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Summary: We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T‐cell depletion and no post‐transplant cyclophosphamide. The primary end‐point of the study was leukaemia‐free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non‐significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non‐relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non‐significantly different LFS following CBT in adult patients with secondary versus de novo AML. [ABSTRACT FROM AUTHOR]

Background: Intracranial hemorrhage is seen more frequently in acute leukemia patients compared to the general population. Besides leukemia‐related risk factors, also risk factors that are present in the general population might contribute to hemorrhagic complications in leukemia patients. Of those, cardiovascular risk factors leading to chronic vascular damage could modulate the occurrence of intracranial hemorrhage in these patients, as during their disease and treatment acute endothelial damage occurs due to factors like thrombocytopenia and inflammation. Objectives: Our aim was to explore if cardiovascular risk factors can predict intracranial hemorrhage in acute leukemia patients. Methods: In a case‐control study nested in a cohort of acute leukemia patients, including 17 cases with intracranial hemorrhage and 55 matched control patients without intracranial hemorrhage, data on cardiovascular risk factors were collected for all patients. Analyses were performed via conditional logistic regression. Results: Pre‐existing hypertension and ischemic heart disease in the medical history were associated with intracranial hemorrhage, with an incidence rate ratio of 12.9 (95% confidence interval [CI] 1.5 to 109.2) and 12.1 (95% CI 1.3 to110.7), respectively. Conclusion: Both pre‐existing hypertension and ischemic heart disease seem to be strong predictors of an increased risk for intracranial hemorrhage in leukemia patients. [ABSTRACT FROM AUTHOR]

Summary: Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole‐resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould‐active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft‐versus‐host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole‐resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR‐based detection of azole‐resistance. This study (DB‐MSG 002) will re‐evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole‐resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Blood cultures (BCs) are essential in the evaluation of neutropenic fever. Modern BC systems have significantly reduced the time‐to‐positivity (TTP) of BC. This study explores the probability of bacteraemia when BCs have remained negative for different periods of time. Methods: All adult patients with neutropenia and bacteraemia were included (January 2012‐February 2016). Predictive clinical factors for short (≤16 hours) and long (>24 hours) TTP were determined. The residual probability of bacteraemia was estimated for the scenario of negative BC 24 hours after collection. Results: The cohort consisted of 154 patients, accounting for 190 episodes of bacteraemia. Median age of 61 years, 60.5% were male. In 123 (64.7%) episodes, BC yielded a single Gram‐positive micro‐organism and in 49 (25.8%) a Gram‐negative micro‐organism (median TTP 16.7, 14.5 hours respectively, P < .01). TTP was ≤24 hours in 91.6% of episodes. Central line‐associated bacteraemia was associated with long TTP. The probability of bacteraemia if BC had remained negative for 24 hours was 1%‐3%. Conclusions: The expected TTP offers guidance in the management of patients with neutropenia and suspected bacteraemia. The knowledge of negative BC can support a change in working diagnosis, and impact clinical decisions as soon as 24 hours after BC collection. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (alloSCT) for patients with refractory anaemia may result in a 50% event-free survival, but the high non-relapse mortality (NRM) precludes a general application of this therapeutic modality. This study evaluated the impact of various pre-transplant variables, including disease duration, intensity of the conditioning regimen, type of donor and year of transplantation on outcome. The study population consisted of 374 patients; 244 were transplanted from human leucocyte antigen (HLA)-identical siblings and 130 patients from matched unrelated donors. The median age was 39 years. One hundred and two patients were transplanted after reduced intensity conditioning (RIC). The overall 4-year survival was 52%. The 4-year survival of patients transplanted with HLA-identical sibling donors and matched unrelated donors was 52% and 50%, respectively. Multivariate analysis showed an improved survival ( P = 0·05) and a lower NRM ( P = 0·02) when the transplantation was performed in recent years. Increasing age, and disease duration of >12 months were associated with inferior survival. RIC resulted in a similar survival despite an increased relapse risk ( P = 0·02). This improved outcome permits alloSCT in patients older than 50 years of age, even with the use of matched unrelated donors. AlloSCT should be preferentially performed early after diagnosis after careful analysis of prognostic variables. [ABSTRACT FROM AUTHOR]

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor., (© 2024 Wiley Periodicals LLC.)

A disease risk index (DRI) has been defined for stratifying heterogeneous cohorts of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). This index defines 4 distinct groups with different outcomes, dividing patients by disease type and status and considering cytogenetics for acute myeloid leukaemia and myelodysplastic syndromes (MDS). Recently, the DRI has been refined to include rare diseases and improve MDS stratification by blast percentage and response to prior therapy. Previous reports on DRI include only a small number of UCBT recipients. The current study aims to determine the applicability of the DRI for patients undergoing unrelated cord blood transplantation (UCBT). We retrospectively analysed 2530 adults receiving UCBT between 2004 and 2014. Diagnosis was acute leukaemia (AL) in 66% of the cases. Overall survival (OS) at 2 years was 56 ± 3% for patients with low DRI (n = 352), 46 ± 1% for intermediate DRI (n = 1403), 28 ± 2% for high (n = 489) and 20 ± 4% for very high DRI (n = 109) (P < 0·001). In the multivariate model, DRI remained an independent risk factor for OS. Similar findings were observed for PFS and DRI. Our results show the applicability of DRI for stratifying UCBT recipients and confirm the prognostic value of this simple and robust tool in this setting., (© 2017 John Wiley & Sons Ltd.)