Secondary failure of platelet recovery in patients treated with high-dose thiotepa and busulfan followed by autologous s
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Secondary failure of platelet recovery in patients treated with high‑dose thiotepa and busulfan followed by autologous stem cell transplantation Fumiya Wada1 · Momoko Nishikori1 · Masakatsu Hishizawa1 · Mitsumasa Watanabe2 · Akiko Aiba3 · Toshiyuki Kitano3 · Yayoi Shimazu4 · Takero Shindo1 · Tadakazu Kondo1 · Akifumi Takaori‑Kondo1 Received: 5 August 2020 / Revised: 1 September 2020 / Accepted: 13 September 2020 © Japanese Society of Hematology 2020
Abstract Autologous stem cell transplantation (ASCT) with high-dose thiotepa and busulfan is a treatment option for patients with central nervous system (CNS) lymphoma. We report here the occurrence of secondary failure of platelet recovery (SFPR) in three out of 24 patients who received high-dose thiotepa and busulfan followed by ASCT. Although there was no obvious abnormality in the primary platelet engraftment as well as the recovery of other blood cells, they developed SFPR with a median time to onset of day 38, and the platelets gradually recovered over several months with steroid therapy. During the same period, there was no development of SFPR among 50 patients who received ASCT with a conditioning regimen of MEAM (ranimustine, etoposide, cytarabine, and melphalan) or high-dose melphalan. However, one of the two patients who received a conditioning regimen of busulfan and melphalan developed SFPR, suggesting that the use of a busulfan-based conditioning regimen may be one of the risk factors for SFPR. It is important to be aware of this possible adverse effect of ASCT with high-dose thiotepa and busulfan to ensure timely diagnosis and prevention of subsequent serious complications. Keywords Busulfan · Thiotepa · Autologous stem cell transplantation · Secondary failure of platelet recovery
Introduction Primary central nervous system lymphoma (PCNSL) is a rare lymphoma subtype that is confined to the central nervous system (CNS), such as brain parenchyma, cranial nerves, leptomeninges, and spinal cord. Secondary CNS lymphoma (SCNSL), on the other hand, occurs together with or consequently to systemic lymphomas, often within the leptomeningeal compartment. Both CNS lymphomas are associated * Momoko Nishikori [email protected]‑u.ac.jp 1
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara‑cho, Sakyo‑ku, Kyoto 606‑8507, Japan
2
Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan
3
Department of Hematology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan
4
Department of Hematology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
with unfavorable outcomes, mainly because of the poor penetration of chemotherapeutic agents into the CNS due to the presence of the blood–brain barrier. Thiotepa is a lipid-soluble alkylating agent that has a high capability of penetrating the blood–brain barrier, and it is recognized as a beneficial treatment option for CNS lymphomas. Its usefulness is described especiall
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