European Journal of Haematology最新文献

Background: Disseminated intravascular coagulation (DIC) is a devastating disease of the coagulation system. We examined the association between ABO blood type and short-term mortality in patients with infection-associated DIC.

Methods: The study cohort was drawn from the Danish Disseminated Intravascular Coagulation (DANDIC) cohort. Our subcohort was restricted to patients with infection-associated DIC. All-cause 30-day and 90-day mortality were computed by Kaplan-Meier estimates and odds ratios between ABO blood types were examined using logistic regression analysis adjusted for age, sex, comorbidity, and location of infection. Blood type O was used as a reference.

Results: The DANDIC cohort included 3023 patients with DIC. Among these, 1853 (61%) had infection-associated DIC. Data on ABO blood type were unavailable in 34 patients (1.8%), who were excluded. The median age was 68 years and 58.2% were males. The 30-day mortality ranged between 38.6% and 42.5% and the 30-day mortality odds ratios were 1.15 (95% confidence interval (CI), 0.92-1.42) for blood type A; 0.84 (95% CI, 0.49-1.43) for AB; and 0.95 (95% CI, 0.67-1.33) for B compared to blood type O.

Conclusions: We found no clinically meaningful difference in short-term mortality between the various ABO blood types in patients with infection-associated DIC.

The introduction of tyrosine kinase inhibitors has considerably improved the life expectancy (LE) for patients with chronic myeloid leukemia (CML). Evaluating health-related quality of life within the treatment pathway remains crucial. Using the Swedish CML register, we included 991 adult patients with chronic-phase (CP) CML diagnosed 2007 to 2017, with follow-up until 2018. We developed a multistate model to estimate the loss in LE (LLE) and loss in quality-adjusted life expectancy (LQALE) for the patient population compared to the general population, along with the respective proportions of losses relative to the general population. All patients with CP-CML had a relatively low reduced LE but with larger LQALE. The maximum LLE within age/sex subgroups was 5.7 years (general population LE: 43.2 years vs. CP-CML LE: 37.5 years) for females diagnosed at age 45 years, with LQALE of 12.0 quality-adjusted life years (QALYs) (general population QALE: 38.2 QALYs vs. CP-CML QALE: 26.3 QALYs). Across all ages, the proportions of LLE ranged from 9% to 15%, and the proportions of LQALE were 29% to 33%. Despite a low LLE, our findings reveal a greater LQALE for patients with CP-CML. Further improvements in management of CP-CML are thus warranted to successfully address the prevailing medical needs.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients. Indeed, 2 out of 14 TP53-mutated patients (14%) randomized to a DEC + ATRA-containing regimen lived for > 36 months. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.

Objectives: This study investigated healthcare utilisation in general practice and hospitals in the 2 years preceding a diagnosis of haematological cancer and the association with patient pathways.

Methods: The nationwide register-based cohort study included 12 994 patients diagnosed with leukaemia, multiple myeloma and lymphoma in 2014-2018 and 10 matched references. Patient pathways were analysed in unplanned routes (acute admission up to 1 month's prior diagnosis) and elective routes (other routes, e.g., cancer patient pathways).

Results: Female patients in unplanned diagnostic pathways had more contacts to general practice from 19 months before the diagnosis compared to their matched references; with IRR increasing from 1.14 (95% confidence interval (CI) 1.05-1.24) to 2.27 (95% CI 2.13-2.41) at 30-60 days before the diagnosis. Female patients had more point-of-care tests, hospital contacts and radiological investigations at 17, 24 and 17 months, respectively, before diagnosis compared to their references. Similar patterns were seen for male patients, although with a later onset of increase. No healthcare use variations were seen between patients diagnosed in unplanned versus elective pathways.

Conclusions: Increased healthcare utilisation was seen in general practice and hospitals up to 24 months preceding a diagnosis, which may indicate a diagnostic window for detecting haematological cancer earlier.

Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause-specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen-Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow-up of 10 years (interquartile range, [IQR]: 5.9-17.4). Median age was 39 years (IQR: 27-56), median cumulative doxorubicin dose was 250 mg/m² (IQR: 200-300). The CVD cumulative incidences were 4.7% (95% CI: 3.6-5.7) for patients versus 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) versus 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) versus 8.2% (95% CI: 7.4-9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.

Asymptomatic lymphocytosis poses a common challenge in haematology. Immunophenotyping can establish whether a clonal population is present, but it is expensive and the benefit of diagnosing asymptomatic patients is unproven. This study aimed to establish data to guide the use of immunophenotyping. We analysed the proportion of lymphocytosis in full blood count (FBC) samples across a five-year period within a large UK National Health Service (NHS) trust. Persistent lymphocytosis was present in 0.18% (437/242678) of repeat community samples. Of samples sent for immunophenotyping, 743/784 (95%) with a lymphocyte count > 10 × 10⁹/L had a clonal population, compared to 223/1696 (14%) with a lymphocyte count < 5 × 10⁹/L. We followed up a longitudinal cohort of asymptomatic patients with clonal lymphocytosis to determine how many required treatment. The minority (11/46) of patients needed treatment within 9 years of follow-up. Of patients needing treatment, 10/11 (91%) had a presenting lymphocyte count > 10 × 10⁹/L. In all cases, treatment was initiated when the patient became symptomatic. We propose a lymphocyte count threshold of > 10 × 10⁹/L for referral and immunophenotyping in patients with asymptomatic lymphocytosis. This approach aims to balance safety and cost-effectiveness and reflects uncertainty in the value of diagnosis for asymptomatic patients.

Background: Acute Chest Syndrome (ACS) is the leading cause of death in children with sickle cell disease (SCD) in the US-about half of the children who develop ACS present initially with pain.

Methods: Here, we studied biomarkers to differentiate ACS from vaso-occlusive crises (VOC) in children with SCD who presented with pain to the emergency department (ED). We conducted a prospective cohort study of consecutive patients who presented to the ED with pain and were discharged with ACS or VOC between March, 2017 and February, 2020.

Results: We identified 7 patients with ACS and 19 patients with VOC. The two groups were comparable in age and sex. All patients with ACS had asthma versus 42% of the VOC group. The ACS group had lower weight and BMI z-scores. Patients with ACS compared to VOC had significantly higher respiratory rates, lower O₂ saturation, and longer hospital stays. They also had higher white blood cell count, glucose level (> 99 mg/dL), anion gap (> 9 mEq/L), sPLA2 (> 7 pg/mL), IFN-γ (> 17.8 pg/mL), IL-10 (1.54 pg/mL), and IL-12 (> 0.5 pg/mL) levels.

Conclusions: We identified biomarkers associated with ACS development in children with SCD presenting with pain that allow for earlier ACS interventions to reduce mortality and morbidity.

Background: Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy.

Aim: The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy.

Data sources: Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024.

Study eligibility criteria: Studies (prospective, retrospective cohort, cross-sectional, one arm, survey, follow-up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post-pregnancy remission status comparison.

Methods: The quality of research was checked using the New Castle-Ottawa risk-of-bias tool. A meta-analysis model with a random effect distribution, coupled with meta-regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed.

Results: Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%-20%). Heterogeneity was low in the present meta-analysis (I ²  = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%-11%) for spontaneous abortion, 4% (95% CI, 1%-11%) for preterm premature rupture of membranes, 10% (95% CI, 3%-28%) for premature rupture of membranes, 6% (95% CI, 3%-11%) for fetal growth restriction, 5% (95% CI, 2%-13%) for intrauterine fetal death, 12% (95% CI, 5%-26%) for post-partum hemorrhage, 74% (95% CI, 45%-91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%-80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01-0.14), whereas neonatal mortality was 7% (95% CI, 0.03-0.18). The odds of AA complete remission were better in pre-pregnancy than post-pregnancy (OR = 0.36; 95% CI = 0.08-1.66), although the results remain insignificant. The leave-one-out sensitivity analysis did not change the pooled estimates for the primary outcome.

Conclusion: A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden.

Background: The molecular architecture of acute myeloid leukemia (AML) is heterogeneous. Obesity has been identified as a risk factor for the development of AML. There remains a scarcity of data elucidating the specific genetic profile of AML in obese patients.

Methods: We conducted a review of adult patients treated at our institution for newly diagnosed AML from January 1, 2017, to January 1, 2023. Obesity is defined as BMI > 30 kg/m². Demographic, clinical, laboratory, and pathologic data were collected retrospectively. The primary outcome of interest was the molecular features of obese compared to non-obese AML patients. The secondary outcome was overall survival (OS). Inverse probability of treatment weights (IPTW) used to balance both groups on several confounding variables.

Results: A total of 185 patients were included in the analysis. 90 (49%) were obese. Compared with non-obese patients, obese patients were younger and more likely to be females (55 vs. 63, p = 0.04, 55% vs. 38%, p value, p = 0.02, respectively). After matching on age, gender, and ethnicity, obese patients exhibit lower rates of total number of gene mutations (median 2.7 vs. 3.2, p = 0.05), significantly lower rates of mutations in transcriptional factor genes (15.7% vs. 33.2%, p = 0.01), and near-significant in spliceosome genes (12% vs. 22.3%, p = 0.08), and higher rates of NPM1 mutation (23.3% vs. 12.6%, p = 0.08). Median OS was not significantly different in the matched cohort.

Conclusions: The molecular features of obese AML patients significantly differ from non-obese counterparts. These findings suggest distinct underlying mechanisms in leukemogenesis in obese patients.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in relapsed or refractory large B cell lymphoma, but real-world evidence is needed to confirm safety and efficacy when facing the unique challenges of a wide geographical catchment area.

Methods: We reviewed patients treated with commercially available CAR-T at a medium-sized single center in Canada (The Ottawa Hospital) between December 2020 and July 2022 (Canadian implementation started in 2020).

Results: Fifty-one patients (59% male, median age 62) traveled a median distance of 655 km (range 3-3659) for treatment. Median time from apheresis to CAR-T infusion was 36 days (range 26-81). With a median follow-up of 383 days (95% CI: 333-480), median progression-free survival (PFS) and overall survival (OS) were 257 days (95% CI: 92-NE) and 422 days (95% CI: 106-NE), respectively. The median PFS for out-of-province patients was 115 days (95% CI: 91-NE) versus 280 days for in-province patients (95% CI: 142-NE), p = 0.12. Multivariate analysis demonstrated that distance from treatment center (p = 0.05) and refractory disease status (p = 0.003) were independently associated with shorter PFS. The time from the last disease progression to CAR-T referral was longer for out-of-province patients, but there was no difference in the time of referral to CAR-T consult, apheresis, or CAR-T infusion between in-province and out-of-province patients.

Conclusion: Our results confirm that despite the complexity of CAR-T therapy administration, Ottawa can effectively provide commercial CAR-T therapy in a timely fashion for patients from across the country.