Am J Blood Res 2012;2(4):243-253
Original Article
Kinetics of iron removal by phlebotomy in patients with iron overload after
allogeneic hematopoietic cell transplantation
Ann-Kathrin Eisfeld , Rainer Krahl, Nadja Jaekel, Dietger Niederwieser, Haifa Kathrin Al-Ali
Department of Hematology/Oncology, University of Leipzig, Germany
Received October 19, 2012; Accepted November 13, 2012; Epub November 25, 2012; Published November 30, 2012
Abstract: Excess body iron could persist for years after allogeneic hematopoietic cell transplantation (HCT) with possible
deleterious sequels. An iron depletive therapy with phlebotomy seems rational. Kinetics of iron removal by phlebotomy without
erythropoietin support in non-thalassemic adult patients with iron overload after HCT and the impact of pre- and post-HCT
hemochromatosis (HFE) genotype on iron mobilization were investigated. Patients and methods: Phlebotomy was initiated in
61 recipients of allografts due to hematologic malignancies (median age 48 years) after a median of 18 months. The
prephlebotomy median serum ferritin (SF) was 1697ng/ml and the median number of blood transfusions 28 units. Alanine
aminotransferase (ALT)/aspartate aminotransferase (AST), alkaline phosphates (AP), and bilirubin were elevated in 55.7%,
64% and 11.5% patients respectively. HFE-genotype was elucidated by polymerase chain reaction using hybridization probes
and melting curve analysis. Results: Phlebotomy was well-tolerated irrespective of age or conditioning. A negative iron
balance in 80% of patients (median SF 1086 ng/ml) and a rise in hemoglobin were observed (p<0.0001). Higher transfusional
burden and SF were associated with a greater iron mobilization per session (p=0.02). In 58% of patients, a plateau after an
initial steady decline in SF was followed by a second decline under further phlebotomy. The improvement in ALT (p=0.002),
AST (p=0.03), AP (p=0.01), and bilirubin (p<0.0001) did not correlate with the decline in SF. Mutant HFE-gene variants were
detected in 14/55 (25%) pre-HCT and 22/55 (40%) patients post-HCT. Overall, dissimilar pre- and posttransplantational HFE-
genotypes were detected in 20/55 (40%) patients. Posttransplantational mutant HFE variants correlated with a slower decline
in SF (p=0.007). Conclusions: Phlebotomy is a convenient therapy of iron overload in survivors of HCT. A negative iron balance
and a rise in hemoglobin were observed in the majority of patients. Liver dysfunction improved irrespective of SF reduction
suggesting a probable rapid decline of the deleterious labile plasma iron. In recipients of grafts with mutant HFE variants a
“mixed chimerism” of HFE in body tissues might be created with a change in the set point for iron regulation. The transient
plateau in SF after an initial decline might reflect iron mobilization from various tissues. (AJBR1210003).
Keywords: Iron overload, ferritin, phlebotomy, allogeneic HCT
Address all correspondence to:
Dr. Haifa Kathrin Al-Ali
Department of Hematology/Oncology
University of Leipzig, Johannesallee 32a
04103 Leipzig, Germany.
Phone: +49-341-97 13081; Fax: +49-341-97 13103
E-mail: alah@medizin.uni-leipzig.de
Original Article
Kinetics of iron removal by phlebotomy in patients with iron overload after
allogeneic hematopoietic cell transplantation
Ann-Kathrin Eisfeld , Rainer Krahl, Nadja Jaekel, Dietger Niederwieser, Haifa Kathrin Al-Ali
Department of Hematology/Oncology, University of Leipzig, Germany
Received October 19, 2012; Accepted November 13, 2012; Epub November 25, 2012; Published November 30, 2012
Abstract: Excess body iron could persist for years after allogeneic hematopoietic cell transplantation (HCT) with possible
deleterious sequels. An iron depletive therapy with phlebotomy seems rational. Kinetics of iron removal by phlebotomy without
erythropoietin support in non-thalassemic adult patients with iron overload after HCT and the impact of pre- and post-HCT
hemochromatosis (HFE) genotype on iron mobilization were investigated. Patients and methods: Phlebotomy was initiated in
61 recipients of allografts due to hematologic malignancies (median age 48 years) after a median of 18 months. The
prephlebotomy median serum ferritin (SF) was 1697ng/ml and the median number of blood transfusions 28 units. Alanine
aminotransferase (ALT)/aspartate aminotransferase (AST), alkaline phosphates (AP), and bilirubin were elevated in 55.7%,
64% and 11.5% patients respectively. HFE-genotype was elucidated by polymerase chain reaction using hybridization probes
and melting curve analysis. Results: Phlebotomy was well-tolerated irrespective of age or conditioning. A negative iron
balance in 80% of patients (median SF 1086 ng/ml) and a rise in hemoglobin were observed (p<0.0001). Higher transfusional
burden and SF were associated with a greater iron mobilization per session (p=0.02). In 58% of patients, a plateau after an
initial steady decline in SF was followed by a second decline under further phlebotomy. The improvement in ALT (p=0.002),
AST (p=0.03), AP (p=0.01), and bilirubin (p<0.0001) did not correlate with the decline in SF. Mutant HFE-gene variants were
detected in 14/55 (25%) pre-HCT and 22/55 (40%) patients post-HCT. Overall, dissimilar pre- and posttransplantational HFE-
genotypes were detected in 20/55 (40%) patients. Posttransplantational mutant HFE variants correlated with a slower decline
in SF (p=0.007). Conclusions: Phlebotomy is a convenient therapy of iron overload in survivors of HCT. A negative iron balance
and a rise in hemoglobin were observed in the majority of patients. Liver dysfunction improved irrespective of SF reduction
suggesting a probable rapid decline of the deleterious labile plasma iron. In recipients of grafts with mutant HFE variants a
“mixed chimerism” of HFE in body tissues might be created with a change in the set point for iron regulation. The transient
plateau in SF after an initial decline might reflect iron mobilization from various tissues. (AJBR1210003).
Keywords: Iron overload, ferritin, phlebotomy, allogeneic HCT
Address all correspondence to:
Dr. Haifa Kathrin Al-Ali
Department of Hematology/Oncology
University of Leipzig, Johannesallee 32a
04103 Leipzig, Germany.
Phone: +49-341-97 13081; Fax: +49-341-97 13103
E-mail: alah@medizin.uni-leipzig.de
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