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High-dose Carboplatin/Etoposide/Melphalan increases risk of thrombotic microangiopathy and organ injury after autologous stem cell transplantation in patients with neuroblastoma

Bone Marrow Transplantation volume 53, pages 1311–1318 (2018)Cite this article

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Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplant that can result in multi-organ failure (MOF). Patients undergoing high-dose chemotherapy with autologous stem cell transplant (aHCT) for neuroblastoma require good organ function to receive post-transplant radiation and immunotherapy. We examined TA-TMA incidence and transplant outcomes in patients with neuroblastoma receiving different transplant preparative regimens. Sixty patients underwent aHCT using high-dose chemotherapy: 41 patients received carboplatin/etoposide/melphalan (CEM), 13 patients busulfan/melphalan (Bu/Mel) and six patients received tandem transplant (cyclophosphamide/thiotepa and CEM). TA-TMA with MOF was diagnosed in 13 patients (21.7%) at a median of 18 days after aHCT. TA-TMA occurred in 12 patients receiving CEM and in 1 after cyclophosphamide/thiotepa. There were no incidences of TA-TMA after Bu/Mel regimen. Six of 13 patients with TA-TMA and MOF received terminal complement blocker eculizumab for therapy. They all recovered organ function and received planned post-transplant therapy. Out of seven patients who did not get eculizumab, two died from TA-TMA complications and four progressed to ESRD. We conclude that the CEM regimen is associated with a high incidence of clinically significant TA-TMA after aHCT and eculizumab can be safe and effective treatment option to remediate TA-TMA associated MOF.

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Acknowledgements

We thank Dr. Tsuyoshi.Fukuda and Dr. Kana Mizuno from Division of Pharmacology at CCHMC for eculizumab PK/PD studies, Dr. Bradley.Dixon and Ms.Thelma Kathman and the staff of the Nephrology Clinical Laboratory at CCHMC for their assistance with eculizumab serum concentration and CH50 testing, Dr. Ralph Gruppo and Ms. Mary Block and the staff of Hematology Clinical laboratory at CCHMC for their assistance with sC5b-9 testing, Ms. Sue Pinkard and the Hoxworth Blood Center team at the University of Cincinnati for their assistance with therapeutic plasma exchange procedures, Mark Mueller, RN and Suzanne Berger, RN for coordinating neuroblastoma patient care.

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Authors and Affiliations

  1. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Sonata Jodele, Christopher E. Dandoy, Kasiani Myers, Gregory Wallace, Adam Lane & Stella M. Davies

  2. Department of Pharmacy, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Ashley Teusink-Cross

  3. Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Brian Weiss

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  1. Sonata Jodele
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Correspondence to Sonata Jodele.

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Conflict of interest

SJ and SD have a US Provisional patent application for methods and compositions related to transplant-associated thrombotic microangiopathy. The remaining authors declare that they have no conflict of interest.

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Jodele, S., Dandoy, C.E., Myers, K. et al. High-dose Carboplatin/Etoposide/Melphalan increases risk of thrombotic microangiopathy and organ injury after autologous stem cell transplantation in patients with neuroblastoma. Bone Marrow Transplant 53, 1311–1318 (2018). https://doi.org/10.1038/s41409-018-0159-8

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