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Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome
Kupesiz, F. T., Hazar, V., Eker, N., Guler, E., Yesilipek, M. A., Tuysuz, G., Kupesiz, A.
Journal of pediatric hematology/oncology. 2020
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. STUDY DESIGN Retrospective observational cohort study. AIMS To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia in order to assess the necessity of reducing iron load. PATIENTS AND METHODS Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. RESULTS Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43+/-9.42 and 118.56+/-10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival. CONCLUSIONS In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.
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Improved survival outcomes and restoration of graft-vs-leukemia effect by deferasirox after allogeneic stem cell transplantation in acute myeloid leukemia
Cho, B. S., Jeon, Y. W., Hahn, A. R., Lee, T. H., Park, S. S., Yoon, J. H., Lee, S. E., Eom, K. S., Kim, Y. J., Lee, S., et al
Cancer medicine. 2019
Abstract
Deferasirox is an oral iron-chelating agent having possible antileukemia and immune modulatory effects. Few reports have evaluated deferasirox in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the impact of deferasirox after allo-HSCT in acute myeloid leukemia (AML). Of 326 consecutive patients undergoing allo-HSCT in remission, analysis of 198 patients not receiving deferasirox revealed the negative prognostic effect of hyperferritinemia (≥1000 ng/mL) before and after allo-HSCT on survival mainly due to increase in relapse. Of 276 patients with hyperferritinemia at 1 month after allo-HSCT, 128 patients (46%) received deferasirox. Deferasirox induced a faster decline in serum ferritin level with a manageable safety profile, which significantly reduced relapse rather than nonrelapse mortality, resulting in better survival compared to patients not receiving deferasirox. Of note, the deferasirox group had a significantly higher incidence of chronic graft-vs-host disease, indicating improved graft-vs-leukemia (GVL) effects evidenced by the presence of suppressed regulatory T cells and sustained higher proportion of NK cells in peripheral blood. This study firstly demonstrates the improved survival and restoration of GVL effects of patients with AML by deferasirox, which also clarifies the detrimental effect of hyperferritinemia through after allo-HSCT.
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Potential anti-leukemic activity of iron chelation after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia
Michallet, M., Sobh, M., Labussiere, H., Lombard, C., Barraco, F., El-Hamri, M., Thomas, X., Chapuis-Cellier, C., Nicolini, F. E.
Leukemia & Lymphoma. 2017;58(1):237-240
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Prevalence and risk factors of iron overload after hematopoietic stem cell transplantation for childhood acute leukemia: a LEA study
Sirvent, A., Auquier, P., Oudin, C., Bertrand, Y., Bohrer, S., Chastagner, P., Poiree, M., Kanold, J., Thouvenin, S., Perel, Y., et al
Bone Marrow Transplantation. 2017;52(1):80-87
Abstract
Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucemie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level 350ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.
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Association between pretransplant iron overload determined by bone marrow pathological analysis and bacterial infection
Ohmoto, A., Fuji, S., Miyagi-Maeshima, A., Kim, S. W., Tajima, K., Tanaka, T., Okinaka, K., Kurosawa, S., Inamoto, Y., Taniguchi, H., et al
Bone Marrow Transplantation. 2017;52(8):1201-1203