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.

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.

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.

Elevated Serum Ferritin Predicts the Delay of Engraftment and High Incidence of Blood Stream Infection within 100 Days After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1135-1135 ◽  
Author(s):  
Heiwa Kanamori ◽  
Takayoshi Tachibana ◽  
Hirotaka Takasaki ◽  
Masatsugu Tanaka ◽  
Yoshiaki Ishigatsubo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Serum Ferritin ◽  
Disease Risk ◽  
Blood Stream Infection ◽  
Blood Stream ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Abstract 1135 Poster Board I-157 Background Iron overload is thought to be a risk factor for morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). This study particularly evaluated the impact of pre-transplant iron overload on blood stream infection (BSI) which is one of transplant related mortality (TRM) after allogeneic HSCT for hematologic malignancies. Patients and methods The level of serum ferritin, a surrogate marker of iron overload, was measured before the beginning of the conditioning procedure in adult patients who underwent allogeneic HSCT between January 2000 and December 2008. A total of 154 patients (pts) included 93 pts with acute myeloid leukemia (AML), 40 pts with acute lymphoid leukemia (ALL), and 21 pts with myelodysplastic syndrome (MDS). The median age was 43 years (range, 17-63 years). There were 80 males and 74 females. A disease risk at the time of transplant indicated a standard risk in 97 pts and a high risk in 57 pts. Myeloablative conditioning (MAC) was employed for 123 pts and reduced intensity conditioning (RIC) was for 31 pts. Bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT) were done for 98, 28, and 28 pts, respectively. Logistic regression model was used for statistical analysis. Results The median level of serum ferritin at pre-transplant was 1031 ng/ml (range: 31-11,500). The patients were divided into 2 groups (low ferritin group and high ferritin group) according to the median level of pre-transplant ferritin. There was no significant difference between the low and high ferritin groups for pre-transplant factors such as age, diagnosis and disease risk. Forty-three patients (28%) experienced BSI within 100 days after HSCT. In univariate analysis, the incidence of BSI was significantly low in the low ferritin group (P=0.040) and PBSCT (P=0.010). However, the incidence of BSI was not associated with age (under 50 yrs vs. more than 50 yrs), conditioning regimen (MAC vs. RIC), and disease risk (standard vs. high). Patients receiving PBSCT had significantly lower incidence of BSI by multivariate analysis (hazard ratio (HR) =0.141, 95%CI: 0.028-0.706, P=0.017). In subgroup analysis of 114 patients with AML/MDS, the low incidence of BSI was associated with PBSCT (HR=0.135, 95%CI: 0.025-0.717, P=0.019) and the low ferritin group (HR=0.352, 95%CI: 0.146-0.848, P=0.020) by multivariate analysis. The time to engraftment was shorter in the low ferritin group (median: 14 days, range: 4-41 days) compared with the high ferritin group (15 days, 0-51 days) with statistical significance (P=0.0293). Conclusions/Methods Pre-transplant serum ferritin was a predictor for TRM, especially BSI within 100 days following allogeneic HSCT. Furthermore, iron overload before transplant adversely affects the time to engraftment in myeloid malignancies, and this relationship may somewhat influence on the onset of BSI. Disclosures No relevant conflicts of interest to declare.

Significant Impact Of Iron Chelation After Allogeneic Hematopoetic Stem Cell Transplantation On Disease Recurrence: Potential Anti-Leukemic Activity

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 180-180 ◽  
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Helene Labussiere ◽  
Marie Y. Detrait ◽  
...  
Keyword(s):  
Stem Cell ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Disease Recurrence ◽  
Hazard Ratio ◽  
Iron Chelators ◽  
Myeloid Leukemias

Abstract Iron overload (IO), primarily related to multiple red blood cell transfusions, is a relatively common complication in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Elevated pre-transplant ferritin level, a surrogate marker of iron overload, was demonstrated to be an important cause of mortality and morbidity in patients who have undergone allo-HSCT. Excessive iron accumulation results in tissue damage and organ failure, mainly as a result of the generation of free radicals that cause oxidative damage and organ dysfunction. Iron chelators have been widely used leading to normalisation for ferritine level and lower IO-related complications. As iron has a fundamental role in cell survival affecting pathways involved in DNA synthesis, cell differentiation, and apoptosis, some studies evaluated the anti-proliferative activity of iron chelators in cancer and leukemia patients on disease recurrence. The objective of this study was to determine at a first time the impact of serum ferritin level measured at time of allogeneic HSCT in adult patients with hematological disorders on the different outcomes and to investigate at a second time the role of iron chelation on relapse incidence. We included 158 patients, 100 males and 58 females with a median age of 45 years (18-67) who underwent allo-HSCT between 2002 and 2010. There were 83 acute myeloid leukemias, 10 chronic myeloid leukemias, 11 myelodysplastic syndromes, 7 myeloproliferative disorders, 19 myelomas, 9 non-Hodgkin lymphomas, 6 Hodgkin diseases, 5 aplastic anemias and 3 hemoglobinopathies. Sixty-seven (42%) patients were sex mismatched (F→M:37; M→F:30); for ABO compatibility, 61% were compatible, 18% had minor incompatibility and 21% had major incompatibility. Concerning the HSCT procedures, 60 patients (38%) received peripheral blood stem cell and 98 (62%) received bone marrow from 97 (61%) HLA related donors [matched, n=76; mismatched, n=21], and 61 (39%) HLA unrelated donors [matched, n=36; mismatched, n=25] after myeloablative [n=64, (41%)] or reduced intensity conditioning [n=94, (59%)]. At transplantation, 91 (58%) were in complete remission (CR) or chronic phase [CR1: n=61 (67%); ≥CR2: n=30 (33%)]. The median serum ferritin level at HSCT was 1327 microg./l (26-14136); 31(20%) patients had a level 26-500, 33 (21%) had a level 500-2500, and 94 (59%) >2500. There was no significant correlation between the different ferritin levels, disease kind and status at HSCT. After transplantation, 23 patients received iron chelating agents after a serum ferritin level of 1000 microg/l and stopped when the level decreased below 1000. The cumulative incidence of acute GVHD ≥ II at 3 months was 14% (11-16.5) with 10.5% (8-13) for grade III and 7% (5-9) for grade IV; the 1 year cumulative incidence of limited and extensive chronic GVHD were 4% (2-6) and 12.4% (9-16) respectively. After a median follow-up of 18 months (1-106), the 5 years OS probability was 65% for patients with ferritin level below 500 microg./l, 39% for level between 500 and 2500 microg./l and 28% for level > 2500 micog./l, [Hazard ratio= 3.5 (1.5-8.1), p=0.002]; this was explained by a significant higher TRM in patients with level >2500 [Hazard ratio= 4.3 (1.02-18), p=0.04]. Interestingly, we found in multivariate analysis that patients receiving iron chelators had significantly better OS [5 years OS= 59% vs. 34% for non-chelated patients, Hazard ratio= 0.34 (0.15-0.76), p=0.008], (Figure 1a), and experienced less disease relapse [5 years relapse incidence= 18% vs. 41% for non-chelated patients, Hazard ratio= 0.22 (0.07-0.73), p=0.012], (Figure 1b). In conclusion, we confirmed the negative impact of iron overload on the outcomes allo-HSCT recipients. More importantly, we demonstrated that iron chelators have a positive impact in reducing disease relapse by the possible mechanism of iron deprivation in leukemic cells. This clinical observation needs to be confirmed by prospective randomized trials.Figure 1a: Overall survival probability and b: relapse incidence in patients with or without iron chelationFigure 1. a: Overall survival probability and b: relapse incidence in patients with or without iron chelation Disclosures: Michallet: Novartis: Honoraria, Research Funding. Nicolini:Novartis: Consultancy, Honoraria, Research Funding.

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)

Sign in / Sign up

Export Citation Format

Share Document