7. Treatment I – Transfusion therapy and iron chelation, hematopoietic growth factors S109

dependent on RBC transfusions, 2.3% on plt transfusions;for Int-2/High patients these numbers were 63.4% and33.3%, respectively. Among newly-diagnosed patients, 43%chose current therapy based on symptoms, 34% based onlab values. The numbers for follow-up patients were 37%and 40%, respectively.Discussion: MDS-related thrombocytopenia and anemia isa common finding, even in newly-diagnosed MDS patients.A higher IPSS risk classification was more often associatedwith transfusion dependence.

P128 Retrospective survey highlights the ironburden in Japanese transfusion-dependentpatients with MDS

M. Takatoku1 °, T. Uchiyama2, S. Okamoto3,Y. Kanakura4, K. Sawada5, M. Tomonaga6, S. Nakao7,T. Nakahata2, M. Harada8, T. Murate9, K. Ozawa1. 1JichiMedical Univ; 2Kyoto Univ; 3Keio Univ; 4Osaka Univ;5Akita Univ; 6Nagasaki Univ; 7Kanazawa Univ; 8KyushuUniv; 9Nagoya Univ, Japan*E-mail: roy.mazucco@mudskipper.biz

Introduction: The myelodysplastic syndromes (MDS) areamongst the most common anemias requiring red bloodcell (RBC) transfusion therapy in Japan. The aim ofthis evaluation was to investigate transfusion history, ironoverload, iron chelation therapy and mortality in Japanesepatients with transfusion-dependent anemias, includingMDS.Methods: A subset of this retrospective survey collecteddata from transfusion-dependent, iron-overloaded patientswith MDS in Japan from Aug 2001 to Dec 2005.The patients’ medical chart histories were assessed byquestionnaires at onset of transfusion dependence (TD), startof chelation therapy with deferoxamine (DFO) and at endof study (EOS). In this study, TD was defined as >2 RBCunits/month for �6 months (in Japan 1 RBC unit=200mL).Results: Data from 152 Japanese patients with MDS wereanalysed. The table illustrates the patients’ transfusionburden, serum ferritin (SF) levels in all patients and in thosewho received DFO, and causes of death, stratified by IPSSrisk group. No statistically significant difference was foundbetween the SF levels of the various IPPS risk groups. SFlevels increased in all patients, even in those who receivedDFO. The proportion of patients with a clinically significantSF level (�1000 ng/mL) increased from 22% to 53% fromTD onset to EOS in those who had received DFO therapy,and from 27% to 34% in those who were chelation-naıve. Ofthe 152 patients studied, 94 remain transfusion dependent,10 are independent of transfusion, and the outcome of fouris unknown. There were 44 deaths in total, attributed tomultiple causes in some patients.

IPSS risk category

Low (n) Int-1 (n) Int-2 (n) High (n)

Mean duration of TD, months 40.4 (19) 30.2 (71) 16.2 (25) 13.1 (17)Total mean transfusions, n 219.3 (19) 146.5 (71) 129.1 (24) 63.5 (17)SF levels, naıve patientsAt TD onset, ng/mL 4273 (2) 1554 (20) 1397 (3) 1343 (7)At EOS, ng/mL 4178 (3) 3397 (15) 5844 (9) 3709 (4)

SF levels, DFO-treated patientsAt start of DFO, ng/mL 3587 (8) 2409 (22) 4998 (5) 2100 (1)At EOS, ng/mL 4093 (9) 4305 (27) 5705 (6) 1550 (1)

Causes of deaths (n = 61a)Iron overload (cardiac or liverfailure), n (%)

1 (2.3) 9 (20.5) 1 (2.3) 0

MDS (leukemia, bleeding orinfections)b, n (%)

3 (6.8) 16 (36.4) 13 (29.6) 11 (25)

Other, n (%) 0 4 (9.1) 1 (2.3) 0

aThere were 44 deaths, attributed to multiple causes in some patients.bThere were a further two deaths attributed to MDS in patients whose IPSS riskcategory was unknown.

Conclusions: This retrospective study shows a heavyiron burden in transfusion-dependent patients with MDSin Japan, irrespective of IPSS risk group. Iron overloadcontributed to the cause of death in 25% of cases in thisstudy. Despite treatment with DFO in some patients, SFincreased in all groups, possibly reflecting non-continuouschelation in the patients who received DFO. This might becaused by the difficulty in administering DFO to patientswith MDS who may be at risk of infection or bleedingbecause of peripheral cytopenia. Furthermore, most patientsin Japan receive DFO treatment on an outpatient basis. Itis important to assess iron burden and use effective ironchelation therapy to reduce associated morbidity/mortalityin patients with MDS.

P129 Severe iron overload in patients withmyelodysplastic syndromes (MDS) enrolledin a large study of deferasirox (Exjade®,ICL670)

N. Gattermann1 °, M. Schmid2, D. Vassilieff3, C. Rose3,M.G. Della Porta4, C. Finelli5, K. Taylor6, J.F. Seymour7,J.W. Lee8, P. Jakobs9, G. Domokos9, D. Hadler9.1Heinrich-Heine-Univ, Dusseldorf, Germany; 2UnivHosp Ulm, Ulm, Germany; 3on behalf of the FrenchMDS Group (GFM), France; 4Policlinico S Matteo,Pavia, Italy; 5Policlinico S Orsola, Bologna, Italy; 6MaterHosp, Brisbane, Australia; 7Peter MacCallum CancerCtr, Melbourne, Australia; 8St Mary’s Hosp, Seoul, SouthKorea; 9Novartis Pharma AG, Basel, Switzerland*E-mail: andrew.jones@mudskipper.biz

Introduction: Many patients with MDS have longstandinganaemia and increased gastrointestinal iron absorption,become transfusion dependent and subsequently developsecondary iron overload, which can impact on survival.Although iron chelation therapy has been suggested to bebeneficial in MDS, many patients are inadequately treated

S110 Posters

due to the demanding regimen of parenteral deferoxamine(Desferal®, DFO) infusions, or to uncertainty regardingthe value of chelation in MDS patients who may have alimited life expectancy. Analysis of data from an ongoingtrial with the once-daily, oral chelator deferasirox wasperformed to evaluate baseline iron burden and the need-to-treat transfusional iron overload in a subgroup of MDSpatients.Methods: The overall trial is a 1-year, multicentrestudy enrolling patients aged �2 years with a rangeof transfusion-dependent anaemias, including MDS. Atbaseline, all patients had serum ferritin levels >1000 ng/mL,or <1000 ng/mL and a history of multiple transfusionsand a liver iron concentration (LIC) >2mg Fe/g dw(assessed via non-invasive magnetic resonance imaging[MRI]). Deferasirox starting dose was determined basedon blood transfusion frequency.Results: To date, 281 patients with MDS have been enrolled(Table). Of these, 144 (51.2%) were naıve to chelation ther-apy, while 135 (48.0%) had previously received chelationtherapy, including DFO (n = 119), deferiprone (Ferriprox®;n = 27) or DFO/deferiprone combination (n = 13); chelationhistory was unavailable from two patients. At the timeof enrolment, overall median serum ferritin levels were2755 ng/mL (range 969–9465; mean±SD, 3172±1707).Currently, baseline LIC data are only available from10 MDS patients in the MRI subgroup. However, in thesepatients median LIC was 9.4mg Fe/g dw (range 1.8−32.5;mean±SD, 13.6±10.6); values were >7mg Fe/g dw in sixpatients.

Patient demographics and characteristicsa

Patients (n = 193)

Mean age ±SD, years (range) 67.7±9.6 (27–87)Male : female 117 : 76Caucasian : oriental : other 169 : 22 : 2History of hepatitisb, n (%) 8 (4.2)History of splenectomy, n (%) 5 (2.6)Transfusion historyMedian transfusions in previous yearc (range) 18.5 (0–96)Median years on transfusiond (range) 2.0 (0–13)

aNot all demographic information is available yet, so data are presentedfor 193 patients, except bn = 191, cn = 192 and dn = 183.

Discussion: High baseline serum ferritin and LIC inthis population of MDS patients indicates significant ironburden above published clinically acceptable thresholds.For the previously-chelated patients this indicates that theirtreatment regimen was not providing adequate managementof their iron burden, while for the chelation-naıve patientsthese data clearly indicate a need for chelation therapy.

P130 The importance of iron stores in thechelation treatment of patients withmyelodysplastic syndromes

P. Nielsen1 °, T.H. Bruemmendorf1, N. Kroger1, R. Grosse1,R. Engelhardt1, O. Leismann1, R. Fischer1,3, A.R. Zander1.1Medical University Center Hamburg-Eppendorf,Germany; 2Novartis Pharma GmbH, Nuernberg, Germany;3Children’s Hospital & Research Center Oakland, USA*E-mail: nielsen@uke.uni-hamburg.de

Introduction: In the past, iron overload resulting fromred blood cell transfusions was not adequately treated inpatients with myelodysplastic syndromes. Age and multi-morbidity together with the cumbersome treatment with s.c.deferoxamine were the main reasons for a reluctance to treatpatients with such a chelator. The availability of novel oralchelators may change this attitude in the future. First of all,an efficient chelation treatment has to compete with the ironinflux from transfusions before depletion of accumulatediron stores can take place. The necessary chelation doseadjustment can only be managed if total body iron storescan be sufficiently estimated. Especially in these patients,serum ferritin (SF) levels can vary independently from thetrue iron stores as assessed by liver iron concentration (LIC)measurements and the relationship between LIC and ferritinis not constant.Methods: In the present study, a total of 30 transfusedpatients (age: 26−75 y) with myelodysplasia (MDS: n = 17),osteomyelofibrosis (OMF: n = 4), severe aplastic anemia(SAA: n = 9) were measured by SQUID biomagneticliver susceptometry (BLS) and their liver and spleenvolumes were scanned by sonography at the Hamburgbiosusceptometer. Less than 25% were treated with DFO.LIC (mg/g-liver wet weight, conversion factor of about 6for mg/g-dry weight) and volume data were retrospectivelyanalyzed.Results: LIC values ranged from 280 to 7413 with a medianvalue of 2145mg/g-liver, while ferritin concentrations werebetween 710 and 10396mg/l. The ratio of SF/LIC rangedfrom 0.4 to 5.2 [(mg/l)/(mg/g-liver)]. The Spearman rankcorrelation between SF and LIC was found to be highlysignificant (RS = 0.78, p< 0.001), however, prediction by thelinear regression was poor (R2 = 0.36) as found also in otheriron overload diseases. Hepatomegaly was present in 50%of the patients with liver volumes measured between 998and 4141 ml. The resulting total body iron stores (TBI)were calculated from LIC and body weight (Angelucciet al, N Engl J Med 2000;343:327−31) and from LIC andliver volume assuming 80% of storage iron within the liver(Fischer et al, Am J Hematol 1999;60:289−99).Discussion: The two methods of calculating TBI storesare related by the liver volume and the conversion factorbetween the magnetic biopsy (in vivo wet-weight) and theneedle biopsy (in vitro dry-weight). Only for a normal