The prognostic implications of
genotype in T-cell acute lymphoblastic leukemia are incompletely understood. We performed comprehensive genetic and clinico-biological analyses of T-cell acute ...lymphoblastic leukemia patients with
mutations treated during the GRAALL-2003 and -2005 studies. Eighteen of 198 cases (9.1%) had
alterations. Two patients also had
mutations in non-leukemic cell DNA, providing the first potential evidence of age-related clonal hematopoiesis in T-cell acute lymphoblastic leukemia.
mutation was associated with older age (median 43.9 years
29.4 years,
<0.001), immature T-cell receptor genotype (53.3%
24.4%,
=0.016) and lower remission rates (72.2% mutated
94.4% non-mutated,
=0.006).
alterations were significantly associated with worse clinical outcome, with higher cumulative incidence of relapse (HR 2.33, 95% CI: 1.05-5.16,
=0.037) and markedly poorer event-free survival (HR 3.22, 95% CI: 1.81-5.72,
<0.001) and overall survival (HR 2.91, 95% CI: 1.56-5.43,
=0.001). Adjusting for age as a covariate, or restricting the analysis to patients over 40 years, who account for almost 90% of
-mutated cases, did not modify these observations. In multivariate analysis using the risk factors that were used to stratify treatment during the GRAALL studies,
mutation was significantly associated with shorter event-free survival (HR 2.33, 95% CI: 1.06 - 4.04,
=0.02). Altogether, these results identify
genotype as a predictor of aggressive T-cell acute lymphoblastic leukemia biology. The GRAALL-2003 and -2005 studies were registered at
as
and
, respectively.
Introduction: Immediate empirical antibiotic therapy is mandatory in febrile chemotherapy-induced neutropenia, but its optimal duration is unclear, especially in patients with fever of unknown origin ...(FUO).
Objectives: The primary objective of this 20-month prospective observational study was to evaluate the feasibility and safety of short-term antibiotic treatment in afebrile or febrile patients exhibiting FUO, irrespective of their neutrophil count. The secondary objective was to describe the epidemiology of all episodes of febrile neutropenia.
Methods: In the first phase of the study, empirical antibiotic therapy in FUO patients was stopped after 48 h of apyrexia, in accordance with European Conference on Infections in Leukaemia guidelines (n = 45). In the second phase of the study, antibiotics were stopped no later than day 5 for all FUO patients, regardless of body temperature or leukocyte count (n = 37).
Results: Two hundred and thirty-eight cases of febrile neutropenia in 123 patients were included. Neither the composite endpoint (p = .11), nor each component (in-hospital mortality (p = .80), intensive care unit admission (p = 0.48), relapse of infection ≤48 h after discontinuation of antibiotics (p = .82)) differed between the two FUO groups. Violation of protocol occurred in 17/82 episodes of FUO without any major impact on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented another FUO, respectively. One hundred and fifty-six episodes of febrile neutropenia (65.5%) were clinically or microbiologically documented, including 85 bacteremia.
Conclusions: These results suggest that early discontinuation of empirical antibiotics in FUO is safe for afebrile neutropenic patients.
Abstract
Background
Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk ...neutropenic patients with haematological malignancies.
Methods
A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence.
Results
Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences 71.2% (121/170) versus 71.3% (127/178), P = 0.97, admission in ICUs 6.5% (11/170) versus 11.2% (20/178), P = 0.17, septic shock 0.6% (1/170) versus 3.9% (7/178), P = 0.07 and 30 day mortality 1.4% (2/147) versus 2.7% (4/150), P = 0.084. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher 27.1% (46/170) versus 11.8% (21/178), P < 0.01 and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence HR = 2.31 (95% CI = 1.4–3.8), P < 0.001 and stage III–IV oral mucositis with bacteraemia HR = 2.26 (95% CI = 1.22–4.2), P = 0.01.
Conclusions
After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.
Direct oral anticoagulants (DOACs) have been approved to treat and prevent thrombotic events. However, they are not yet labeled for use in patients with active cancers. Myeloproliferative neoplasms ...(MPNs) are clonal chronic disorders with a high incidence of thrombotic events, for which low-dose aspirin (LDA) is the standard drug treatment. We analyzed efficacy and safety of DOACs prescription in patients treated for MPNs. An MPN database, the OBENE registry, was established at our institution. We collected biological and clinical data from diagnosis to last follow-up for every patient included in this study. Thrombotic and hemorrhagic events and hematologic evolutions were categorized as major events in the database. Of the 760 MPN patients in the OBENE registry, 25 (3.3%) were treated with a DOAC. Median follow-up duration was 2.1 years (0.12–4.3 years). The reasons for prescribing DOACs were atrial fibrillation and thrombotic events for 13 and 12 patients, respectively. We only observed one thrombotic event (4%) and three major hemorrhagic events (12%). A case–control study did not detect a significant difference in thrombotic or hemorrhagic events in patients treated with LDA and DOACs. These preliminary results suggest that DOACs may be highly efficient and safe for use in MPN patients.
We report the results from a multicentre retrospective study of 220 adult patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) for therapy-related acute myeloid ...leukaemia (t-AML). Median age at t-AML diagnosis was 56 years, with a prior history of haematological (45%) or breast (34%). Median time from cytotoxic exposure to t-AML diagnosis was 54.7 months. At transplant, around 20% of patients had measurable residual disease and 3% of patients were not in complete remission. The median follow-up was 21.4 months (Q1-Q3, 5.9-52.8). At 12 months, overall survival (OS), event-free survival (EFS), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS) were 60.7% (95% CI 54.6-67.5), 52.8% (95% CI 46.5-68.4), and 44.1% (95% CI 37.6-51.8), respectively. At 5 years, OS, EFS, and GRFS were 44.1% (95% CI 37.4-52.1), 40.4% (95% CI 33.9-48.1), and 35.3% (95% CI 28.8-43.3), respectively. At last follow-up, 44% of patients were in complete remission (n = 96) and transplant-related mortality accounted for 21% of all deaths (n = 119). Multivariable analysis revealed that uncontrolled t-AML at transplant was associated with lower EFS (HR 1.94, 95% CI 1.0-3.7, p = 0.041). In conclusion, alloHSCT for t-AML shows encouraging results and offers additional opportunity with the emergence of novel pre-graft therapies.
We report a case of pulmonary mucormycosis in a patient with T-cell acute lymphoblastic leukemia. The diagnosis of mucormycosis was initially based on mycological examination of a pulmonary specimen. ...However, we describe how it could have been made 2 months earlier using polymerase chain reaction assays targeting Mucorales species on serum specimens.
Allogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype ...abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio sHR: 0.58 0.32-1.07; p = 0.080) and a MSD (sHR: 0.56 0.28-1.11; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome.
The purpose of this study was to identify the incidence, causes and impact of non-adherence to oral and subcutaneous chronic treatments for patients with polycythemia vera or essential ...thrombocythemia. Patients receiving cytoreductive drugs for polycythemia vera or essential thrombocythemia were recruited at our institution (
registry). They completed a one-shot questionnaire designed by investigators (
study). Data about complications (thrombosis, transformation and death) at any time in the patient's life (before diagnosis, up until consultation and after the completion of the questionnaire) were collected. Sixty-five (22.7%) of 286 patients reported poor adherence (<90%) to their treatment with cytoreductive drugs and 46/255/18%) also declared non-adherence to antithrombotic drugs. In total, 85/286 patients (29.7%) declared they did not adhere to their treatment. Missing an intake was rare and was mostly due to forgetfulness especially during occupational travel and holidays. Patients who did not adhere to their treatment were characterized by younger age, living alone, having few medications but a high numbers of pills and determining their own schedule of drug intake. Having experienced thrombosis or hematologic evolution did not influence the adherence rate. Non-adherence to oral therapy was associated with a higher risk of phenotypic evolution (7.3
1.8%,
=0.05). For patients treated for polycythemia vera or essential thrombocythemia, non-adherence to cytoreductive and/or antithrombotic therapies is frequent and is influenced by age, habitus and concomitant treatments, but not by disease history or treatment side effects. Phenotypic evolution seems to be more frequent in the non-adherent group.
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