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Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia.
Bone Marrow Transplant. 2000 Oct; 26(7):711-6.BM

Abstract

To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were > first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen for bone marrow transplantation of patients with AML with a low relapse rate. However, conditioning with 30 mg/kg rather than 45 mg/kg etoposide resulted in less toxicity and a better overall survival due to a lower transplant-related mortality. Bone Marrow Transplantation (2000) 26, 711-716.

Authors+Show Affiliations

Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11042650

Citation

Kröger, N, et al. "Dose-dependent Effect of Etoposide in Combination With Busulfan Plus Cyclophosphamide as Conditioning for Stem Cell Transplantation in Patients With Acute Myeloid Leukemia." Bone Marrow Transplantation, vol. 26, no. 7, 2000, pp. 711-6.
Kröger N, Zabelina T, Sonnenberg S, et al. Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia. Bone Marrow Transplant. 2000;26(7):711-6.
Kröger, N., Zabelina, T., Sonnenberg, S., Krüger, W., Renges, H., Stute, N., Finkenstein, F., Mayer, U., Holstein, K., Fiedler, W., Colberg, H., Sonnen, R., Kuse, R., Braumann, D., Metzner, B., del Valle, F., Erttmann, R., Kabisch, H., & Zander, A. R. (2000). Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia. Bone Marrow Transplantation, 26(7), 711-6.
Kröger N, et al. Dose-dependent Effect of Etoposide in Combination With Busulfan Plus Cyclophosphamide as Conditioning for Stem Cell Transplantation in Patients With Acute Myeloid Leukemia. Bone Marrow Transplant. 2000;26(7):711-6. PubMed PMID: 11042650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia. AU - Kröger,N, AU - Zabelina,T, AU - Sonnenberg,S, AU - Krüger,W, AU - Renges,H, AU - Stute,N, AU - Finkenstein,F, AU - Mayer,U, AU - Holstein,K, AU - Fiedler,W, AU - Colberg,H, AU - Sonnen,R, AU - Kuse,R, AU - Braumann,D, AU - Metzner,B, AU - del Valle,F, AU - Erttmann,R, AU - Kabisch,H, AU - Zander,A R, PY - 2000/10/24/pubmed PY - 2001/2/28/medline PY - 2000/10/24/entrez SP - 711 EP - 6 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 26 IS - 7 N2 - To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were > first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen for bone marrow transplantation of patients with AML with a low relapse rate. However, conditioning with 30 mg/kg rather than 45 mg/kg etoposide resulted in less toxicity and a better overall survival due to a lower transplant-related mortality. Bone Marrow Transplantation (2000) 26, 711-716. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/11042650/Dose_dependent_effect_of_etoposide_in_combination_with_busulfan_plus_cyclophosphamide_as_conditioning_for_stem_cell_transplantation_in_patients_with_acute_myeloid_leukemia_ L2 - https://doi.org/10.1038/sj.bmt.1702598 DB - PRIME DP - Unbound Medicine ER -