Busulfan dosing (Q6 or Q24) with adjusted or actual body weight, does it matter?

Clemmons, Amber B.; Evans, Sarah; DeRemer, David L.; Awan, Farrukh T.

doi:10.1177/1078155214541571

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Except that using adjusted weight to calculate pre-targeted doses required more frequent increments according to pharmacokinetics in both dosing schedules. (26) These studies confirmed that when using target dosing for Bu, both dosing schedules are equivalent. These smaller studies support the findings of our study that represent contemporary clinical practices in North America.…”

Section: Discussionsupporting

confidence: 59%

Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies

Pasquini

Le‐Rademacher

Zhu

et al. 2016

Biology of Blood and Marrow Transplantation

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Busulfan (Bu)-containing regimens are commonly used in myeloablative regimens prior to allogeneic hematopoietic cell transplantation (HCT). Yet, there is considerable variability on how Bu is administered related to frequency (four times a day, Q6 or daily, Q24) and the combination with other chemotherapeutic agents (cyclophosphamide, Cy or fludarabine, Flu). A prospective cohort study of recipients of Bu-based conditioning according to contemporary practices was used to compare different approaches in using Bu (BuCy Q6 N=495; BuFlu Q24 N=331; BuCy Q24 N=96; BuFlu Q6 N=91) in patients with myeloid malignancies from 2009 to 2011. BuFlu Q24 recipients were more likely to be older and tended to have worse performance status and higher comorbid burden. The cumulative incidence of hepatic veno-occlusive disease (p=0.4), idiopathic pneumonia (p=0.5) and seizures (p=0.5) did not differ across groups. One-year HCT related mortality ranged from 12% to 16% (P=0.8), three-year relapse incidences ranged from 32% to 36% (p=0.8) and three-year overall survival ranged from 51% to 58% (p=0.2) across groups. This study demonstrates that the use of intravenous Bu Q6 or Q24 or accompanied by Cy or Flu have similar outcomes in the myeloablative setting for treatment of myeloid malignancies.

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Section: Discussionsupporting

confidence: 59%

Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies

Pasquini

Le‐Rademacher

Zhu

et al. 2016

Biology of Blood and Marrow Transplantation

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“…Other isoenzymes (GSTM1, GSTT1, and GSTP1) are involved in the metabolism of Bu but to a much lower extent. 6,7 The glutathione family has a high rate of polymorphisms, and this is believed to contribute to 20%-95% of the variation seen in Bu pharmacokinetics. 8 The impact of glutathione S-transferase (GST) polymorphisms on the clinical outcomes of hematopoietic stem cell transplantation (HSCT) is controversial.…”

Section: Introductionmentioning

confidence: 99%

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation

Al-Riyami

Al-Khabori

Balushi

et al. 2022

Therapeutic Drug Monitoring

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Background: Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 (GSTA1). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase (GST) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT.Methods: This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1, GSTT1, GSTA1, and GSTP1. Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes.Results: A total of 135 patients were included. The mean Bu clearance was 3.7 6 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss (P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease (P = 0.04). Double non-null GSTM1 and GSTT1 and nonnull GSTM1 increased the risk of mortality (P = 0.034 and 0.021, respectively).Conclusions: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

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“…The decrease in the food intake and reduction of body weight is observed in patients with myeloid leukemia who are treated with Butene dimethylsulphonate (Bulsufan). In addition to belonging to the same family, Bulsufan has a very similar chemical structure to EDS, which may have influenced the food intake alteration of animals treated with EDS Clemmons et al 2014). Despite the reduction in body weight, no alterations were observed in the weight of most target-organs of animals treated with EDS, demonstrating that this compound did not promote systemic toxicological effects, since it has already been established that the variation of the weight of these organs can be used as parameter of toxicity (Sellers et al, 2007;Wolfsegger et al, 2009).…”

Section: -Discussionmentioning

confidence: 99%

Avaliação da administração oral do etano dimetanosulfato como uma alternativa quimioesterelizante para roedores

Flávia Quiarato Lozano

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Busulfan dosing (Q6 or Q24) with adjusted or actual body weight, does it matter?

Abstract: Further prospective studies are warranted to elucidate which weight is most likely to achieve goal AUC and subsequent optimal patient outcomes.

Cited by 7 publications

References 27 publications

Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies

Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation

Avaliação da administração oral do etano dimetanosulfato como uma alternativa quimioesterelizante para roedores

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