Prognostic Impact of Elevated Serum Ferritin in Patients Undergoing Myeloablative Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 595-595 ◽  
Author(s):  
Philippe Armand ◽  
Corey S. Cutler ◽  
Haesook T. Kim ◽  
Vincent T. Ho ◽  
John Koreth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Ferritin Level ◽  
Elevated Serum ◽  
Albumin Level ◽  
Prognostic Impact ◽  
Disease Free

Abstract Patients undergoing allogeneic stem cell transplantation (alloSCT) for hematologic malignancies are often highly transfused, and thus at risk for transfusion-associated iron overload. In other settings, such as thalassemia or hemochromatosis, iron overload has been associated with organ toxicity, particularly hepatotoxicity, as well as with an increased susceptibility to infection. Since hepatic and infectious complications are frequent and life-threatening in patients undergoing alloSCT, iron overload could potentially be an important contributor to treatment-related morbidity and mortality after transplantation. We studied 935 consecutive patients who underwent myeloablative alloSCT at our institution between 1997 and 2005. A pre-transplant serum ferritin level, which we used as a surrogate measure of iron load, was available for 600 of the 935 patients (64%). The median ferritin level was 864ng/ml. The percentage of patients with serum ferritin ≥1000ng/ml was 47%. This percentage varied significantly between disease types, being lowest (6%) in patients with CML and highest (79%) in patients with AML. A ferritin level ≥1000ng/ml was associated with significantly worse overall and disease-free survival, as shown in the figure. Figure Figure This was confirmed in proportional hazards models using the following covariates: age, type and stage of disease, cytogenetic risk group for AML and MDS, conditioning regimen, HLA match, graft source, GVHD prophylaxis regimen, CMV serostatus, gender, prior transplant, and year of transplantation. In this model, the hazard ratio for mortality associated with ferritin ≥1000ng/ml was 1.7 (95%CI=1.3 to 2.4, p=0.0005). In competing risks regression analysis, using the same covariates, an elevated serum ferritin was associated with a significant increase in non-relapse mortality (NRM) (HR=1.6, p=0.02), but not with a significant increase in the risk of relapse. The greatest impact of elevated serum ferritin on survival and NRM was in patients with MDS (HR for mortality=3.0, p=0.001). Because serum ferritin is an acute phase reactant, we performed the same analyses using pre-transplant albumin level as an additional covariate that could reflect general inflammatory state. Although albumin level was of independent prognostic significance, its inclusion in the multivariate models did not alter the conclusions. Finally, in logistic regression analyses, elevated serum ferritin was associated with a non-significant increase in the risk of veno-occlusive disease (OR=1.6, p=0.09), but not in an increased risk of acute GVHD (OR=0.9, p=0.4) or specifically of acute liver GVHD (OR=1.2, p=0.5). Conclusions: in patients undergoing myeloablative alloSCT, and particularly in those with MDS, an elevated serum ferritin is associated with significantly higher NRM, as well as significantly lower disease-free and overall-survival. Our results could be helpful in estimating prognosis for patients who are candidates for myeloablative alloSCT. They also pave the way for prospective trials on the impact of iron overload and on the possible beneficial role of iron chelation in this patient population.

Prognostic Impact of Posttransplantation Serum Ferritin In Allogeneic Stem Cell Transplantation for Leukemia or Myelodysplastic Syndrome.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3444-3444
Author(s):  
Heiwa Kanamori ◽  
Takayoshi Tachibana ◽  
Ayumi Numata ◽  
Masatsugu Tanaka ◽  
Yoshiaki Ishigatsubo ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Disease Risk ◽  
Ferritin Level ◽  
Standard Risk

Abstract Abstract 3444 Background: Although pretransplantation iron overload is an adverse prognostic factor in patients undergoing allogeneic stem cell transplantation (SCT), the impact of posttransplantation iron overload on the outcome is not clear. In this study, we retrospectively assessed the association of the posttransplantation serum ferritin level with the result of transplantation in patients surviving for 1 year or more after SCT. Patients and Methods: The serum level of ferritin, a marker of iron overload, was measured at the time of preconditioning and then annually in adult patients who underwent SCT between January 2000 and December 2008. Patients who received repeat transplantation or died within 1 year after the first SCT were excluded. There were 107 patients (pts), including 51 pts with acute myeloid leukemia, 30 pts with acute lymphoblastic leukemia, 14 pts with myelodysplastic syndrome, and 12 pts with chronic myelogenous leukemia. Their median age was 41 years (range: 16–60 years), with 52 males and 55 females. The disease risk at transplantation was standard risk in 82 pts and high risk in 25 pts. Myeloablative preconditioning was employed for 87 pts and reduced-intensity preconditioning was done for 20 pts. Bone marrow transplantation, peripheral blood stem cell transplantation, and cord blood transplantation were performed in 74, 25, and 8 pts, respectively. The serum ferritin level was categorized as low (< 1000 ng/ml) or high (≥ 1000 ng/ml). Patients who had one or more high ferritin levels after SCT were classified into the high ferritin group. Results: The median serum ferritin level before transplantation and 1, 2, 3, 4 and 5 years after SCT was 770 (n=107), 695 (n=75), 590 (n=65), 552 (n=61), 476 (n=51), and 430 (n=44) ng/ml, respectively. The median amount of red blood cells (RBC) transfused within 1 year after SCT was 6 units (range: 0–128). Patients receiving more than 6 units of RBC had significantly higher serum ferritin levels from 1 to 3 years after SCT. Patients with chronic graft-versus-host disease (cGVHD) showed significantly higher serum ferritin levels from 2 to 4 years after SCT compared to patients without chronic GVHD. There was no significant difference between the low and high pretransplantation ferritin groups with respect to 5-year overall survival (OS) (78% vs 82%, p=0.329). On univariate analysis, factors associated with worse 5-year OS included a high disease risk at transplantation (vs standard risk: 60 vs 87%, p=0.009), higher amount of RBC transfusion after SCT (vs lower: 73 vs 87%, p=0.015), the presence of cGVHD (vs absence: 73 vs 90%, p=0.023) and a high ferritin level after SCT (vs low ferritin: 64 vs 91%, p<0.001). A high ferritin after SCT was independently associated with worse 5-year OS according to multivariate analysis (relative to low ferritin; hazard ratio (HR), 3.42; 95% confidence interval (CI), 1.21–9.71; p=0.021). In addition multivariate analysis showed that a high disease risk (HR, 2.64; CI, 1.05–6.58; p=0.037) and a high ferritin level after SCT (HR, 5.24; CI, 1.94–14.27; p=0.001) were independent determinants of 5-year disease-free survival. Furthermore, the cumulative incidence of relapse was significantly higher in patients without cGVHD (HR, 3.44; CI, 1.19–9.92; p=0.023) and those with high ferritin levels after SCT (HR, 5.53; CI, 1.86–16.45, p=0.002). The cumulative non-relapse mortality rate was significantly higher in patients with cGVHD and high ferritin levels after SCT according to univariate, but not multivariate, analysis. Conclusions: Elevation of the serum ferritin level after SCT was significantly associated with a worse outcome for patients surviving more than 1 year, although various factors including RBC transfusion and/or cGVHD might have a role in the increase of posttransplantation serum ferritin. These results might help to decide which patients should be treated with iron chelating therapy after SCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4586-4588 ◽  
Author(s):  
Philippe Armand ◽  
Haesook T. Kim ◽  
Corey S. Cutler ◽  
Vincent T. Ho ◽  
John Koreth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Iron overload could be a significant contributor to treatment-related mortality (TRM) for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). We studied 590 patients who underwent myeloablative allogeneic HSCT at our institution, and on whom a pretransplantation serum ferritin was available. An elevated pretransplantation serum ferritin level was strongly associated with lower overall and disease-free survival. Subgroup multivariable analyses demonstrated that this association was restricted to patients with acute leukemia or myelodysplastic syndrome (MDS); in the latter group, the inferior survival was attributable to a significant increase in TRM. There was also a trend toward an increased risk of veno-occlusive disease in patients with high ferritin. Our results argue that iron overload plays an important role in transplantation outcome for patients with acute leukemia or MDS, as it does in thalassemia. They also suggest future prospective trials to examine the potential benefit of chelation therapy in this setting.

scholarly journals Prognostic Impact of Posttransplantation Iron Overload after Allogeneic Stem Cell Transplantation

2013 ◽  
Vol 19 (3) ◽  
pp. 440-444 ◽  
Author(s):  
Sara C. Meyer ◽  
Alix O’Meara ◽  
Andreas S. Buser ◽  
André Tichelli ◽  
Jakob R. Passweg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Prognostic Impact

Influence of Pretransplantation Serum Ferritin on Children Beta-Thalassemia Major Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5520-5520
Author(s):  
Yongsheng Ruan ◽  
Xuedong Wu ◽  
Xiaoqin Feng ◽  
Yuelin He ◽  
Chunfu Li
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Hematopoietic Stem

Abstract Objectives: To evaluate the influence of pretransplantation serum ferritin on children β-thalassemia major (β-TM) undergoing allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis of 266 HLA-matched children with β-TM from January 2009 and November 2014 was performed. Transplantation conditioning regimen of these children was the NF-08-TM protocol. Median follow-up time was 28 months (3~62months). We observed the relationship between pretransplantation serum ferritin level and transplantation complications which included infection, graft versus host disease(GVHD),veno-occlusive disease(VOD) and death. Results: Transplantation-related death occurred in 18 of 266 patients (6.8%). Five-year overall survival (OS) was found to be 92.8%. Among various complications, only infection was significantly associated with the high serum ferritin level (t=-2.673, P=0.008), especially serum ferritin above 3449.5μg/L(P=0.000). Meanwhile infection was the most common complication and severe infection would be main cause of deaths. Conclusions: NF-08-TM conditioning regimen was the optimization for HLA-matched β-TM patients. High pretransplantation serum ferritin level would bring high infection occurrence. Disclosures No relevant conflicts of interest to declare.

Markers of Iron Overload Are Poor Prognostic Factors in Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5228-5228
Author(s):  
Rebecca Connor ◽  
Istvan Molnar ◽  
James Lovato ◽  
Manisha Grover ◽  
David Hurd ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Transferrin Receptor ◽  
Serum Transferrin Receptor ◽  
Iron Parameters

Abstract Transfusional iron overload is common in survivors of acute leukemia and hematopoietic stem cell transplantation and might cause long-term liver dysfunction. Routine evaluation for iron overload in such patients is recommended because excess iron can be readily removed from the body via phlebotomy or chelation. Iron overload might be associated with worse survival after stem cell transplantation in these diseases. We were interested in determining whether levels of the iron binding protein ferritin or the serum transferrin receptor (TfR) were predictive for survival. In a prospective study, we examined the correlation between iron parameters at the time of transplantation and overall survival. Serum ferritin, transferrin saturation, and TfR were measured before preparative regimen on patients who underwent hematopoietic stem cell transplantation between 1999 and 2004 for the diagnosis of aplastic anemia, MDS or acute leukemia (n=79). We used the number of transfusions before transplantation as a measure of iron load. Among these iron markers, serum ferritin correlated the most with the number of transfusions, regardless of remission status. High ferritin (&gt;1,500 ng/ml), low TfR (≤4 μg/ml) and low TfR/log ferritin ratio (≤2) were associated with shorter survival (p=0.005, 0.04, and 0.001 respectively)(Figure 1). Among acute leukemia patients in remission, there was no difference in overall survival between patients with high or low iron markers. Markers of iron excess (serum ferritin &gt;1,500 ng/ml, TfR/log ferritin ratio ≤2) at the time of stem cell transplantation is associated with shorter survival in MDS, aplastic anemia and acute leukemia with active disease. These results demonstrate that knowledge of patient ferritin and TfR levels can aid in risk stratification. The results also suggest that patients with high levels of ferritin may benefit from iron chelation before treatment. Figure 1: Overall Survival based on iron parameters (A) Serum Ferritin (B) Serum Transferrin Receptor (C) TfR (mcg/ml) divided by log ferritin (ng/ml) Figure 1:. Overall Survival based on iron parameters (A) Serum Ferritin (B) Serum Transferrin Receptor (C) TfR (mcg/ml) divided by log ferritin (ng/ml)

1-Year Results From A Prospective Randomized Trial Comparing Phlebotomy with Deferasirox for the Treatment of Iron Overload in Pediatric Patients with Thalassemia Major Following Curative Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 904-904 ◽  
Author(s):  
Adlette Inati ◽  
Nada Sbeiti ◽  
Evelyne Khoriaty ◽  
M Domenica Cappellini ◽  
Suzanne Koussa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Randomized Trial ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Research Funding ◽  
Thalassemia Major ◽  
Prospective Randomized Trial ◽  
Significant Difference

Abstract Abstract 904 Background: As a result of previous transfusions, β-thalassemia major (TM) patients who have undergone curative hematopoietic stem cell transplantation (HSCT) are at increased risk of iron overload. There are, however, limited data on iron removal in such patients with either phlebotomy (PHL) or iron chelation. The aim of this study was to compare the efficacy, safety and convenience of the oral iron chelator deferasirox (DFX; Exjade®) with PHL for the treatment of iron overload in children with TM following HSCT, over a 1-year period. Methods: LB03T is a prospective, randomized trial enrolling children with TM aged 2-<18 yrs who had undergone HSCT. Patients were chelation-naïve, hepatitis B- and C-negative, with confirmed iron overload (serum ferritin ≥500 ng/mL on ≥2 monthly occasions, and liver iron concentration [LIC] >3 mg Fe/g dry weight [dw]). Eligible patients were randomized to PHL (6 mL/kg blood/2 weeks) or DFX (10 mg/kg/day starting dose; 5 mg adjustments up to 20 mg/kg/day were permitted). One of the primary endpoints was change in LIC assessed using magnetic resonance imaging techniques. Changes in serum ferritin levels, hemoglobin (Hb), total iron binding capacity (TIBC), non-transferrin-bound iron (NTBI), adverse events (AEs) and compliance with study treatment (PHL: ratio of performed:planned; DFX: tablet count) were also assessed. Convenience of treatment was evaluated using parents' responses to pre-prepared questions. Results: 27 patients were randomized to DFX or PHL; one patient randomized to PHL refused treatment, hence 12 patients received DFX and 14 received PHL. Mean age was 12.4 yrs and 53.8% were male. Patients were followed up for a mean of 12.0 months. 2 and 5 patients had DFX dose increases to 15 and 20 mg/kg/day, respectively. Mean DFX dose at last visit was 11.0 and 18.1 ng/mL in the LIC≤7 and LIC>7 groups, respectively. Median serum ferritin was significantly reduced from baseline over 12 months with DFX (–497.5 ng/mL, P=0.004 vs baseline) and PHL (–901.8 ng/mL, P<0.0001 vs baseline); there was no significant difference between groups (P=0.425). Mean LIC (for 20 patients with evaluable LIC following 1 yr of treatment) was significantly reduced with DFX (–5.78 mg Fe/g dw, P=0.0005 vs baseline) and PHL (–3.27 mg Fe/g dw, P=0.050 vs baseline); no significant difference between groups (P=0.270). In patients with serum ferritin levels ≥1000 ng/mL at baseline, DFX resulted in a significantly greater decrease in mean LIC than PHL (–8.1 vs –3.5 mg Fe/g dw, P=0.048; Table). For TIBC, the increase with DFX was significantly greater than with PHL (P=0.0003). NTBI decreased significantly from baseline by –1.91 μmol/L (P=0.014; n=9) with DFX (baseline 2.0 μmol/L) and –2.83 μmol/L (P=0.0015; n=11) with PHL (baseline 2.3 μmol/L); there was no significant difference between groups (P=0.362). NTBI and LIC were positively correlated (R=0.565; P=0.0026) at baseline and at last follow-up (R=0.881; P<0.0001). Baseline mean Hb was 12.5 and 12.6 g/dL in the DFX and PHL groups, respectively; levels were maintained with DFX (change –0.17 g/dL; P=0.426) (PHL: change –0.53 g/dL; P=0.033); no significant difference between groups (P=0.279). AEs reported for patients receiving DFX were skin rash [n=1], gastrointestinal upset [n=1], increased liver function tests [n=1]; for patients receiving PHL, difficulty with venous access [n=4] and distress during procedure [n=1] were reported. Compliance was excellent for 11 (91.7%) and 12 (85.7%); good for 1 (8.3%) and 1 (7.1%); and poor with 0 and 1 (7.1%) patients receiving DFX or PHL, respectively. Parents of 13/14 children randomized to PHL desired their children to receive DFX due to pain, risk of anemia and longer/more frequent hospital visits associated with PHL. Parents of 1/14 children were satisfied with PHL due to concerns over possible AEs with DFX. Conclusions: In pediatric post-HSCT patients with TM, both LIC and serum ferritin were reduced with DFX and PHL over 1 year. In patients with higher baseline iron burden, DFX decreased LIC to a greater extent than PHL. TIBC was also significantly increased with DFX compared with PHL. DFX dose adjustments from 10 to 20 mg/kg/day were required to achieve therapeutic goals in some patients, underscoring the need for appropriate and timely dose adjustments. DFX had a clinically manageable safety profile, compliance was high and the majority of parents with children receiving PHL stated a desire to switch to DFX. Disclosures: Inati: Novartis: Honoraria, Research Funding, Speakers Bureau. Cappellini:Novartis: Speakers Bureau. Taher:Novartis: Honoraria, Research Funding.

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