Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS

Lima, Marcos de; Couriel, Daniel R.; Thall, Peter F.; Wang, Xuemei; Madden, Timothy; Jones, Roy B.; Shpall, Elizabeth J.; Shahjahan, Munir; Pierre, Betty; Giralt, Sergío; Körbling, Martin; Russell, James A.; Champlin, Richard E.; Andersson, Börje S.

doi:10.1182/blood-2004-02-0414

Cited by 395 publications

(373 citation statements)

References 46 publications

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“…The initial report by the MD Anderson group of FB4 in MAC-eligible patients showed a remarkably low NRM of 14% at 3 years after SCT. 26 When this regimen was explored in older patients with more comorbidities, more similar to our FT regimen, NRM rate was also more similar, reaching 26% at 3 years. 27 Multivariate analysis showed that an HCT-CI 42 and advanced disease were the factors predicting for NRM, and when adjusting for these factors, FT conditioning was not associated with excess NRM.…”

Section: Discussionmentioning

confidence: 99%

Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity

Shimoni

Shem‐Tov

Volchek

et al. 2012

Bone Marrow Transplant

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Allo-SCT with reduced-intensity conditioning (RIC) results in lower non-relapse mortality (NRM), but higher relapse rate than myeloablative conditioning (MAC) in AML/myelodysplastic syndromes (MDS). Novel regimens with intensive anti-leukemic activity, but with limited toxicity will be of benefit. In all, 85 patients with AML/MDS, not eligible for MAC, were given fludarabine-treosulfan conditioning (FT). Outcomes were compared with those in patients given fludarabine-BU RIC (FB2, n ¼ 106) or reduced-toxicity (RTC) conditioning (FB4, fludarabine and myeloablative BU dose, n ¼ 85). The 5-year NRM was 29%, 20% and 18% after FT, FB2 and FB4, respectively (P ¼ NS). Multivariate analysis (MVA) identified comorbidity score (HCT-CI) 42 and advanced disease as adverse factors with no independent impact of regimen. The 5-year relapse rate was 36%, 47% and 40%, respectively (P ¼ 0.17). MVA identified advanced disease as the major adverse factor, while FT had significantly lower relapse rate (hazard ratio 0.6, P ¼ 0.03). The 5-year survival (OS) was 37% with advanced disease. HCT-CI 42 and age X50 were found as adverse factors. The 5-year OS was 46%, 44% and 50% after FT, FB2 and FB4 in early-intermediate-stage disease (P ¼ NS) and 33%, 9% and 28% in advanced disease, respectively (P ¼ 0.02). FT is an RTC regimen with intensive anti-leukemia effect in MAC non-eligible patients.

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Section: Discussionmentioning

confidence: 99%

Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity

Shimoni

Shem‐Tov

Volchek

et al. 2012

Bone Marrow Transplant

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“…6,7 However, favorable outcomes of non-TBI-based RIC transplantation were also reported. 8 Thus, the impact of low-dose TBI on outcomes after allo-HSCT remains controversial, and it is unknown whether the addition of low-dose TBI to RIC is beneficial for AML patients. Therefore, we conducted a retrospective analysis to elucidate the clinical impact of low-dose TBI on outcomes after allo-HSCT from a HLA-matched-related donor in the setting of fludarabine-based RIC.…”

mentioning

confidence: 99%

Impact of low-dose TBI on outcomes of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for AML

Aoki

Seo

Kanamori

et al. 2015

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for patients with advanced hematologic malignancy, including those with AML. 1 However, allo-HSCT after conventional myeloablative conditioning (MAC) may be associated with a high rate of transplant-related complications. Reduced intensity conditioning (RIC) was developed with the purpose of reducing regimen-related toxicity. 2,3 RIC is increasingly used for allo-HSCT for AML patients who are otherwise considered unfit for MAC.The primary objective of low-dose TBI in RIC is inhibition of the host immune response to facilitate engraftment. 4,5 Several studies have suggested that the addition of low-dose TBI to the conditioning regimen improved outcomes of transplantation. 6,7 However, favorable outcomes of non-TBI-based RIC transplantation were also reported. 8 Thus, the impact of low-dose TBI on outcomes after allo-HSCT remains controversial, and it is unknown whether the addition of low-dose TBI to RIC is beneficial for AML patients. Therefore, we conducted a retrospective analysis to elucidate the clinical impact of low-dose TBI on outcomes after allo-HSCT from a HLA-matched-related donor in the setting of fludarabine-based RIC.Clinical data were collected from the registry database of the Japan Society for Hematopoietic Cell Transplantation. Patients with AML (excluding acute promyelocytic leukemia) aged 16 years or older who underwent fludarabine-based RIC allo-HSCT from an HLA-matched-related donor between January 2000 and December 2012 were extracted from the database. Patients who underwent two or more HSCT were excluded. We retrospectively analyzed the clinical impact of low-dose TBI on outcomes after RIC allo-HSCT. Overall survival (OS), relapse, nonrelapse mortality (NRM) and hematological recovery of patients who received low-dose TBI as a part of fludarabine-based RIC (TBI group) were compared with those of patients who did not receive TBI (non-TBI group). Low-dose TBI was defined as ⩽ 4 Gy, as previously reported. 9 Fludarabine-based RIC was defined as RIC containing fludarabine 120-180 mg/m 2 . Definitions of RIC other than TBI were as follows: oral busulfan o9 mg/kg (or IV injection in equivalent doses) or melphalan ⩽ 140 mg/m 2 . 10 Cytogenetic subgroups were classified according to the Southwest Oncology Group (SWOG) definition. 11 Neutrophil engraftment was defined as the continuous achievement of neutrophil counts 500 × 10 6 /l or higher. Platelet recovery was also defined as continuous achievement of neutrophil counts 50 × 10 9 /l or higher without transfusion. This study was approved by the Institutional Review Board of the Kanagawa Cancer Center. Table 1 shows patients characteristics. Of the 409 patients, 108 patients were in the TBI group and 301 patients were in the non-TBI group. A higher proportion of patients underwent bone marrow transplantation (BMT) (P o 0.001) and received cyclosporine for GvHD prophylaxis (P = 0.006) in the TBI group. The proportion of male patients (P = 0.07) and patients who un...

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“…7 Based on recent publications, there is reason to believe that the sequence and timing of the respective drug may also influence outcome in the clinical setting. The concomitant use of Flu and Bu in a 4-5-day combination yields very similar outcomes, [8][9][10][11][12][13][14][15] especially in high-risk patient subpopulations. In contrast, investigators who use sequential administration of the two drugs reported similar low non-relapse mortality, but possibly a higher post-transplant relapse risk, especially in high-risk patients.…”

mentioning

confidence: 85%

Pretransplant conditioning with fludarabine and IV busulfan, reduced toxicity and increased safety without compromising antitumor efficacy and overall treatment effect?

Andersson

Valdez

2016

Bone Marrow Transplant

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Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS

Cited by 395 publications

References 46 publications

Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity

Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity

Impact of low-dose TBI on outcomes of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for AML

Pretransplant conditioning with fludarabine and IV busulfan, reduced toxicity and increased safety without compromising antitumor efficacy and overall treatment effect?

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