Published online 14 January 2009
Haematologica, Vol 94, Issue 2, 295-296 doi:10.3324/haematol.2008.001651
Copyright © 2009 by Ferrata Storti Foundation

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Transfusion Iron Overload

Italian Society of Hematology guidelines for thalassemia and non-invasive iron measurements: author reply

Emanuele Angelucci¹, Giovanni Barosi², Monia Marchetti², Sante Tura³

¹ Hematology Department and BMT Unit, Cancer Center "Armando Businco", Cagliari
² Laboratory of Clinical Epidemiology, Fondazione IRCCS Policlinico S. Matteo, Pavia
³ Istituto di Ematologia ed Oncologia Medica "Seragnoli", Università di Bologna, Italy

Correspondence: Emanuele Angelucci, MD. Hematology Department and BMT Unit, Cancer Center "Armando Businco", via Edward Jenner, 09121 Cagliari, Italy. E-mail:emnang{at}tin.it

Key words: clinical practice guidelines, systematic review, thalassemia major, SQUID, biomagnetic liver susceptometry..

We greatly appreciated the comments of Dr Nielsen and colleagues on the guidelines for the management of iron overload in thalassemia we produced on behalf of the Italian Society of Hematology.¹ Dr Nielsen and colleagues are concerned about our interpretation of data regarding the accuracy of biomagnetic liver susceptometry (BLS) as a non-invasive method for assessing liver iron concentration. By analyzing the existing evidence, we relied on the only two references dealing with a correlation between BLS and liver iron concentration by biopsy in patients with thalassemia. Our conclusion on the inaccuracy of BLS was mainly grounded on a paper published as an abstract by Piga et al.² in which the sentence "on average, the LIC data obtained from BLS and biopsy were related by a factor of 0.46" was interpreted as 0.46 being the correlation coefficient of the two measurements. Thus, from this factor, we derived a R² of 0.21. We also relied on the conclusion of the abstract that states "overall, LIC from biopsy was generally larger than that obtained from BLS".

Regarding the use of SQUID/BLS after the first study published by Gary Brittenham in 1982,³ no other published study has confirmed the capability of SQUID to predict hepatic iron concentration with adequate methods. Any validation study of a new diagnostic quantitative procedure must compare the new methodology with a reference gold standard. Particularly a determination coefficient (R²) with a prediction interval (95% CI) should be reported.

Above all in this specific case the 95% prediction interval would be reasonably narrow not extending over the identified threshold for iron concentration tissue damage and death risk.⁴ In the setting of iron overload, the reference standard is the validated biochemical determination of hepatic iron concentration adequate, non cirrhotic, liver biopsy specimens.⁵ We are not aware of any such study with results similar to that reported by Dr Brittenham with similar 95% confidence prediction interval. Studies comparing SQUID/BLS with other technologies are of minor relevance. Moreover the cited debate on dry weight-wet weight relationship developed after an industry sponsored trial,² which, although important for future development, raises concern for the thousands of determinations performed for clinical practice before 2006.

In conclusion, although SQUID/BLS is a highly scientific methodology, because of the limited availability, the limited literature in peer reviewed journals, the reported difficulties, and the availability of other non-invasive methods (MRI-R2) it appears rational to recommend its utilization only inside clinical trials.

TOP References

 

1. Angelucci E, Barosi G, Camaschella C, Cappellini MD, Cazzola M, Galanello R, et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders. Haematologica 2008;93:741-52.[Abstract/Free Full Text]
2. Piga A, Fisher R, Harmatz P, St Pierre TG, Longo F, Fung E, et al. Comparison of LIC obtained from biopsy, BLS and R2-MRI in iron overloaded patients with β-thalassemia, treated with deferasirox (Exjade, ICL670). Blood 2005;106:755a.
3. Brittenham GM, Farrell DE, Harris JW, Feldman ES, Danish EH, Muir WA, et al. Magnetic-susceptibility measurement of human iron stores. N Engl J Med 1982;307:1671-5.[Abstract]
4. Olivieri NF. The {beta}-Thalassemias. N Engl J Med 1999;341:99-109.[Free Full Text]
5. Angelucci E, Brittenham GM, McLaren CE, Ripalti M, Baronciani D, Giardini C, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med 2000;343:327-31.[Abstract/Free Full Text]

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