Mediterranean Journal of Hematology and Infectious Diseases最新文献

Background: The therapeutic landscape of hematological malignancies has expanded rapidly, increasing survival but also exposing patients to pharmacokinetic variability and clinically relevant drug-drug interactions. Therapeutic drug monitoring (TDM) offers a pharmacokinetics-informed strategy to individualize dosing, yet its real-world implementation across drug classes and healthcare settings remains insufficiently characterized.

Methods: We conducted an international, cross-sectional online survey (December 2023-February 2024) assessing availability, utilization, and clinical impact of TDM in patients with hematological malignancies. Physicians from multiple specialties reported institutional practices, turnaround times, drug-specific monitoring strategies, and treatment modifications based on TDM results.

Results: A total of 209 physicians from 32 countries participated, predominantly from Europe (92%). TDM was widely accessible (97%), mainly performed onsite (79%), and perceived as beneficial by nearly all respondents (99%). Routine TDM was most frequently used for classical agents (methotrexate, cyclosporin A), antifungals, and antibiotics, but substantial interest was reported for targeted therapies, including BCL-2 inhibitors, BCR-ABL tyrosine kinase inhibitors, FLT3 inhibitors, and Bruton tyrosine kinase inhibitors. Treatment was modified based on TDM results by 71% of respondents, with faster turnaround times strongly associated with clinical action. Limited assay availability, delayed reporting, and insufficient clinical evidence were identified as key barriers to broader implementation.

Conclusions: TDM is widely available and perceived as clinically useful in the management of hematological malignancies, frequently informing treatment decisions. While firmly established for classical agents and anti-infectives, clinicians express growing interest in extending TDM to targeted therapies. Optimizing turnaround times, expanding assay availability, and integrating pharmacokinetics-informed dosing into clinical trials may further clarify the role of TDM within precision medicine approaches in hematology.

Background: Scrub typhus is a leading cause of febrile illness across the Asia-Pacific region. Doxycycline is the first-line therapy, with azithromycin as an alternative; sequential treatment (doxycycline followed by azithromycin) is used for nonresponders. However, comparative real-world effectiveness for sequential therapy remains uncertain.

Methods: We conducted a single-center, non-interventional target-trial emulation at the 970th Hospital of the People's Liberation Army (January 2023 - June 2025). Consecutive patients ≥12 years receiving oral doxycycline, azithromycin, or sequential doxycycline/azithromycin treatment were included. The primary outcome was 48-hour defervescence sustained ≥24 h without antipyretics. Secondary outcomes were time to defervescence, Day 5 failure, complications, length of stay, 28-day mortality, and safety. Confounding was addressed using inverse probability weighting (generalized boosted models). The confirmatory comparison (doxycycline vs azithromycin) was limited to non-pregnant initiators (pregnancy excluded due to structural non-overlap) to satisfy positivity. The sequential pathway was explored descriptively with time-varying and 48-hour landmark analyses.

Results: We analyzed 512 patients (doxycycline 206, azithromycin 208, and sequential 98). Crude 48-hour defervescence was 82.0%, 78.8%, and 66.3%, respectively. In the confirmatory inverse probability of treatment weighting (IPTW) analysis, doxycycline vs azithromycin showed no difference (adjusted RR 1.03, 95% CI 0.95-1.12; p=0.34). Weighted time-to-event analysis was concordant (aHR 1.08, 95% CI 0.96-1.21; p=0.20). Secondary outcomes were similar between monotherapies (Day-5 failure aRR 0.83, 95% CI 0.56-1.24; complications aRR 0.94, 95% CI 0.66- 1.33; median length of stay 5 [IQR 4-7] days in both; 28-day mortality 1.6% overall). The sequential switch group had lower crude 48-hour defervescence, consistent with escalation after early non-response. Pairwise causal contrasts involving the sequential pathway were not presented due to structural bias.

Conclusions: Oral doxycycline and azithromycin demonstrated comparable effectiveness and safety for early defervescence in routine care. Inferior crude outcomes with sequential therapy likely reflect clinical escalation. Multi-center validation and randomized trials are warranted.

Background: Eltrombopag (ELT) is an established thrombopoietin receptor agonist (TPO-RA) for chronic immune thrombocytopenia (ITP), yet accumulating translational evidence indicates clinically relevant iron-chelating activity. Adult primary ITP-focused data characterizing longitudinal iron trajectories during ELT remain limited. We assessed whether ELT exposure is independently associated with iron deficiency (ID) in routine practice.

Methods: In this multicenter retrospective study, adults with ITP were evaluated with longitudinal monitoring of platelet count, ferritin, transferrin saturation (Tsat), hemoglobin (Hb), and mean platelet volume (MPV). Within-patient change was defined as the difference between baseline and follow-up (Δ). Outcomes were compared by ELT exposure and dose strata. Multivariable linear regression was used to identify independent determinants of Δ-ferritin, adjusting for age, gender, relapse status, and iron replacement therapy (IRT).

Results: The cohort included 283 adults with ITP; 110 received ELT (median 25 months). ELT was associated with greater declines in ferritin and Tsat (p<0.001), with a dose-graded effect across 25-75 mg and earlier iron depletion at higher dose intensity. In relapsed patients not receiving ELT, the mean Δ-ferritin was positive and did not differ by bleeding status. In multivariable linear regression, ELT was the dominant independent predictor of lower Δ-ferritin (B≈-79.8 μg/L, p<0.001), whereas age, gender, and relapse were not significant; IRT attenuated ferritin decline but did not negate ELT effects.

Conclusion: ELT exposure was independently associated with ID, supporting a clinically meaningful ELT-related iron chelation phenotype in routine practice. Monitoring and timely correction of ID during ELT therapy may mitigate a modifiable contributor to fatigue during follow-up.

Background: The study aimed to compare the incidence and course of febrile neutropenia (FN) and factors affecting mortality in hematologic patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either fresh or cryopreserved grafts.

Methods: The clinical data of 155 patients who underwent allo-HSCT at our hematology clinic between 2010 and 2023 were retrospectively analyzed. The incidence of bloodstream infection (BSI) and FN-related mortality was analyzed in these patients. Factors affecting FN-related mortality were examined using a logistic regression model.

Results: A total of 143 patients who developed FN were included in the study. Ninety-eight patients underwent transplantation with fresh stem cells, and 45 patients with cryopreserved stem cells. The duration of FN episodes was similar between groups (p = 0.077); however, the duration of deep neutropenia (neutrophils < 100/mm³) was significantly longer in the cryopreserved group (11.56 ± 4.84 vs. 7.78 ± 3.03; p < 0.001). GNB infections and invasive fungal infections were more frequent in the cryopreserved group (p = 0.009 and p < 0.001, respectively). In the logistic regression model, the most important determinants of FN-related mortality were duration of the FN episode (OR 1.18; 95% CI 0.99-1.41; p = 0.046) and higher hematopoietic cell transplantation comorbidity index (HCT-CI) score (score 1; p = 0.014 and score 2; p = 0.039).

Conclusions: This study demonstrated that, regardless of graft type, prolonged FN duration and a high HCT-CI score are the primary determinants of mortality. Therefore, clinical management of patients should also address these risk factors.

Background: Invasive procedures such as bone marrow aspiration (BMA) and lumbar puncture (LP) are essential in the management of pediatric leukemia but often induce significant state anxiety. This cross-sectional study aimed to evaluate procedural state anxiety using the Chinese Version of the State Anxiety Scale for Children (CSAS-C) and identify associated socio-demographic and clinical factors in Chinese pediatric leukemia patients.

Methods: A convenience sample of 119 patients aged 8-18 years with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) undergoing BMA or LP was recruited from a tertiary pediatric oncology center in China. State anxiety was assessed via the CSAS-C (score range: 20-60, higher scores indicating greater anxiety). Socio-demographic (gender, age, education) and clinical data (diagnosis, treatment history, procedural type, site, history) were collected. Data were analyzed using R software (version 4.4.3). Non-normally distributed variables were presented as median (P25, P75). Group comparisons employed the Mann-Whitney U test for two groups and the Kruskal-Wallis test with Dunn's post-hoc for multiple groups, with P < 0.05 considered significant.

Results: The overall median CSAS-C score was 27.0 (21.0, 32.0), indicating mild to moderate anxiety. Significantly higher anxiety was associated with younger age (8-12 years; P < 0.001), primary school education (P < 0.001), AML diagnosis (P = 0.004), hospitalization setting (P < 0.001), and first-time procedures (P < 0.001). No significant differences were observed by gender (P = 0.439), treatment history (P = 0.066), or procedural type (P = 0.238). Multivariable linear regression confirmed that first-time procedures were an independent predictor of higher anxiety (β = 11.82, p = 0.001), with a marginal effect for lumbar puncture (β = 7.16, p = 0.056).

Conclusion: Procedural state anxiety is prevalent among pediatric leukemia patients undergoing BMA or LP, particularly in younger, less educated, AML, inpatient, and novice patients. These findings underscore the need for tailored anxiety-reduction interventions in pediatric oncology to improve patient experience and compliance.

Background: Relapse remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation (AHSCT) in acute leukemia. Post-transplant surveillance commonly relies on measurable residual disease (MRD) and donor chimerism monitoring; however, their relative predictive value and optimal timing remain uncertain.

Aims: To compare the prognostic performance of MRD and donor chimerism in predicting relapse after AHSCT in adult patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Methods: This retrospective cohort included 264 adults (186 AML, 78 ALL) who underwent AHSCT. MRD was assessed by multiparametric flow cytometry on day 28 and at months 3 and 12, and chimerism by short tandem repeat PCR. Cox regression identified independent relapse predictors.

Results: Relapse occurred in 95 patients (68 AML, 27 ALL). In AML, MRD positivity at month 3 (HR 3.69, p<0.001) and mixed total chimerism at month 3 (HR 2.47, p=0.029) independently predicted relapse and were associated with inferior overall and disease-free survival. MRD detected relapse earlier and with greater sensitivity than chimerism. In ALL, total mixed chimerism at month 3 was associated with relapse in univariate analysis, whereas MRD showed limited statistical power due to small sample size.

Conclusion: Post-transplant MRD monitoring at month 3 provides superior risk stratification compared with chimerism in AML. In ALL, both approaches appear complementary, but conclusions are limited by cohort size. Disease-specific, risk-adapted surveillance strategies are warranted.