Andrew Grigg

Austin Health, Melbourne, Victoria, Australia

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Publications (178)837.58 Total impact

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    ABSTRACT: Introduction: Early ASCT improves progression-free survival (PFS) but not overall survival (OS) in poor prognosis DLBCL treated with R-CHOP immuno-chemotherapy (Stiff P et al., NEJM 2013). Furthermore, indiscriminate ASCT exposes those poor-risk patients destined to remain in CR with R-CHOP alone to unnecessary toxicity. Here, the role of interim PET/CT to risk-stratify is controversial. One confounding factor is that interim PET/CT is typically performed after 2 (or 3) cycles of chemotherapy when FDG-avidity likely reflects a mix of residual cancer cells and inflammation; in contrast, interim PET/CT after cycle 4 may be more representative of resistant lymphoma. We hypothesized that: 1. assessment of DLBCL patients by interim PET/CT after 4 cycles (iPET4) of R-CHOP-14 allows greater specificity of FDG-avidity; and, 2. for patients with iPET4-positivity, early treatment intensification with R-ICE chemotherapy followed by Zevalin-BEAM conditioning and ASCT results in 2‑yr PFS that is equivalent to interim-PET/CT-negative patients treated with R-CHOP alone. Methods: We conducted a prospective multicenter phase 2 study which enrolled DLBCL patients ≤ 70 yrs with either IPI=2-5, or IPI =0-1 with tumor bulk (≥ 7.5 cm), and who were considered fit for ASCT. All patients underwent a diagnostic PET/CT at study entry and were planned to receive 4 cycles of R-CHOP-14 and supported with Pegfilgrastim. Cycle 5 of R-CHOP-14 was delayed 7 days, and an interim PET/CT scan was undertaken at d17-d20 post-4th R-CHOP-14, the delay intended to reduce the impact of rebound inflammation after R-CHOP. All interim PET/CT scans were assessed centrally by a core group of imaging specialists using International Harmonization Project (IHP) criteria with mediastinal blood pool as the reference. Biopsy to confirm residual tumor was not mandated. iPET4-positive patients received 3 cycles of R-ICE followed by ASCT with Zevalin-BEAM conditioning; those who were iPET4-negative received a further 2 cycles of R-CHOP-14 plus 2 doses of Rituximab. Results: A total of 162 patients were enrolled from 20 Australian centers; 11 patients were excluded because of failure to meet inclusion criteria. Baseline characteristics of the 151 evaluable patients included: median age 57 yrs (range, 21 to 69), 40% aged > 60 yrs, 62% males, 79% stages 3 or 4, 13% ECOG PS > 1, 78% elevated LDH, 48% extranodal sites > 1, 54% bulky disease ≥ 7.5 cm, 20% IPI=0-1, 27% IPI=2, 31% IPI=3, and 23% IPI=4-5. No interim PET/CT scan was performed in 8 patients due to progressive disease (PD) (1), bowel perforation (2), toxicity (3), and dose delays ≥ 2 weeks (2). Interim PET/CT scans were undertaken at d17-d20 in 62% and d14-d16 in another 23%. Of the 143 patients with interim PET/CT, 101 (71%) were deemed iPET4-negative and 42 (29%) were iPET4-positive. Interestingly, the baseline characteristics were comparable between iPET4-negative and iPET4-positive patients. Of the 101 iPET4-negative patients, 5 failed to complete therapy due to PD (3), toxicity (1), or infection (1). Of the 42 iPET4-positive patients, 10 failed to complete intensification therapy due to PD (6), 2nd malignancy (1), or consent withdrawal (3). Among iPET4-positive patients undergoing ASCT, there was 1 treatment-related death due to viral infection. At a median follow-up of 35 months, the Kaplan-Meier (KM) estimate of 2-yr PFS and OS for the entire eligible cohort of 151 pts was 72% and 85%, respectively. For the 101 iPET4-negative and 42 iPET4-positive patients, 2-yr PFS was 74% and 67% (P=0.32) (Figure 1), and 2-yr OS was 88% and 78% (P=0.11) (Figure 2), respectively. Among iPET4-negative and iPET4-positive patients with IPI=3-5, 2-yr PFS was 65% and 69% (P=0.74), and 2-yr OS was 81% and 83% (P=0.85), respectively. Conclusions: Patients with poor risk DLBCL who are interim PET/CT-positive after 4 cycles of R-CHOP-14 and switched to intensification with R-ICE followed by ASCT with Zevalin-BEAM have favorable rates of PFS and OS that are equivalent to that seen for patients who are interim PET/CT-negative. This study supports further investigation of treatment intensification in patients with poor risk DLBCL who are interim PET/CT-positive after 4 cycles of immuno-chemotherapy. The study was supported in part by Roche Products Pty. Ltd, Amgen Australia Pty. Ltd, and Bayer Australia Ltd. Figure 1: Progression Free Survival by Interim PET/CT Figure 2: Overall survival by Interim PET/CT Disclosures: Hertzberg: Janssen-Cilag: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Celgene: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Amgen: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Novartis: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; AbbVie: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; BMS: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Takeda Oncology: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Roche: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Gilead: Honoraria , Membership on an entity’s Board of Directors or advisory committees . Gill: AbbVie: Honoraria ; Roche: Research Funding ; Sanofi Aventis: Research Funding ; Roche: Honoraria . Ho: Celgene: Other: Travel . Cull: Janssen-Cilag: Membership on an entity’s Board of Directors or advisory committees ; Amgen: Other: Travel . Grigg: Pfizer: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Novartis: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; BMS: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Roche: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Amgen: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Gilead: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Merck: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Takeda: Honoraria , Membership on an entity’s Board of Directors or advisory committees . Lewis: Amgen: Other: Travel ; Roche: Honoraria , Other: Travel . Renwick: Amgen: Other: Travel ; Bayer: Speakers Bureau . Seymour: Genentech, Inc.: Membership on an entity’s Board of Directors or advisory committees ; Celgene: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Other: Travel support , Speakers Bureau ; AbbVie: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Other: Travel support , Research Funding , Speakers Bureau ; Incyte: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Infinity: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Roche: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Other: Travel support , Research Funding ; Takeda: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Janssen: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Phebra: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Gilead: Honoraria , Membership on an entity’s Board of Directors or advisory committees .
    No preview · Conference Paper · Dec 2015
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    ABSTRACT: Objectives: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD. Methods: A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective. Results: Ninety-eight patients were included in the audit; 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal amphotericin B and an azole. Five proven/probable and six possible IFD cases were identified. Proven/probable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven/probable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4%; P = 0.024). For every five patients receiving PAP, one proven/probable IFD case would be prevented. Proven/probable IFD was associated with an additional median cost of 121 520 Australian dollars (95% CI: 90 781-180 141 Australian dollars; P < 0.001) compared with patients without IFD. Conclusions: This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk.
    Full-text · Article · Oct 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Background Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. Methods Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0.15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. Findings 124 patients were enrolled between Nov 10, 2004, and Sept 23, 2009, with data cutoff of March 15, 2012. Four (3%) patients died early. After a median follow-up of 4.2 years (IQR, 3.2-5.2), the 5 year freedom from relapse was 95% (95% CI 89-98), disease-free survival was 95% (89-98), event-free survival was 90% (83-94), and overall survival was 94% (89-97). The comparison with APML3 data showed that hazard ratios were 0.23 (95% CI 0.08-0.64, p=0.002) for freedom from relapse, 0.21 (0.07-0.59, p=0.001) for disease-free survival, 0.34 (0.16-0.69, p=0.002) for event-free survival, and 0.35 (0.14-0.91, p=0.02) for overall survival. Interpretation Incorporation of arsenic trioxide in initial therapy induction and consolidation for acute promyelocytic leukaemia reduced the risk of relapse when compared with historical controls. This improvement, together with a non-significant reduction in early deaths and absence of deaths in remission, translated into better event-free and overall survival.
    No preview · Article · Sep 2015
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    ABSTRACT: Targeted MEK inhibition is an emerging therapy in a number of solid tumors. It holds particular promise in BRAF V600E mutation-positive malignant melanoma, where constitutive activation and cell growth through the MAP kinase (MAPK) pathway is well established. In vitro and pre-clinical research indicates that MAPK pathway activation is important in chronic myeloid leukemia (CML) leukemogenesis however the potential of MEK inhibition has not yet been investigated clinically in the setting of such hematological malignancies. We report a case of complete hematological response of CML to MEK inhibition in a patient with synchronous metastatic melanoma, who received treatment with combination BRAF and MEK1/2 inhibitors. We studied the effects of these agents on proliferation and outgrowth of myeloid precursors, and longitudinal shifts in peripheral blood phenotyping during the course of treatment. A model cell line system was used to examine the effects of dabrafenib and trametinib on MAPK and BCR-ABL1-signalling. After 35 weeks on treatment with BRAF and MEK inhibitors, complete hematologic response was observed without recourse to BCR-ABL1-targeted therapy. MEK inhibition was principally responsible for impaired proliferation of both mature and primitive myeloid precursors, as well as growth and hemoglobinization of erythroid precursors. Paradoxical activation of the MAPK pathway was seen in response to BRAF inhibitor therapy but this was easily overcome by clinically-relevant doses of concurrent MEK inhibitor. These studies suggest that further evaluation of the optimal MAPK targeting approach is warranted to extend therapeutic options in CML. Copyright © 2015, American Association for Cancer Research.
    No preview · Article · Jul 2015 · Clinical Cancer Research
  • Eliza A Hawkes · Andrew Grigg · Geoff Chong
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    ABSTRACT: Cancers can evade the host immune system by inducing upregulation of immune inhibitory signals. Anti-programmed cell death-1 (PD-1) monoclonal antibodies block these inhibitory signals allowing the host to mount an immune response against malignant cells. This class of drugs is active in solid tumours, where upregulation of cell-surface PD-1 ligand proteins is nearly uniform. Because lymphoma is a malignancy of immune system cells, the role of the PD-1 pathway in these neoplasms is more complex. However, early clinical trials using PD-1 inhibitors have shown significant clinical activity in various subtypes of relapsed lymphoma. In this Review, we assess the scientific literature on the role of the PD-1 pathway in lymphoma, the relevant clinical data for PD-1 inhibition, and future strategies for this next generation of anticancer agents. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · May 2015 · The Lancet Oncology
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    Eliza A Hawkes · Geoff Chong · Andrew Grigg

    Preview · Article · Feb 2015 · Journal of Clinical Oncology
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    ABSTRACT: TIDEL-II was designed to optimise outcomes for newly-diagnosed chronic phase chronic myeloid leukemia (CP-CML) patients. Two sequential cohorts enrolled a total of 210 patients, all commencing imatinib 600 mg/day, with a planned dose escalation to 800mg/day for patients with imatinib plasma trough level <1000 ng/mL on day 22 (19%). Patients were then assessed with molecular treatment targets: BCR-ABL1 ≤10%, ≤1% and ≤0.1% at 3, 6 and 12 months, respectively. Cohort I patients who failed to achieve targets were escalated to imatinib 800 mg/day (if on 600mg/day), then subsequently switched to nilotinib 400 mg BID for failing the same target 3 months later. Cohort II patients who failed to achieve targets switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of study patients remained on imatinib, and 30% were on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed MMR was achieved in 64% and 73% at 12 and 24 months, respectively. MR(4.5) at 24 months was 34%. Overall and transformation-free survival was 96% and 95% at 3 years, respectively. This trial supports the feasibility and efficacy of an imatinib-based approach with selective switching to nilotinib. Trial Registration #ACTRN12607000325404. Copyright © 2014 American Society of Hematology.
    Full-text · Article · Dec 2014 · Blood
  • P. Yeh · J. Lokan · A. Anantharajah · A. Grigg
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    ABSTRACT: Vanishing bile duct syndrome (VBDS) in association with Hodgkin lymphoma (HL) is well described but not well understood. We report an unusual case of a 75-year-old patient presenting with biopsy-proven VBDS and immunodeficiency, without identifiable cause, which showed a waxing and waning course, culminating in the development of HL 18 months later. To our knowledge, this is the first adult case in which VBDS preceded the diagnosis of HL by such a long period.
    No preview · Article · Dec 2014 · Internal Medicine Journal
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    Full-text · Article · Oct 2014 · Haematologica
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    ABSTRACT: The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-κB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-κB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies.
    Full-text · Article · Oct 2014 · British Journal of Haematology
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    ABSTRACT: We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph +) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCR-ABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph + acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph + ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCR-ABL targeting without compromising clinical outcomes.
    No preview · Article · Sep 2014 · Leukemia and Lymphoma
  • L. J. Worth · M.A. Slavin · S. Heath · J. Szer · A.P. Grigg
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    ABSTRACT: The effectiveness of ethanol locks for prevention of central venous catheter (CVC)-associated bloodstream infection (CLABSI) in adult haematology patients has not been thoroughly evaluated. This study aimed to compare prospectively heparinized saline with 70% ethanol locks using 2 h dwell time in patients with tunnelled CVCs. In saline (N = 43) and ethanol (N = 42) groups, CLABSI rates were 6.0 [95% confidence interval (CI): 3.4–9.8] and 4.1 (95% CI: 1.9–7.7) per 1000 CVC days, respectively (P = 0.42). In the ethanol group, two exit-site infections and one tunnel/pocket infection were observed. Reduction in device-associated infection was not achieved with prophylactic 70% ethanol locks in patients with haematological malignancy and tunnelled CVCs.
    No preview · Article · Sep 2014 · Journal of Hospital Infection
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    ABSTRACT: The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 109/l and ≤50 × 109/l) idiopathic thrombocytopenic purpura (ITP). Patients received two doses of rituximab (1000 mg) on days 1 and 15 and were followed-up on weeks 1–8, 12, 26, 39 and 52. A total of 122 patients were included in the safety population; efficacy was analysed in 108 patients. Overall response rate (ORR) at week 8, defined as the proportion of patients achieving complete response (CR; platelet count >150 × 109/l) or partial response (PR; platelet count >50 × 109/l) was 44%. Therapeutic response, defined as achieving a response at week 8, with at least a minor response (MR; platelet count >30 × 109/l), sustained up to weeks 26 and 52 and accompanied by a reduction in ITP medications, was achieved in 44% (week 26) and 35% (week 52) of patients, respectively. Treatment was well tolerated with no safety concerns. While this study failed to meet its primary endpoint of an ORR of 50%, the efficacy of two fixed doses of rituximab appear to provide similar efficacy to the standard 375 mg/m2 four-dose schedule in relapsed/chronic ITP.
    No preview · Article · Jul 2014 · British Journal of Haematology
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    ABSTRACT: In CML patients, a BCR-ABL1 value >10% at 3 months of therapy is statistically associated with poorer outcome, yet many of these patients still achieve satisfactory outcomes. We investigated 528 first-line imatinib-treated patients to determine whether patients with the poorest outcome can be better discriminated at 3 months. All outcomes were significantly superior for the 410 patients with BCR-ABL1 ≤10% at 3 months, P<.001. However, the poorest outcomes among the 95 evaluable patients with BCR-ABL1 >10% at 3 months were identified by the rate of BCR-ABL1 decline from baseline; assessed by estimating the number of days over which BCR-ABL1 halved. Patients with BCR-ABL1 halving time less than 76 days (n=74) had significantly superior outcomes compared to patients whose BCR-ABL1 values did not halve by 76 days (n=21); 4 year overall survival 95% versus 58%, P=.0002; progression-free survival 92% versus 63%, P=.008; failure-free survival 59% versus 6%, P<.0001; and MMR 54% versus 5%, P=.008. By multivariate analysis, the halving time was an independent predictor of outcome in this poor risk group. Our study has highlighted that the rate of BCR-ABL1 decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The Iris trial was registered at as NCT00006343. The Tops trial was registered at as NCT00124748. The TIDEL I trial was registered at as ACTRN12607000614493. The TIDEL II trial was registered at as ACTRN12607000325404.
    Full-text · Article · May 2014 · Blood
  • A. Arumugaswamy · S. He · H. Quach · J. Brotchie · A. Grigg

    No preview · Article · May 2014 · Internal Medicine Journal
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    ABSTRACT: Increasing dose intensity (DI) of chemotherapy for patients with aggressive non-Hodgkin lymphoma (NHL) may improve outcomes at the cost of increased toxicity. This issue was addressed in a randomised trial aiming to double the DI of myelosuppressive drugs. Between 1994 and 1999, 250 patients with previously untreated aggressive NHL were randomised to treatment with 6 cycles of three weekly standard (s) or intensive (i) chemotherapy: s-CEOP – cyclophosphamide 750 mg/m2, epirubicin 75 mg/m2, vincristine 1.4 mg/m2 all on day 1 and prednisolone 100 mg days 1-5; i-CEOP – cyclophosphamide 1500 mg/m2, epirubicin 150 mg/m2, vincristine 1.4 mg/m2 all on day 1 and prednisolone 100 mg days 1-5. Primary endpoint was 5-year overall survival (OS). Relative to s-CEOP patients, i-CEOP patients achieved a 78% increase in the DI of cyclophosphamide and epirubicin. Despite this, there was no significant difference in any outcome: 5-year OS (56.7% i-CEOP; 55.1% s-CEOP; P=0.80); 5-year PFS (41% i-CEOP; 43% s-CEOP; P=0.73), 5-year TTP (44% i-CEOP; 47% s-CEOP; P=0.72) or CR + unconfirmed CR (CRu) rates (53% i-CEOP; 59% s-CEOP; P=0.64). Long-term follow up at 10 years also showed no significant differences in OS, PFS, or TTP. The i-CEOP arm had higher rates of febrile neutropenia (70% vs 26%), hospitalisations, blood product utilisation, haematological and gastrointestinal toxicities, and lower QOL scores during treatment, although without significant differences 6 months later. In the treatment of aggressive NHL in the pre-rituximab era, increasing DI did not result in improved outcomes while at the same time lead to increased toxicity.
    No preview · Article · May 2014 · American Journal of Hematology
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    ABSTRACT: To identify favored choice of transplantation in patients with acute promyelocytic leukemia in second complete remission. We studied 294 acute promyelocytic leukemia (APL) patients receiving allogeneic (n=232) or autologous (62) hematopoietic cell transplantation (HCT) in second complete remission (CR2) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006 including pre-HCT PML/RAR∝ status in 155 (49% of allogeneic and 66% of autologous). Patient characteristics and transplant characteristics including treatment related mortality, overall survival, and disease free survival were collected and analyzed for both univariate and multivariate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous 63% (49-75%) compared to allogeneic 50% (44-57%) (p=0.10) and overall survival (OS) 75% (63-85%) vs. 54% (48-61%) (p=.002) Multivariate analysis showed significantly worse DFS after allogeneic HCT (HR=1.88, 95% CI=1.16-3.06, p=0.011) and age >40 years (HR=2.30, 95% CI 1.44-3.67, p=0.0005). OS was significantly worse after allogeneic HCT (HR=2.66, 95%CI 1.52-4.65, p=0.0006; age >40 (HR=3.29, 95% CI 1.95-5.54, p<0.001) and CR1<12 months (HR=1.56 95% CI 1.07-2.26, p=0.021). Positive pre-HCT PML-RAR∝ status in 17/114 allogeneic and 6/41 autologous transplants did not influence relapse, treatment failure or survival in either group. The survival advantage for autografting was attributable to increased 3 years TRM: allogeneic 30%; autologous 2%, and GVHD. We conclude that autologous HCT yields superior overall survival for APL in CR2. Long term DFS in autologous recipients, even with MRD+ grafts remains an important subject for further study.
    Full-text · Article · Mar 2014 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: Patients with lymphoma who have experienced a first relapse or progression and have disease deemed sensitive to salvage chemotherapy nevertheless have a high likelihood of having a second relapse. To decrease the likelihood of a second relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), interferon (IFN) α-2b was given in a prospective randomized international trial. In this trial, 221 patients with varying histologic diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell, 20 peripheral T-cell, 3 high-grade B-cell non-Hodgkin lymphoma, and 54 Hodgkin lymphoma) were randomly assigned to receive no further treatment (arm A: 117 patients) or IFNα-2b, 3 MU three times weekly, for 18 months (arm B: 104 patients). In arm B, 21 patients (20%) did not receive IFNα-2b because of early progression or absence of hematologic recovery, 29 patients (28%) completed the 18 months of treatment, and 54 patients (52%) interrupted treatment because of progression (23%) or toxicity (29%). Event-free survival and overall survival were not different between the two arms on an intent-to-treat analysis and also if analysis was restricted to patients who were alive and had not experienced disease progression three months after transplantation. The study was not sufficiently powered to evaluate effects in histologic subtypes. In this trial, post-autograft IFNα-2b did not improve outcomes in a heterogeneous group of patients with lymphoma.
    Full-text · Article · Oct 2013 · The Oncologist
  • Emma Verner · Cecily Forsyth · Andrew Grigg
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    ABSTRACT: Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPN) but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPN specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in 9 of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events with the majority of these occurring prior-to or within three months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPN and have important clinical consequences for management.
    No preview · Article · Jul 2013 · Leukemia & lymphoma
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    ABSTRACT: As a group of more than 100 experts in chronic myeloid leukemia (CML), we draw attention to the high prices of cancer drugs, with the particular focus on the prices of approved tyrosine kinase inhibitors for the treatment of CML. This editorial addresses the multiple factors involved in cancer drug pricing and their impact on individual patients and health care policies, and argues for the need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies.
    Full-text · Article · May 2013 · Blood

Publication Stats

6k Citations
837.58 Total Impact Points


  • 2011-2015
    • Austin Health
      Melbourne, Victoria, Australia
  • 2006-2015
    • University of Melbourne
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 2014
    • Australasian Leukaemia and Lymphoma Group
      East Melbourne, Victoria, Australia
  • 1993-2014
    • Royal Melbourne Hospital
      • • Department of Radiology
      • • Department of Nephrology
      Melbourne, Victoria, Australia
    • Alfred Hospital
      Melbourne, Victoria, Australia
  • 2012
    • Melbourne Health
      Melbourne, Victoria, Australia
  • 2005
    • Hanson Institute
      Tarndarnya, South Australia, Australia
  • 1998
    • St. Vincent Hospital
      Green Bay, Wisconsin, United States
  • 1992-1996
    • Vancouver General Hospital
      • Department of Pathology and Laboratory Medicine (UBC)
      Vancouver, British Columbia, Canada