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Marked improvement of cardiac function early after non-myeloablative BMT in a heavily transfused patient with severe aplastic anemia and heart failure

Bone Marrow Transplantation volume 40, pages 593–595 (2007)Cite this article

Allogeneic stem cell transplantation (allo-SCT) is one of the curative treatment options for patients with severe aplastic anemia (SAA). However, since multiple transfusions can cause organ damage such as heart failure, diabetes mellitus and liver dysfunction due to iron overload, the majority of heavily transfused patients with SAA would not tolerate the intensive conditioning regimens followed by allo-SCT. In addition, multiple transfusions also can sensitize the patients with alloantigens, resulting in the high risk of graft rejection. Non-myeloablative SCT (NST) has been developed to reduce regimen-related toxicities (RRT), especially for patients with poor organ function or advanced age, but it may be more frequently associated with graft rejection. Recently, several trials have utilized an NST regimen to reduce RRT and overcome graft rejection in the heavily transfused and allo-immunized SAA patients, using fludarabine in combination with melphalan1, 2 or cyclophosphamide.3, 4

In this patient, the prompt improvement in cardiac function 3 months after BMT might not have correlated with the hematologic changes, since his hemoglobin concentration had not yet increased at that time, which had still required RBC transfusions. In addition, iron deposition still remained in the heart as seen in the CT scan. Therefore, the decrease in iron stores or amelioration of hemochromatosis by the successful BMT cannot account for the prompt improvement of left ventricular systolic function. It was recently reported from postmortem examinations that a fraction of cardiomyocytes from female patients who had undergone sex-mismatched allo-BMT were positive for Y chromosome staining, suggesting that donor-derived bone marrow cells can contribute to cardiomyocyte formation.5 Animal experiments also have demonstrated that cardiac function improves several weeks after BMT, possibly through cell fusion or trans-differentiation, although the exact mechanisms remain to be determined.6, 7 Therefore, in this case, donor-derived bone marrow cells might partially contribute to the amelioration of cardiac dysfunction, rather than a decrease in iron deposition by the successful BMT resulted in an improvement in heart failure due to hemochromatosis. In this context, bone marrow cells as a stem cell source might be suitable for patients with organ damage, since bone marrow cells contain hematopoietic and mesenchymal stem cells, which can differentiate into other tissues such as cardiomyocytes to repair the injured organs.6, 8

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  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Y Kunisaki, K Takase, T Miyamoto, M Fukata, A Nonami, K Kamezaki, Y Kaji, H Gondo, M Harada & K Nagafuji

  2. Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    T Miyamoto

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Correspondence to T Miyamoto.

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Kunisaki, Y., Takase, K., Miyamoto, T. et al. Marked improvement of cardiac function early after non-myeloablative BMT in a heavily transfused patient with severe aplastic anemia and heart failure. Bone Marrow Transplant 40, 593–595 (2007). https://doi.org/10.1038/sj.bmt.1705764

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