Reliability of a pretransplant i.v. BU test dose performed 2 weeks before myeloablative FluBu conditioning regimen

Beri, R.; Chunduri, S.; Sweiss, Karen; Peace, David; Mactal-Haaf, Christina; Dobogai, Lisa C.; Shord, Stacy S.; Quigley, John G.; Chen, Y H; Mahmud, Nadim; Rondelli, Damiano

doi:10.1038/bmt.2009.133

Cited by 28 publications

(44 citation statements)

References 20 publications

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“…Test dose strategies have been reported to be useful [15][16][17]. However, no significant correlation was observed between AUC values for the test dose and first dose in our study.…”

Section: Discussioncontrasting

confidence: 82%

Trough level monitoring of intravenous busulfan to estimate the area under the plasma drug concentration–time curve in pediatric hematopoietic stem cell transplant recipients

et al. 2015

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Optimizing systemic busulfan exposure, the area under the concentration-time curve (AUC), improves the outcomes for hematopoietic stem cell transplantation (HSCT). The AUC is conventionally calculated using six plasma concentrations (AUC(0-∞)) drawn after the first of 16 intravenous busulfan doses given as a 2-h infusion every 6 h. The aim of the present study was to develop limited sampling strategies using three or fewer busulfan concentrations to reliably calculate AUC(0-∞) in patients undergoing HSCT. We investigated the pharmacokinetics of busulfan 46 times in 29 pediatric patients receiving intravenous busulfan. Limited sampling strategies using one, two, or three plasma busulfan concentrations were developed by multiple linear regression that showed excellent agreement with AUC(0-∞). In single-point sampling strategies, the AUC(0-∞) predicted based on C(6) (trough level: busulfan plasma concentration 6 h after the start of the infusion) was significantly correlated with, and not statistically different from, actual values as follows: AUC(0-∞) = 2556.5 C6 + 320.9 (r(2) = 0.929, P < 0.0001, mean bias 0.282 %, precision 7.91 %). In contrast, the predicted AUCs derived from the other sampling single points did not meet the criteria. The trough level well correlated with actual AUC(0-∞), suggesting that this time-point is acceptable for busulfan monitoring.

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“…Test dose strategies have been reported to be useful [15][16][17]. However, no significant correlation was observed between AUC values for the test dose and first dose in our study.…”

Section: Discussioncontrasting

confidence: 82%

Trough level monitoring of intravenous busulfan to estimate the area under the plasma drug concentration–time curve in pediatric hematopoietic stem cell transplant recipients

et al. 2015

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“…One potential explanation for the higher incidence of TEC in our patients is that pharmacokinetically based doses of BU tend to be higher than those based upon body surface area. 19 In addition, it is possible that the relatively late onset of TEC obscured the relationship between the conditioning regimen and toxicity. Of note, other BU-containing regimens have been reported to lead to hyperpigmentation in flexural areas and acral erythema 20 or a 'rash' with desquamation 21 (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant

Parker

Cooper

Seropian

et al. 2012

Bone Marrow Transplant

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I.v. BU plus fludarabine is an effective conditioning regimen for myeloid neoplasias with low treatment-related mortality. At standard doses, cutaneous toxicity has been reported in o5% of cases. As we observed a much higher incidence of cutaneous toxicity in patients who received predominantly pharmacokinetically based doses of BU, we performed a retrospective analysis of 61 patients who received i.v. BU plus fludarabine ( þ / À antithymocyte globulin; ATG) as a conditioning regimen before allogeneic PBSC transplant. Of the 58 evaluable patients, 33 (57%) developed cutaneous toxicity that fell within the spectrum of toxic erythema of chemotherapy (TEC). The median onset of TEC was 22 days and most patients had multiple sites of involvement, with the groin, axillae and palms/soles being the favored sites. In men, scrotal involvement, sometimes severe, was also commonly observed. Initially, allergic reactions to antibiotics, fungal infections and GVHD were also considered until the clinical presentation of TEC became well recognized. In all patients, the skin healed without specific therapy but resolution often required several weeks. This series suggests that TEC is common after BU/fludarabine þ / À ATG and it is important for transplant physicians to recognize, particularly as misdiagnosis could lead to inappropriate treatment.

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“…busulfan was administered at a total dose of 12.8 mg/kg, or to target an AUC of 4800 mmol/min, as previously described. 5 GVHD prophylaxis consisted of standard methotrexate (day 1 at 15 mg/m 2 , and on days 3, 6 and 11 at 10 mg/m 2 ) and tacrolimus (from day -2). Tacrolimus level was maintained at 5-15 ng/ml until day 180 unless the patient experienced GVHD or disease recurrence.…”

Section: Transplantationmentioning

confidence: 99%

Comorbidity index does not predict outcome in allogeneic myeloablative transplants conditioned with fludarabine/i.v. busulfan (FluBu4)

Patel

Sweiss

Nimmagadda

et al. 2010

Bone Marrow Transplant

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The assessment of a hematopoietic stem cell transplant (HSCT)-specific comorbidity index (HCT-CI) has been developed to predict the risk of TRM in patients undergoing allogeneic HSCT. As the myeloablative fludarabine/i.v. busulfan (FluBu4) regimen has been associated with limited extra-hematologic toxicity, we analyzed whether the HCT-CI represents a useful tool in transplant patients conditioned with this regimen. Of the 52 consecutive patients who received an allogeneic HSCT with FluBu4 at our institution, 50 were evaluable for assessing pre-transplant HCT-CI. Patients were divided into three groups: score 0 (n ¼ 7); score 1-2 (n ¼ 17) and score 43 (n ¼ 26). The three groups did not differ significantly in age, diagnosis, previous lines of chemotherapy and type of donor. High-risk disease was present in 57% of low, 82% of intermediate and 85% of high HCT-CI score groups (P ¼ ns). Two-year TRM and OS was 14.3 and 85.7% in the low score group, 23.5 and 58.8% in the intermediate score group and 15.4 and 50% in the high HCT-CI score group (P ¼ ns). In this study, the HCT-CI lacked sensitivity to reliably predict TRM although patients with no comorbidities showed a trend for improved survival.

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Reliability of a pretransplant i.v. BU test dose performed 2 weeks before myeloablative FluBu conditioning regimen

Cited by 28 publications

References 20 publications

Trough level monitoring of intravenous busulfan to estimate the area under the plasma drug concentration–time curve in pediatric hematopoietic stem cell transplant recipients

Trough level monitoring of intravenous busulfan to estimate the area under the plasma drug concentration–time curve in pediatric hematopoietic stem cell transplant recipients

Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant

Comorbidity index does not predict outcome in allogeneic myeloablative transplants conditioned with fludarabine/i.v. busulfan (FluBu4)

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