Acta Haematologica最新文献

Introduction: Limited studies report anxiety and depression prevalence and their correlations with prognosis in acute myeloid leukemia (AML). Even worse, their risk factors for AML remained unclear. This study aimed to investigate the prevalence, risk factors, and prognostic value of anxiety and depression in AML patients.

Methods: Totally, 132 de novo AML patients, 60 non-malignant hematological disease patients (as disease controls), and 60 healthy controls were enrolled. Anxiety and depression status were evaluated by the Hospital Anxiety and Depression Scale (HADS) in all participants.

Results: HADS-anxiety score (8.2 ± 3.2 vs. 6.1 ± 2.9 vs. 4.7 ± 2.8), anxiety rate (48.5% vs. 25.0% vs. 10.0%), HADS-depression score (7.8 ± 3.0 vs. 5.8 ± 3.0 vs. 4.0 ± 2.8), and depression rate (43.2% vs. 23.3% vs. 8.3%) were highest in AML patients, followed by disease controls, and the lowest in healthy controls (all p < 0.001). Multivariate logistic regression analysis identified that factors independently associated with anxiety included male (p = 0.002, odds ratio [OR] = 0.240), smoking (p = 0.043, OR = 2.474), education duration (p = 0.024, OR = 0.889), and NCCN high-risk stratification (p = 0.008, OR = 2.347), while those independently associated with depression were age (p = 0.005, OR = 1.055), single/divorced/widowed status (p = 0.014, OR = 3.149), NCCN high-risk stratification (p = 0.002, OR = 3.077), and white blood cell (WBC) (p < 0.001, OR = 1.062). Additionally, depression was correlated with shorter accumulating event-free survival (p = 0.012) and overall survival (p = 0.041) in AML patients, whereas anxiety was not.

Conclusions: Anxiety and depression are prevalent, among which depression is associated with poor survival profile, but anxiety is not; moreover, age, male, education, single/divorced/widowed status, smoking, NCCN high-risk stratification, and WBC were independent related factors of anxiety and depression in AML patients.

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare subtype of aggressive extranodal non-Hodgkin lymphoma. Currently, there is no standard of care for the treatment of refractory or relapsed PCNSL (r/r PCNSL). We conducted a prospective single-arm phase II study to evaluate zanubrutinib plus cytarabine for r/r PCNSL.

Methods: Using Simon's two-stage design, we analyzed 34 patients who received high-dose cytarabine (3.0 g/m2 once daily) for 2 days and zanubrutinib (160 mg twice daily) for 21 days each cycle for up to 6 cycles. The study was registered at www.chictr.org.cn as #ChiCTR2000039229.

Results: The median follow-up was 19 months. The overall response rate was 64.7% (95% confidence interval [CI], 47.9-78.5%) with a complete remission or unconfirmed complete remission rate of 47.1% (16/34) and a partial remission rate of 17.6% (6/34). The median progression-free survival was 4.5 months (95% CI, 1.5-9.4), and the median OS was 18 months (95% CI, 9.5 to not estimable). The median duration of the response was 9 months (95% CI, 3.2 to not estimable). The most common treatment-emergent adverse events were thrombocytopenia (55.9%). No treatment-related death occurred.

Conclusion: Zanubrutinib and cytarabine showed efficacy in r/r PCNSL with an acceptable safety profile.

Background: Acute myeloid leukemia (AML) is a heterogenous disease that affects mostly older adults with varying baseline health and functional status. Treatment options have expanded for older adults, ranging from less intensive chronic therapies to intensive induction strategies with curative intent. Despite this, outcomes remain poor with advancing age due to underlying disease biology and variability in treatment tolerance. Reliance on chronological age alone, however, increases risks of both over- and under-treatment. Strategies to better characterize fitness in the context of therapy are needed to optimize decision-making and enhance clinical trial design.

Summary: Geriatric assessment (GA) is a series of validated tools that evaluate multiple health and functional domains of an older adult including physical function, comorbidities, cognition, nutrition, psychological health, and social support. While studies of GA in AML remain limited, current evidence shows that it is feasible to perform GA among older adults starting therapy for AML. GA measures including those assessing physical function, cognition, and mood are associated with mortality and toxicity in both intensive and less intensive treatment settings.

Key messages: In this review, we discuss the existing evidence to support use of GA in AML and highlight implications for clinical practice and future research.

Introduction: Prediction of outcomes following allogeneic hematopoietic cell transplantation (HCT) remains a major challenge. Machine learning (ML) is a computational procedure that may facilitate the generation of HCT prediction models. We sought to investigate the prognostic potential of multiple ML algorithms when applied to a large single-center allogeneic HCT database.

Methods: Our registry included 2,697 patients that underwent allogeneic HCT from January 1976 to December 2017. 45 pretransplant baseline variables were included in the predictive assessment of each ML algorithm on overall survival (OS) as determined by area under the curve (AUC). Pretransplant variables used in the EBMT ML study (Shouval et al., 2015) were used as a benchmark for comparison.

Results: On the entire dataset, the random forest (RF) algorithm performed best (AUC 0.71 ± 0.04) compared to the second-best model, logistic regression (LR) (AUC = 0.69 ± 0.04) (p < 0.001). Both algorithms demonstrated improved AUC scores using all 45 variables compared to the limited variables examined by the EBMT study. Survival at 100 days post-HCT using RF on the full dataset discriminated patients into different prognostic groups with different 2-year OS (p < 0.0001). We then examined the ML methods that allow for significant individual variable identification, including LR and RF, and identified matched related donors (HR = 0.49, p < 0.0001), increasing TBI dose (HR = 1.60, p = 0.006), increasing recipient age (HR = 1.92, p < 0.0001), higher baseline Hb (HR = 0.59, p = 0.0002), and increased baseline FEV1 (HR = 0.73, p = 0.02), among others.

Conclusion: The application of multiple ML techniques on single-center allogeneic HCT databases warrants further investigation and may provide a useful tool to identify variables with prognostic potential.

Hyperhemolysis syndrome (HHS) is a rare and severe posttransfusion complication characterized by the destruction of both recipient and donor red blood cells. The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound sickle cell disease (SCD)/β0-thalassemia and alloimmunization after transfusion of packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.

Background: Measurable residual disease (MRD) test positivity during and after treatment in patients with acute myeloid leukemia (AML) has been associated with higher rates of relapse and worse overall survival. Current approaches for MRD testing are not standardized leading to inconsistent results and poor prognostication of disease. Pertinent studies evaluating AML MRD testing at specific times points, with various therapeutics and testing methods are presented.

Summary: AML is a set of diseases with different molecular and cytogenetic characteristics and is often polyclonal with evolution over time. This genetic diversity poses a great challenge for a single AML MRD testing approach. The current ELN 2021 MRD guidelines recommend MRD testing by quantitative polymerase chain reaction in those with a validated molecular target or multiparameter flow cytometry (MFC) in all other cases. The benefit of MFC is the ability to use this method across disease subsets, at the relative expense of suboptimal sensitivity and specificity. AML MRD detection may be improved with molecular methods. Genetic characterization at AML diagnosis and relapse is now standard of care for appropriate therapeutic assignment, and future initiatives will provide the evidence to support testing in remission to direct clinical interventions.

Key messages: The treatment options for patients with AML have expanded for specific molecular subsets such as FLT3 and IDH1/2 mutated AML, with development of novel agents for NPM1 mutated or KMT2A rearranged AML ongoing, but also due to effective venetoclax-combinations. Evidence regarding highly sensitive molecular MRD detection methods for specific molecular subgroups, in the context of these new treatment approaches, will likely shape the future of AML care.

Introduction: Tumor lysis syndrome (TLS) occurs frequently during induction therapy for acute lymphoblastic leukemia (ALL). Patients are categorized into intermediate- or high-risk based on the lactate dehydrogenase (LDH) value and white blood cell (WBC) count, according to an expert panel, although no effort has been made to analyze TLS in ALL and its potential consequences.

Methods: We retrospectively analyzed TLS, variables associated with its occurrence, and its impact on overall survival (OS) and mortality during induction in a cohort of ALL patients in their first induction regimen.

Results: A total of 138 patients were included, 52.9% were male and the median age at diagnosis was 34 years. Most of them were treated with hyper-CVAD (39.1%) or a modified CALGB 10403 regimen (37.7%). TLS was identified in 42 patients (30.4%), and half of them fulfilled criteria for clinical TLS (C-TLS). Median OS was the lowest in C-TLS patients. An LDH 3 times greater than its upper laboratory normal (ULN) value and a WBC count equal to or greater than 50×109/L were associated with TLS development, and being male, hyperuricemia and an LDH 3 times greater than its ULN value were associated with C-TLS development. C-TLS and acute kidney injury were associated with excess mortality during induction.

Conclusion: TLS was identified in almost one-third of ALL patients during induction therapy. Different thresholds for LDH value and WBC count as well as other variables could identify patients at risk of developing this complication, which is associated with shorter OS. C-TLS confers a higher risk for mortality during induction.

Introduction: Liver dysfunction is common in patients with hemophagocytic lymphohistiocytosis (HLH). However, whether the severity of liver injury is associated with the prognosis of patients with HLH remains to be determined. This study aims to assess the association of the severity of liver involvement with short-term prognosis among adult patients with HLH.

Methods: A retrospective study was performed from January 2012 to December 2020, including 150 patients with newly diagnosed HLH and liver injury.

Results: The majority of our cohort suffered from mild to moderate hepatic damage, presenting with Child-Turcotte-Pugh (CTP) class A (55, 36.7%) or B (74, 49.3%). The prevalence of acute liver failure (ALF) was 9.3% in our cohort. The overall 30-day mortality rate was 49.3% among the study population. HLH patients with ALF showed an extremely adverse prognosis, with a mortality rate as high as 92.9%. In a multivariate analysis, age ≥60 years (p = 0.016), blood urea nitrogen (BUN) ≥7 μmol/L (p < 0.001), and malignancy-associated HLH (p < 0.001) at the diagnosis of HLH were identified as being strongly correlated with 30-day prognosis. An excellent predictive power was found. Among the predictive scores used to assess early death of HLH patients with liver injury, the prognostic efficiency of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) (AUROC: 0.936 ± 0.0211) and SOFA score (0.901 ± 0.026) were significantly better than those of the APACHE II (p < 0.001), model for end-stage liver disease score (p < 0.001) and CTP scores (p < 0.001).

Conclusion: Patients with old age, elevated BUN, and malignancy had inferior survival. CLIF-SOFA and SOFA enable more accurate prediction of early death in HLH patients with liver injury than other liver-specific and general prognostic models.