Iron Overload in Allogeneic Hematopoietic Cell Transplantation Outcome: A Meta-Analysis

Armand, Philippe; Kim, Haesook T.; Virtanen, Johanna; Parkkola, Riitta; Itälä‐Remes, Maija; Majhail, Navneet S.; Burns, Linda J.; DeFor, Todd E.; Trottier, Bryan; Platzbecker, Uwe; Antin, Joseph H.; Wermke, Martin

doi:10.1016/j.bbmt.2014.04.024

Cited by 69 publications

(72 citation statements)

References 32 publications

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“…53 Nevertheless, it needs to be remembered that ferritin is an acceptable but imperfect surrogate of true iron overload. In contrast to SF, the association between iron overload as assessed by liver iron content by magnetic resonance imaging and survival after HSCT is still controversial.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Jaekel

Lieder

Albrecht

et al. 2015

Bone Marrow Transplant

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Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of 480%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n = 6), skin (n = 3), elevated transaminases (n = 1) and creatinine (n = 1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

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Section: Discussionmentioning

confidence: 99%

“…In contrast to SF, the association between iron overload as assessed by liver iron content by magnetic resonance imaging and survival after HSCT is still controversial. 53 Thus, the adverse prognosis of SF might be related to other not yet well-studied pathologies such as labile plasma iron.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Jaekel

Lieder

Albrecht

et al. 2015

Bone Marrow Transplant

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“…The trends suggest a possible prognostic effect, although it does not appear as strong as suspected based on the ferritin-related literature, and it may be restricted to certain subgroups. [61]. (4) An increased risk of infectious complications, in particular, invasive fungal infections, appears to be an important component of the unfavorable influence of IOL.…”

Section: Iron Overload and Allogeneic Stem Cell Transplantation (Sct)mentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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“…9 There is also a possibility that the adverse prognostic impact of pre-transplant hyperferritinemia might be ascribed to other precipitating factors in addition to the iron overload. [10][11][12][13][14] Reduced intensed toxicity conditioning regimens may attenuate the impact of iron overload related end-organ toxicity when compared to the myeloablative conditioning. [15][16][17][18] Iron overload may predispose to a higher rate of infections associated with transplantation.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Iron Overload on Transplant-Related Complications and Prognosis of Acute Leukemias.

Malkan¹

2016

UHOD

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The impacts of serum iron parameters and/or radiological evidence of systemic iron overload on the prognosis of hematopoietic stem cell transplantation (HSCT) in acute leukemia are controversial. Unfortunately, some of the studies evaluating iron overload in transplant setting did not precisely show the patients with iron overload, mainly due to ignoring consideration of transferrin saturation along with hyperferritinemia for elimination of non-iron overload etiologies of hyperferritinemia. The aim of this study is to assess the effect of iron overload on transplantation related complications and prognosis in acute leukemia. Patients who undergone allogeneic HSCT for acute leukemia in Hacettepe University Medical School Department of Hematology were screened retrospectively in order to find cases with serum iron tests within 9 months before transplant. The endpoints investigated were overall and disease-free survivals, acute and chronic graft-versus-host disease and veno-oclussive disease (VOD). There were 84 patients suitable for inclusion. When various ferritin plus transferrin saturation (TS) cut-off values were investigated for a possible relationship with major transplant-related complications/results only ferritin> 2000 plus TS> 45% was found to have an association with VOD at borderline significance (p= 0.067). In conclusion, we observed a non-significant borderline relationship between iron overload and post-transplant VOD. We did not confirm other post-transplant complications reported in the literature. It must be noticed that although many studies intended to investigate the relationship between iron status and transplant outcomes, only a few of them have really looked for the effect of iron overload. Keywords: Iron overload, Acute leukemia, Transplantation ÖZET Akut Löseminin Prognozu ve Transplantasyonla İlişkili Komplikasyonlarına Demir Yükselmesinin EtkisiSerum demir parametrelerinin ve/veya radyolojik olarak saptanan sistemik demir yüklenmesinin, kök hücre nakli (KHN) yapılmış akut lösemi hastalarının prognozuna olan etkisi tartışmalıdır. Ne yazık ki, demir yüklenmesinin transplantasyona olan etkisini araştıran bazı çalışmalarda demir yüklenmesi olan hastalar doğru bir şekilde saptanamamıştır. Bunun nedeni hiperferritineminin demir yüklenmesi dışındaki sebeplerinin göz ardı edilmesidir. Bu çalışmanın amacı, demir yüklenmesinin akut lösemi hastalarının prognozuna ve transplantasyon ile ilişkili komplikasyonlarına olan etkisinin araştırılmasıdır. Transplantasyon öncesi dokuzuncu aya kadar olan serum demir testleri olan hastaları bulmak amacıyla, Hacettepe Üniversitesi Tıp Fakültesi Hematoloji Departmanı'nda allojenik KHN yapılan hastalar retrospektif olarak taranmıştır. Çalışma sonlanım noktaları, genel ve hastalıksız sağkalım süreleri, akut ve kronik graft versus host hastalığı ve venookluziv hastalıktır (VOH). Çalışmaya alınma kriterlerine uyan 84 hasta mevcuttu. Transplant ilişkili komplikasyonlar ile demir yüklenmesi arasında bir ilişki bulabilmek amacı ile transferrin satürasyonu (TS) ...

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Iron Overload in Allogeneic Hematopoietic Cell Transplantation Outcome: A Meta-Analysis

Cited by 69 publications

References 32 publications

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Iron overload in myelodysplastic syndromes (MDS)

The Impact of Iron Overload on Transplant-Related Complications and Prognosis of Acute Leukemias.

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