Characterization of the Cynomolgus Macaque Model of Marburg Virus Disease and Assessment of Timing for Therapeutic Treatment Testing.

Marburg virus (MARV) causes severe disease and high mortality in humans. The objective of this study was to characterize disease manifestations and pathogenesis in cynomolgus macaques exposed to MARV. The results of this natural history study may be used to identify features of MARV disease useful in defining the ideal treatment initiation time for subsequent evaluations of investigational therapeutics using this model.

Long-term outcomes of corticosteroid graft versus host disease prophylaxis in peripheral blood allogeneic haemopoietic stem cell transplant: a comparative cohort analysis.

Background: Corticosteroids (CSs) have previously been incorporated into graft versus host disease (GVHD) prophylaxis regimens for bone marrow (BM) and haemopoietic stem cell transplant (HSCT).

Aims: To assess the impact of prophylactic CS in HSCT using peripheral blood (PB) stem cells.

Methods: Patients were identified from three HSCT centres receiving a first PB-HSCT between January 2011 and December 2015 from a fully human leukocyte antigen (HLA)-matched sibling or unrelated donor for acute myeloid leukaemia or acute lymphoblastic leukaemia.

Targeting MCL-1 and BCL-2 with polatuzumab vedotin and venetoclax overcomes treatment resistance in R/R non-Hodgkin lymphoma: Results from preclinical models and a Phase Ib study.

The treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge. Here, we identify the pro-survival BCL-2 protein family member MCL-1 as a resistance factor for the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma (NHL) cell lines and primary NHL samples. Mechanistically, we show that the antibody-drug conjugate polatuzumab vedotin promotes MCL-1 degradation via the ubiquitin/proteasome system.

SUBA-Itraconazole for Primary Antifungal Prophylaxis After Allogeneic Hematopoietic Cell Transplantation.

Background: Itraconazole (ITZ) is an effective agent when used as primary invasive fungal disease (IFD) prophylaxis, but is limited by drug tolerability and variability in serum concentrations. A new formulation, SUBA-itraconazole (for "super bioavailability"; S-ITZ), addresses the limitations of conventional ITZ formulations.

Methods: We conducted a retrospective cohort study at 2 Australian centers to evaluate the safety, tolerability, and effectiveness of S-ITZ as primary antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients without grade II-IV acute graft-vs-host disease, from day 1 until approximately day 100 (cohort A) or day 1 until neutrophil engraftment (cohort B).

Spontaneous coronary artery dissection in the third trimester-Implications for investigation and delivery.

This case of spontaneous coronary artery dissection in pregnancy highlights the diagnostic, treatment and delivery dilemmas in the antepartum period. This is a rare condition that usually manifests in the postpartum period. This case provides multidisciplinary considerations that were encountered for optimal maternal and fetal outcome.

Dynamics of Epstein-Barr virus on post-transplant lymphoproliferative disorders after antithymocyte globulin-conditioned allogeneic hematopoietic cell transplant.

Background: The use of antithymocyte globulin (ATG) in allogeneic hematopoietic cell transplant (HCT) is associated with an increased risk of Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD). The dynamics and outcomes of EBV-DNAemia are not well described in this population.

Methods: We retrospectively assessed the kinetics of EBV-DNAemia after ATG conditioning of HCT recipients.

Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre-transplant predictors of survival, reactivation, and spontaneous clearance.

Background: Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT).

Method: We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre-transplant predictors of CMV reactivation, clinically significant CMV infection (cs-CMVi, defined as CMV viral load >1000 IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized pre-emptive therapy approach to identify at-risk groups to target prevention strategies.

Results: Cs-CMVi was most common in D-/R+ unrelated donor transplants (URD).

Unrelated Donor Transplant Recipients Given Thymoglobuline Have Superior GRFS When Compared to Matched Related Donor Recipients Undergoing Transplantation without ATG.

Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.

The prevalence and pregnancy outcomes of intrahepatic cholestasis of pregnancy: A retrospective clinical audit review.

Background: To determine the prevalence and outcomes of intrahepatic cholestasis of pregnancy.

Methods: A review comparing intrahepatic cholestasis of pregnancy pregnancies to all other pregnancies in three tertiary care Australian hospitals over a 36-month period.

Results: There were 43,876 pregnancies.

Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: assessment and management of cardiovascular risk factors.

Several BCR-ABL1 tyrosine kinase inhibitors (TKIs) are approved for the first-line treatment of chronic phase chronic myeloid leukaemia (CML). Disease control is achieved in the vast majority of patients and disease-specific survival is excellent. Consequently, there is now emphasis on managing comorbidities and minimising treatment-related toxicity.

Serum levels, safety and tolerability of new formulation SUBA-itraconazole prophylaxis in patients with haematological malignancy or undergoing allogeneic stem cell transplantation.

Objectives: To assess therapeutic levels, safety and tolerability of a novel formulation SUBA-itraconazole (where SUBA stands for SUper BioAvailability) when compared with conventional itraconazole liquid when used as antifungal prophylaxis in patients undergoing allogeneic HSCT or in haematological malignancy patients with an intermediate/high risk of invasive fungal infection (IFI).

Methods: This was a single-institution, prospective cohort study using a historical control group as the comparator.

Results: A total of 57 patients were assessed: 27 in the SUBA-itraconazole cohort and 30 in the liquid itraconazole cohort.

Resolution of aquaporin-4 antibodies in a woman with neuromyelitis optica treated with human autologous stem cell transplant.

We report a 47-year-old woman with highly active neuromyelitis optica (NMO) and persistent high titre anti-aquaporin-4 antibodies (anti-AQP-4) who was resistant to multiple immune therapies until she underwent autologous hematopoietic stem cell transplant (auto-HSCT). NMO is the only demyelinating disease with a clinically useful serum biomarker, aquaporin-4, a water channel protein expressed on astrocytes. Anti-AQP-4 antibodies correlate with NMO disease activity and animal models strongly suggest the antibody is pathogenic.

Relevance of linguistic and cultural training among non-clinical personnel at the University of Mississippi Medical Center: a qualitative study.

Background: An academic medical center presents a unique environment where non-clinical staff provide vital services to a cross-section of people. A medical Spanish course was offered to a non-clinical department, campus police, in response to the growing number of Hispanics or Latinos seeking care within the health center.

Method: In October 2007, a structured group discussion with six course participants was convened at the end of the Occupational Spanish course, using a topic guide to direct the conversation.

Intrahepatic cholestasis of pregnancy: diagnosis and management; a survey of Royal Australian and New Zealand College of Obstetrics and Gynaecology fellows.

Background: Intrahepatic cholestasis of pregnancy (ICP) is an uncommon obstetric condition characterised by intense maternal pruritis and biochemical abnormality. There is a degree of contention regarding the diagnosis and management of ICP, and currently, there are no nationally accepted guidelines.

Aims: To conduct a survey of Fellows and Members of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) regarding their diagnosis and management ICP.

A multicenter phase 2 study of risk-adjusted salvage chemotherapy incorporating vinorelbine and gemcitabine for relapsed and refractory lymphoma.

Background: Administration of salvage chemotherapy to patients with relapsed or refractory lymphoma is associated with significant toxicity. Vinorelbine and gemcitabine are novel chemotherapeutic agents with minimal overlapping toxicity. We present a phase 2 study of vinorelbine and gemcitabine with or without ifosfamide administered in an ambulatory care setting for relapsed or refractory lymphoma.

Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy.

We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88% and 90%, and major molecular responses (MMRs) were 47% and 73%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n = 60), MMR rates by 12 and 24 months were 55% and 77% compared with 32% and 53% in patients averaging less than 600 mg (P = .

A phase II study of liposomal daunorubicin, in combination with cyclophosphamide, vincristine and prednisolone, in elderly patients with previously untreated aggressive non-Hodgkin lymphoma.

Liposomal daunorubicin (DaunoXome) was substituted for doxorubicin in the CHOP regimen, aiming to reduce toxicity and maintain or improve efficacy in elderly patients. Eligibility criteria included: age >or=60 years; previously untreated aggressive non-Hodgkin Lymphoma (NHL) and performance status (PS) 0-2. Treatment was cyclophosphamide 750 mg/m(2), vincristine 1.

BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria.

Purpose: In the first years of imatinib treatment, BCR-ABL remained detectable in all but a small minority of patients with chronic myeloid leukemia. We determined whether BCR-ABL continues to decline with longer imatinib exposure and the incidence and consequence of undetectable BCR-ABL.

Experimental Design: BCR-ABL levels were measured in a subset of 53 imatinib-treated IRIS trial patients for up to 7 years (29 first-line, 24 second-line).

Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia.

Purpose: Intrinsic sensitivity to imatinib, based on measurement of inhibitory concentration 50% for imatinib, is variable in untreated patients with chronic myeloid leukemia (CML). This suggests that patient-tailored dosing may be more rational than a fixed dose for all. Dose optimization potentially could be based on accurate measurement of the level of BCR-ABL kinase inhibition achieved in vivo.

Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-alpha.

Background: Interferon-alpha (IFN-alpha) confers a survival advantage for the minority of patients with chronic myeloid leukemia (CML) who achieve a complete cytogenetic response. The question of whether IFN-alpha-responsive patients can experience further improvements with imatinib has not been answered. Imatinib offers clear quality of life advantages.

Pegfilgrastim to support CHOP-14 in elderly patients with non-Hodgkin's lymphoma.

This study investigated whether pegfilgrastim support would enable on-schedule delivery of dose-dense cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP-14) to elderly patients with non-Hodgkin's lymphoma (NHL). Thirty patients 60 years of age and older with aggressive NHL were evaluated after receiving up to six cycles of CHOP-14 supported with pegfilgrastim. The median age was 68 years (range 61 - 74).