Abstract

Abstract 5181

Background:

Despite the recent availability of multiple therapeutic options for chelation therapy, severe iron overload remains a significant cause of morbidity and mortality in a small group of patients with thalassemia major (TM). Every effort to induce negative iron balance for these patients is warranted. In this context, combination of deferasirox (DFX) and deferoxamine (DFO) may be of significant value. In this report, we present the paregoric use of DFX and DFO in severely iron overloaded thalassemic patients.

Patients and Methods:

Five patients (3 Males, 2 females) have been treated with DFX and DFO as a last rescue measure. In these patients previous combined treatment with DFO and DFP had failed. Informed consent and approval for the use of this schema as paregoric therapy was obtained by patients and hospital. The main inclusion criteria for this treatment were: LIC>30 mg/gr d. w. and T2* cardiac <10 msec. Treatment consisted of daily DFX at 30–40 mg/kg/day and DFO at 40–50 mg/kg/day for 3–6 days/week.

Results:

Patients' characteristics, results and toxicity are shown in table 1 and 2. Improvement in iron load status ranged widely during a follow-up from 1 to 3 yrs. LIC reduced in 4/5 patients, cardiac T2* increased in 3/5 patients, while LVEF showed no significant changes. Ferritin levels improved in 2/5 patients. Deterioration of safety parameters necessitated not to discontinue treatment.

Conclusions:

These data in the use of combination therapy of DFX and DFO suggest a potential modality of chelation therapy in severely iron overloaded patients. Response was variable and seemed not to be always related to compliance or the duration of treatment. Increase of serum creatinin and AST in all patients is a considerable problem in patients with persistent significant iron overload and already impaired hepatic and renal function, despite having been treated with different schema of iron chelation. Longer and cautious follow-up is needed to come to reliable conclusions.

Table 1
Effectiveness
MRI - LICMRI - T2* cardiacMRI - LVEFFerritin
No.Start Age/genderComplianceBase1st year2nd year3rd yearChangeBase1st year2nd year3rd yearChangeBase1st year2nd year3rd yearChangeBase1st year2nd year3rd yearChange
 years/m-f  mg/gr d.w. msec ìg/L 
32,4/f Fair 42,5 51 42,5 33,6 −20,9 5,3 5,6 7,2 20 63,4 64,9 69,3 69 8,8 5682 8150 8600 7700 35,5 
25,5/m Fair 36,5 36,5 25,6  −29,8 2,7 2.65  11,1 71 65,9 69,1  −2,7 5.400 5300 3500  −35,2 
26,5/m Fair 42,5 25,6   −39,7 3,5 2,6   −25,7 62,6 60,9   −2,7 3200 3300   3,1 
29,0/f Poor 39,5 42,5 42,5 44 11,4 7,1 4,2 3,9 3,2 −54,9 60 62 61,1  1,8 11000 12000 12400 11550 
29,47/m Poor 42,5 36,5 19,7 11,7 −72,5 4,5 100 55,4 55,78 47,9 52,8 −4,7 8500 8650 6000 3350 −60,6 
Effectiveness
MRI - LICMRI - T2* cardiacMRI - LVEFFerritin
No.Start Age/genderComplianceBase1st year2nd year3rd yearChangeBase1st year2nd year3rd yearChangeBase1st year2nd year3rd yearChangeBase1st year2nd year3rd yearChange
 years/m-f  mg/gr d.w. msec ìg/L 
32,4/f Fair 42,5 51 42,5 33,6 −20,9 5,3 5,6 7,2 20 63,4 64,9 69,3 69 8,8 5682 8150 8600 7700 35,5 
25,5/m Fair 36,5 36,5 25,6  −29,8 2,7 2.65  11,1 71 65,9 69,1  −2,7 5.400 5300 3500  −35,2 
26,5/m Fair 42,5 25,6   −39,7 3,5 2,6   −25,7 62,6 60,9   −2,7 3200 3300   3,1 
29,0/f Poor 39,5 42,5 42,5 44 11,4 7,1 4,2 3,9 3,2 −54,9 60 62 61,1  1,8 11000 12000 12400 11550 
29,47/m Poor 42,5 36,5 19,7 11,7 −72,5 4,5 100 55,4 55,78 47,9 52,8 −4,7 8500 8650 6000 3350 −60,6 
Table 2
Safety
Creat. Clearance*Serum CreatinineAST
No.BaseMinBaseMaxBaseMax
ml/minmg/dlIU/l
1 118,16 116,6 0,59 0,65 143 148 
2 101,21 94,7 1,01 0,97 71 98 
3 165,87 74,9 0,63 1,32 60 83 
4 85,8 68,8 0,84 1,4 245 317 
5 124,13 79,9 0,77 1,04 77 97 
Safety
Creat. Clearance*Serum CreatinineAST
No.BaseMinBaseMaxBaseMax
ml/minmg/dlIU/l
1 118,16 116,6 0,59 0,65 143 148 
2 101,21 94,7 1,01 0,97 71 98 
3 165,87 74,9 0,63 1,32 60 83 
4 85,8 68,8 0,84 1,4 245 317 
5 124,13 79,9 0,77 1,04 77 97 
*

as astimated using the Cockgroft-Gault equation.

Disclosures:

Ladis:Novartis: Consultancy, Honoraria, Research Funding; Apopharma: Consultancy, Honoraria, Research Funding. Kattamis:Apopharma: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Author notes

*

Asterisk with author names denotes non-ASH members.