The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload

Jensen, Peter D. Ørberg; Heickendorff, Lene; Pedersen, Bent; Bendix-Hansen, Knud; Jensen, F. T.; Christensen, T.; Boesen, Anne Marie; Ellegaard, J.

doi:10.1046/j.1365-2141.1996.d01-1795.x

Cited by 183 publications

(137 citation statements)

References 24 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…In contrast to other studies [5], we could not observe any significant changes in hemoglobin levels and RBC requirements, no patient became transfusion independent. The lack of improvement of the erythropoietic activity is possibly explained by the relatively low number of patients in our study.…”

Section: Discussioncontrasting

confidence: 99%

“…The lack of improvement of the erythropoietic activity is possibly explained by the relatively low number of patients in our study. Furthermore, the relatively short period of chelation treatment may also contribute to this result, as the hematological improvement was reported to become evident mostly after 12 months [5].…”

Section: Discussionmentioning

confidence: 99%

“…If untreated, iron overload may cause damages in liver, heart, pancreas, brain, joints, and endocrine tissues [2][3][4], increasing morbidity and the risk of early death [1]. As phlebotomy is not an option in MDS, the only way to remove toxic iron and to prevent complications of transfusion-dependent iron overload is, to date, rigorous iron chelation therapy [5].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

View full text Add to dashboard Cite

International audienceBlood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade®) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53–91) were enrolled. Deferasirox administered in a once-daily dose of 20–30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 µg/L (range 665–6,900) to 413 µg/L (range 105–3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 µmol/g ( = 0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine β2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Transfusion dependency leads to decreased quality of life [11] as well as life expectancy [12;13] and produces enormous cost to patients and the health care system [14;15]. Further, transfusion dependent patients with a good long term prognosis require iron chelation therapy for prophylaxis against secondary hemosiderosis [16][17][18]. Although erythropoiesis-stimulating agents (ESA) are not FDA-approved for MDS, they are commonly used off label in this disease.…”

Section: Discussionmentioning

confidence: 99%

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

et al. 2010

View full text Add to dashboard Cite

Background: No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no cost study of MDS exists in Germany, the objective of this study was to assess and analyse costs of transfusion-dependent low/intermediate-1 risk MDS in Germany from a payers' perspective. Patients and methods: 116 low/intermediate-1 risk transfusion-dependent MDS patients with and without isolated 5q-deletion from seven centers were identified. Claims data and patient records of the previous five years were used to collect health care utilization data retrospectively. Publicly available tariff books and remuneration schemes were applied to evaluate mean costs per year in Euro with 2007 as base year. Results: The annual cost of MDS patients was estimated at €14,883. Subgroup analyses showed differences in patient's characteristics and outcomes among patients treated at a hospital based versus an office based setting. Patients treated at the hospital based registry show higher cost where as the reasons for that still need to be detected. Overall per annum direct costs range from €12,543 (SD 12,967) to €24,957 (SD 36,399) in different subgroups of patients. In both groups, patients with 5q-deletion use more medication than those without deletion. Mean costs for medication in the office based setting are €5,902 for patients with isolated 5q-deletion vs. €3,932 with no deletion, respectively. Conclusion: MDS leads to a high health care utilization and resulting costs for the health care system which requires a detailed analysis of underlying services.Response to Reviewers: For reasons of a better outline, we decided to respond to your comments in a word document which is attached. Response to reviewer's comments Reviewer's comments ResponsesReviewer #1:In this retrospective study, the authors have evaluated the annual cost of MDS transfused patients in Germany. They stated that patients with 5q-deletion used significantly more resources and especially more medication than those without deletion. This paper raise two majors Criticisms : -1st. The way the data were retrospectively collected raise some issues.In fact the authors compared MDS and del5q but the collection of data were rather different in the two groups and this might also (in part) explain the difference observed in the two groups.Thank you for raising this point. We are aware of this limitation and tried to point it out in the discussion. As this was addressed as a major point by the first reviewer we decided that the respective section needed a revision, which we did in the results and discussion section.To further address this point that was also raised by the editor we conducted additional analyses of the data and present results for the center 7 (MDS registry at a university) separately in a new table 3. By this the differences in data collection and composition of the respective cohorts can be reflected. The fi...

show abstract

“…Note in this regard that 6 patients with serum ferritin levels >1000μg/L were not chelated because their physician did not consider the threshold for chelation achieved, and 7 because there had not been sufficient prior RBC transfusions. Lastly, there is evidence that, in some patients, effective long-term chelation (1-4 years) may stimulate haemopoiesis resulting in a return to transfusion independence [40] and decrease cardiac iron content [41]. This emphasizes the importance of applying generally accepted guidelines for iron chelation treatment while also considering individual patient factors beyond these guidelines to offer patients individualized treatment plans.…”

Section: Discussionmentioning

confidence: 99%

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

et al. 2011

View full text Add to dashboard Cite

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 ABSTRACT Transfusion-dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions.Transfusion-dependency is associated with leukemic progression and shorter survival.Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76 and median age at diagnosis of MDS was 74. Patients had received an average of 13.4+7.6 RBC units in the past four months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1550g/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of IPSS, FAB, and/or WHO status, though chelated patients had received more RBC transfusions (p=0.014).Iron chelation therapy may be underutilized in transfusion-dependent patients.

show abstract

The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload

Cited by 183 publications

References 24 publications

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

Contact Info

Product

Resources

About