Accurate, reliable laboratory reference ranges are essential for effective clinical evaluation and monitoring. We present robust reference ranges established for haematology, coagulation and haematinic parameters using the Sysmex XE 2100, CA 1500 and Beckman-Coulter Access analysers. Blood samples were taken from 250 healthy laboratory personnel and routine haematology, coagulation and haematinic parameter analysis performed. Our data represent findings from an extensive study to establish reference ranges in healthy adults.

The prognosis for patients with respiratory syncytial virus (RSV) or parainfluenza virus type 3 (PIV3) respiratory tract infection post allogeneic haematopoietic progenitor cell transplant (HPCT) is historically poor. The use of oral ribavirin (RBV) has not been widely studied in this patient population. We examined the outcomes of 15 consecutive patients (RSV, n ¼ 13 and PIV3, n ¼ 2) treated with oral RBV post HPCT. Oral RBV was commenced at a starting dose of 10 mg/kg/day, increasing to a maximum dose of 60 mg/kg/day depending on response and tolerance. At diagnosis, seven patients had upper respiratory tract infection (URTI) and eight had lower respiratory tract infection (LRTI). The starting RBV dose of 10 mg/kg/day did not prevent the progression of URTI to LRTI in any patient. However, with dose escalation, six of the seven patients responded to RBV therapy and survived their infective episode. Of the eight patients presenting with LRTI, six patients survived their infection, again after dose escalation of RBV. There was no dose-limiting toxicity seen in any patient. Our results indicate that oral RBV has clinical efficacy in the treatment of RSV/PIV3 infection post HPCT. However, a starting dose of 10 mg/kg/day appears ineffective; we recommend a starting dose of 20 mg/kg/day in this patient group.

Patients receiving treatment for acute myeloid leukemia (AML) commonly experience life-threatening complications requiring intensive care unit (ICU) support. This is a retrospective study of 505 patients with newly diagnosed AML who were treated with intensive chemotherapy between January 1999 and December 2010. Eighty-three patients (16.4%) were identified who had required 92 ICU admissions. The indication for ICU admission was hemodynamic instability in 47.0% of patients and respiratory impairment in 42.2%. The underlying pathology was most commonly infection (77.1%). Vasopressors were required in 67.5% of admissions, mechanical ventilation in 60.2% and hemodialysis in 15.7%. Rates of survival to hospital discharge and 12 months were 59.0% and 41.3%, respectively. Mechanical ventilation use and higher fibrinogen were independently associated with mortality prior to hospital discharge, and mechanical ventilation use and AML cytogenetic risk group were predictive of mortality within 12 months of ICU admission. By providing a more accurate estimation of a patient's chance of recovery, such prognostic factors may contribute to decision-making about the appropriateness of admission to the ICU or continuation of intensive life-sustaining measures.

Key Points Practices in early-stage FL are variable and include radiation alone, systemic therapy, CMT, or observation. Each practice resulted in similar excellent outcomes; randomized trials are required to determine the optimal treatment.

The optimal initial therapy for treatment of adult acute lymphoblastic leukemia is yet to be defined. Hyper-CVAD has become a widely used treatment for adult acute lymphoblastic leukemia, although publication of outcomes is largely limited to single-center experience. We performed a retrospective analysis of 63 patients treated with Hyper-CVAD at two Australian institutions between 1995 and 2007. Complete remission was obtained in 86% of patients, with an induction mortality of 8%. Treatment-related toxicity was high, resulting in premature cessation of planned treatment in 29% of patients achieving CR. Survival estimates were comparable to previously published experience, with estimated 5-year overall and progression-free survival of 48% and 42%, respectively. Allogeneic stem cell transplant was performed in 22% of patients in first complete remission, with encouraging survival outcomes (estimated 5-year overall survival 75%, progression free survival 82%). Hyper-CVAD is an effective and tolerable induction strategy for adult ALL, and is suitable for use prior to allogeneic stem cell transplant in first complete remission.

Our findings support the use of the free light chain assay in the diagnostic work-up of patients with suspected AL amyloidosis, and also as a sensitive biomarker of response to therapy.

Introduction Midostaurin is the only approved FLT3 inhibitor for combination with intensive induction and consolidation chemotherapy in newly diagnosed patients with FLT3 mutant AML. The FLT3 inhibitor, sorafenib, was investigated in the randomized SORAML trial (Röllig, Lancet Onc 2015), in combination with intensive chemotherapy (IC) for newly diagnosed adults with AML <60 years. A sub-group analysis of 46 patients with FLT3-ITD, indicated a trend for improved overall survival (OS) in the sorafenib (SOR) arm compared to placebo (PBO). Methods The Australasian Leukaemia and Lymphoma Group (ALLG) conducted a randomized phase 2 study [ACTRN12611001112954] in 99 adults aged 18-65 years with newly diagnosed FLT3-ITD positive (allelic ratio (AR) ≥0.05) AML to determine whether addition of SOR to IC would improve event-free survival (EFS). The study was powered to identify a 25% increase in 2-year EFS with SOR. Patients 18-55 yrs received induction with IDAC-3 (idarubicin [IDA] 12 mg/m2 D1-3 and ara-C 1.5 g/m2 BD D1,3,5,7); patients 56-65 received 7+3 (IDA 12 mg/m2 D1-3 and ara-C 100 mg/m2 D1-7 IVI). Patients were randomized 2:1 to SOR or PBO 400 mg BD on days 4-10 of induction and each consolidation cycle. Due to the pharmacokinetic interaction between SOR and azoles, antifungal prophylaxis during induction was with AmBisome 5 mg/kg IV twice weekly. For consolidation, patients 18-55 yrs received 2 cycles of IcE (IDA 9 mg/m2 D1-2, ara-C 100 mg/m2 D1-5 IVI and etoposide 75 mg/m2 D1-5), those 56-65 yrs received 2 cycles of IDAC-2 (IDA 12 mg/m2 D1-2 and ara-C 1g/m2 BD D1,3,5). Maintenance was with SOR/PBO 400 mg bd days 1-28 for 12 cycles. Allogeneic HCT (allo-HCT) was at investigator discretion. SOR/PBO was not continued post allo-HCT. The primary endpoint was EFS without censoring for allo-HCT with events defined as failure to achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi), relapse or death. Pre-specified secondary endpoints included overall response rate (ORR) defined as CR and CRi, tolerability, EFS according to FLT3-ITD AR < or ≥ 0.7 and impact of randomization on allograft outcome. Results Between Jan 2013-May 2018, 18 centers randomized 99 patients to induction with either SOR (n=65) or PBO (n=33); one patient later found to be FLT3-ITD negative was excluded. Patient characteristics are shown in Table 1. Treatment arms were balanced apart from fewer patients in the SOR arm with NPM1 mutant AML. Deliverability of therapy was comparable, with commencement of consolidation in 78% and 79% and maintenance therapy in 32% and 27% in the SOR and PBO arms, respectively. The overall response rate (ORR) was high in both arms; 91% in the SOR (CR 80%, CRi 11%) and 94% in the PBO (CR 70%, CRi 24%) arm. In the SOR arm, 5% achieved partial remission, went off study and were deemed treatment failures. With a median overall follow-up of 25 mo, there was no significant difference in EFS (HR 0.87 95% CI 0.50-1.49; P=0.61)(Fig A) or OS (HR 0.70 95% CI 0.38-1.29; P=0.26)(Fig. B), nor in a sensitivity analysis with censoring at HCT. 2 yr EFS was 47.9% (SOR) vs 45.4% (PBO) and 2-year OS 66.8% (SOR) vs 56.4% (PBO). Hematopoietic cell transplant (HCT) in CR1 was performed in 62% and 58% in the SOR and PBO arms, respectively. For patients in CR1, 2 yr OS post-HCT was 78.5% (SOR) vs 54.2% (PBO)(Fig C). Suggestive of an on-target effect against FLT3-ITD, the impact of SOR on OS appeared greater for patients with higher FLT3-ITD AR ≥0.7 (Fig. D) (Table 2). Only one early death (within 30 days) was recorded in each treatment arm. The frequency of grade 3-4 adverse events (AEs) were similar between the two arms, apart from palmar-plantar rash, reported as drug-related in 15.4% and 6.1% pts in the SOR and PBO arms, respectively. Correlative studies will be reported in a companion abstract. Conclusions SOR did not improve EFS when combined with intensive chemotherapy in adults with newly diagnosed FLT3-ITD AML. Although not powered for significance, SOR showed a trend for improved OS among patients with higher FLT3-ITD AR or receiving HCT in CR1. Further exploration of more potent FLT3 inhibitors in the pre- and post-allograft setting are warranted for patients with newly diagnosed FLT3 mutant AML. Acknowledgements: The ALLG AMLM16 trial was funded through an Australian Government NHMRC grant and a research grant from the Leukaemia Foundation of Australia. Bayer supplied sorafenib and Gilead AmBisome. Disclosures Wei: Roche: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Astra Zeneca: Honoraria, Research Funding; Janssen: Honoraria; Macrogenics: Honoraria. Enjeti:Novartis: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; Bayer: Speakers Bureau; Sanofi: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. D'Rozario:Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Marlton:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Verner:Janssen Cilag Pty Ltd.: Research Funding. Hahn:Roche: Honoraria; Astra Zeneca: Honoraria. Hiwase:Novartis Australia: Research Funding. Anstee:Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Levis:FujiFilm: Honoraria, Research Funding; Amgen: Honoraria; Daiichi-Sankyo: Honoraria; Menarini: Honoraria; Astellas: Honoraria, Research Funding. Bajel:Abbvie: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria. Roberts:Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties; Janssen: Research Funding; Servier: Research Funding; AbbVie: Research Funding. OffLabel Disclosure: Sorafenib for FLT3-ITD AML

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