Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

Table 2

Published data showing the impact of pretransplantation serum ferritin levels on survival in HSCT recipients.

	Patient type and number	Type of HSCT	Outcome measures	Key results
Armand et al. 2007 [24]	590 patients with a variety of disorders (primarily CML, AML, or MDS)	Allogeneic (myeloablative)	Retrospective evaluation of 5-year overall survival, treatment-related mortality, disease-free survival and relapse	(i)  Elevated pre-transplantation serum ferritin strongly associated with lower overall- and  disease-free  survival (ii)  Subgroup  analysis  showed association restricted to patients with AML or MDS
Mahindra et al. 2008 [25]	315 Hodgkin or nonHodgkin lymphoma patients	Autologous	Retrospective evaluation of 6-year overall survival and relapse mortality	(i)  Pre-transplantation serum ferritin levels of >685 ng/mL associated with significantly lower overall and relapse-free survival (𝑃=.002 and .021, resp.)
Pullarkat et al. 2008 [8]	190 patients with lymphoma/myeloma or acute leukemia/myeloid malignancy	Allogeneic (myeloablative)	Prospective evaluation of day 100 survival, acute GVHD and infection complications	Elevated serum ferritin (≥1000 ng/mL)   associated  with (i)  increased  mortality  and decreased overall survival (𝑃=.038 and  .004, resp.), (ii)  increased  acute  GVHD  and increased blood stream infections (𝑃=.009 and  .042, resp.)
Platzbecker et al. 2008 [26]	172 patients with MDS	Allogeneic (myeloablative)	Retrospective assessment of the impact of transfusion dependence on patient prognosis	Transfusion dependence did not impact directly on overall survival, but transfusion burden, reflected by serum ferritin,   correlated  with (i)  greater  probability  of  acute GVHD (𝑃=.03) (ii)  inferior  overall  survival  in  patients with serum ferritin levels of >1000 ng/mL (𝑃=.03)
Kim et al. 2009 [27]	38 patients with hematologic malignancies	Allogeneic (reduced intensity conditioning)	Retrospective assessment of transplantation outcome after RIST	Elevated serum ferritin (≥1000 ng/mL)  resulted  in (i)  reduced  disease-free  survival (35.8% versus 80.6% in nonoverloaded patients,  𝑃=.01); (ii)  reduced  overall  survival (27% versus 54.6% in the iron nonoverload group, 𝑃=.03)
Kataoka et al. 2009 [28]	264 patients with a variety of disorders, (primarily acute myelogenous/lymphoblastic leukemia, CML or MDS)	Allogeneic (myeloablative and nonmyeloablative)	Retrospective evaluation of 5-year survival, nonrelapse mortality, GVHD and infection	Serum ferritin levels of ≥599 ng/mL  resulted  in: (i)  lower  overall  survival, higher nonrelapse  mortality  (𝑃<.001) (ii)  patients  with  high  serum ferritin levels were more likely to die of infection and organ failure (𝑃<.01  and <.019,  resp.); (iii)  no  significant  difference  in incidence of acute GVHD
Mahindra et al. 2009 [29]	64 patients with a variety of disorders (primarily AML, nonHodgkin lymphoma, or MDS)	Allogeneic (nonmyeloablative)	Prospective evaluation of 5-year survival	(i)  Pre-transplantation serum ferritin levels of >1615 ng/mL associated with significantly lower overall survival (𝑃=.012)
Lee et al. 2009 [30]	101 pediatric patients with a variety of disorders (primarily acute lymphoblastic/myeloid leukemia, and aplastic anemia)	Allogeneic (myeloablative)	Retrospective analysis of 5-year survival	(i)  Serum ferritin levels of >1000 ng/mL associated with reduced overall and event-free survival (𝑃=.001)
Mahindra et al. 2009 [31]	222 patients with myeloid or lymphoid leukemia, nonHodgkin lymphoma or MDS	Allogeneic (myeloablative)	Retrospective evaluation of survival and GVHD	Pre-transplantation serum ferritin levels of >1910 ng/mL  resulted  in (i)  reduced  overall  and  relapse-free survival (𝑃=.003 and  .003, resp.); (ii)  reduced  chronic  GVHD  (𝑃=.019); (iii)  increased  nonrelapse  mortality (𝑃=.042)

AML: acute myeloid leukemia; CML: chronic myeloid leukemia; GVHD: graft-versus-host disease.