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ABSTRACT: BACKGROUND: Fluconazole, posaconazole and voriconazole are used prophylactically in patients with acute myeloid leukaemia (AML). This study evaluated the clinical and economic outcomes of these agents when used in AML patients undergoing consolidation chemotherapy. METHODS: A retrospective chart review (2003-10) of AML patients receiving consolidation chemotherapy was performed. Patients were followed through their first cycle of consolidation chemotherapy. Antifungal prescribing patterns, clinical outcomes and resource consumptions were recorded. A decision analytical model was developed to depict the downstream consequences of using each antifungal agent, with success defined as completion of the designated course of initial antifungal prophylaxis without developing invasive fungal disease (IFD). Cost-effectiveness and sensitivity analyses were performed. RESULTS: A total of 106 consecutive patients were analysed. Baseline characteristics and predisposing factors for IFD were comparable between groups. Three IFDs (one proven, one probable and one suspected) occurred, all in the posaconazole group. Patients receiving posaconazole had the highest rate of intolerance requiring drug cessation (13% versus 7% in each of the fluconazole and voriconazole groups). Fluconazole conferred overall savings per patient of 26% over posaconazole and 13% over voriconazole. Monte Carlo simulation demonstrated a mean cost saving with fluconazole of AU$8430 per patient (95% CI AU$5803-AU$11 054) versus posaconazole and AU$3681 per patient (95% CI AU$990-AU$6319) versus voriconazole. One-way sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This is the first study to show that, in the setting of consolidation therapy for AML, fluconazole is the most cost-effective approach to antifungal prophylaxis compared with posaconazole or voriconazole.
Journal of Antimicrobial Chemotherapy 03/2013; · 5.07 Impact Factor
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Leukemia & lymphoma 12/2011; 53(7):1415-6. · 2.40 Impact Factor
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ABSTRACT: Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs. 8%, P=0.011), premature discontinuations (46% vs. 22% P<0.001) and empiric antifungal treatment (31% vs. 8.5%, P<0.001). Microbiologically confirmed infections were molds. Posaconazole compared to other drugs was associated with fewer courses requiring computed-tomography (43% vs. 26%, P<0.001). Adoption of voriconazole/posaconazole has decreased invasive fungal disease incidence, empiric antifungal treatment and for posaconazole, computed-tomography demand, with effectiveness of posaconazole comparable to clinical trial experience.
Haematologica 11/2011; 97(3):459-63. · 6.42 Impact Factor
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ABSTRACT: Voriconazole and posaconazole are used prophylactically against invasive fungal infection (IFI) in patients with acute myeloid leukaemia (AML). The current study attempted to evaluate the economics of voriconazole versus posaconazole for prophylaxis in AML.
A 6 year (2003-09) retrospective chart review of AML patients was performed at a major Australian tertiary hospital. Patients were followed through the induction stage of chemotherapy, estimating outcome probabilities and prescribing patterns of antifungal prophylaxis. Cost inputs were obtained from the latest Australian sources. A decision analytical model was developed to depict options and consequences involved in the prophylaxis, including success, survival, possible and proven IFIs, and discontinuations due to intolerance. A cost-benefit analysis and an uncertainty study through sensitivity analyses were performed.
Fifty-six and 38 patients were evaluated in the voriconazole and posaconazole groups, respectively. Baseline demographic characteristics were not significantly different between the study cohorts. Posaconazole was associated with an overall cost saving of AU$17,458 (29%) per patient over voriconazole. The posaconazole group was associated with lower rate of death, as well as lower probability of discontinuation because of possible infections and intolerance to oral administration. The voriconazole group was associated with fewer proven infections. As per sensitivity analyses, results were highly robust over variations in all costs and probabilities in the model. Monte Carlo simulation suggested a 91.6% chance for posaconazole to cost less than voriconazole.
This is the first economic evaluation of voriconazole versus posaconazole; where posaconazole appears to be more cost-beneficial than voriconazole as antifungal prophylaxis in AML.
Journal of Antimicrobial Chemotherapy 03/2010; 65(5):1052-61. · 5.07 Impact Factor
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ABSTRACT: Functional polymorphisms in the thiopurine methyl transferase (TPMT) gene have been associated with varying levels of enzyme activity and the occurrence of toxicity related to thiopurines. A total of 98 patients (66 pediatric and 32 adults) with precursor B acute lymphoblastic leukemia (Pre-B ALL) were evaluated for TPMT gene polymorphisms. The inability to tolerate 6-mercaptopurine (6-MP) at conventional doses was considered as a surrogate marker of hematologic toxicity. The allele frequency of TPMT*2, *3A, *3B and *3C in the study population was 0.5, 0, 0 and 2.6%, respectively, similar to the frequency observed in other Asian populations. Five patients were heterozygous for TPMT*3C variant allele, and one of these patient's was compound heterozygous with TPMT*2 variant as the other allele. The impact of TPMT polymorphisms on the toxicity and treatment outcome was assessed in 66 pediatric patients only, as there was no variant TPMT detected in the adult patients. Three of the 5 patients (60%) heterozygous for TPMT*2 or TPMT*3C polymorphisms and 12/61 patients (20%) with wild type TPMT genotype had more than 10% of reduction of 6-MP dose (P=0.07). The presence of TPMT polymorphisms did not seem to completely explain the variation in 6-MP toxicity in this small group of patients. Other novel variants in TPMT or variations in the genes involved in transport and biotransformation of 6-MP need to be evaluated in the Indian population.
Medical Oncology 10/2009; 27(4):1046-9. · 2.14 Impact Factor
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Ashish Bajel,
Ming Yin Lin,
Prudence A Hill,
David Goodman,
Chris McCormack,
Peter Foley,
Jill Davison,
Dirk Hönemann,
Melita Kenealy,
Stephen Lade,
Gail Ryan,
Henry Miles Prince
Leukemia & lymphoma 10/2009; 50(12):2083-5. · 2.40 Impact Factor
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British Journal of Haematology 06/2009; 147(1):2. · 4.94 Impact Factor
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British Journal of Haematology 06/2009; 147(5):591. · 4.94 Impact Factor
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ABSTRACT: Limited data exists on the long-term treatment outcome and prognosis of childhood ALL in India.
Three hundred and seven children (1-14 years) with acute lymphoblastic leukemia (ALL) were treated with a modified BFM protocol 76/79 between 1985 and 2003. Treatment outcome and prognostic factors were evaluated.
The median age was 6 years; 78% had B lineage acute lymphoblastic leukemia and 22% had T lineage disease. Good prednisolone response was observed in 82% of cases. Two hundred and seventy-three children (91.6%) achieved complete remission; with 2% induction-related mortality and 6.4% having resistant disease. 52% of all evaluable patients and 56.8% of complete responders are in continuous complete remission (CCR) at a median follow up of 62 months (30-194 months). The median event free survival (EFS) was 114 months. The estimated 5 year overall survival, EFS and disease free survival was 59.8%, 56%, and 53.9%, respectively. The prognostic factors adversely affecting the EFS were poor prednisolone response, resistant disease and WBC count greater than 20 x 10(9)/L at diagnosis. The 5 year EFS in the favorable risk group (age 1-9 years, WBC count less than 20 x 10(9)/L and prednisolone good response) was 73.1 +/- 4.9%.
This report examines a cohort of children with ALL treated with a BFM protocol in India with adequate follow up and demonstrates the need for cost effective improvements.
Pediatric Blood & Cancer 09/2008; 51(5):621-5. · 1.89 Impact Factor
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ABSTRACT: Although iron is a relatively abundant element in the universe, it is estimated that more than 2 billion people worldwide suffer from iron deficiency anemia. Iron deficiency results in impaired production of iron-containing proteins, the most prominent of which is hemoglobin. Cellular iron deficiency inhibits cell growth and subsequently leads to cell death. Hemochromatosis, an inherited disorder results in disproportionate absorption of iron and the extra iron builds up in tissues resulting in organ damage. As both iron deficiency and iron overload have adverse effects, cellular and systemic iron homeostasis is critically important. Recent advances in the field of iron metabolism have led to newer understanding of the pathways involved in iron homeostasis and the diseases which arise from alteration in the regulators. Although insight into this complex regulation of the proteins involved in iron homeostasis has been obtained mainly through animal studies, it is most likely that this knowledge can be directly extrapolated to humans.
European Journal Of Haematology 09/2008; 81(6):411-24. · 2.61 Impact Factor
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ABSTRACT: Imatinib, a small molecule tyrosine-kinase inhibitor, has become the standard drug therapy for all phases of CML. Dasatinib (BMS-354825), a multi-targeted kinase inhibitor of BCR-ABL and SRC kinases exhibits potent activity with high hematologic and cytogenetic response rates in CML patients and has an acceptable toxicity profile. Periorbital oedema, epiphora and rarely retinal oedema are the ocular toxicities reported with imatinib. Here we report a case of imatinib related macular oedema which did not recur on treatment with dasatinib. Possible mechanism of retinal oedema and its implications have been discussed.
Leukemia Research 06/2008; 32(11):1789-90. · 2.92 Impact Factor
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ABSTRACT: Arsenic trioxide, as a single agent, has proven efficacy in inducing molecular remission in patients with acute promyelocytic leukemia (APL). There is limited long-term outcome data with single-agent As2O3 in the management of newly diagnosed cases of APL. Between January 1998 to December 2004, 72 newly diagnosed cases of APL were treated with a regimen of single-agent As2O3 at our center. Complete hematologic remission was achieved in 86.1%. At a median follow-up of 25 months (range: 8-92 months), the 3-year Kaplan-Meier estimate of EFS, DFS, and OS was 74.87% +/- 5.6%, 87.21% +/- 4.93%, and 86.11% +/- 4.08%, respectively. Patients presenting with a white blood cell (WBC) count lower than 5 x 10(9)/L and a platelet count higher than 20 x 10(9)/L at diagnosis (n = 22 [30.6%]) have an excellent prognosis with this regimen (EFS, OS, and DFS of 100%). The toxicity profile, in the majority, was mild and reversible. After remission induction, this regimen was administered on an outpatient basis. Single-agent As2O3, as used in this series, in the management of newly diagnosed cases of APL, is associated with responses comparable with conventional chemotherapy regimens. Additionally, this regimen has minimal toxicity and can be administered on an outpatient basis after remission induction.
Blood 05/2006; 107(7):2627-32. · 9.90 Impact Factor
