High‐dose busulfan and the risk of pulmonary mortality after autologous stem cell transplant

Kalaycio, Matt; Pohlman, Brad; Kuczkowski, Elizabeth; Rybicki, Lisa; Andresen, Steve; Sobecks, Ronald; Bolwell, Brian J.

doi:10.1111/j.1399-0012.2006.00581.x

Cited by 16 publications

(9 citation statements)

References 15 publications

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“…The cohort was at a 5.2-fold increased risk of deaths due to pulmonary compromise, and at a 1.7-fold increased risk of deaths due to cardiac causes. The risk of death due to cardiopulmonary disease was especially elevated in patients with HL and NHL, due to exposure to chest radiation and pulmonary and cardiotoxic chemotherapy prior to aHCT 20,21 and as part of conditioning 22–24 .…”

Section: Discussionmentioning

confidence: 99%

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies

Vanderwalde

Laddaran

et al. 2012

Leukemia

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The probability of survival is conventionally calculated from autologous hematopoietic cell transplantation (aHCT). Conditional survival takes into account the changing probability of survival with time survived, but is not known for aHCT populations. We determined disease-, and cause-specific conditional survival for 2388 patients treated with aHCT over a period of 20 years at a single institution. A total of 1054 deaths (44% of the cohort) were observed: 78% attributed to recurrent disease; 9% to subsequent malignancies; and 6% to cardiopulmonary disease. Estimated probability of relative survival was 62% at 5 and 50% at 10 years from aHCT. On the other hand, 5-year relative survival was 70%, 75%, 81%, and 88% after having survived 1, 2, 5, and 10 years after aHCT, respectively. The cohort was at a 13.9-fold increased risk of death compared with the general population (95%CI=13.1–14.8). The risk of death approached that of the general population for 10-year survivors (SMR=1.4, 95%CI=0.9–1.9), with the exception of female Hodgkin lymphoma patients transplanted before 1995 at age 40 years or younger (SMR=6.0, 95%CI=1.9–14.0). Among those who had survived 10 years, non-relapse-related mortality rates exceeded relapse-related mortality rates. This study provides clinically relevant survival estimates after aHCT, and helps inform interventional strategies.

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Section: Discussionmentioning

confidence: 99%

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies

Vanderwalde

Laddaran

et al. 2012

Leukemia

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“…Bu with Mel. However, when oral Bu was combined with etoposide and cyclophosphamide, the 5-year incidence of pulmonary mortality was noted to be 3.6% occurring at a median of 5 months following transplant [45]. …”

Section: Discussionmentioning

confidence: 99%

Intravenous Busulfan Plus Melphalan Is a Highly Effective, Well-Tolerated Preparative Regimen for Autologous Stem Cell Transplantation in Patients with Advanced Lymphoid Malignancies

Kebriaei

Madden

Kazerooni

et al. 2011

Biology of Blood and Marrow Transplantation

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We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous SCT. Bu 130 mg/m2 was infused daily for 4 days, either as a fixed dose per BSA, or to target an average daily AUC of 5,000 uMol-min, determined by a test dose of i.v. Bu at 32 mg/m2 given 48 hours prior to the high dose regimen, followed by a rest day, followed by two daily doses of Mel at 70mg/m2. Stem cells were infused the following day. 80 patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 uMol-min. 102 patients [Hodgkin's Lymphoma (HL) n=49, Non Hodgkin's Lymphoma (NHL) n=12, Multiple Myeloma (MM) =41] with median age 44 years (range 19 to 65 years) were treated. 2-year overall survival (OS) and progression-free survival (PFS) rates were 85% and 57%, respectively, for patients with HL, 67% and 64%, respectively, for patients with NHL, and 82% and 42%, respectively, for patients with MM. The regimen was very well-tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel is well-tolerated. Disease control is encouraging, and should be explored in larger phase II studies.

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“…Unfortunately, however, busulfan has a narrow therapeutic plasma concentration range . Supratherapeutic concentrations lead to lethal toxicity, including pulmonary toxicity, hepatic veno‐occlusive disease, and seizures, while subtherapeutic concentrations lead to graft rejection and disease relapse . Therapeutic drug monitoring (TDM) can reduce the incidence of seizures …”

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confidence: 99%

Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

Kawazoe

Funaki

Kim

2018

The Journal of Clinical Pharma

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Busulfan is the most common chemotherapy agent used in allogeneic hematopoietic cell transplant (HCT) conditioning regimens. As narrow therapeutic index and interpatient variability exists in the effectiveness and toxicity of conditioning regimens, personalizing intravenous busulfan therapy is desirable. Population pharmacokinetic-based approaches have been applied to therapeutic drug monitoring for the purpose of personalizing therapy. A population pharmacokinetic analysis with the objective of personalizing therapy in Japanese patients was conducted by integrating pediatric patient data with adult patient data. McCune's model, a 2-compartment model that includes maturation of clearance and allometric scaling of clearance and volume of distribution, was used for the analysis. McCune's model could precisely describe the Japanese data, and the estimated parameters were similar to McCune's results for non-Japanese, indicating that there are no racial differences in busulfan pharmacokinetics. Using this model, the plasma concentrations for once-daily dosing were simulated to adapt new dosage regimens for the benefit and convenience of both patients and medical staff. The predicted busulfan concentrations were within the therapeutic range.

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High‐dose busulfan and the risk of pulmonary mortality after autologous stem cell transplant

Cited by 16 publications

References 15 publications

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies

Intravenous Busulfan Plus Melphalan Is a Highly Effective, Well-Tolerated Preparative Regimen for Autologous Stem Cell Transplantation in Patients with Advanced Lymphoid Malignancies

Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

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