COMPARISON OF NEW FLU-BU12-TG CONDITIONING WITH THE STANDARD BU-CY MYELOABLATIVE REGIMEN IN PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA

Ludek Raida,Beata Katrincsakova,Jana Vondrakova,Karel Indrak,Edgar Faber,Zuzana Pikalova,Iva Skoumalova,Zuzana Rusinakova,Marie Jarosova,Jaromir Hubacek,Pavel Tucek,Pavel Kurfurst

doi:10.5507/bp.2011.040

Ludek Raida, Beata Katrincsakova + Show 10 more

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https://doi.org/10.5507/bp.2011.040

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Journal: Biomedical Papers	Publication Date: Dec 1, 2011
Citations: 5	License type: cc-by

Affiliation: Palacký University, Olomouc

Abstract

This study compares the outcomes of patients with high-risk acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (SCT) after conditioning combining busulfan (16 mg/kg orally) and cyclophosphamide (120 mg/kg intravenously) (BU-CY) with those allografted after administration of fludarabine (150 mg/m(2) intravenously), busulfan (12 mg/kg orally) and thymoglobulin (6 mg/kg intravenously) (FLU-BU12-TG). SCT after BU-CY and FLU-BU12-TG was performed in 21 and 10 AML patients. There were no significant differences between groups in number of patients treated in complete disease remission, gender, age, donors, CD34+, mononuclear cell (MNC) count in the graft and follow-up period. However, significantly more SCTs from unrelated (90% vs. 19%; p=0.00018) and HLA-mismatched donors (50% vs. 0%; p=0.0004) were performed in the FLU-BU12-TG group. The Cox proportional hazards model was used to assess the risk of post-transplant AML relapse and non-relapse mortality (NRM). The probability of post-transplant 2-year event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. No significant differences were found between the FLU-BU12-TG and BU-CY groups in risk of AML relapse (HR=1.036; 95% CI [0.102 - 10.47]; p=0.9), post-transplant NRM (HR=0.25; 95% CI [0.031 - 1.96]; p=0.18), 2-year EFS (89% vs. 43%; p=0.19) or OS (79% vs. 57%; p=0.23). These pilot results demonstrate the efficacy of the new FLU-BU12-TG conditioning regimen in patients allografted for high-risk AML. This conditioning might become an alternative approach in patients at high risk of severe post-transplant complications after the standard BU-CY myeloablative regimen.

Highlights

The BU-CY chemotherapy regimen is one of the most frequent types of myeloablative conditioning used in allogeneic SCTs
A busulfan dose of 16 mg/kg combined with cyclophosphamide in BU-CY is necessary to eliminate and successfully control the AML clone? Myeloablation can be achieved with a busulfan dose of 12 mg/kg b.w. without the addition of cyclophosphamide associated with higher toxicity[3]
This risk could be avoided with less intensive post-transplant graft-versus-host disease (GVHD) prophylaxis using cyclosporine A (CSP-A) only and shortening the period of immunosuppression

Summary

Introduction

Essential immunoablative effects leading to the achievement of stable donor cell engraftment may be provided with fludarabine and thymoglobulin. Such a regimen (FLU-BU12-TG) might be less toxic despite the myeloablative dose of busulfan and considered as conditioning with reduced toxicity. There may be some arguments against the use of thymoglobulin due to a potential decrease in graft-versus-leukemia (GVL) reaction and a higher relapse risk[4]. This risk could be avoided with less intensive post-transplant graft-versus-host disease (GVHD) prophylaxis using cyclosporine A (CSP-A) only and shortening the period of immunosuppression. Some experience with conditioning combining fludarabine, busulfan (a dose of 8 mg/kg b.w.) and thymoglobulin and using different intensity of posttransplant GVHD prophylaxis (CSP-A alone vs. CSP-A and mycophenolate mofetil) was published by Mohty et al this study did not confirm any significant difference in the incidence of acute or chronic GVHD and overall survival in regard to the used prophylaxis[5]

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