Role of flow cytometry in the assessment of restoration of hematopoiesis during standard Exjade® treatment in patients with low- intermediate I risk myelodysplastisc syndromes, a pilot study

Some evidence is provided that iron-chelation therapy may alter normal or
restore ineffective hematopoiesis in MDS possibly due to the elimination of the
toxic effects of iron on the level of the bonemarrow compartment. In a small
series, Jensen et al., showed during long-term follow-up changes in peripheral
blood counts and Hb requirements of 11 patients with myelodysplastic syndromes
(MDS) during iron chelation treatment with desferrioxamine for up to 60
months.20 The erythroid marrow activity was indirectly evaluated by repeated
determinations of the serum transferrin receptor concentration. The efficacy of
iron chelation was evaluated by repeated quantitative determination of the
liver iron concentration by magnetic resonance imaging. Reduction in the Hb
requirement ( > or = 50%) was seen in 7/11 (64%) patients. Five patients (46%)
became blood transfusion independent. Platelet counts increased in 7/11 (64%)
patients and the neutrophil counts in 7/9 (78%) evaluable patients. All
patients in whom iron chelation was highly effective showed improvement of
erythropoietic output accompanied by an increase in the serum transferrin
receptor concentration. It is concluded that reduction in cytopenia in MDS
patients may be accomplished by treatment with desferrioxamine, if the iron
chelation is efficient and the patients are treated for a sufficiently long
period of time.
To combine the recent knowledge on the role of flow cytometry in MDS and the
observation that adequate iron-chelation may improve ineffective hematopoeisis
in MDS, it is hypothesized that flow cytometry may either identify patients who
may benefit from iron-chelation and flow cytometry may underscore the role of
adequate chelation in restoring myelodysplasia in MDS.

- Primary objective:
To evaluate the flow cytometric characteristics of the bone marrow compartment
before and during treatment with Exjade® in low and intermediate-I risk
myelodysplastic syndromes.

- Secondary objectives:
To correlate the flow cytometric characteristics of the of the bone marrow
compartment before and during treatment with Exjade® in low and intermediate-I
risk myelodysplastic syndromes with clinical, hematological and biochemical
parameters reflecting iron overload as specified below:
- clinical signs of disease including WHO performance state, symptoms related
to anemia, bleeding disorders reflecting impaired
trombocyte function and infections
- hematological parameters including Hb, trombocyte and leucocyte count [WBC
differential]
- biochemical parameters including renal and hepatic function, glucose, amylase
and ferritin

Patient population: Patients with low/intermediate-1
risk myelodysplastic syndrome
Study design: An explorative study, monocenter, open
label
Duration of treatment: 2 years
Number of patients: 20 patients
Planned start and end of recruitment: Start of recruitment: I 2011
End of recruitment: IV 2013

Not applicable