Pharmacokinetic-Directed High-Dose Busulfan Combined with Cyclophosphamide and Etoposide Results in Predictable Drug Levels and Durable Long-Term Survival in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

Zhang, Hongzheng; Graiser, Michael; Hutcherson, Donald; Dada, M. Olufemi; McMillan, Stephanie; Ali, Zahir; Flowers, Christopher R.; Waller, Edmund K.

doi:10.1016/j.bbmt.2012.02.006

Cited by 31 publications

(27 citation statements)

References 23 publications

(27 reference statements)

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“…[22][23][24] Therapeutic drug monitoring and subsequent pharmacokinetic directed dosing of BU, regardless of formulation, has been associated with lower non-relapse mortality and improved OS and PFS. [25][26][27] Pharmacokinetic directed dosing of BU may optimize therapy further and limit potential toxicities. 28 Despite these limitations, our study provides insight into optimal dosing practices in obese patients.…”

Section: Discussionmentioning

confidence: 99%

Outcomes after autologous SCT in lymphoma patients grouped by weight

Lau

Weber

Earl

et al. 2015

Bone Marrow Transplant

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Obesity continues to be an increasing global health issue contributing to the complexity of chemotherapy dosing in the field of SCT. Investigation into the optimal dosing weight used to calculate chemotherapy doses in obese patients undergoing SCT is limited and inconclusive. Our single-center, retrospective study compared safety and efficacy outcomes by body mass index (BMI) for 476 adult lymphoma patients who underwent auto-SCT with a myeloablative chemotherapeutic regimen of BU, CY and etoposide dosed using adjusted body weight. Three weight groups categorized based on BMI were defined: normal/underweight ⩽ 24.9 kg/m 2 , overweight 25-29.9 kg/m 2 and obese ⩾ 30 kg/m 2 . Severity of mucositis, incidence of secondary malignancy, incidence of bacteremia and median hospital length of stay did not differ among the groups. The median times to absolute neutrophil count and platelet recovery were 10 days (P = 0.75) and 14 days (P = 0.17), respectively. Obese patients had a lower 100-day mortality compared with other weight groups, although this did not translate into an OS benefit. OS and disease relapse were similar among the groups. Our study demonstrates that use of adjusted body weight to calculate chemotherapy doses does not negatively have an impact on outcomes in obese patients undergoing auto-SCT with BU, CY and etoposide.

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Section: Discussionmentioning

confidence: 99%

Outcomes after autologous SCT in lymphoma patients grouped by weight

Lau

Weber

Earl

et al. 2015

Bone Marrow Transplant

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“…In our regimen, reduction of the busulfan dose was substituted by the addition of another drug, etoposide, which is highly effective in lymphomas. It was possible that drug modifications would result in more favorable pharmacokinetics and enhanced efficacy [18]. It must be kept in mind that IV busulfan seems to attain more predictable pharmacokinetics and a low toxicity profile compared with oral busulfan, which has unpredictable absorption and wide variability [19,20].…”

Section: Rationale For Development Of a New Conditioning Regimenmentioning

confidence: 99%

Carmustine, etoposide, cytarabine and melphalan versus a newly designed intravenous busulfan-based Busulfex, etoposide and melphalan conditioning regimen for autologous hematopoietic cell transplant: a retrospective matched-pair analysis in advanced Hodgkin and non-Hodgkin lymphomas

Sakellari

Mallouri

Batsis

et al. 2015

Leukemia & Lymphoma

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Optimal conditioning remains a challenge in lymphomas. We designed a regimen consisting of Busulfex, etoposide and melphalan (BuEM). We retrospectively analyzed the outcome of patients conditioned with carmustine, etoposide, cytarabine and melphalan (BEAM) or BuEM in matched-pair analysis on a planned 2:1 ratio. Eighty-seven patients treated with BEAM who fulfilled the matching criteria were randomly selected. Two-year progression-free survival/overall survival (PFS/OS) were 63.2%/76.7% for BEAM vs. 65.6%/79.8% for BuEM after 64.7 and 42.7 months, respectively. Furthermore, marginally better PFS and OS were noted in Hodgkin lymphoma (HL) after BuEM. In multivariate analysis, PFS was superior in HL, chemosensitive disease and complete remission post-transplant. BEAM correlated with faster engraftment, reduced infections, less mucositis and liver toxicity, and BuEM with less need for blood cell and platelet transfusions and granulocyte colony-stimulating factor administration. In conclusion, BuEM was well tolerated and equally highly efficacious as BEAM for non-Hodgkin lymphoma and offered marginally significantly improved PFS and OS in HL with acceptable toxicity and zero mortality.

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“…[27] Three-year PFS has ranged from 31% to 47%, with OS rates of around 43% at three years. [23,27,[38][39][40] (Table 2) In addition to single-arm trials, two non-randomized comparative studies have been performed comparing the BuCyE regimen to BEAM. [23,27] In both the studies, there were no differences found in either efficacy or toxicity outcomes between patients given BuCyE or BEAM.…”

Section: Bucyementioning

confidence: 99%

Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

Isidori¹,

Christofides

Visani³

2016

Leukemia & Lymphoma

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High-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) is the standard treatment for relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Until recently, carmustine, etoposide, cytarabine and melphalan (BEAM) was the most commonly used conditioning regimen in this setting, given its acceptable efficacy and tolerability. Despite reasonable success with BEAM, carmustine is associated with a number of acute and late toxicities. Moreover, recent supply and cost issues for this agent have created an urgent need for alternative conditioning regimens. As such, etoposide and melphalan (VP16/MEL) or busulfan, cyclophosphamide, and etoposide (BuCyE) are currently being used with limited success. A number of novel conditioning regimens that replace carmustine with other agents are under investigation, which may provide effective alternatives to BEAM. In considering novel agents to replace carmustine, bendamustine may provide the best alternative, as demonstrated by the results of a number of phase II, multicenter, controlled studies.

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Pharmacokinetic-Directed High-Dose Busulfan Combined with Cyclophosphamide and Etoposide Results in Predictable Drug Levels and Durable Long-Term Survival in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

Cited by 31 publications

References 23 publications

Outcomes after autologous SCT in lymphoma patients grouped by weight

Outcomes after autologous SCT in lymphoma patients grouped by weight

Carmustine, etoposide, cytarabine and melphalan versus a newly designed intravenous busulfan-based Busulfex, etoposide and melphalan conditioning regimen for autologous hematopoietic cell transplant: a retrospective matched-pair analysis in advanced Hodgkin and non-Hodgkin lymphomas

Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

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