Comparison of 100-day mortality rates associated with i.v. busulfan and cyclophosphamide vs other preparative regimens in allogeneic bone marrow transplantation for chronic myelogenous leukemia: Bayesian sensitivity analyses of confounded treatment and center effects

Abstract

Summary:We evaluated the 100-day mortality rates associated with busulfan-based myeloablative conditioning regimens based on data from 1812 chronic myelogenous leukemia patients who underwent allogeneic blood or marrow transplantation (allotx). In all, 47 patients received intravenous (i.v.) busulfan and cyclophosphamide (i.v.BuCy2) with allotx at MD Anderson Cancer Center (MDACC) during 1995-1999. The remaining 1765 patients, whose data were supplied by the International Bone Marrow Transplant Registry (IBMTR), received alternative preparative regimens, primarily Cy-total body irradiation (B45%) or oral BuCy (B35%) during 1997-1998. As patients were not randomized between conditioning regimens, the i.v.BuCy2-versus-alternative treatment effect is confounded with a possible center effect due to nontreatment differences associated with factors differing between MDACC and the IBMTR centers. Additional complications are that the i.v.BuCy2-MDACC patients all survived 100 days, and three prognostic subgroups were included. Bayesian sensitivity analyses were performed to assess treatment effect on the probability of 100-day mortality, over a range of possible MDACC-versus-IBMTR center effects. For these patients, the posterior probability that i.v.BuCy2 was superior to alternative conditioning regimens ranges from 0.54 to 0.99, depending on prognosis and the magnitude of the assumed center effect.

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

“…In the referenced study, nonrelapse mortality at 100 days after transplantation was 12% after related and 13% after MUD transplantations. Nonrandomized comparisons between patients treated with intravenous BuCy2 and those receiving unadjusted oral BuCy or TBI-based therapy appear to favor the intravenous busulfan-based conditioning regimen, 7,8,43 although definitive data from randomized studies are lacking. We hypothesized that the more precise dose delivery achieved with intravenous busulfan and a tighter …”

Once-daily i.v. BU-based conditioning regimen before allogeneic hematopoietic SCT: a study of influence of GST gene polymorphisms on BU pharmacokinetics and clinical outcomes in Chinese patients

“…BU were the traditional four times daily dosing. 3,7,9,11,12 In recent years, studies have shown that once-daily i.v. BU had the same clinical efficacy as i.v.…”

“…BU has been proven to have better bioavailability, reliable systemic drug exposure with more predictable blood levels and lower toxicity than oral BU. [1][2][3][4][5][6][7][8][9][10] I.v. formulation of BU has become the preferred option in conditioning treatment for HSCT.…”

Allogeneic hematopoietic SCT for adults AML using i.v. BU in the conditioning regimen: outcomes and risk factors for the occurrence of hepatic sinusoidal obstructive syndrome

“…Also it has been reported to decrease the incidence of hepatic SOS compared with oral BU, therefore decreasing morbidity and mortality after allo-HSCT. 15,[19][20][21][22][23] The pathogenesis of SOS is thought to involve chemotherapy and radiation-induced damage to the sinusoidal endothelium, resulting in endothelial injury, microthrombosis, subendothelial damage and cytokine activation. 24,25 Severe SOS is typically associated with multi-organ failure and high mortality.…”