J Korean Med Sci.  2012 Apr;27(4):363-369. 10.3346/jkms.2012.27.4.363.

Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Affiliations
  • 1Faculty of Human Medicine, Hannover Medical School, Hannover, Germany.
  • 2Faculty of Medicine, University of British Columbia, Vancouver, Canada.
  • 3Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kwsped@skku.edu
  • 4Department of Pediatrics, Dong-A Medical Center, Dong-A University College of Medicine, Busan, Korea.

Abstract

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.

Keyword

High-Dose Chemotherapy; Autologous Stem Cell Transplantation; Iron Overload; Deferasirox; Iron Chelation Treatment; Neuroblastoma

MeSH Terms

Antigens, CD34/metabolism
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Benzoic Acids/therapeutic use
Blood Transfusion/*adverse effects
Child
Child, Preschool
Creatinine/blood
Ferritins/blood
Follow-Up Studies
Humans
Infant
Iron Chelating Agents/therapeutic use
Iron Overload/*etiology
Neuroblastoma/drug therapy/*therapy
Retrospective Studies
Risk Factors
*Stem Cell Transplantation
Transplantation, Autologous
Triazoles/therapeutic use

Figure

  • Fig. 1 Serum ferritin during post-SCT follow-up. (A) Serum ferritin level peaks at one month after the second HDCT/autoSCT and steadily decreases without iron chelation. (B) Ferritin level at 1 yr after the second HDCT/autoSCT remaines high and 47.7% of the patients had ferritin levels greater than 1,000 ng/mL. (C) Serum ferritin level at 1 yr after the second HDCT/autoSCT has a positive correlation with RBC transfusion amount during 1 yr after the second HDCT/autoSCT.

  • Fig. 2 Organ dysfunction at 1 yr after the second HDCT/autoSCT. There was no difference in major organ function prior to the second HDCT/autoSCT between the two groups. However, serum creatinine level (A) and alanine aminotransferase level (B) are significantly higher in patients with high ferritin levels at 1 yr after the second HDCT/autoSCT.

  • Fig. 3 Transfusion amount and serum ferritin according to the number of CD34+ cells. A less number of CD34+ cells (< 2 × 106/kg) in the second HDCT/autoSCT is associated with a greater amount of RBC transfusion for 1 yr after the second HDCT/autoSCT (A), and accordingly, a higher ferritin level at 1 yr after the second HDCT/autoSCT (B).


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