Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major

Ann N Y Acad Sci. 2016 Mar;1368(1):115-21. doi: 10.1111/nyas.13027. Epub 2016 Mar 21.

Abstract

Solid evidence has established the negative impact of high iron burden and related tissue damage on the outcome of hemopoietic stem cell transplantation for thalassemia major. Recent improvements in our knowledge of iron metabolism have been focused on elevated non-transferrin-bound iron and labile plasma iron levels in the peritransplantation period as potential contributors to tissue toxicity and subsequent adverse transplant outcome. As mouse models have shown, iron overload can injure bone marrow hematopoiesis by increasing reactive oxygen species. The Pesaro experience, conducted in the deferoxamine-only era, clearly defined three iron-related factors (liver fibrosis, hepatomegaly, and quality of lifelong chelation) as significantly affecting transplant outcome. The detrimental effect of iron has only been clarified in recent years. Active interventional strategies are ongoing. Although successful hematopoietic stem cell transplantation clinically resolves the thalassemia marrow defect, patients still remain carriers of iron overload and of all the clinical complications acquired during prior years of transfusion therapy. Therefore, adequate "iron diagnosis" and management is mandatory after hemopoietic stem cell transplantation. In transplanted thalassemia patients, body iron should be returned to within the normal range. Phlebotomy is the gold standard to reduce iron burden; though deferoxamine is a proven, acceptable alternative, clinical investigations on deferasirox are ongoing.

Keywords: LPI; NTBI; hematopoietic stem cell transplantation; iron overload; thalassemia.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzoates / administration & dosage
  • Deferasirox
  • Disease Management*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / trends*
  • Humans
  • Iron Chelating Agents / administration & dosage
  • Iron Overload / blood*
  • Iron Overload / epidemiology
  • Iron Overload / therapy*
  • Triazoles / administration & dosage
  • beta-Thalassemia / blood*
  • beta-Thalassemia / epidemiology
  • beta-Thalassemia / therapy*

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Deferasirox