ORCID Profile
0000-0002-5983-753X
Current Organisation
University of Adelaide
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Publisher: SAGE Publications
Date: 2019
Abstract: For the treatment of mature B cell malignancies including chronic lymphocytic leukemia (CLL), the last 5 years has brought major advances in the application of targeted therapies. Whilst monoclonal anti-CD20 agents such as rituximab have a central role in combination with traditional cytotoxic therapy, their combination with novel agents that target the B cell receptor signaling pathway and other intracellular mechanisms of B cell proliferation is a new approach to treatment. Venetoclax is a highly specific novel agent inhibiting the bcl-2 anti-apoptotic pathway and has potent activity in CLL. Its combination with rituximab results in deeper and more durable responses and this regimen is a valuable option in the treatment of relapsed or refractory CLL including adverse prognostic variants such as cases that are fludarabine refractory or harbor the 17p chromosomal deletion. This review centers on the use of venetoclax and rituximab in relapsed or refractory CLL.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.TRANSCI.2014.02.021
Abstract: By convention, peripheral blood stem cell products for autologous transplantation are evaluated for quality by CD34(+) cell dose at the time of harvesting. A CD34(+) cell dose in excess of 2.0 × 10(6)/kg of recipient body weight is considered adequate for haematopoietic engraftment. Viable CD34(+) cell numbers are enumerated in most laboratories using the ISHAGE single platform flow cytometric method which utilizes monoclonal antibodies to CD45, CD34 and 7 amino actinomycin D (7AAD) dye exclusion. One hundred and six consecutive autologous transplantation procedures underwent viable CD34(+) cell enumeration at the time of harvesting and post thaw prior to re-infusion. Neutrophil and platelet engraftment and markers of haematopoietic support were analyzed. Mean pre-cryopreservation viable CD34(+) numbers were 4.882 × 10(6)/kg. Mean post thaw viable CD34(+) numbers were 3.234 × 10(6)/kg. Mean loss of viable CD34(+) cells with processing and cryo-preservation was 1.648 × 10(6)/kg (33%). For neutrophil engraftment, there was no significant difference between high (⩾ 3.0 × 10(6)/kg) and low (<1.5 × 10(6)/kg) post thaw viable CD34(+) cell counts (p=0.545). For platelet engraftment, there was however a significant difference observed between the high and low pre infusion viable CD34(+) groups (p<0.001). Additionally, significant differences were seen between the post thaw viable CD34(+) cell count and the associated length of hospital admission, days of use of G-CSF post transplantation, use of antibiotics in the post transplantation period and transfusion support in the post transplantation period. A significant loss of viable CD34(+) cells occurs during processing, cryopreservation and thawing. Low numbers of viable CD34(+) cells infused post thaw will still result in adequate neutrophil engraftment however may delay platelet engraftment. Low viable CD34(+) cell numbers have significant effects on admission duration and use of haematopoietic supportive measures with consequent effects on healthcare resources.
Publisher: American Society of Hematology
Date: 25-05-2017
DOI: 10.1182/BLOOD-2016-05-718171
Abstract: Inhibition of RNA Pol I by CX-5461 treats aggressive AML and outperforms standard chemotherapy regimens. CX-5461 induces p53-dependent apoptosis, p53-independent cell-cycle defects and differentiation, and reduces LICs.
Publisher: Wiley
Date: 08-10-2019
DOI: 10.1002/PRP2.526
Abstract: Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK). It is metabolized by GSTZ1, which has common polymorphisms altering enzyme or promoter activity. GSTZ1 is also irreversibly inactivated by DCA. In the first clinical trial of DCA in a hematological malignancy, DiCAM (DiChloroAcetate in Myeloma), we have examined the relationship between DCA concentrations, GSTZ1 genotype, side effects, and patient response. DiCAM recruited seven myeloma patients in partial remission. DCA was administered orally for 3 months with a loading dose. Pharmacokinetics were performed on day 1 and 8. Trough and peak concentrations of DCA were measured monthly. GSTZ1 genotypes were correlated with drug concentrations, tolerability, and disease outcomes. One patient responded and two patients showed a partial response after one month of DCA treatment, which included the loading dose. The initial half‐life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant. Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (−1002A, rs7160195) for GSTZ1 . This patient displayed the strongest response, but also the strongest neuropathy. Overall, serum concentrations of DCA were sufficient to inhibit the constitutive target PDK2, but unlikely to inhibit targets induced in cancer. Promoter GSTZ1 polymorphisms may be important determinants of DCA concentrations and neuropathy during chronic treatment. Novel dosing regimens may be necessary to achieve effective DCA concentrations in most cancer patients while avoiding neuropathy.
Publisher: Wiley
Date: 10-10-2022
DOI: 10.1111/IMJ.15910
Abstract: Haemopoietic stem cell transplant (HSCT) is a well‐established treatment option for many haematologic immunologic and oncologic diseases, allowing the safe administration of high‐dose chemotherapy. Increased risk of acute renal injury is associated with HSCT however, the risk of chronic kidney injury in autologous HSCT remains unclear. This cohort study investigates the incidence of chronic renal injury and its predisposing factors in a single‐centre population of 139 patients who underwent autologous HSCT. Estimated glomerular filtration rate (eGFR) was measured at baseline and at 3, 6, 12 and 24 months following autologous stem cell reinfusion and used as a marker of renal dysfunction. A significant reduction in mean eGFR of patients was observed from baseline (80.62 ± 2.97 mL/min) to 24 months (71.54 ± 4.14 mL/min), independent of primary diagnosis ( P = 0.0019). At baseline, 12% of the cohort had stage 3 or worse chronic renal injury and this increased to 38% by 24 months. By univariate analysis, age at baseline greater than the mean of 58 years and the occurrence of acute kidney injury during the peritransplant period emerged as predictive factors for the development of chronic kidney disease at 24 months. The current results indicate there is an increased incidence of chronic renal injury in patients who have undergone autologous peripheral blood haemopoietic stem cell transplantation therapy and this injury is potentiated by the autologous stem cell transplant procedure.
Publisher: Wiley
Date: 08-2021
DOI: 10.1111/IMJ.15263
Abstract: Australia and New Zealand have achieved excellent community control of COVID‐19 infection. In light of the imminent COVID‐19 vaccination roll out in both countries, representatives of all adult and paediatric allogeneic bone marrow transplant and cellular therapy (TCT) centres as well as representatives from autologous transplant only centres in Australia and New Zealand collaborated with infectious diseases specialists with expertise in TCT on this consensus position statement regarding COVID‐19 vaccination in TCT patients in Australia and New Zealand. It is our recommendation that TCT patients, should have expedited access to high‐efficacy COVID‐19 vaccines given that these patients are at high risk of morbidity and mortality from COVID‐19 infection. We also recommend prioritising vaccination of TCT healthcare workers and household members of TCT patients. Vaccination should not replace other public health measures in TCT patients given the effectiveness of COVID‐19 vaccination in TCT patients is unknown. Furthermore, given the limited available data, prospective collection of safety and efficacy data of COVID‐19 vaccination in this patient group is a priority.
Publisher: Future Medicine Ltd
Date: 02-2022
Abstract: We report on the presentation and outcome of a 28-year-old female who developed red cell aplasia following alemtuzumab therapy for relapsing remitting multiple sclerosis. The patient also developed synchronous immune thrombocytopenia and immune neutropenia, but not aplastic anemia. This patient received high dose steroids, intravenous immunoglobulin (iv.Ig), rituximab, red cell transfusions, vincristine, G-CSF, cyclosporin and mycophenolate to treat the combination of cytopenias over a period of 6 months with subsequent improvement in bone marrow function. While alemtuzumab has several recognized autoimmune complications, little is known about the potential hematological side effects. The combination of red cell aplasia, immune thrombocytic purpura and autoimmune neutropenia has not previously been described in the literature following alemtuzumab immunotherapy and highlights the importance of monthly blood monitoring post alemtuzumab administration.
No related grants have been discovered for James D'Rozario.