Background and Objective. Chelation therapy is often necessary for patients who undergo chronic transfusion therapy for myelodysplastic syndromes. In these patients, deferoxamine, the most widely used chelating agent, has been reported to be effective in reducing the iron burden and the transfusion requirement. Unfortunately, compliance with the drug, that is usually administered by slow subcutaneous infusion via a battery operated pump, is often poor, especially in elderly patients

Aurora Vassanelli

Caterina Borgna-Pignatti

Giorgio Gandini

Giuseppe Aprili

Marzia De Gironcoli

Massimo Franchini

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Abstract
Subcutaneous bolus injection of deferoxamine in adult patients affected
by onco-hematologic diseases and iron overload
CATERINA BORGNA-PIGNATTI,* MASSIMO FRANCHINI, GIORGIO GANDINI, AURORA VASSANELLI,
MARZIA DE GIRONCOLI, GIUSEPPE APRILI
*Department of Clinical and Experimental Medicine-Pediatrics, University of Ferrara; Immunohematology and Transfusion
Center, Policlinico Borgo Roma, Verona, Italy
Haematologica 1998; 83:788-790 original paper
Correspondence: C. Borgna-Pignatti, Dipartimento di Medicina Clinica
e Sperimentale, Sezione di Pediatria, via Fossato di Mortara 17/19,
44100 Ferrara, Italy. 
Phone: international +39-0532-295856 • Fax: international +39-
0532-202103 • E-mail: bre@dns.unife.it
Background and Objective. Chelation therapy is
often necessary for patients who undergo chronic
transfusion therapy for myelodysplastic syndromes.
In these patients, deferoxamine, the most widely
used chelating agent, has been reported to be effec-
tive in reducing the iron burden and the transfusion
requirement. Unfortunately, compliance with the
drug, that is usually administered by slow subcuta-
neous infusion via a battery operated pump, is often
poor, especially in elderly patients. 
Design and Methods. To verify efficacy and tolera-
bility of deferoxamine by subcutaneous bolus injec-
tion as compared to the conventional pump-driven
slow infusion, eleven patients affected by onco-
hematologic diseases were given 2 g of deferoxam-
ine diluted in 10 mL of distilled water over twelve
hours by continuous infusion, or by bolus injection in
two divided doses.
Results. Mean urinary excretion was comparable
with the two methods, being 9,183±4,349 µg/48h
after two daily subcutaneous bolus injections and
8,291±3,970 µg/48h with the slow infusion. The
bolus injection was preferred by all eleven patients,
who chose to continue chelation therapy by this
method.
Interpretation and Conclusions. The iron excretion
induced by bolus injection is not statistically differ-
ent from that induced by subcutaneous infusion. The
side effects are acceptable. Subcutaneous bolus
injection of deferoxamine is an acceptable alterna-
tive to slow, pump-driven infusion. 
©1998, Ferrata Storti Foundation
Key words: deferoxamine, chelation, iron overload, bolus
injection, myelofibrosis
Chronically transfused patients develop ironoverload which in time becomes responsiblefor variable degrees of organ damage and
dysfunction. Chelation therapy is therefore neces-
sary to prevent or decrease the iron burden. The
almost universally used chelating drug is deferoxam-
ine (DF) that needs to be infused parenterally and
that, because of its short half-life, is usually adminis-
tered subcutaneously over 8 to 12 hours by means of
a battery-operated portable pump.1 In addition to
its chelating effects, DF has been reported to be effec-
tive in reducing the transfusion requirement.2,3 How-
ever, compliance with this treatment is often poor,
especially in adult or elderly patients with hemato-
logic and myeloproliferative disorders. Recently it has
been reported in a group of thalassemic patients4
that the administration of deferoxamine by subcuta-
neous bolus administration twice a day is as effective
as the slow subcutaneous infusion. We tested the effi-
cacy and tolerability of this new therapeutic modali-
ty in a population of adult patients undergoing trans-
fusional therapy for chronic onco-hematologic dis-
orders.
Materials and Methods
Eleven patients, 51 to 77 years of age (median age
63 years) were enrolled in this prospective study. All
patients were affected by onco-hematologic diseases
and were regularly transfused (two units of concen-
trated erythrocytes every 2 to 3 weeks) at the Trans-
fusion Center of the University of Verona. Informed
consent was obtained from all patients before enrol-
ment in this study. 
Patients’ characteristics are reported in Table 1.
Patients were enrolled alternatively to start with
continuous infusion or bolus injection in two divid-
ed doses. Any previous chelation therapy (by con-
tinuous infusion in all but one patient) was discon-
tinued 48 hours before the test. 
Continuous infusion
Each patient self administered 2 g of DF  diluted
in 10 mL of distilled water over twelve hours, subcu-
taneously  in the abdominal wall in  two consecutive
nights and collected urine, at home,  from the begin-
ning of the first infusion and for 48 hours. Since there
is a high variability in iron excretion in each patient,
24 hr collections were not considered adequate.
Bolus injection
The same daily amount of DF was administered in
two divided doses, twelve hours apart, each diluted in
10 mL of distilled water. The injection was done by
means of a 25 gauge scalp needle at the rate of about
1 mL/min, as tolerated. Particular attention was giv-
en to avoiding direct injection of the product into a
vessel. Urine was again collected for 48 hours, at
home, starting with the first bolus injection. Both con-
tinuous and bolus infusions were performed in the 48
hours preceding transfusion. The two tests were car-
ried out two weeks apart, in different transfusion
cycles. Vitamin C supplementation was not given. Uri-
nary iron excretion was measured by atomic absorp-
tion spectrophotometry. Side effects were recorded
by all patients on a specifically prepared form.
Comparison of iron excretion was performed by
paired t test analysis.
Results
The mean 48-hour deferoxamine-induced urinary
iron excretion was 9,183±4,349 µg/48h (range 4,144
to 17,640) after two daily subcutaneous bolus injec-
tions and 8,291±3,970 µg/48h (range 2,556 to
14,510) after subcutaneous infusion. The 48-hour
urinary iron excretion for each patient is reported in
the table. Nine patients had a higher 48-hour urinary
iron excretion after subcutaneous bolus injection
than after subcutaneous infusion of DF. The differ-
ence between the two methods of drug administra-
tion was not statistically significant (p = 0.2 by paired
t test). There was no difference in whether the bolus
or the pump was administered first. Side effects were
mild local swellings and were of similar intensity with
both methods. One patient complained of reddening
and pain during the first bolus injection. The symp-
toms did not reappear during the subsequent injec-
tions. At the end of the study all eleven patients chose
to continue chelation therapy by the bolus method.
Discussion
Compliance with slow subcutaneous infusion of
deferoxamine by means of a portable pump is often
poor. Therefore, the search for new chelators, or
improved methods of administration of the old one,
is ongoing. Following a preliminary report by Jensen
et al.,3 it has recently been shown that DF adminis-
tered as a bolus injection is effective and well toler-
ated in young patients with thalassemia.4 Similar
data were later duplicated by others.5 The toxicity of
the oral chelator deferiprone is at present under
scrutiny.6 In addition, a phase I trial to assess the tol-
erability of a modified form of DF, that should be
injected as a daily bolus of a small amount of prod-
uct has just been completed.7 However, until such or
other products are available for widespread use, the
bolus administration of DF might be a valid alterna-
tive, as confirmed by the findings in the present study,
especially for elderly patients with acquired blood
disorders, who tolerate poorly the burden of pump-
driven subcutaneous infusion. All of our adult
patients, in fact, chose to continue chelation thera-
py by bolus injection. However, the level of iron load-
ing in these patients was relatively low and therefore
the potential efficiency of chelation may be less with
the repeated bolus injection if dose response curves
with the two approaches were determined. Since
there is a high variability in iron excretion in each
Bolus deferoxamine in adults 789
Table 1. Patients’ characteristics and iron excretion.
Pt Diagnosis* Sex Age Ferritin 48-h urinary iron 48-h urinary iron
(years) (mg/L) excretion after s.c. excretion after s.c.
bolus injection (mg/48h) pump infusion (mg/48h)
1 MFI F 61 1,705 8,450 6,870
2 MDS, RA F 54 1,400 8,728 10,218
3 MDS, RAEB M 77 2,236 17,640 14,510
4 MFI M 61 2,100 7,880 11,530
5 MDS, RAEB-t M 77 3,140 4,243 2,556
6 CML, CF F 48 1,670 13,000 11,390
7 NHL, LG F 77 1,130 4,144 3,737
8 MDS, RA F 51 685 7,703 6,790
9 MDS, RAEB F 76 1,186 10,990 8,262
10 MFI M 66 660 4,360 3,400
11 EA F 69 6,400 13,885 3,400
*MFI = idiopathic myelofibrosis; MDS = myelodysplastic syndrome; RA = refractory anemia; RAEB = refractory anemia with excess of blast cells; RAEB-t = refracto-
ry anemia with excess of blast cells in transformation to acute myeloid leukemia; CML = chronic myelogenous leukemia; CF = chronic phase; NHL = non Hodgkin’s
lymphoma; LG = low grade; EA = erythroid aplasia.
patient, even 48 hr collections could be inadequate,
although our results are very similar to those of pre-
vious studies.  A word of warning is needed regard-
ing the risk of allergy that, according to recent
reports8,9 could be increased by pulsatile injections,
as compared to slow infusion, of DF. In addition, a
study is ongoing to evaluate the levels of non-trans-
ferrin bound iron maintained by the DF bolus. On the
other hand, intravenous and/or continuous delivery
of DF may involve the risk of developing lung injury.10
Larger long-term trials will be necessary for estab-
lishing long-term efficacy and safety of this method
to treat hemosiderosis. 
Contributions and Acknowledgments
CB-P was responsible for study design (with MF and GA)
and for writing the paper; MF and GA were also responsible
for data handling and statistical analysis; GG was responsi-
ble for recrutiment of the patients and discussion of the pro-
ject; AV and MDG organized the urine collection and mea-
sured the study parameters.
Funding
This work was supported in part by 40% and 60% grants
from the Ministero dell'Università e della Ricerca Scientifica,
Italy to CBP.
Disclosures
Conflict of interest: none.
Redundant publications: no substantial overlapping with
previous papers.
Manuscript processing
Manuscript received February 25, 1998; accepted June 9,
1998.
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C. Borgna-Pignatti et al.790


Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload

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Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload

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