Clinical and Biological Characterization of Patients with Low/Intermediate-1 Risk Myelodysplastic Syndrome and Iron Overload

Abstract Abstract 4956 Introduction. Patients with Myelodysplastic Syndrome (MDS) are susceptible to developing iron overload as a response to the red blood cell (RBC) transfusions and ineffective hematopoiesis. This iron overload (IOL) is characterized by an increase in oxygen-reactive species accompanied by a decrease in antioxidants, and results in hepatic, cardiac and endocrine disorders, as well as an increased risk of infection. Ineffective hematopoiesis promotes iron absorption at intestinal level. This process is enhanced by the presence of mutations in the hereditary hemochromatosis gene (HFE). This study aims to define the features that accompany patients with iron overload, comparing them to a MDS population at diagnosis. Patients and methods. 34 low/int-1 MDS patients (International Prognostic Score System, IPSS) were assessed, 22 of them at diagnosis and 12 patients when IOL was developed. Peripheral blood samples were drawn after informed consent was obtained from the patient or the patient′s guardians in accordance with the Declaration of Helsinki. The analyzed parameters were: WHO classification, sex, age, blood count, number of RBC units received, iron metabolism, and mutations of the HFE gene. Liver damage was estimated by measuring Alanine transaminase (ALT) levels, and liver iron concentration (LIC) detected by Magnetic Resonance (MR). Likewise, levels of labile plasmatic iron (LPI) (eLPI Assay Kit, Aferrix) were quantified by spectrofluorimetric determination. Oxidative damage was assessed by quantifying the modified base 8-oxo-2-hydroxi-deoxiguanosine (8-oxo-dG) by means of High-Performance Liquid Chromatography (HPLC) and the O2− anion levels by flow cytometry. Results. According to the WHO classification, 72. 2% of cases with MDS and IOL assessed belonged to Refractory Sideroblastic Anemia (RSA) group, unlike 27. 3% of patients at diagnosis (p=0. 0265). In comparison to diagnosis patients, IOL subjects presented lower mean age (76 vs. 81 years; p=0. 0172), hemoglobin levels (7. 5 ± 0. 4 vs. 10. 3 ± 0. 3 g/dl; p<0. 0001), and red blood cell count (2. 3 ± 0. 1 vs. 3. 0 ± 0. 1×109/l; p<0. 0001). Moreover, higher levels of ferritin (median 1147 vs. 219 μg/dl; p<0. 0001), Transferrin Saturation Index (TSI) (median 89. 4 vs. 31. 5%; p<0. 0001) and ALT (median 14. 9 vs. 11. 0 U/l; p=0. 0263) were observed when compared to the diagnosis patients. On the other hand, among IOL patients the average levels for LIC were 13. 8 ± 2. 0 mg Fe/g (normal levels <4. 0 mg Fe/g), and higher LPI concentrations were detected (median 1. 2 vs. 0. 1 U; p<0. 0001). These patients received an average of 28 ± 9 RBC units. Interestingly, two of the patients developed IOL without previously having received any transfusions; both of whom were diagnosed with RSA, having the H63D mutation of the HFE gene. Regarding the oxidative damage, in patients with IOL a significant increase of 8-oxo-dG (p=0. 0040) and O2− anions (p=0. 0157) was observed. Conclusions. Disclosures: Carbonell: Novartis Farmacéutica, S. A.: Research Funding; Universitat de València: Research Funding.

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Iron Overload In Adult Allogeneic Hematopoietic Stem Cell Transplantation Survivors: Quantification of Iron Burden by Determining Non-Transferrin-Bound Iron.

Blood ◽

10.1182/blood.v116.21.3455.3455 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3455-3455

Author(s):

Tatsunori Goto ◽

Katsuya Ikuta ◽

Emi Yokohata ◽

Daisuke Koyama ◽

Koichi Onodera ◽

...

Keyword(s):

Risk Factor ◽

Stem Cell ◽

Blood Cell ◽

Iron Overload ◽

Hematopoietic Stem Cell ◽

Red Blood Cell ◽

Research Funding ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Excess Iron

Abstract Abstract 3455 Background: Iron overload (IO) is a relatively common complication in allogeneic hematopoietic stem cell transplant (AHSCT) recipients who frequently need red blood cell transfusions. The estimation of IO is currently based on serum ferritin (SF) level, but in HSCT recipients, many confounding factors can result in ferritin overestimation. Non-transferrin-bound iron (NTBI), which is detected in conditions of iron overload when transferrin becomes fully saturated and unable to bind excess iron, is thought to catalyze the formation of reactive radicals. We studied the prevalence of IO in adult AHSCT survivors and quantified IO by determining NTBI. Methods: A total of 116 patients were enrolled in this study, who underwent their first AHSCT in our institute, survived ≥100 days from AHSCT in continuous remission and were returning for follow-up at our institute between August 2009 and March 2010. Results: The median age at AHSCT was 37 (range, 17–65) years. Primary diagnosis included acute leukemia/myelodysplastic syndrome (n=77) and aplastic anemia (n=14). Conditioning regimens were myeloablative (n=81) and reduced intensity (n=35). Donors were HLA-matched (n=99) and mismatched (n=17), and related (n=48) and unrelated (n=68). Graft sources were bone marrow (n=89), peripheral blood (n=18) and cord blood (n=9). Graft-versus-host disease (GVHD) prophylaxis consisted of a combination of short-term methotrexate and tacrolimus (n=66) or cyclosporine (n=50). The incidence of grade II-IV acute GVHD was 22%, and that of chronic GVHD was 49%. The median SF level was 911 (range, 14–10, 500) ng/ml, and 49 patients (42%) had hyperferritinemia (HF) (SF>1000 ng/ml). The median time from HSCT to SF assessment was 1276 (range, 134–4213) days, and was similar between patients with and without HF. No significant correlation was found between HF and the presence of cGVHD (p=0.48). There was a moderate correlation between SF level and the number of packed red blood cell units transfused from the diagnosis of underlying disease (ρ=0.69, p<0.0001). Only 22 of the 67 patients (33%) without HF had at least 1 abnormal liver function test (LFT), including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transpeptidase (γ-GTP) and alkaline phosphatase (ALP), whereas 31 of the 49 patients (63%) with HF (p=0.001). The median AST, ALT, and γ-GTP values determined at the time of iron status assessment were significantly higher in patients with HF. In multivariate analysis, HF was a significant risk factor for the presence of abnormal LFTs (OR=3.5; 95% CI=1.6-7.6). Six patients with HF evaluated by MRI all had findings suggesting liver hemosiderosis. The rate of diabetes showed a higher tendency in patients with HF compared to those without HF (27% versus 12%; p=0.053). The median NTBI value was significantly higher in patients with HF (median, 0.72 μmol/l; range, 0.28–2.09 μmol/l) compared to those without it (median, 0.28 μmol/l; range, 0.04–0.55 μmol/l) (p<0.0001). In addition, there was a statistically significant correlation between SF and the NTBI level (ρ=0.74, p<0.0001). All of the patients with HF showed more than the normal range of NTBI (male: 0.206 ± 0.091; female: 0.212 ± 0.095 mmol/l). Conclusion: At first, we assume that SF after AHSCT is affected by alloimmune reaction and infection and SF could not be used for precise monitoring of IO. However, the current study demonstrated that SF was well correlated with NTBI and that SF can be used for monitoring IO after AHSCT. Humans do not have any physiological mechanisms to excrete excess iron, and the current study showed that many long-term survivors after AHSCT, independently of RBC transfusion, had HF and high NTBI levels. It suggested that IO is a common feature after AHSCT. HF is an independent risk factor for abnormal LFTs in AHSCT survivors as well as diabetes to a lesser extent. These results prompt us to further evaluate the benefit of iron chelating therapy or phlebotomy for patients who suffer from liver dysfunction or diabetes. Disclosures: Sasaki: Novartis Pharma K. K.: Research Funding. Kohgo: Novartis Pharma K. K.: Research Funding.

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Pre-transplant red blood cell and platelet transfusion burden in de novo myelodysplastic syndrome undergoing allogeneic transplantation

Transplantation and Cellular Therapy ◽

10.1016/j.jtct.2021.05.003 ◽

2021 ◽

Author(s):

Takaaki Konuma ◽

Jun Aoki ◽

Yukiyasu Ozawa ◽

Naoyuki Uchida ◽

Takeshi Kobayashi ◽

...

Keyword(s):

Blood Cell ◽

Myelodysplastic Syndrome ◽

Red Blood Cell ◽

Platelet Transfusion ◽

De Novo ◽

Allogeneic Transplantation

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Disappearance of Oxidative Damage to Red Blood Cell Membranes in Uremic Patients Following Renal Transplant

ASAIO Transactions ◽

10.1097/00002480-198907000-00116 ◽

1989 ◽

Vol 35 (3) ◽

pp. 533-534 ◽

Cited By ~ 3

Author(s):

MASSIMO TACCONE-GALLUCCI ◽

RICCARDO LUBRANO ◽

ANNA BELLI ◽

CARLO MELONI ◽

MASSIMO MOROSETTI ◽

...

Keyword(s):

Renal Transplant ◽

Blood Cell ◽

Oxidative Damage ◽

Red Blood Cell ◽

Cell Membranes ◽

Uremic Patients ◽

Red Blood Cell Membranes

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Updates in Red Blood Cell and Platelet Transfusions in Preterm Neonates

American Journal of Perinatology ◽

10.1055/s-0039-1691775 ◽

2019 ◽

Vol 36 (S 02) ◽

pp. S37-S40 ◽

Cited By ~ 4

Author(s):

Enrico Lopriore

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Neonatal Intensive Care ◽

Preterm Neonates ◽

Delayed Cord Clamping ◽

International Consensus ◽

Cord Clamping ◽

Increased Risk ◽

Transfusion Guidelines ◽

Platelet Transfusions

AbstractAnemia and thrombocytopenia occur frequently in preterm neonates and the majority of them require at least one blood transfusion during the first few weeks of life. However, there is no international consensus on optimal transfusion management neither for red blood cell nor for platelet transfusions, resulting in large worldwide variations in transfusion practices between neonatal intensive care units. In the past decade, several studies performed in adults, infants as well as neonates showed that restrictive transfusion guidelines are just as safe as liberal guidelines. In fact, some studies even showed that liberal guidelines could be associated with an increased risk of morbidity and mortality, suggesting that too many transfusions may have a deleterious effect. In a recent randomized trial in preterm neonates with thrombocytopenia, the liberal transfusion group (receiving more platelet transfusions) had a significantly higher rate of death or major bleeding than the restrictive group (receiving less transfusions). In preterm neonates with anemia, the available evidence is also limited and controversial. Two large randomized controlled trials (ETTNO and TOP) are currently assessing the safety and effectiveness of liberal versus restrictive red blood cell transfusions. Results of these large two studies, including the long-term neurodevelopment outcome, are eagerly awaited. Until then, reduction of anemia of prematurity by implementation of effective preventive measures, such as delayed cord clamping and minimization of iatrogenic blood loss, remain of paramount importance.

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Iatrogenic Iron Overload in an End Stage Renal Disease Patient

Case Reports in Oncology ◽

10.1159/000507979 ◽

2020 ◽

Vol 13 (2) ◽

pp. 760-763

Author(s):

Majd M. Aldwairi ◽

Mohamed A. Yassin

Keyword(s):

Renal Failure ◽

Blood Cell ◽

Iron Overload ◽

Red Blood Cell ◽

Disease Patient ◽

Intravenous Iron ◽

Human Erythropoietin ◽

Red Blood Cell Transfusions ◽

Stage Renal Disease ◽

End Stage

Iron overload is a common complication in patients with chronic renal failure treated with dialysis prior to the availability of recombinant human erythropoietin therapy. Iron overload was the result of hypoproliferative erythroid marrow function coupled with the need for frequent red blood cell transfusions to manage symptomatic anemia. The repetitive use of intravenous iron with or without the use of red blood cell transfusions also contributed to iron loading and was associated with iron deposition in liver parenchymal and reticuloendothelial cells. Here we report a 56-year-old female with end-stage renal failure who underwent kidney transplant twice and found to have iatrogenic iron overload with excess intravenous iron treated conservatively.

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Myelodysplastic syndrome: the other cause of anemia in end-stage renal disease patients undergoing dialysis

Scientific Reports ◽

10.1038/s41598-020-72568-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Min-Yu Chang ◽

Sheng-Fung Lin ◽

Shih-Chi Wu ◽

Wen-Chi Yang

Keyword(s):

Blood Cell ◽

Renal Disease ◽

Myelodysplastic Syndrome ◽

Red Blood Cell ◽

End Stage Renal Disease ◽

Refractory Anemia ◽

Research Database ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Abstract In end-stage renal disease (ESRD) patients receiving dialysis, anemia is common and related to a higher mortality rate. Erythropoietin (EPO) resistance and iron refractory anemia require red blood cell transfusions. Myelodysplastic syndrome (MDS) is a disease with hematopoietic dysplasia. There are limited reports regarding ESRD patients with MDS. We aim to assess whether, for ESRD patients, undergoing dialysis is a predictive factor of MDS by analyzing data from the Taiwan National Health Insurance Research Database. We enrolled 74,712 patients with chronic renal failure (ESRD) who underwent dialysis and matched 74,712 control patients. In our study, we noticed that compared with the non-ESRD controls, in ESRD patients, undergoing dialysis (subdistribution hazard ratio [sHR] = 1.60, 1.16–2.19) and age (sHR = 1.03, 1.02–1.04) had positive predictive value for MDS occurrence. Moreover, more units of red blood cell transfusion (higher than 4 units per month) was also associated with a higher incidence of MDS. The MDS cumulative incidence increased with the duration of dialysis in ESRD patients. These effects may be related to exposure to certain cytokines, including interleukin-1, tumor necrosis factor-α, and tumor growth factor-β. In conclusion, we report the novel finding that ESRD patients undergoing dialysis have an increased risk of MDS.

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Allogeneic Leukocyte-Reduced Red Blood Cell Transfusion Is Associated with Postoperative Infectious Complications and Cancer Recurrence after Colon Cancer Resection

Digestive Surgery ◽

10.1159/000498865 ◽

2019 ◽

Vol 37 (2) ◽

pp. 163-170 ◽

Cited By ~ 1

Author(s):

Andrew-Paul Deeb ◽

Christopher T. Aquina ◽

John R.T. Monson ◽

Neil Blumberg ◽

Adan Z. Becerra ◽

...

Keyword(s):

Colon Cancer ◽

Blood Cell ◽

Red Blood Cell ◽

Cancer Recurrence ◽

Infectious Complications ◽

Oncologic Outcomes ◽

Red Blood Cell Transfusion ◽

Elective Resection ◽

Increased Risk ◽

The Impact

Background/Aims: Transfusion rates in colon cancer surgery are traditionally very high. Allogeneic red blood cell (RBC) transfusions are reported to induce immunomodulation that contributes to infectious morbidity and adverse oncologic outcomes. In an effort to attenuate these effects, the study institution implemented a universal leukocyte reduction protocol. The purpose of this study was to examine the impact of leukocyte-reduced (LR) transfusions on postoperative infectious complications, recurrence-free survival, and overall survival (OS). Methods: In a retrospective study, patients with stage I–III adenocarcinoma of the colon from 2003 to 2010 who underwent elective resection were studied. The primary outcome measures were postoperative infectious complications and recurrence-free and OS in patients that received a transfusion. Bivariate and multivariable regression analyses were performed for each endpoint. Results: Of 294 patients, 66 (22%) received a LR RBC transfusion. After adjustment, transfusion of LR RBCs was found to be independently associated with increased infectious complications (OR 3.10, 95% CI 1.24–7.73), increased odds of cancer recurrence (hazard ratio [HR] 3.74, 95% CI 1.94–7.21), and reduced OS when ≥3 units were administered (HR 2.24, 95% CI 1.12–4.48). Conclusion: Transfusion of LR RBCs is associated with an increased risk of infectious complications and worsened survival after elective surgery for colon cancer, irrespective of leukocyte reduction.

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