title: 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.
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 microg Fe/g wet weight [ww]) or severe IO (LIC >2,000 microg Fe/g ww). Fifty-seven patients had a ferritin level <1000 ng/mL: the median time between HSCT and assessment of ferritin level was 1006 days (range, 93-5239 days), significantly different from the median time of 183 days (range, 78-2957 days) in the 45 patients with a ferritin level >1000 ng/mL. Out of 42 patients evaluated by SQUID, 29 had moderate to severe IO (median LIC value, 1493 microg 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 microg Fe/g ww to 625 microg 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.
authors.affiliation: Hematology 2 Unit, San Giovanni Battista Hospital and University, Turin, Italy. abusca@molinette.piemonte.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Busca
authors.forename: Michele
authors.initials: M
authors.lastname: Falda
authors.forename: Paola
authors.initials: P
authors.lastname: Manzini
authors.forename: Sergio
authors.initials: S
authors.lastname: D'Antico
authors.forename: Adriano
authors.initials: A
authors.lastname: Valfrè
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Calabrese
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiappella
authors.forename: Stefano
authors.initials: S
authors.lastname: D'Ardia
authors.forename: Filomena
authors.initials: F
authors.lastname: Longo
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D055664:Electrochemical Techniques / Q000295:instrumentation*; D005260:Female; D005293:Ferritins / Q000097:blood; D006086:Graft vs Host Disease / Q000150:complications; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007501:Iron / Q000032:analysis / Q000097:blood / Q000378:metabolism; D019190:Iron Overload / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D008099:Liver / Q000737:chemistry / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000453:epidemiology; D009894:Opportunistic Infections / Q000150:complications; D018962:Phlebotomy; D012307:Risk Factors; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005293:Ferritins; D007501:Iron