Non‐transferrin‐bound iron in haematological patients during chemotherapy and conditioning for autologous stem cell transplantation

Sahlstedt, Leila; Bonsdorff, Leni von; Ebeling, Freja; Parkkinen, Jaakko; Juvonen, Eeva; Ruutu, Tapani

doi:10.1111/j.1600-0609.2009.01310.x

Cited by 36 publications

(25 citation statements)

References 19 publications

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“…The pattern observed with LPI levels in our study matches patterns reported for NTBI levels in similar populations undergoing autologous HSCT [16,17]. The fact that the majority of the patients presented with increased LPI levels shortly after conditioning and during the aplasia phase and returned to having normal LPI levels upon engraftment is consistent with the hypothesis that inhibition and reconstitution of erythropoietic activity following myeloablative chemotherapy play a leading role in the kinetics of the appearance and disappearance of LPI [16].…”

Section: Discussionsupporting

confidence: 88%

“…Some authors speculated on the impact of unbound iron in relation to toxicity in HSCT patients, based mainly on the fact that the time of appearance of NTBI concurred with the onset of toxicity [17,24]. In our study, it was shown that baseline LPI levels could predict the occurrence of grade III or IV toxicity.…”

Section: Discussionmentioning

confidence: 52%

“…It has been assumed that NTBI becomes detectable when transferrin saturation exceeds 80% [16,17,21]. However, measuring NTBI in plasma does not necessarily reflect the amount of the essentially redox-active forms of iron, as these may not be detected in samples with increased NTBI levels [4].…”

Section: Discussionmentioning

confidence: 99%

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Assessment of Labile Plasma Iron in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Naoum¹,

Espósito

Ruiz³

et al. 2013

Acta Haematol

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Body iron disorders have been reported after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT). There is a concern that labile plasma iron (LPI), the redox-active form of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. In order to better understand the LPI kinetics and its determinants and implications, we undertook sequential LPI determinations before and after conditioning until engraftment in 25 auto-HSCT patients. Increased LPI was present in only 5 patients before starting conditioning. Shortly after conditioning, LPI levels were increased in 23 patients, with peak at day 0, returning to normal range upon engraftment in 21 patients. Overall, LPI levels correlated weakly with serum ferritin and more strongly with transferrin saturation; however, both parameters were apparently not applicable as surrogate markers for increased LPI. Although this was a small cohort, logistic regression suggested that baseline LPI levels could predict occurrence of grade III or IV toxicity. In conclusion, LPI kinetics is influenced by aplasia following conditioning and engraftment. Measuring LPI before starting conditioning can offer an opportunity to predict toxicity and, perhaps, the need for chelation therapy.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 52%

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Assessment of Labile Plasma Iron in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Naoum¹,

Espósito

Ruiz³

et al. 2013

Acta Haematol

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“…On the basis of this, it would seem imprudent to use ferritin or MRI as surrogate markers for LPI, and large prospective studies measuring LPI will need to be done to determine whether this parameter influences HSCT outcomes. It may also be that the previously described increase in LPI after transplantation (in particular, from the conditioning regimen) [27] is more important than pre-HSCT LPI in mediating iron-dependent toxicity in this setting.…”

Section: Discussionmentioning

confidence: 99%

Iron Overload in Patients with Acute Leukemia or MDS Undergoing Myeloablative Stem Cell Transplantation

Armand

Kim

Rhodes

et al. 2011

Biology of Blood and Marrow Transplantation

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Patients with hematologic malignancies undergoing allogeneic stem cell transplantation (HSCT) commonly have an elevated serum ferritin prior to HSCT, which has been associated with increased mortality after transplantation. This has led to the suggestion that iron overload is common and deleterious in this patient population. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. We report a prospective study of 48 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS) under going myeloablative HSCT, using magnetic resonance imaging (MRI) to estimate liver iron content (LIC) and cardiac iron. The median (and range) pre-HSCT value of serum ferritin was 1549 ng/ mL (20–6989); serum hepcidin, 59 ng/mL (10–468); labile plasma iron, 0 LPI units (0.0–0.9). Eighty-five percent of patients had hepatic iron overload (HIO), and 42% had significant HIO (LIC ≥5.0 mg/gdw). Only 1 patient had cardiac iron overload. There was a strong correlation between pre-HSCT serum ferritin and estimated LIC (r =.75), which was mostly dependent on prior transfusion history. Serum hepcidin was appropriately elevated in patients with HIO. Labile plasma iron elevation was rare. A regression calibration analysis supported the hypothesis that elevated pre-HSCT LIC is significantly associated with inferior post-HSCT survival. These results contribute to our understanding of the prevalence, mechanism, and consequences of iron overload in HSCT.

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“…24 The inhibition of iron utilization in erythrocytes by chemotherapeutic agents and irradiation further increases NTBI levels. 25 Hydroxyl radical reactions by NTBI exacerbate mucosal damage caused by chemotherapeutic agents and irradiation, which allows bacterial organisms to enter through circulation. 26 In addition, iron is an important nutrient for the proliferation of bacteria and fungi.…”

Section: Discussionmentioning

confidence: 99%

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Kanda

Mizumoto

Ichinohe

et al. 2010

Bone Marrow Transplant

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Although fluoroquinolones or other antibiotics are commonly used to prevent bacterial infections after hematopoietic cell transplantation (HCT), because of the growing presence of multidrug-resistant microorganisms, it is important to identify patients who are more likely to benefit from antibacterial prophylaxis. To evaluate risk factors for early bacterial infection after allogeneic HCT, we retrospectively analyzed clinical data for 112 consecutive adult patients with hematological malignancies who received transplants without any antibacterial prophylaxis. The cumulative incidence of bacterial infection at 30 days after transplantation was 16%. Among various pre-transplant factors, only high serum ferritin (4700 ng/mL, 47 patients) and high C-reactive protein (CRP) (40.3 mg/dL, 28 patients) levels were significantly associated with the development of bacterial infection in a multivariate analysis (hazard ratio (95% confidence interval): ferritin, 4.00 (1.32-12.17); CRP, 3.64 (1.44-9.20)). In addition, septic shock and sepsis with organ failure were exclusively observed in patients who had high ferritin and/or high CRP levels. These results suggest that pretransplant serum ferritin and CRP levels can be useful markers for predicting the risk of early bacterial infection after allogeneic HCT. It may be prudent to limit antibacterial prophylaxis to patients with predefined risk factors to ensure the safety of HCT with the use of fewer antibiotics.

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Non‐transferrin‐bound iron in haematological patients during chemotherapy and conditioning for autologous stem cell transplantation

Cited by 36 publications

References 19 publications

Assessment of Labile Plasma Iron in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Assessment of Labile Plasma Iron in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Iron Overload in Patients with Acute Leukemia or MDS Undergoing Myeloablative Stem Cell Transplantation

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

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