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Association between pretransplant iron overload determined by bone marrow pathological analysis and bacterial infection

Bone Marrow Transplantation volume 52, pages 1201–1203 (2017)Cite this article

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Iron overload (IO) before allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is regarded as a poor prognostic factor after allo-HSCT, although there is controversy regarding the clinical relevance.1 Previous studies identified pretransplant IO as a poor prognostic factor after allo-HSCT, whereas other studies including a meta-analysis using liver magnetic resonance imaging showed no association between pretransplant IO and poor overall survival (OS).2, 3 Although serum ferritin (SF) is the most widely used indicator of total body iron burden, its level is affected by factors causing inflammation such as infection or active disease, and before red blood cell transfusions.4 The development of assays to easily and accurately determine IO is warranted from a clinical standpoint because the oral iron chelating agent deferasirox is commercially available. With only a few studies directly assessing IO by pathological approaches, the impact of pathologically determined IO especially on clinical outcomes has not been fully clarified.5, 6, 7 Here, we compared clinical relevance of IO estimated by Prussian blue staining on post-transplant outcomes with that by SF.

Pretransplant serum ferritin (SF) was measured for 193 adult patients with acute leukemia and myelodysplastic syndromes undergoing first allo-HSCT in our institution between 2006 and 2013. Except for two participating in a phase I study, and 22 whose bone marrow samples before allo-HSCT were unavailable or inappropriate for pathological analysis, 169 patients were included in further analyses. A pretransplant SF level of 800 ng/mL was defined as the cut-off value as the median level in this study, and this cut-off was used to divide patients into two groups: low-ferritin group, SF<800 ng/mL; and high-ferritin group, SF⩾800 ng/mL. Prussian blue staining was newly performed for this study using stored bone marrow specimens, and cases with a few stained granules within normal range were assigned as negative, whereas those with focally or diffusely stained iron granules as positive by two pathologists (Supplementary Figure 1). The covariates included in the statistical analyses were sex, age, diagnosis, pretransplant SF level, conditioning regimen, disease status at allo-HSCT, stem cell sources, HLA disparity, GvHD prophylaxis and positivity of Prussian blue staining. Analysis of complications after allo-HSCT included the incidences of bacterial infection, bacteremia, fungal infection, aspergillus infection, acute GvHD, and veno-occlusive disease (VOD), where each complication was judged based on clinical decision from medical records or mycological and pathological data. Febrile neutropenia was included in bacterial infection because it is a clinically important adverse event, which is considered to be closely associated with bacterial infection. The end points included the P of OS and the cumulative incidences of relapse or progression, non-relapse mortality (NRM) and complications after HSCT including infectious diseases. Survival curves were estimated using the Kaplan–Meier method, and P-values were calculated using the log-rank test. Relapse or progression, NRM and complication incidences were calculated using cumulative incidence curves. Univariate and multivariate analyses of risk factors for OS were performed using Cox proportional hazards regression models, and the Fine and Gray regression model was used for analysis of relapse or progression, NRM, and complications. Categorical and continuous variables were analyzed using the Fisher’s exact test and Student’s t-test, respectively. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University).

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Acknowledgements

We thank C Kina and S Miura for their technical assistance with immunohistochemistry. This study was supported by grant from the National Cancer Research and Development Fund (26-A-26).

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Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    A Ohmoto, S Fuji, S-W Kim, K Tajima, T Tanaka, K Okinaka, S Kurosawa, Y Inamoto & T Fukuda

  2. Department of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan

    A Ohmoto, A Miyagi-Maeshima & H Taniguchi

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  1. A Ohmoto
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Correspondence to S Fuji.

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Ohmoto, A., Fuji, S., Miyagi-Maeshima, A. et al. Association between pretransplant iron overload determined by bone marrow pathological analysis and bacterial infection. Bone Marrow Transplant 52, 1201–1203 (2017). https://doi.org/10.1038/bmt.2017.93

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