Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation: Quantification of Iron Burden by a Superconducting Quantum Interference Device (SQUID) and Therapeutic Effectiveness of Phlebotomy

Alessandro Busca, Michele Falda, Paola Manzini, Sergio D'Antico, Adriano Valfrè, Franco Locatelli, Roberto Calabrese, Annalisa Chiappella, Stefano D'Ardia, Filomena Longo, Antonio Piga

Research output: Contribution to journalArticle

Abstract

Iron overload (IO) is a known adverse prognostic factor in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia and appears to play a similar role in patients with other hematologic disorders. The estimation of IO is based primarily on serum ferritin level; however, many confounding factors can result in ferritin overestimation, especially in HSCT recipients. The aim of the present study was to quantify IO after HSCT using a superconducting quantum interference device (SQUID), and to evaluate the impact of IO on hepatic function and infections. In addition, the feasibility of iron depletion was investigated. A total of 102 consecutive allogeneic HSCT recipients admitted to our outpatient department between December 2005, and December 2007, were analyzed. Primary diagnosis included acute leukemia/myelodysplastic syndrome in 61% of cases. Assessment of IO after HSCT included serum ferritin; in those with hyperferritinemia (ferritin > 1000 ng/mL), liver iron concentration (LIC) was evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to patients with moderate IO (LIC 1000-2000 μg Fe/g wet weight [ww]) or severe IO (LIC >2000 μg Fe/g ww). Fifty-seven patients had a ferritin level 1000 ng/mL. Out of 42 patients evaluated by SQUID, 29 had moderate to severe IO (median LIC value, 1493 μg Fe/g ww [range, 1030-3253]). In a multivariate analysis, a significant correlation was found between a ferritin level >1000 ng/mL and the presence of at least one abnormal liver function test (LFT) ORo = 6.8; 95% CI = 2.2-20.6). In addition, the rate of proven/probable invasive fungal disease was significantly higher in the patients with hyperferritinemia (13% vs 0%; P = .006). Nineteen of the 24 patients considered eligible for iron-depletion therapy underwent regular phlebotomy; 13 completed the program in a median of 287 days (range, 92-779 days), reaching the target of a ferritin level <500 ng/mL; LIC was significantly reduced (median, 1419 μg Fe/g ww to 625 μg Fe/g ww; P <.001) in 8 of the 9 patients who were revaluated by SQUID at the end of the iron-depletion program. In conclusion, the measurement of LIC obtained by SQUID documented the presence of moderate/severe IO in 69% of the patients with a high ferritin level. Our data showed that in HSCT recipients, high ferritin level is an independent risk factor for abnormal LFTs, and IO may be considered a potential risk factor for fungal infections. A phlebotomy program may be feasible in two-thirds of the patients who might benefit from iron depletion.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2010

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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