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Severe renal insufficiency is not an absolute pitfall to autologous stem cell transplantation with BeEAM (bendamustine, etoposide, cytarabine, melphalan) conditioning regimen

Bone Marrow Transplantation volume 54, pages 1173–1175 (2019)Cite this article

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High-dose therapy with autologous stem cell transplantation (ASCT) is a key procedure in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) therapy in first line for young patients with high risk lymphoma (i.e., plasmablastic lymphoma (PBL), mantle cell lymphoma), or in relapsed/refractory patients who respond to salvage chemotherapy [1,2,3]. BEAM (carmustine 300 mg/m2 IV on day (D)−6, etoposide 100 mg/m2 IV bid on D−5 to 2, cytarabine 100 mg/m2 IV bid on D −5 to 2, melphalan 140 mg/m2 on D−1) is the most used conditioning regimen for therapeutic intensification in NHL or HL [1]. Recently, an alternative regimen called BeEAM with Bendamustine 160 mg/m2 IV on D-7 and 6 in place of carmustine, has demonstrated high efficacy with limited toxicity in relapsed/refractory NHL [4]. Bendamustine (Levact®; Mundipharma International Ltd) combines the alkylating activity of the mustard group with the antimetabolite activity of the purine analog structure. Mechanisms of bendamustine action include mitotic catastrophe induction, chekpoints inhibition, apoptosis stimulation, and extensive DNA damage [5]. Bendamustine is metabolized in the liver and excreted in the feces (90%) or urine (<10%), but very few pharmacological data are available concerning carmustine metabolism in patients with renal insufficiency.

Although renal insufficiency does not adversely affect hematopoietic stem cell collection, post-transplant engraftment, transfusion requirement and mucositis occurrence [6] patients with HL or NHL, with serum creatinine > 2.5 mg/dL (175 or 221 µmol/l) are usually not considered eligible for ASCT in most of transplant centers [1].

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References

  1. Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH87-2 protocol—a groupe d’Etude des lymphomes de l’Adulte study. J Clin Oncol J Am Soc Clin Oncol. 2000;18:3025–30.

    Article  CAS  Google Scholar 

  2. Castillo JJ, Winer ES, Stachurski D, Perez K, Jabbour M, Milani C, et al. Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma. Leuk Lymphoma. 2010;51:2047–53.

    Article  Google Scholar 

  3. Al-Malki MM, Castillo JJ, Sloan JM, Re A. Hematopoietic cell transplantation for plasmablastic lymphoma: a review. Biol Blood Marrow Transplant. 2014;20:1877–84.

    Article  Google Scholar 

  4. Visani G, Stefani PM, Capria S, Malerba L, Galieni P, Gaudio F, et al. Bendamustine, etoposide, cytarabine, melphalan, and autologous stem cell rescue produce a 72% 3-year PFS in resistant lymphoma. Blood. 2014;124:3029–31.

    Article  CAS  Google Scholar 

  5. Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, et al. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008;14:309–17.

    Article  CAS  Google Scholar 

  6. Tricot G, Alberts DS, Johnson C, Roe DJ, Dorr RT, Bracy D, et al. Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res. 1996;2:947–52.

    CAS  PubMed  Google Scholar 

  7. Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, et al. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014;124:2306–12.

    Article  CAS  Google Scholar 

  8. Garciaz S, Coso D, Schiano de Collela J-M, Broussais F, Stoppa A-M, Aurran T, et al. Bendamustine-based conditioning for non-Hodgkin lymphoma autologous transplantation: an increasing risk of renal toxicity. Bone Marrow Transplant. 2016;51:319–21.

    Article  CAS  Google Scholar 

  9. Cull G, O’Halloran S, Ilett KF. Therapeutic drug monitoring for busulfan in plasma during conditioning chemotherapy for autologous stem cell transplantation in relapsed primary cerebral lymphoma. Ther Drug Monit. 2010;32:333–7.

    Article  Google Scholar 

  10. Bodge MN, Reddy S, Thompson MS, Savani BN. Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic kidney disease: analysis of the literature and recommendations. Biol Blood Marrow Transplant. 2014;20:908–19.

    Article  Google Scholar 

  11. Kal HB, van Kempen-Harteveld ML. Renal dysfunction after total body irradiation: dose-effect relationship. Int J Radiat Oncol Biol Phys. 2006;65:1228–32.

    Article  Google Scholar 

  12. Cheson BD, Brugger W, Damaj G, Dreyling M, Kahl B, Kimby E, et al. Optimal use of bendamustine in hematologic disorders: Treatment recommendations from an international consensus panel - an update. Leuk Lymphoma. 2016;57:766–82.

    Article  CAS  Google Scholar 

  13. Ciccolini J, Monjanel-Mouterde S, Bun S-S, Blanc C, Duffaud F, Favre R, et al. Population pharmacokinetics of etoposide: application to therapeutic drug monitoring. Ther Drug Monit. 2002;24:709–14.

    Article  CAS  Google Scholar 

  14. Smith GA, Damon LE, Rugo HS, Ries CA, Linker CA. High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency. J Clin Oncol. 1997;15:833–9.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Hematology and Cellular Therapy Department, La Conception, University Hospital of Marseille, Marseille, France

    L. Farnault, G. Venton, V. Ivanov, R. Arcani, P. Roche, C. Mercier, J. Colle & RT Costello

  2. Pharmacy, ONCOPHARMA Unit, Timone Hospital, University Hospital of Marseille, Marseille, France

    B. Pourroy

  3. Department of Nephrology, La Conception, University Hospital of Marseille, Marseille, France

    N. Jourde-Chiche

  4. UMR_S 1076, Vascular Research Center of Marseille, Marseille, France

    N. Jourde-Chiche

  5. Pharmacy Unit, La Conception, University Hospital of Marseille, APHM, Marseille, France

    R. Fanciullino

  6. SMARTc Unit, Pharmacokinetics Laboratory, UMR_911 CRO2 AMU, Marseille, France

    R. Fanciullino

  7. Aix Marseille Université, INSERM UMR_S 1090, Technological Advances for Genomics and Clinics, Marseille, France

    RT Costello

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Farnault, L., Venton, G., Pourroy, B. et al. Severe renal insufficiency is not an absolute pitfall to autologous stem cell transplantation with BeEAM (bendamustine, etoposide, cytarabine, melphalan) conditioning regimen. Bone Marrow Transplant 54, 1173–1175 (2019). https://doi.org/10.1038/s41409-019-0467-7

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