Clinical relevance of an objective - limit of detection - limit of quantification - based flow cytometry approach for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial

Using a multiparametric flow cytometry (MFC) assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients affected with Acute Myeloid Leukemia (AML). This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined MRD threshold of 0.035% bone marrow residual leukemic cell (RLC) calculated on mononuclear cells, 154 (59%) were negative (MRD<0.035%) and 107 (41%) were positive (MRD≥0.035%). Using LOD and LOQ, we selected the following categories of patients: 1) LODneg if RLC were below LOD (74; 28.4%); 2) LODpos-LOQneg if RLC were between LOD and LOQ (43; 16.5%); and 3) LOQpos if RLC were above LOQ (144; 54.4%). Two-year overall survival (OS) of these 3 categories was 75.4% vs. 79.8% vs. 66.4%, respectively (p=0.1197). Due to superimposable outcome, LODneg and LODpos-LOQneg categories were combined. Two-year OS of LODneg/LODpos- LOQneg patients was 77.0% versus 66.4% of LOQpos individuals (P=0.043). Such a figure was challenged in multivariate analysis (p=0.048, HR 0.628, 95% CI 0.396-0.997) that confirmed the independent role of LOD-LOQ approach in influencing OS. In the AML1310 protocol, using the threshold of 0.035%, 2-year OS of MRD<0.035% and MRD≥0.035% patients was 74.5% vs. 66.4%, respectively (p=0.3521). In conclusion, the use of LOD-LOQ method results in a more sensitive detection of MRD that, in turn, translates in a more accurate recognition of patients with different outcome

Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT

Allogeneic haemopoietic cell transplant (allo-HCT) may be curative in acute myeloid leukaemia (AML) in second complete remission (CR2) but the impact of reduced intensity (RIC) versus myeloablative conditioning (MAC) is uncertain. The Acute Leukaemia Working Party of the European Society for Blood and Bone Marrow Transplantation Registry studied an AML CR2 cohort characterised by age ≥ 18 years, first allo-HCT 2007–2016, available cytogenetic profile at diagnosis, donors who were matched family, volunteer unrelated with HLA antigen match 10/10 or 9/10 or haplo-identical. The 1879 eligible patients included 1010 (54%) MAC allo-HCT recipients. In patient

Primary Prophylaxis of Invasive Fungal Diseases in Allogeneic Stem Cell Transplantation: Revised Recommendations from a Consensus Process by Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Abstract This document updates and expands the recommendations on primary prophylaxis of invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe and evaluate current information and practice regarding risk stratification and primary antifungal prophylaxis during the pre-engraftment and postengraftment phases after allo-HSCT. The revised recommendations were based on the evaluation of recent literature including a large, prospective, multicenter epidemiological study of allo-HSCT recipients conducted among the GITMO transplantation centers during the period of 2008 to 2010. It is intended as a guide for the identification of types and phases of transplantation at low, standard, and high risk for IFD, according to the underlying disease, transplantation, and post-transplantation factors. The risk stratification was the critical determinant of the primary antifungal approach for allo-HSCT recipients

abo mismatching and haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia a report from the alwp of the ebmt

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Highly Sensitive HBsAg, Anti-HBc and Anti HBsAg Titres in Early Diagnosis of HBV Reactivation in Anti-HBc-Positive Onco-Haematological Patients

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for >18 months, were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27-40509) IU/mL, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median (IQR): 81 (49-541) U/L). An anti-HBc > 3 cut-off index (COI) plus anti-HBs persistently/declining to <50 mIU/mL was predictive for HBV-R (OR (95% CI): 9.1 (2.7-30.2); 63% of patients with vs. 15% without this combination experienced HBV-R (p < 0.001)). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at >2 time points, also predicts HBV-R (OR (95% CI): 13.8 (3.6-52.6); 50% of positive vs. 7% of negative patients to these markers experienced HBV-R (p = 0.001)). HS-HBs and anti-HBc titration proved to be useful early markers of HBV-R. The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring

Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation

Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation

Gender, age and diagnosis effect on self-perceived pain in hematological patients: retrospective analysis of two case series.

We have read with great interest the paper by Ahmed and colleagues (1), entitled " Does gender affect self-perceived pain in cancer patients? -A meta-analysis "

Abundance, rarity and invasion debt among exotic species in a patchy ecosystem

Community assembly through species invasions is a long-term process, for which vital information regarding future trends can be contained in current patterns. Using comparative analyses of native and exotic plant assemblages from meadow patches on islands in British Columbia, Canada, we examined multiple lines of evidence for ‘invasion debt’, a latent expansion of exotic species populations. We show that: (1) short-dispersing species are underrepresented compared to their long-dispersing counterparts in exotic species only; (2) among species that are invasive elsewhere in North America, a greater proportion of long dispersers are common in the study area and a greater proportion of short dispersers are rare; and (3) time since arrival in the study region is positively related to number of occurrences in exotic species. In addition, we show that a suite of exotic species possesses the facility of rapid long-distance dispersal and ability to establish viable populations on even the most isolated and least disturbed patches. While some highly-dispersive exotic species can rapidly colonize new areas, short dispersers appear to exhibit invasion debt, with their potential distributions only being realized in the long term. Removing or even reducing populations of many rapid colonizers could be extremely difficult; however, for species exhibiting patterns most consistent with invasion debt, an opportunity exists for monitoring and removal to help reduce potential competition with native species

Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission : a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

Background: Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT) from matched sibling donor compared to autologous transplantation (auto-HSCT); however, there is scarcity of literature confronting auto-HSCT with allo-HSCT from unrelated donor (UD-HSCT), especially mismatched UD-HSCT. Methods: We retrospectively compared outcome of allogeneic transplantation from matched (10/10 UD-HSCT) or mismatched at a single HLA-locus unrelated donor (9/10 UD-HSCT) to autologous transplantation in patients with AML in first complete remission (CR1). A total of 2879 patients were included; 1202 patients received auto-HSCT, 1302 10/10 UD-HSCT, and 375 9/10 UD-HSCT. A propensity score-weighted analysis was conducted to control for disease risk imbalances between the groups. Results: Matched 10/10 UD-HSCT was associated with the best leukemia-free survival (10/10 UD-HSCT vs auto-HSCT: HR 0.7, rho = 0.0016). Leukemia-free survival was not statistically different between auto-HSCT and 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 0.8, rho = 0.2). Overall survival was similar across the groups (10/10 UD-HSCT vs auto-HSCT: HR 0.98, rho = 0.84; 9/10 UD-HSCT vs auto-HSCT: HR 1.1, rho = 0.49). Notably, in intermediate-risk patients, OS was significantly worse for 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 1.6, rho = 0.049), while it did not differ between auto-HSCT and 10/10 UD-HSCT (HR 0.95, rho = 0.88). In favorable risk patients, auto-HSCT resulted in 3-year LFS and OS rates of 59 and 78 %, respectively. Conclusions: Our findings suggest that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor, auto-HSCT should be considered as a valid option, as better survival appears to be provided by auto-HSCT compared to mismatched UD-HSCT. Finally, auto-HSCT provided an encouraging outcome in patients with favorable risk AML.Peer reviewe