Tolerance and efficacy of total body irradiation and cladribine prior to allogeneic hematopoietic cells transplantation in patients with acute myeloid leukemia and myelodysplastic syndromes — synopsis of clinical study
, 1
Abstract
Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is a standard of care for patients with acute myeloid leukemia (AML) and patients with intermediate and high-risk myelodysplastic syndrome (MDS). Despite many years of experience. there is still no standard for conditioning regimen. The aim of this study is to analyse the efficacy and safety of a conditioning treatment with cladribine in combination with total body irradiation (TBI).
Material and methods: A group of 40 adult patients referred for allo-HCT due to AML and MDS are to be enrolled in the study. The inclusion criteria are: informed consent, chemo-sensitivity for cladribine treatment regimens (when used in induction therapy), age 18–60, and performance status 0–2 according to World Health Organization. The conditioning regimen consists of cladribine and TBI at a total dose of 12 Gy in three fractions given over three consecutive days. The goal of the study is to assess the tolerability and efficacy of the regimen.
Results: Our results may stimulate further investigation in this field i.e. phase III trials to compare this regimen to others.
Conslusion: A myeloablative conditioning regimen consisting of total body irradiation in combination with cladribine may contribute to improved outcomes after allo-HCT for AML and MDS patients.
Keywords: allo-HCTmyeloablative regimentransplantationcladribinetotal body irradiationTBI
References
- Stelljes M, Bornhauser M, Kroger M, et al. Cooperative German Transplant Study Group. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood. 2005; 106(9): 3314–3321.
- Bornhäuser M, Kienast J, Trenschel R, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012; 13(10): 1035–1044.
- Holowiecki J, Grosicki S, Robak T, et al. Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004; 18(5): 989–997.
- Hołowiecki J, Grosicki S, Kyrcz-Krzemien S, et al. Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome--Polish Adult Leukemia Group (PALG) pilot study. Ann Hematol. 2008; 87(5): 361–367.
- National Comprehensive Cancer Network. Bone Cancer (Version 3.2021). http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf (March 02, 2021).
- Holowiecki J, Grosicki S, Giebel S, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012; 30(20): 2441–2448.
- Markova M, Barker JN, Miller JS, et al. Fludarabine vs cladribine plus busulfan and low-dose TBI as reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation: a prospective randomized trial. Bone Marrow Transplant. 2007; 39(4): 193–199.
- Saito T, Kanda Y, Nakai K, et al. Immune reconstitution following reduced-intensity transplantation with cladribine, busulfan, and antithymocyte globulin: serial comparison with conventional myeloablative transplantation. Bone Marrow Transplant. 2003; 32(6): 601–608.
- Giralt S, Thall PF, Khouri I, et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood. 2001; 97(3): 631–637.
