Efficacy and safety of deferasirox estimated by serum ferritin and labile plasma iron levels in patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia with transfusional iron overload

Transfusion ◽  
2015 ◽  
Vol 55 (7) ◽  
pp. 1613-1620 ◽  
Author(s):  
Il-Hwan Kim ◽  
Joon-Ho Moon ◽  
Sung-Nam Lim ◽  
Sang-Kyun Sohn ◽  
Hoon-Gu Kim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Aplastic Anemia ◽  
Serum Ferritin ◽  
Myeloid Leukemia ◽  
Efficacy And Safety ◽  
Plasma Iron ◽  
Acute Myeloid

Efficacy and Safety of Deferasirox Estimated By Serum Ferritin and Labile Plasma Iron Levels in Patients with Aplastic Anemia, Myelodysplastic Syndrome, or Hematologic Malignancy with Transfusional Iron Overload

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2676-2676
Author(s):  
Il hwan Kim ◽  
Young Don Joo ◽  
Joon Ho Moon ◽  
Sung Nam Lim ◽  
Sang Kyun Sohn ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Aplastic Anemia ◽  
Serum Ferritin ◽  
Hematologic Malignancy ◽  
Thyroid Function Tests ◽  
Efficacy And Safety ◽  
Plasma Iron ◽  
Gonadal Dysfunction ◽  
Transfusion Requirements

Abstract INTRODUCTION Patients receiving red blood cell (RBC) transfusions are at risk of iron overload. Humans do not have a physiologic mechanism to excrete excess iron, and total body iron is regulated primarily by the rate of absorption. Transfusion induced Iron overload can cause significant organ damage and is an important cause of morbidity and mortality. METHODS This study was an open-label, single-arm, prospective, phase 4, multicenter clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or hematologic malignancy (HM). Eligibility criteria were serum ferritin (SF) levels ≥1000 ng/mL and ongoing transfusion requirements. For evaluation of the iron overload, SF and transferrin saturation (TFST) were measured every 4 weeks, and labile plasma iron (LPI) levels were regularly followed once every 6 months. Patients received DFX at an initial dose of 20 mg/kg/day for up to 1 year. RESULTS A total of 109 patients were enrolled. SF levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p=0.003). The median absolute reduction in SF levels was -389 ng/mL (range -5428 to 3788) in AA (p=0.029), -567 ng/mL (range -3040 to 4969) in MDS (p=0.136), and -552 ng/mL (range -2899 to 5451) in HM (p=0.057). Median TFST reduction was -14.9% (range -69.4 to 71.0) in all patients (n = 65, p = 0.064). In the MDS and HM groups, TFST decreased significantly from baseline: -14.9% (range -57.4 to 52.2) in the MDS group (p = 0.040) and -16.3% (range -69.2 to 20.8) in the HM group (p = 0.005), while TFST reduction in the AA group was -7.4% (range -58.3 to 71.0) (p = 0.790). Baseline LPI levels were within normal laboratory ranges in all groups. Mean LPI levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p=0.035). The mean LPI reduction in each group was -0.23±0.41 μmol/L (p=0.220) in AA, -0.26±0.51 μmol/L (p=0.110) in MDS, and -0.19±0.70 μmol/L (p=0.336) in HM. All of the AEs related with DFX were grade 1 or 2, and there were no severe AEs (grade ≥3) reported during the study period. Gastrointestinal disorders were commonly observed among groups (n=32, 29.4%), including diarrhea in 8.3%, nausea in 7.4%, and abdominal discomfort in 5.5% of patients. Overall differences in end organ function, including heart, pancreas, thyroid, and gonad, between baseline and 1-year follow up were not statistically significant. No significant differences in LVEF at 1-year after DFX treatment were seen (p = 0.103). Pancreatic dysfunction measured by FBS (p = 0.480) and C-peptide (p = 0.096) levels did not appear to be affected by iron overload during DFX treatment. The results of thyroid function tests (TFT) were not significantly different between the pre- and post-treatment periods in terms of TSH (p = 0.207), free T3 (p = 0.259), or free T4 (p = 0.654) levels. Gonadal dysfunction was not observed during the DFX treatment. DISCUSSION ICT may be an appropriate option for patients with HM or higher risk MDS. In the current study, DFX successfully reduced serum ferritin and LPI levels in HM from baseline to 1 year of treatment. The roles of ICT or DFX during treatment for HM on infection risk and survival benefits need to be elucidated in prospective studies. In conclusion, DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all patients. Disclosures No relevant conflicts of interest to declare.

Aplastic anemia evolving into overt myelodysplastic syndrome/acute myeloid leukemia with t(3;5)(p25;q31)

2002 ◽  
Vol 137 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Eri Kawata ◽  
Junya Kuroda ◽  
Shinya Kimura ◽  
Yuri Kamitsuji ◽  
Yutaka Kobayashi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Acquired hemoglobin H disease in a patient with aplastic anemia evolving into acute myeloid leukemia

2004 ◽  
Vol 122 (6) ◽  
pp. 273-275 ◽  
Author(s):  
Maria Stella Figueiredo ◽  
Perla Vicari ◽  
Eliza Yuriko Sugano Kimura ◽  
Sandra Vallin Antunes ◽  
Mihoko Yamamoto
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Myeloid Leukemia ◽  
Fetal Hemoglobin ◽  
First Case ◽  
Brazilian Patient ◽  
Long Term Follow Up ◽  
Acute Myeloid

CONTEXT: The prognosis of severe aplastic anemia has improved since the introduction of bone marrow transplantation and treatment with antithymocyte globulin. In contrast to the success of these protocols, studies with long term follow-up have shown the occurrence of clonal diseases such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome and acute leukemia in aplastic anemia. CASE REPORT: We report the first case of a Brazilian patient with aplastic anemia who developed myelodysplastic syndrome and acute myeloid leukemia showing acquired hemoglobin H and increased fetal hemoglobin.

Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 786-790 ◽  
Author(s):  
Seiji Kojima ◽  
Akira Ohara ◽  
Masahiro Tsuchida ◽  
Toru Kudoh ◽  
Ryoji Hanada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Myeloid Leukemia ◽  
Monosomy 7 ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7 ± 3.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.

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