant infectious
complications. Evidence of chronic and intermittent intravascular
hemolysis (elevated LDH, total bilirubin, and/or reticulocytosis)
also occurs in patients with PNH. Aggressive supportive care
including frequent RBC transfusions is common. However, with
the use of anti-complement therapy transfusion requirements
should decrease.
Hematopoietic stem cell transplantation is the only curative
option for patients with PNH. Recommendations for transplant
in adults include bone marrow failure, recurrent life-threatening
thromboembolic disease, and refractory transfusion-dependent
hemolytic anemia [7]. Our center considers HSCT in all
patients with PNH if a suitable matched sibling donor is available.
If the patient is diagnosed with MDS or has PNH-related
complications (e.g., recurrent thrombosis), we broaden our
recommendation to include alternative related or URD. To
reduce the likelihood of developing GVHD we recommend
T-cell depletion for all PNH patients with mismatched or URD
transplants. Of note, with the advent of anti-complement
therapy, pure hemolytic anemia is no longer a clear indication
for HSCT. Our series includes 5 pediatric patients treated with
HSCT. Mortality for 2 of our patients following TCD–HSCT was
related to infection and prior thrombosis. Graft failure in 1 patient
was followed by a successful secondary unmodified transplant,
and the patient remains alive and disease-free. Our 2 most
recently transplanted patients are both alive and disease-free

post-transplant highlighting that improved supportive and peri-
HSCT care may translate into improved survival in this cohort
of patients.
A novel alternative treatment option for patients with PNH
includes the humanized monoclonal antibody eculizumab which
blocks the activation of terminal complement complex (C5b-9) at
C5 [13]. While not curative, eculizumab is licensed for use in
patients >18 years of age, and we have safely used it in 3 of the
patients in this series. We recommend the use of eculizumab for
PNH patients over 18 years of age without a suitable HSCT donor
who will maintain treatment adherence. A similar approach to
patients with PNH <18 years of age may be warranted.
Based on our own experience it is important to monitor the
hemoglobin, LDH, and CH50 prior to eculizumab, which identi-
fies rapid metabolizers who require a shorten interval between
drug administration.
This single center series of pediatric patients with PNH high-
lights key distinctions and similarities between PNH in children
and adults. Significantly, the proportion of children with PNH
who present with bone marrow failure and without hemoglobin-
uria is a stark contrast to the proportion of adults with PNH
who present with these symptoms. Furthermore our series, along
with the series published by Ware et al. [1], suggest a comparable
incidence of thrombosis for children and adult patients with PNH.
This report also includes the spontaneous resolution of low-grade
myelodysplasia which may indicate these features do not consti-
tute a clear indication for early HSCT. Delay in diagnosis of
PNH is common and clinicians should have a high degree of
suspicion for the diagnosis of PNH when evaluating patients
with AA, MDS, unexplained Coombs-negative hemolysis, or
thrombosis. With this analysis, we hope to help reduce the rate
Pediatr Blood Cancer DOI 10.1002/pbc
Pediatric PNH: MSKCC Single Center Review 5
of under-diagnosis, time to diagnosis, and highlight the prognosis
following treatment for pediatric patients with PNH. While
HSCT remains the only curative option, its risk must be consid-
ered relative to the patient’s disease severity, adherence,
and response to long-term treatment with anticoagulation and/or
anticomplement therapy.
ACKNOWLEDGMENT
The authors thank Mr. Joseph Olechnowicz for his skilled
work.
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