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Colita A, Colita A, Bumbea H, et al. LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation. Front Oncol. 2019;9:892doi: 10.3389/fonc.2019.00892.
Colita, A., Colita, A., Bumbea, H., Croitoru, A., Orban, C., Lipan, L. E., Craciun, O. G., Soare, D., Ghimici, C., Manolache, R., Gelatu, I., Vladareanu, A. M., Pasca, S., Teodorescu, P., Dima, D., Lupu, A., Coriu, D., Tomuleasa, C., & Tanase, A. (2019). LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation. Frontiers in oncology, 9892. https://doi.org/10.3389/fonc.2019.00892
Colita, Andrei, et al. "LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation." Frontiers in oncology vol. 9 (2019): 892. doi: https://doi.org/10.3389/fonc.2019.00892
Colita A, Colita A, Bumbea H, Croitoru A, Orban C, Lipan LE, Craciun OG, Soare D, Ghimici C, Manolache R, Gelatu I, Vladareanu AM, Pasca S, Teodorescu P, Dima D, Lupu A, Coriu D, Tomuleasa C, Tanase A. LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation. Front Oncol. 2019 Sep 10;9:892. doi: 10.3389/fonc.2019.00892. eCollection 2019. PMID: 31552193; PMCID: PMC6746965.
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Front Oncol. 2019 Sep 10;9:892. doi: 10.3389/fonc.2019.00892. eCollection 2019.

LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation.

Frontiers in oncology

Andrei Colita, Anca Colita, Horia Bumbea, Adina Croitoru, Carmen Orban, Lavinia Eugenia Lipan, Oana-Gabriela Craciun, Dan Soare, Cecilia Ghimici, Raluca Manolache, Ionel Gelatu, Ana-Maria Vladareanu, Sergiu Pasca, Patric Teodorescu, Delia Dima, Anca Lupu, Daniel Coriu, Ciprian Tomuleasa, Alina Tanase

Affiliations

  1. Department of Hematology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
  2. Department of Stem Cell Transplantation, Coltea Clinical Hospital, Bucharest, Romania.
  3. Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
  4. Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
  5. Department of Stem Cell Transplantation, University Hospital, Bucharest, Romania.
  6. Department of Hematology, Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
  7. Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj Napoca, Romania.
  8. Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
  9. Department of Hematology, Fundeni Clinical Institute, Bucharest, Romania.

PMID: 31552193 PMCID: PMC6746965 DOI: 10.3389/fonc.2019.00892

Abstract

High-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in patients with malignant lymphomas. In Europe over 8,000 ASCTs for lymphoma were performed out of a total of 40,000 transplants according to the European Bone Marrow Transplant (EBMT) activity survey in 2017. ASCT is considered the standard treatment for eligible patients failing to achieve remission after first line chemotherapy or patients with relapsed or refractory lymphomas, including classical Hodkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, as well as consolidation therapy in first remission in mantle cell lymphoma. BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) is the most commonly used conditioning regimen for ASCT in patients with relapsed/refractory (R/R) lymphomas in Europe, whereas the CBV (cyclophosphamide, BCNU, and etoposide) regimen is also widely used in North America. Recently, concerns regarding BCNU toxicity as well as restricted availability of BCNU and melphalan has determined an increasing number of transplant centers to use alternative conditioning regimens. Currently, only a few comparative studies, most of them retrospective, between different conditioning protocols regarding efficacy and toxicity have been published. Thus, in the current manuscript, we report the experience of 2 transplant centers in ASCT in R/R lymphomas with three types of conditioning: BEAM, CLV (cyclophosphamide, lomustine, etoposide) and LEAM (lomustine, etoposide, cytarabine, and melphalan), with the aim to evaluate the results of alternative conditioning regimens using lomustine (LEAM and CLV) and compare them with the standard BEAM regarding early toxicity, engraftment, and transplant related mortality (TRM). All patients developed grade IV neutropenia, anemia with/without transfusion necessity. Severe thrombocytopenia with transfusion requirements is reported in most cases. Median time to platelet engraftment and neutrophil engraftment was 13 days (range) and 10 days (range), respectively. Gastrointestinal toxicity was the most common non-hematologic toxicity after all three conditioning regimens. Oral mucositis in various grades from I to IV was diagnosed in most cases. Other side effects include vomiting, diarrhea, colitis, and skin rash but with low severity grades. For the LEAM arm, one patient died after transplant, before engrafting, one patient didn't achieve platelet engraftment in day 100, one patient developed grade 3 upper gastrointestinal bleeding, one patient died (grade 5 toxicity) with acute renal failure, one patient developed hypoxic events up to grade 4 acute respiratory failure and one patient developed grade 3 itchy skin rash. For the CLV arm, one patient died after transplant, before engrafting, one patient developed grade 3 colitis, one patient with grade 3 hepatic cytolysis, one patient with cardiac toxicity followed by death (grade 5) caused by an acute myocardial infarction with ST elevation and one patient with pulmonary toxicity clinically manifested with grade 3 pleurisy. For the BEAM arm, one patient developed grade 3 cardiac toxicity with sinus bradycardia and afterwards grade 4 with acute pulmonary edema, three patients presented a grade 3 pruritic skin rash and two patients developed grade 3 seizures. In the present study we presented the differences that were observed between BEAM, LEAM, and CLV conditioning regimens offering clinical arguments for an SCT practitioner choice in the ideal situation, but also of choice for alternative regimens in the case that one regimen cannot be used.

Keywords: autologous stem cell transplantation; conditioning chemotherapy; real-life data; relapsed/refractory lymphoma; retrospective analysis

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