S150 Abstracts for Publication / Leukemia Research 35 (2011) S143–S150

376

Combination of deferasirox and deferoxamine for management

of iron overload in myelodysplastic syndromes in hepatopathic

patient: A case report

C. Cerchione1, G. Cerciello1, R. Della Pepa1, R. Ciancia1,

M. Matarazzo2, F. Alfinito1, F. Pane1. 1Dipartimento di Biochimica e

Biotecnologie Mediche, 2Dipartimento di Medicina Interna, Universita

di Napoli Federico II, Napoli, Italy

Myelodysplastic Syndromes (MDS) are a heterogeneous group of

haematopoietic stem cell disorders characterized by cytopenia and

hyperplastic bone marrow: in this context red blood cell transfusions

represent a life-saving treatment for patients with chronic anaemia.

Iron overload is the consequence of a long term transfusion therapy

thus it is necessary to prevent this complication by applying a

correct iron chelation therapy. Deferasirox is a well tolerated oral

iron chelator drug that produces relevant benefits but because of

its potential hepatotoxicity it is not recommended for patient with

preexisting hepatic diseases.

Here we report the case of a 62-year-old man affected by HCV

positive cirrhosis and MDS (Refractory Anaemia, IPSS 0.5).

Recombinant Erythropoietin therapy was ineffective and a RBC

transfusion program was started (2 blood package pro month).

At a ferritin serum concentration near 700ng/mL iron chelation

therapy with deferoxamine was proposed in consideration of patient

hepatic disease: compliance to subcutaneous injection was very bad,

transfusion need increased exponentially until to 2 blood package

pro week and serum ferritin concentration reached, in 12 months,

the level of 6198ng/mL.

Since high levels of ferritin correlate with a very dangerous condition

for hepatic cells, therapy with deferasirox was started but at

reduced dosage (10mg/kg/die). Before treatment start an accurate

study of hepatic, renal and cardiac functions was performed. After

three months serum ferritin concentration was not modified as

well as other biochemical parameters, then deferasirox dosage was

gradually increased reaching 30mg/kg/die after two months and

no liver damage was observed. After five months of iron chelation

therapy with deferasirox at full dosage serum ferritin concentration

remained very high (5098ng/mL).

Then, considering all risks related to transfusion dependent

secondary hemochromatosis, with patient informed consent, a

combined iron chelation therapy with deferasirox (30mg/kg/die) and

deferoxamine (2 g/day for 5 days/week) was established and after 3

months serum ferritin concentration lowered to 3000ng/mL.

At the present time, the patient receives 2 RBC package pro week

and, after two years of combined iron chelation therapy, serum

ferritin concentration is at a stable level nearby under 3000ng/mL.

No serious adverse event has been observed.

In conclusion we suggest that combined therapy with deferasirox

and deferoxamine could be considered a safe and almost useful

therapeutic choice in the management of critical transfusion

dependent iron overload in old MDS patients with hepatic disease.

377

Maintenance of normal serum ferritin in a patient with

myelodysplastic/myeloproliferative disease-unclassifiable using

deferasirox. A case report

M. Gaman1, A.M. Vladareanu1, I. Voican1, D. Cisleanu1, H. Bumbea1,

M. Onisai1, A. Alexe1, M. Begu1, A. Vintilescu1, O. Cazaceanu1,

C. Baluta1, A. Ilea2, C. Dobrea2. 1Carol Davila University of Medicine

and Pharmacy, Emergency Universitary Hospital, 2Carol Davila

University of Medicine and Pharmacy, Bucharest, Romania

Introduction: Myelodysplastic/myeloproliferative disease – un-

classifiable (MDS/MPD-U) is a newly clinical entity in WHO

classification. It includes cases with features of both myelodysplasia

and myeloproliferation. It is well known that iron overload causes

multiple organ failure in chronically transfused patients. Optimal

iron chelation therapy is associated with reduced morbidity and

mortality. Furthermore, chelation therapy has been associated with

erythroid responses.

Case report: A 60 year old man was referred to our hospital with

progressive fatigue in 2008. Investigations showed: WBC 3.8×109/L,

with a differential of 53% segmented neutrophils, 3% basophils, 6%

eosinophils, 38% lymphocytes; severe macrocytic anaemia (5.9 g/dl)

and slight thrombocytosis (450× l09/l). Bone marrow aspiration and

biopsy showed hypercellular marrow with 6% blasts, 6% eosinophils

and 5% basophils, with erythroid predominance, megaloblastoid

changes, increased number of megakaryocytes with predominant

hypolobulated forms and moderate fibrosis. Iron stain confirmed the

presence of 17% ringed sideroblasts. Bone marrow and peripheral

blood were submitted for cytogenetic evaluation. Both samples

showed no chromosomal abnormalities. The JAK2 V617F mutation

was negative. Due to the absence of persistent thrombocytosis,

despite the increased number of ringed sideroblasts, a diagnosis

of myelodysplastic/myeloproliferative disease – unclassifiable was

established, according to WHO criteria 2008. Over a 14-month

period, he required transfusion of 4–6 RBC units every 4 weeks and

human recombinated erythropoetin 30000UI weekly to maintain

the hemoglobin above 9 g/dl. In March 2009, the ferritin was

3714.96mg/L. He agreed to receive ICT with deferasirox 20mg/kg

daily. Two months later, the ferritin level was 1907mg/L, but after

6 months of ICT treatment, patient’s serum ferritin level remained

essentially unchanged (1968mg/l). Since inadequate dose titration

was considered to be the cause of suboptimal response, Deferasirox

dose was increased to 30mg/kg/day. By month 8, serum ferritin

levels had decreased to 1209mg/L and by month 12, it further

reduced to 644mg/dl. Patient continued to receive deferasirox

30mg/kg/day and no adverse events had been noted. He required

a decreased number of RBC transfusion (1–2 RBC units every

4 weeks) and human recombinated erythropoetin 30000UI weekly

to maintain the hemoglobin above 9 g/dl. He reported an improved

quality of life.

Conclusion: A significant reduction in transfusion requirement was

observed and was probably dependent on chelation therapy. The

clinical course of our patient is a strong evidence that ICT may

be of clinical benefit for chronically transfused patients although

the experience with its use in Myelodysplastic/Myeloproliferative

disorders is limited.