Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Feb 2012
Multicenter Study Comparative Study Clinical TrialAllogeneic hematopoietic cell transplantation for chronic myelofibrosis in Australia and New Zealand: older recipients receiving myeloablative conditioning at increased mortality risk.
This retrospective registry analysis examined predictive factors for outcome in 57 patients who underwent allogeneic or syngeneic hematopoietic cell transplantation (HCT) for chronic myelofibrosis (CM), either primary (n = 49) or following an antecedent condition (n = 8), reported to the Australasian Bone Marrow Transplant Registry (ABMTRR) between 1993 and 2005. During the 6 years 2000 to 2005, 40 HCTs were performed for CM compared with 17 in the 7 years 1993 to 1999. Twenty-four recipients (42%) were age 50 or over at transplantation; all of these patients were transplanted after 1997, and 15 were given reduced intensity conditioning (RIC) pretransplantation. ⋯ In multivariate analysis, age 50 years and over at transplantation was the only significant independent unfavorable risk factor for survival post-HCT (hazard ratio 2.71, 95% confidence interval 1.16-6.34, P = .02). This study shows a clear increase in annual numbers of allogeneic HCT performed for CM in Australia and New Zealand in recent years. Five-year survival was favorable compared with international studies, but for older recipients who received myeloablative conditioning, mortality risk was elevated.
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Biol. Blood Marrow Transplant. · Feb 2012
Multicenter StudyA Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen.
Children with high-risk acute myelogenous leukemia (AML) (induction failure [IF], refractory relapse [RR], third complete remission [CR3]) have dismal outcomes. Over 80% of AML patients express CD33, a target of gemtuzumab ozogamicin (GO). GO is an active drug in childhood AML but has not been studied in a myeloablative conditioning regimen. ⋯ One-year overall survival (OS) and event-free survival (EFS) was 50% (95% confidence interval [CI], 20.8-73.6). GO combined with Bu/Cy regimen followed by alloSCT is well tolerated in children with poor-risk AML. GO at 7.5 mg/m(2) in combination with Bu/Cy is currently being tested in a phase II study.
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Biol. Blood Marrow Transplant. · Feb 2012
Clinical TrialAccurate targeting of daily intravenous busulfan with 8-hour blood sampling in hospitalized adult hematopoietic cell transplant recipients.
Daily intravenous (i.v.) busulfan is increasingly being used in hematopoietic cell transplantation (HCT) conditioning regimens. Intravenous busulfan doses administered at the traditional frequency of every 6 hours can be targeted ((T)Bu) to a patient-specific concentration at steady state (C(ss)) using therapeutic drug monitoring (TDM). In this report, we describe our experiences with TDM of daily i.v. busulfan in an adult population, with the specific aims of (1) evaluating covariates associated with busulfan clearance, and (2) assessing the feasibility of TDM for outpatient administration of daily (T)Bu with pharmacokinetic sampling over 6 hours. ⋯ In patients receiving CY/(T)BU, no differences in clearance were found between dosing days (P > .36); however, clearance decreased significantly in patients receiving fludarabine-based regimens (P = .0016). Busulfan clearance and C(ss) estimates from pharmacokinetic sampling over 8, 11, or 24 hours were comparable (P > .4). However, pharmacokinetic modeling of individual patient concentration-time data over 6 hours could not reliably estimate busulfan clearance or C(ss).
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Biol. Blood Marrow Transplant. · Feb 2012
Clinical TrialDevelopment and validation of a test dose strategy for once-daily i.v. busulfan: importance of fixed infusion rate dosing.
Intravenous (i.v.) busulfan (Bu) administered once daily in myeloablative transplant regimens is convenient, effective, and relatively well tolerated. Therapeutic drug monitoring is recommended as nonrelapse mortality increases when daily exposure, as determined by the area under the plasma concentration versus time curve (AUC), exceeds 6000 μM·min. We describe sequential studies to achieve accurate prediction of treatment doses of Bu based on the kinetics of a smaller test dose. ⋯ We conclude that a test dose strategy for therapeutic drug monitoring of daily i.v. Bu is accurate if the test and treatment doses are infused at the same rate. This approach allows targeting of therapeutic doses of Bu to desired levels and the potential for improved safety and efficacy.
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Biol. Blood Marrow Transplant. · Feb 2012
Effect of early posttransplantation tacrolimus concentration on the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors.
Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. ⋯ However, the mean blood concentration of tacrolimus during the third week after HSCT was significantly associated with the grades of aGVHD (17.3 ± 2.1 in patients with grades 0-I vs 15.9 ± 2.8 in II-IV and 14.8 ± 2.1 in III-IV; P < .05 and <.01, respectively). Multivariate analysis also demonstrated that higher age (≥35) of donor (odds ratio [OR] = 4.28) and lower mean blood concentrations of tacrolimus during the second (OR = 0.75; 95% confidence interval [CI]: 0.58-0.98) and third weeks (OR = 0.76; 95% CI: 0.58-0.98) after HSCT were significant risk factors for grades II-IV aGVHD (P < .05). We conclude that the early posttransplantation blood concentration of tacrolimus had a significant impact on the development of moderate-to-severe aGVHD after allogeneic HSCT from an unrelated donor.