Safety and Efficacy of BeEAC as a Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphomas

V.O. Sarzhevskii, Anastasiya Aleksandrovna Samoilova, V.Ya. Melnichenko, Yu.N. Dubinina, N.E. Mochkin, D.S. Kolesnikova, D.A. Fedorenko, E.G. Smirnova, A.E. Bannikova, V.S. Bogatyrev,

DOI:

https://doi.org/10.21320/2500-2139-2020-13-2-185-192

Aim. To assess the safety and efficacy of BeEAC as a conditioning regimen prior to autologous hematopoietic stem cell transplantation (auto-HSCT) in relapsed and primary resistant lymphomas (ClinicalTrials.gov NCT03315520).

Materials & Methods. The trial included 113 patients with Hodgkin’s (HL) and non-Hodgkin’s lymphomas (NHL). The patients were included into the protocol during the period from February 2016 to June 2018. Median follow-up was 26 months. Among the patients there were 58 men and 55 women. Median age was 33 years (range 18–65 years). In 72 patients HL and in 41 patients NHL (in 15 diffuse large B-cell lymphoma, in 8 primary mediastinal (thymic) large B-cell lymphoma, in 10 mantle cell lymphoma, in 4 peripheral T-cell lymphoma unspecified, and in 4 patients follicular lymphoma) were diagnosed. BeEAC conditioning regimen consisted of administering 160–200 mg/m2 bendamustine in increasing doses on Day –6 and Day –5 combined with fixed doses of 200 mg/m2 cytarabine every 12 hours, 200 mg/m2 etoposide, and 140 mg/kg cyclophosphamide from Day –4 to Day –1.

Results. In phase 1, when bendamustine dose was increased from 160 mg/m2 to 200 mg/m2, no dose-limiting toxicity was observed. Afterwards patients received 200 mg/m2 of bendamustine. The assessment of tumor status in 2–3 months after auto-HSCT showed that complete remission was achieved in 62.9 % (n = 71) of patients, partial remission in 16.8 % (n = 19) of patients, stabilization in 0.9 % (n = 1) of patients and progression in 15 % (n = 17) of patients. In 5 patients the treatment effect was not assessed. Early post-transplant mortality (up to Day +30) was 3.6 % (n = 4) and overall mortality within the follow-up period (median 26 months) was 23 % (n = 26). Overall survival in the whole cohort of patients for 12, 18, 24, and 36 months was 88 %, 82 %, 78 %, and 64 %, respectively, and progression-free survival was 61 %, 57 %, 54 %, and 40 %, respectively.

Conclusion. BeEAC proved to be relatively safe when applied as a conditioning regimen prior to auto-HSCT in HL and NHL patients. Further data need to be collected to finally assess the efficacy of this regimen and to conduct a retrospective comparative analysis of it and other conditioning regimens in lymphomas.

  • V.O. Sarzhevskii NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • Anastasiya Aleksandrovna Samoilova NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • V.Ya. Melnichenko NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • Yu.N. Dubinina NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • N.E. Mochkin NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • D.S. Kolesnikova NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • D.A. Fedorenko NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • E.G. Smirnova NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • A.E. Bannikova NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
  • V.S. Bogatyrev NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203 ; ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203
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Keywords:

high-dose chemotherapy, autologous hematopoietic stem cell transplantation, conditioning regimens, bendamustine, toxicity

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2020-2

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01.04.2020

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Vol. 13 No. 2 (2020)
BONE MARROW TRANSPLANTATION

How to Cite

Sarzhevskii V.O., Samoilova A.A., Melnichenko V.Y., et al. Safety and Efficacy of BeEAC as a Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphomas. Clinical Oncohematology. Basic Research and Clinical Practice. 2020;13(2):185–192. doi:10.21320/2500-2139-2020-13-2-185-192.

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