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Feasibility of salvage cord blood transplantation following fludarabine, melphalan and low-dose TBI for graft rejection after hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 985–987 (2016)Cite this article

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Graft failure (GF) in allogeneic hematopoietic stem cell transplantation (SCT) is a life-threatening complication because patients are at high risk of severe infection during prolonged neutropenia and also experience organ toxicity due to previous transplantation. Graft rejection is a major cause of graft failure, and is caused by the immune response of the recipient against the immunohematopoietic cells of the donor.1, 2 Cord blood is an important source for salvage transplantation because of its prompt availability and less stringent HLA compatibility. However, cord blood transplantation (CBT) has a risk of prolonged neutropenia and recurrence of GF. Previous studies reported that the rate of neutrophil engraftment of salvage CBT is 58% and the overall survival is 28–33%; the major cause of death was treatment-related mortality (TRM) in 61% cases, especially due to infection (65% of the cases of TRM).3, 4 In cases of immune-associated graft rejection, it is thought that patients should receive reconditioning to efficiently suppress recipient-derived immunity. Considering that fludarabine, melphalan and low-dose TBI conditioning efficiently suppress alloreactive host immunity and ensure engraftment,5 we have performed salvage CBT following this regimen for patients with graft rejection. We carefully assessed infectious complications before salvage CBT because they may be strongly associated with TRM as carryover infections, leading to death after salvage CBT.

The retrospective analysis included eight consecutive patients with distinct hematological diseases, who developed primary or secondary GF following SCT between April 2004 and May 2015 at Kyoto University Hospital. The patients received a salvage CBT following a fludarabine-based regimen. All participants signed an informed consent form to receive therapy. This study was approved by the Institutional Review Board of Kyoto University Hospital in Japan. Patient characteristics are summarized in Table 1. Six patients had advanced disease, except for two patients (Nos. 5 and 6) with AML with a CR status. The median age of the patients was 44 years (range, 18–61 years) at the time of GF. The stem cell sources of the failed transplants were unrelated cord blood in five patients and unrelated bone marrow in three patients (Nos. 6–8). The regimens of the failed transplants were ablative conditioning in three patients (Nos. 2, 5 and 6). Six patients had primary GF, whereas two patients (Nos. 7 and 8) had secondary GF. Chimerism analysis showed complete recipient chimerism at diagnosis of primary GF (except one patient, with recipient-dominant >92%) and rapid replacement with recipient cells at diagnosis of secondary GF, which suggested immunologically mediated graft rejection.

Table 1 Patient characteristics and results of salvage CBT
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Figure 1

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Acknowledgements

We are grateful to the medical, nursing and laboratory staff of the participating departments for their contributions to this study.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    K Ishiyama, J Takeda, T Kondo, N Sugimoto, H Kawabata, T Kitano & A Takaori-Kondo

  2. Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    N Sugimoto

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  1. K Ishiyama
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  2. J Takeda
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  7. A Takaori-Kondo
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Correspondence to T Kondo.

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Ishiyama, K., Takeda, J., Kondo, T. et al. Feasibility of salvage cord blood transplantation following fludarabine, melphalan and low-dose TBI for graft rejection after hematopoietic stem cell transplantation. Bone Marrow Transplant 51, 985–987 (2016). https://doi.org/10.1038/bmt.2016.16

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