Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation

Lim, Zi Yi; Fiaccadori, Valeria; Gandhi, Shreyans; Hayden, Janet; Kenyon, Michelle; Ireland, Robin; Marsh, J. W.; Ho, A Y L; Mufti, Ghulam J.; Pagliuca, Antonio

doi:10.1016/j.leukres.2009.10.028

Cited by 71 publications

(67 citation statements)

References 19 publications

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“…We and other groups have previously demonstrated that high serum ferritin levels before HSCT may reduce OS and EFS after HSCT. [1][2][3][4][5][6][7][8][21][22][23][24] To the best of our knowledge, the present study is the first to confirm these findings using a large prospective cohort.…”

Section: Discussionsupporting

confidence: 78%

“…6,[21][22][23][24] Mahindra et al 21 demonstrated that high serum ferritin levels (41910 ng/mL) reduced the risk of chronic GVHD in patients receiving myeloablative conditioning; this may be due to a reduced immune response with high serum ferritin levels. Sakamoto et al 23 described a high incidence of chronic GVHD in patients with low pretransplant serum ferritin levels ( o880 ng/mL).…”

Section: Discussionmentioning

confidence: 99%

“…Sakamoto et al 23 described a high incidence of chronic GVHD in patients with low pretransplant serum ferritin levels ( o880 ng/mL). Lim et al 22 reported that pretransplant serum ferritin levels did not influence the cumulative incidence of chronic GVHD in patients receiving reduced intensity conditioning. Our findings suggest that high serum ferritin levels before transplantation increase the risk of chronic GVHD.…”

Section: Discussionmentioning

confidence: 99%

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Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

Tanaka

Kanamori

Matsumoto

et al. 2015

Bone Marrow Transplant

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This prospective study aimed to investigate the influence of pretransplant serum ferritin levels on the outcomes of allogeneic hematopoietic SCT (HSCT). In total, 190 patients with acute leukemia or myelodysplastic syndrome were consecutively enrolled. The patients were divided into two groups: low-ferritin group (o 1000 ng/mL) and high-ferritin group (⩾1000 ng/mL). The primary end point was the cumulative incidence of infection within 100 days after HSCT, which was similar between the two groups: bloodstream infection, 35 vs 38%, P = 0.65; bacterial infection, 44 vs 41%, P = 0.68; and fungal infection, 6 vs 8%, P = 0.71. The 1-year adjusted probability of OS of the high-ferritin group was significantly lower than that of the low-ferritin group (76 vs 63%, P = 0.017). Using receiver operating characteristic curve, the threshold of pretransplant serum ferritin levels for bloodstream infection was 1400 ng/mL; the threshold for OS, EFS and non-relapse mortality was 1349 ng/mL. In conclusion, pretransplant serum ferritin levels of ⩾ 1000 ng/mL did not influence the incidence of infection but adversely affected OS after HSCT. A higher threshold of pretransplant serum ferritin levels may predict HSCT outcomes.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

Tanaka

Kanamori

Matsumoto

et al. 2015

Bone Marrow Transplant

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“…However, the precise impact of iron overload on transplant outcomes and the best way to determine it are still an issue of debate in the allo-RIC setting. 31 The development of hyperbilirubinemia had a profound impact on mortality and survival in our patients as described by others. 32 Nevertheless, continuous improvements in transplant outcomes may not allow direct comparisons between ours and other studies conducted in different time points and patient populations.…”

Section: Discussionsupporting

confidence: 64%

Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning

Barba

Martino

Pérez-Simón

et al. 2012

Bone Marrow Transplant

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To analyze the incidence, characteristics and risk factors of hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning (allo-RIC), we conducted a retrospective study in three Spanish centers. We analyzed 452 consecutive patients receiving allo-RIC. Of these, 92 patients (20%) developed marked hyperbilirubinemia (44 mg/day or 468.4 mM) after allo-RIC. The main causes of marked hyperbilirubinemia after transplant were cholestasis due to GVHD or sepsis (n ¼ 57, 62%) and drug-induced cholestasis (n ¼ 13, 14%). A total of 22 patients with marked hyperbilirubinemia (24%) underwent liver biopsy. The most frequent histological finding was iron overload alone (n ¼ 6) or in combination with other features (n ¼ 6). In multivariate analysis, the risk factors for marked hyperbilirubinemia after allo-RIC were non-HLAidentical sibling donors (hazard ratio (HR) 2.2 (95% confidence interval (CI) 1.4 --3.6) P ¼ 0.001), female donors to male recipients (HR 2.1 (95% CI 1.3 --3.3) P ¼ 0.003) and high levels of bilirubin and g-glutamyl transpeptidase before transplant (HR 4.5 (95% CI 2.5 --8.4) Po0.001 and HR 4.6 (95% CI 2.6 --8.1) Po0.001, respectively). Patients with marked hyperbilirubinemia showed higher 4-year nonrelapse mortality (HR 1.3 (95% CI 1 --1.7), P ¼ 0.02) and lower 4-year OS (HR 1.4 (95%CI 1.3 --1.7), Po0.001) than patients without. In conclusion, we confirm that marked hyperbilirubinemia is frequent and diverse after allo-RIC. Development of marked hyperbilirubinemia after allo-RIC is associated with worse outcome of the procedure.

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“…It has recently been reported that iron overload increases the risk of veno-occlusive disease, hepatic dysfunction, and infections after transplantation [3]. It has also been shown that elevated serum levels of pre-transplant ferritin, which is a reliable marker of iron overload, are associated with increased nonrelapse mortality in patients having undergone allo-HSCT [4][5][6]. The pathogenetic mechanisms for iron overload in hematological malignancies are: prolonged dyserythropoiesis, hemolysis, increased intestinal iron absorption, and multiple red blood cell transfusions [7].…”

mentioning

confidence: 99%

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

Şıvgın

Baldane²,

Kaynar³

et al. 2012

neo

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Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction in post-transplant period. Our objective was to investigate the association of pre-transplant ferritin levels with complications and survival after allogeneic hematopoietic stem cell transplantation (alloHSCT).We retrospectively analysed 84 patients' data who had undergone allogeneic HSCT into two groups: patients with a serum ferritin level≥1000ng/ml, and patients with <1000 ng/ml at the time of HSCT.Cox-regression analysis showed that pre-transplant serum ferritin levels were significantly higher in patients who had at least one infectious event compared with those who had no any infectious event in the post-transplant 100 days (p<0.023). Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with a time-to-tx interval <12 months compared with group time-to-tx interval>12 months (p=0.002 and p=0.008 respectively). A higher risk of death was observed in high-ferritin group (hazard ratio=2.27, CI:1.01-5.09, p=0.023 for OS and hazard ratio=2.49, CI:1.12-5.53 p=0.039 for DFS). No significant effect on OS and DFS among groups was observed for variables conditioning regimen, gender and diagnosis. Acute GVHD was more common in patients with a ferritin level ≥1000 ng /mL, but this was not statistically significant (p>0.05). There was no statistical significance in both groups (ferritin≥1000ng /mL and ferritin<1000ng/mL) for relapse rates (p>0.05). Platelet and neutrophil engaftment day was not found statistically significant compared with both groups (p=0.273 and p=0.882, respectively).Pre-transplant ferritin levels may predict poor outcomes in patients who had undergone allogeneic hematopoietic stem cell transplantation.

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Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation

Cited by 71 publications

References 19 publications

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

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Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation

Cited by 71 publications

References 19 publications

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

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Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation