AHMED KADHIM THALASSEMIA CENTER - DUBAI

AHMED KADHIMTHALASSEMIA CENTER - DUBAI

BackgroundIron chelating agents (desferroxamine and

deferazirox) are mainly used to prevent the deleterious effect of iron overload resulted from repeated transfusions in thalassemia and other type of iron loading anemias.

BackgroundThe insight into the mechanism of iron and

oxygen radicals poisoning extended the use of iron chelaters to conditions in which there is no iron overload, such as :-

antioxidant effect - as in rheumatoid arthritis and favism(2, 9,10),

Backgroundantiproliferative effect (some solid tumors) &

antiprotozoal effect (2)

aluminum intoxication as chelater (as in renal failure) (3)

BackgroundNumber of articles report an increase in

erythropoiesis or a reduction in the transfusion requirement during iron chelation therapy. (1, 4, 6, 7, 9)

A variety if mechanisms are possible

BackgroundMechanismslimited cytoreductive effect (4, 6)iron redistribution to the haemopoietic tissue

(1, 9)ferrokinetic changes (4)suppression of increased apoptosis and

mitochondrial damage (4, 8)

BackgroundMechanisms (cont.)in patients with renal failure desferroxamine

and rHu Epo may increase transferrine receptors to enhance cellular uptake of iron. (3, 5)

AimThis study is conducted to evaluate the effect

of using the oral iron chelater deferazirox (Exjade) on the hemoglobin level in thalassemia patients receiving regular blood transfusion in Dubai thalassemia center - UAE.

Material and MethodsA retrospective study.135 B thalassemia major patients receiving

regular blood transfusion every 3-4 weeks and taking Exjade as an iron chelater, started to be given in Sep. 2006.

63 Desferal taking patients group used for comparison, during the same period of time.

Hemoglobin readings were collected from patients medical records, for the period Mar.-Aug. 2006 ( pre Exjade era - Pre) and Feb.-Jun. 2008 (post Exjade era –Post ), for both groups.

Material and MethodsMean of 16 hemoglobin readings were

calculated using Microsoft excel software.Comparison between the means (pre- and

post-) was done with T-test and p value calculated.

Material and MethodsAs p value results were showing highly significant

degrees, for the purpose of comparison these values giving a significance scale with color coding in order to make comparison easier, as in below

extremely sig.<=0.0000005, very high sig.<=0.000005, high sig.<=0.00005, very sig.<=0.0005, sig.<=0.005, less sig.<=0.05, non sig.>0.05.

Material and MethodsStratification of data had been done

according to age groups, sex, serum Ferritin level, HCV status, and presence of complications like, hypoparathyroidisim, hypothyroidism, diabetes, hypogonadisim, cardiac dysfunction, and size of liver and spleen, and whether splenectomy done or not. (Maisem et. al. , unpublished data)

Results

Exjade Desferal

No. of pat 135 63

mean age(yrs) 14.55556 17.01587

mode age(yrs) 10 12

Median(yrs) 13 16

Study Groups

Results mean Hb

difference p value post pre

All PAT 11.10343 10.87582 0.227606 1.01E-06

Exjade Pat

Desferal Pat

mean Hbdifference p value

post pre

All PAT 11.09181 10.82748 0.264325 1.54E-05

Results mean Hb


age 2-12 11.04022 10.76143 0.278787 2.98E-05

age 13-20 11.25538 10.99464 0.260738 0.001484

age >20 11.03704 10.94521 0.091832 0.388641

Exjade Pat

Desferal Pat mean Hb


age 2-1211.09485 10.7859 0.308942 2.23E-06

age 13-20

age >20 11.17183 10.97524 0.19659 0.174942

Age2-20 Exjade 1.28E-07

Results mean Hb


female 11.24339 10.97114 0.272257 3.86E-05

male 10.93363 10.76019 0.173439 0.007705

Exjade Pat

Desferal Pat mean Hb


female 11.39618 11.13483 0.261351 0.002435

male 11.01026 10.72281 0.287451 0.000189

Resultshcv mean Hb


no 11.14925 10.9251 0.22415 1.98E-05

yes 11.13354 10.90947 0.224065 0.063829

Exjade Pat

Desferal Pat hcv mean Hb


no 11.04008 10.78794 0.252137 0.000542

yes 11.31747 10.93814 0.379334 0.003752

ResultsS Ferritin mean Hb


<2000 11.20192 10.93624 0.265676 1.49E-05

=>2000 11.06804 10.90319 0.16485 0.04037

Exjade Pat

Desferal Pat S Ferritin mean Hb


<2000 11.01192 10.714 0.29792 0.011908

=>2000 11.15125 10.87749 0.273764 0.000295

ResultsDiabetes mean Hb


no 11.17582 10.92234 0.253472 1.27E-06

yes 11.11658 10.89824 0.21834 0.877005

Exjade Pat

Desferal PatDiabetes mean Hb


no 11.10329 10.79611 0.307178 4.37E-06

yes 11.11847 11.06492 0.053556 0.792094

ResultsHypothyroidism mean Hb


no 11.12937 10.90366 0.225714 6.28E-06

yes 11.12014 10.90792 0.212221 0.275271

Exjade Pat

Desferal PatHypothyroidism mean Hb


no 11.09149 10.80169 0.289802 9.41E-06

yes 11.26944 11.22426 0.04518 0.905152

ResultsHypoparathyroidisim mean Hb


no 11.1424 10.91948 0.22292 1.06E-05

yes 11.18597 10.95076 0.23521 0.205683

Exjade Pat

Desferal PatHypoparathyroidisim mean Hb


no 11.10415 10.82866 0.27549 1.3E-05

yes 11.112 10.76059 0.351405 0.323714

Results Hypogonadisim mean Hb


no 11.16089 10.89602 0.264869 5.05E-06

yes 11.09876 11.01332 0.085446 0.308713

Exjade Pat

Desferal Pat Hypogonadisim mean Hb


no 11.04303 10.77701 0.266015 0.000187

yes 11.21152 10.90241 0.309108 0.012811

ResultsLiver Size(cm) mean Hb


<3 11.17167 10.9111 0.260572 1.24E-06

>=3 11.07777 10.94971 0.128063 0.224906

Exjade Pat

Desferal Pat Liver Size(cm) mean Hb


<3 11.13641 10.8402 0.2962 0.000204

>=3 11.0179 10.77565 0.242259 0.01067

ResultsSpleen Size (cm) mean Hb


<3 11.15398 10.8903 0.263674 2.54E-06

>=3 10.95084 10.87917 0.071671 0.53241

Exjade Pat

Desferal PatSpleen Size (cm) mean Hb


<3 11.12278 10.80418 0.318601 2.88E-05

>=3 11.02213 10.73617 0.285958 0.029966

ResultsSplenectomy

mean Hbdifference p value

post pre

No 11.07125 10.83904 0.232211 3.12E-06

yes 11.50563 11.33559 0.170037 0.06638

Exjade Pat

Desferal Pat Splenectomy mean Hb


no 11.02013 10.74587 0.274259 4.32E-07

yes 11.08583 11.13047 -0.04464 0.846177

p values

Exj Desf

all pat 1.01E-06 1.54E-05

Age <=12 2.98E-052.23E-06

13-20 0.001484

>20 0.388641 0.174942

Sex F 3.86E-05 0.002435

M 0.007705 0.000189

Hcv Neg 1.98E-05 0.000542

Pos 0.063829 0.003752

s ferrit <2000 1.49E-05 0.011908

>=2000 0.04037 0.000295

Diab Neg 1.27E-06 4.37E-06

Pos 0.877005 0.792094

Sig. Code

Extr. sig.Very H.sigHigh sig.

Very sig.Signif.

Less sig.Non sig.Inverse

age2-20 Exjade 1.28E-07

Exj Desf

Hypothy Neg 6.28E-06 9.41E-06

Pos 0.275271 0.905152

Hypoparat Neg 1.06E-05 1.3E-05

Pos 0.205683 0.323714

Hypogona Neg 5.05E-06 0.000187

Pos 0.308713 0.012811

Liver <3 1.24E-06 0.000204

>=3 0.224906 0.01067

Spleen <3 2.54E-06 2.88E-05

>=3 0.53241 0.029966

Splenectomy No 3.12E-06 4.32E-07

Yes 0.06638 0.846177

Sig. Code

Extr. sig.Very H.sigHigh sig.

Very sig.Signif.

Less sig.Non sig.Inverse

Mean Hb of All Exjade Patients

Mean Hb of All Desferal

Patients

P value

0.227606 0.264325 0.609803

Comparison between the Mean Hb Difference of

Both groups

Discussion Despite absolute raise in Hb levels was more

prominent in Desferal group (not sig.), it was the Exjade group that had the more significant P value between the pre- and post- means.

Sample size could explained this difference.However knowing that subjects in both

groups exposed to a similar conditions, an Exjade effect cannot be neglected.

DiscussionAll of the highly significant P values seen

where complications are not present, an exception is found in HCV +ve and s. Ferritin >2000 patients in the Desferal group.

All the post Hb levels are higher than the pre Hb levels in both groups except Desferal taking splenectomized patients who are older in age and remnant splenic tissue may be responsible.

DiscussionYounger patients had the best P values in

both groups, those also had more reduction in their s.ferritin (Khawla et. al., unpublished data) when using Exjade, better compliance is a possible explanation.

Gender was not conclusive.

Smaller liver and spleen size was associated with a valuable P.

DiscussionThe mean, median and mode age for Desferal

group were 2-3 yrs higher than that of Exjade group, this could be a partial contributor to the difference in P values.

The absolute raise in Hb level is clinically not significant (0.2-0.4 g/dl), however in a center serving more than 400 patients such raise may have an economic impact on blood supply to the center.

ConclusionBoth groups had raise in their Hb levels.Desferal raise was bigger, but not significant.Exjade raise was more significant.The raises are minute but may have effect on

making better blood economy.More studies are needed to prove or disprove

effect of Exjade on Hb levels in transfusion dependent thalassemia patients.

THANK YOU

Thanks ToDr. Khawla BelhoulDr. Maisem BakerDr. Hamid Al QaissyMiss Maitha Mohamed HassanRashid Medical library staff.

References 1- Vreugdenhil G. ,Smeets M. ,Feelders R.A. et al. Iron chelators may enhance erythropoiesis by increasing iron

delivery to haemopoietic tissue and erythropoietin response in iron-loading anemia. Acta Haematol 1993;89:57-60.

2-Voest E.E ,Vreugdenhil G. ,Marx J.J .Iron-Chelating Agents in Non-Iron Overload Conditions. Ann Int Med. 1994; vol 120;6:490-499.

3- Aucella F. ,Vigilante M. ,Scalzulli P. et. al. Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients. Nephrol Dial Transplant 1998;13:1194-1199.

4- Tucci A. A. ,Murru R. ,Alberti D. et. al. Correction of anemia in a transfusion-dependent patient with primary myelofibrosis receiving iron chelation therapy with deferasirox (Exjade ,ICL670).Eurep. J. of Haematol. Journal compilation 2007;78:540-542.

5- Aucella F. ,Vigilante M. ,Scalzulli P. et. al. Synergistic effect of desferrioxamine and recombinant erythropoietin on erythroid precursos proliferation in chronic renal failure. Nephrol Dial Transplant 1999;14:1171-1175.

References 6- P. D. ,Heickendorff L. ,Pedersen B. et.al. The effect of iron chelation on

hemopoiesis in MDS patients with transfusional iron overload. B. J. of Haematol. 1996 ;92(2):288-299.

7- Garma J. D. , Lago F. ,Fonrodona B. Deferrioxamine in the treatment of myelodysplastis syndroms. Haematologica. 1997 Sep-Oct;82(5):639-40.

8- Marsh JH, Hundert M, Schulman P. Desferoxamine-indiced restoration of haematopoiesis in myelofibrosis secondary to myelodysplasia. Br J Haematol. 1990 Sep;76(1):148-9.

9- Giordano N, Fioravanti A, Sancasciani S . et. al. Increased storage of iron and anemia in rheumatoid arthritis: usefulness of desferrioxamine. Br Med J (Clin Res Ed). 1984 Oct 13;289(6450):961-2.

10- Ekert H, Rawlinson I. Deferoxamine and favism. N Engl J Med. 1985 May 9;312(19):1260.

AHMED KADHIM THALASSEMIA CENTER - DUBAI

Documents

Transcript of AHMED KADHIM THALASSEMIA CENTER - DUBAI