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Molecular testing in acute myeloid leukaemia (AML) has continued to dramatically advance in recent years, facilitating the ability to detect residual disease at exponentially lower levels. With the advent of the recently updated ELN consensus recommendations, there is increasing complexity to ordering and interpreting measurable residual disease (MRD) assays in AML. We outline the technology itself in conjunction with the relevant testing timepoints, clinically significant thresholds and potential prognostic and therapeutic significance of MRD testing for the major molecular targets in AML. This practical overview should assist haematologists in incorporating molecular MRD assays routinely into their personalised AML clinical management.

BACKGROUND Bombay phenotype (Oh ) is a rare blood group and poses unique challenges during pregnancy, including an adequate supply of blood products in case of postpartum hemorrhage (PPH) and the risk of hemolytic disease of the fetus and newborn (HDFN). Case reports of antenatal care in this cohort are scarce. Herein, we present a case of twin pregnancy in an Oh woman and outline her multidisciplinary management. We summarize the literature to better inform decision-making and patient blood management in the antenatal care of Oh women. CASE DESCRIPTION A 22-year-old G1P0 presented at 15 weeks gestation with dichorionic diamniotic twins and known Oh phenotype. Hematinics were optimized to minimize anemia. Anti-H titers were tracked and were 1:256 at both 28 and 36 weeks gestation. Regular middle cerebral artery dopplers were performed to assess for fetal anemia. There was constant communication with obstetrics and anesthetics teams. Both autologous frozen and directly donated fresh red cells were available as part of a clear, detailed transfusion plan. Transfusion was not required and neither child was affected by HDFN. The neonates were group O, DAT negative, and group A, DAT positive. Maternal anti-A was detected in the neonatal eluate. CONCLUSION To our knowledge, this is only the second report of twin pregnancy in an Oh female and the first time a detailed transfusion plan has been published. Through employing patient blood management strategies, engaging a collaborative multidisciplinary approach, and establishing a clear delivery plan, the antenatal challenges of Bombay phenotype are surmountable.

Aim: Primary Central Nervous System Lymphoma (PCNSL) [i.e. diffuse large B-cell lymphoma of the CNS] is a rare and poor-prognosis disease occurring predominantly in older patients (median age >60 years old). Prospective studies of two commonly used chemoimmunotherapy (CIT) protocols, MATRix and MPV/Ara-C (± rituximab), have reported 2-year PFS and OS of 57-61% and 69-81% respectively. Our aim was to evaluate registry-reported outcomes of frontline CIT strategies employed at Australasian sites. Method: A retrospective study of consecutive, immunocompetent, adult PCNSL patients (WHO criteria: 2017) treated with curative-intent CIT, from 10 sites (9 Australian, 1 Singaporean) between 1 st January 2009 and 31 st December 2018 (i.e. ten-year period). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier (log-rank) method. Univariate associations were derived using a Cox model with variables p Results: Data was collected on 207 patients, 189 of whom met WHO diagnostic criteria for PCNSL (i.e. diffuse large B-cell lymphoma of the CNS). We excluded patients with insufficient data (6), non-DLBCL histology (6), secondary PCNSL (3) and post-transplant lymphoproliferative disorder (3). Of these, 176 (93%) received curative-intent CIT. The majority (66%) were over 65 years of age (median: 65, range: 25-87); ECOG performance status was ≥ 2 in 31% (data not available for 14% of patients). The majority were male (55%) and had deep structure involvement (64%). International Extranodal Lymphoma Study Group (IELSG) risk criteria could not be calculated in many patients due to missing data (predominantly LDH and CSF protein). CSF involvement was rare (n=23, 13%) but data was only available for 60% of patients. Of the 159 with documented renal function, 26% had renal impairment (defined as Cockroft-Gault creatinine clearance Five CIT regimens were used: MATRix (n=16), MPV/Ara-C + rituximab (Rtx) (n=94), MBVP+- Rtx (n=11), MTX +-Rtx (n=31) and MTX/Ara-C +- Rtx (n=24). Intrathecal chemotherapy was used in only 29 patients (16%), and almost exclusively in combination with R-MPV. Median cumulative MTX dose was 17,500mg/m 2 (range: 1,000-64,000mg/m 2) and 69% received Ara-C (median dose: 12,000mg/m 2 [range: 1,000-44,000mg/m 2]). Eighty percent of patients achieved an overall response at the end of MTX therapy, with 52% achieving a complete response [data unavailable in n=29, 16%]. Estimated 2-year PFS and OS for the entire cohort were 54% (95%CI: 0.46-0.62) and 77% (95%CI: 0.70-0.83) respectively at a median follow-up of 2 years. Older patients (>60yo) had shorter PFS but similar OS compared to their younger counterparts (2-year PFS: 47% vs 68%, p: 0.015, HR: 1.73, 95%CI: 1.11-2.70; 2-year OS: 74% vs 80%, p: 0.145, HR: 1.38, 95%CI: 0.81-2.33). R-MPV achieved superior PFS compared to MATRix although comparison was limited by low numbers in the MATRix cohort (n=16 vs n=94), likely reflective of the census period [2-year PFS: 74% vs 44% p: 0.025, HR 0.41, 95%CI 0.13-1.28]. Neither WBRT (n=57, 32%) nor ASCT (n=13, 7%) conferred a survival advantage but addition of rituximab (n=153, 87%) was associated with improved PFS (p: 0.007, HR: 0.47, 95%CI: 0.19-0.75). On multivariate analysis, type of induction CIT (p: 0.004, HR: 1.42, 95%CI: 1.23-1.42), cumulative MTX dose (p: 0.022, HR: 0.88, 95%CI: 0.83-0.94) and cumulative Ara-C dose (p: 0.016, HR: 0.76, 95%CI: 0.64-0.87) were associated with improved PFS. Cumulative MTX dose (p: 0.02, HR: 0.85, 95%CI: 0.78-0.92) and cumulative Ara-C dose (p: 0.007, HR: 0.67, 95%CI: 0.51-082) were also associated with improved OS. Conclusion: Registry-reported outcomes of contemporary CIT induction for PCNSL are favourable when compared to published trials and historical regimens. PCNSL with contemporary treatment should no longer be considered an invariably poor-prognostic disease. Data supports recent literature highlighting prognostic significance associated with maintenance of chemotherapy dose intensity (Martinez-Calle et al., Br J Haematol. 2020 Aug; 190(3):394-404. doi. 10.1111/bjh.16592). Figure 1 Figure 1. Disclosures Lewis: AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Patents & Royalties: Conference attendance; Novartis: Patents & Royalties: Conference attendance; Roche: Consultancy, Honoraria. Gunjur: Myers Squibb: Honoraria. Ku: Roche: Consultancy; Antegene: Consultancy; Genor Biopharma: Consultancy. Wight: Jannsen: Honoraria, Other: Travel subsidies; Abbvie: Honoraria, Other: Travel subsidies. Shortt: Amgen: Research Funding; Astex: Research Funding; BMS: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Talaulikar: Roche: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Hawkes: Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau; Regeneron: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck KgA: Research Funding; Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Specialised Therapeutics: Consultancy; Antigene: Membership on an entity's Board of Directors or advisory committees. Cheah: MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; AstraZeneca: Consultancy, Honoraria, Other: advisory; Celgene: Research Funding; AbbVie: Research Funding; Beigene: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory; Gilead: Consultancy, Honoraria, Other: advisory. Opat: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Sandoz: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Monash Health: Current Employment. Gregory: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy.