Ahmet Mert Yanık

Background and Objectives: Familial Mediterranean Fever (MEFV) gene variants exhibit a high carrier frequency in the Turkish population and modulate clinical phenotypes through persistent low-grade innate immune activation. However, their role in myeloid malignancies—where aberrant inflammasome signaling contributes to immunopathogenesis—remains poorly defined. We aimed to investigate the carrier frequency and potential disease-modifying role of common MEFV variants in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Materials and Methods: In this retrospective case–control study, 80 clinical evaluations from 75 unique patients with myeloid malignancies (53 AML and 27 MDS, including 5 patients evaluated in both cohorts before and after leukemic transformation) and 186 healthy controls from the Turkish population were analyzed. Four established pathogenic exon 10 variants (M694V, V726A, M680I, and M694I) and two variants of uncertain significance (VUS; K695R and E148Q) were genotyped using rhAmp™ SNP Genotyping and polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assays. Clinical characteristics, blastic progression, and survival outcomes were evaluated. Results: Overall MEFV variant carriage did not differ significantly between the unique patient cohort and healthy controls (24.0% [18/75] vs. 19.9% [37/186], p = 0.462; or 23.8% [19/80] across all disease evaluations, p = 0.479). In the MDS cohort (n = 27), 10 mutant alleles were detected in 9 unique patients (variant frequency: 37.0% vs. 19.9% in controls, p = 0.045; unique carrier frequency: 33.3% vs. 19.9%, p = 0.113), as one female MDS patient was a compound heterozygote (M694V/V726A). Stratified analysis revealed that this enrichment in MDS was driven by established pathogenic exon 10 variants (22.2% [6/27] vs. 9.1% [17/186], p = 0.041; allele frequency: 11.1% [6/54] vs. 4.6% [17/372], p = 0.047), whereas VUS frequencies were comparable (14.8% vs. 10.8%, p = 0.533). Within the MDS group, male patients showed an exploratory trend toward a higher carrier rate than females (60.0% [6/10] vs. 17.6% [3/17], Fisher’s exact p = 0.039). Conversely, MEFV variant frequency in AML mirrored that of controls (20.8% [11/53] vs. 19.9%, p = 0.890). Baseline clinical parameters and overall survival did not differ significantly by genotype, although MEFV-positive MDS patients exhibited a non-significant numerical trend toward a shorter interval to blast progression (12.7 vs. 36.2 months). Conclusions: Our findings provide exploratory, hypothesis-generating evidence suggesting a potential enrichment of pathogenic exon 10 MEFV variants in MDS—particularly among male patients—but not in AML. Given the small sample size and retrospective design, these observations require validation in larger multi-center cohorts, and future studies may explore whether MEFV genotyping offers clinical or prognostic utility in high-prevalence populations.

Background: Immunoglobulin isotype is recorded at diagnosis in every patient with intact-immunoglobulin multiple myeloma, but is not retained in the ISS, R-ISS, or R2-ISS. Methods: We analyzed 196 consecutive patients with IgA or IgG myeloma who underwent upfront autologous stem cell transplantation at a single center (2009–2023). The primary endpoint was progression-free survival (PFS); overall survival (OS) was the secondary endpoint. Cox models used information available at transplantation, including the induction regimen and transplant year, in the complete-case set (n = 131) and after multiple imputation (n = 196). Results: Median PFS was 14.8 versus 30.5 months and OS 43.2 versus 94.2 months in IgA versus IgG patients (both p < 0.001). IgA isotype was associated with inferior PFS (adjusted HR 1.85, 95% CI 1.13–3.02; imputed HR 1.83, 95% CI 1.22–2.73). For OS, the HR was 1.68 (0.98–2.88) in the complete-case analysis and 1.91 (1.24–2.94) after imputation, so its magnitude is uncertain. Models with maintenance gave 1.87 and 1.82. Progression documentation differed by maintenance status. Cytogenetic data were too incomplete to assess independence from genomic risk. Conclusions: In a bortezomib-era transplant cohort, IgA isotype was associated with inferior PFS; the association with OS was of uncertain magnitude. The finding is hypothesis-generating and requires validation in cohorts with complete cytogenetic characterization.

Background and Objectives: The optimal treatment strategy for older patients with acute myeloid leukemia (AML) remains uncertain because treatment selection is influenced by age, comorbidity, functional status, and disease biology. This study explored real-world outcomes with intensive and non-intensive treatment strategies. Materials and Methods: We retrospectively analyzed 69 patients aged ≥ 65 years diagnosed with AML between 2012 and 2022 at a tertiary center. Treatment intensity was defined by regimen. Baseline demographic, clinical, and laboratory parameters were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using log-rank tests. Results: A total of 69 patients were included, with a median age of 71 years. Intensive and non-intensive therapies were administered in 24.2% and 75.8% of treated patients, respectively. The median PFS was 6.7 months, and the median OS was 7.8 months. One- and two-year OS rates were 29% and 9.2%, respectively. No significant differences in PFS or OS were observed between treatment intensity groups. Among response-evaluable patients, complete remission/complete remission with incomplete hematologic recovery (CR/CRi) was achieved in 58.0% of intensively treated patients and 43.3% of those receiving hypomethylating agent (HMA)-based therapy. Among the evaluated baseline variables, only Eastern Cooperative Oncology Group (ECOG) performance status was significantly associated with overall survival. Patients with an ECOG performance status ≥ 2 had significantly shorter OS than those with ECOG p = 0.009). Conclusions: In this real-world cohort of older patients with AML, no statistically significant differences in PFS or OS were observed between intensive and non-intensive treatment strategies. Although CR/CRi rates were numerically higher with intensive therapy, disease progression remained frequent among patients who achieved a response. ECOG performance status was significantly associated with overall survival, highlighting the relevance of functional status in individualized treatment selection. These findings should not be interpreted as evidence of therapeutic equivalence.

Aims: Relapsed or refractory multiple myeloma (RRMM) remains a therapeutic challenge due to treatment resistance, comorbidities, and limited options after multiple therapy lines. Carfilzomib, a second-generation proteasome inhibitor, has demonstrated efficacy when administered once weekly at 70 mg/m² in combination with dexamethasone (wKd70), offering a convenient and effective alternative to twice-weekly schedules.We conducted a retrospective analysis of 32 RRMM patients treated with wKd70 between 2018 and 2023 at a single referral center. Methods: Thirty-two RRMM patients were analyzed retrospectively. Patients with RRMM who received at least one course of carfilzomib at a dose of 70 mg/m² (administered on days 1, 8, and 15 of 28-day cycles) in combination with dexamethasone 40 mg/week were included in the study. Results: The median age was 57.5 years (range: 43–75), and patients had received a median of three prior therapy lines. The overall response rate (ORR) was 62.1% . Median progression-free survival (PFS) was 16 months, and median overall survival (OS) was 51 months . Prior autologous stem cell transplantation was associated with significantly improved PFS and OS. Adverse events were common but mostly mild (grades 1–2) forms. Conclusion: Our findings support wKd70 as an effective and well-tolerated treatment option for RRMM, even in heavily pretreated patients. The favorable survival outcomes compared to historical trials suggest a role for earlier use of this regimen.

Background: Thrombocytopenia develops in roughly one in three intensive care unit (ICU) patients and is associated with worse outcomes. Most prognostic studies treat it as a single entity defined by platelet count (PLT) alone. We examined whether classifying the dominant pathophysiological direction (peripheral consumption versus impaired production), using admission mean platelet volume (MPV), adds prognostic information beyond the count itself. Methods: We analyzed 2188 consecutive adults admitted to a tertiary medical ICU between 2019 and 2023. Patients were classified as: normal platelet count (PLT ≥ 150 × 10⁹/L), consumption-like thrombocytopenia (PLT < 150 × 10⁹/L with elevated MPV), or production-like thrombocytopenia (PLT < 150 × 10⁹/L with normal or low MPV). The primary outcome was all-cause ICU mortality. Multivariable logistic regression adjusted for age, APACHE II score, albumin, creatinine, and malignancy. A prespecified malignancy subgroup analysis included a phenotype interaction term. Results: Of 2188 patients (median age 70 years; 57.6% male), 717 (32.8%) had thrombocytopenia; of these, 703 with available MPV were classified: 249 consumption-like and 454 production-like; the three groups were similar in age and sex distribution (p = 0.002 for age; p = 0.876 for sex). Active malignancy was present in 585 patients (26.7%) and was more frequent in the consumption-like group (34.5% vs. 25.2% PLT-normal; p = 0.008). Overall ICU mortality was 44.4% and differed across phenotypic groups (52.0% consumption-like vs. 46.7% production-like vs. 42.4% PLT-normal; p = 0.010). In the full cohort, consumption-like thrombocytopenia was independently associated with ICU death (OR 1.46, 95% CI 1.08–1.99; p = 0.016); production-like was not (OR 1.12; p = 0.302). In patients with malignancy, the adjusted OR was 2.48 (95% CI 1.37–4.48; p = 0.003); a formal interaction test was significant [interaction OR 2.12 (95% CI 1.08–4.15; p = 0.029)]. Among patients without malignancy, no association was found (OR 1.18; p = 0.397). Conclusions: Classifying thrombocytopenic ICU patients by mechanism rather than count alone identified a higher-risk subgroup. Consumption-like thrombocytopenia was independently associated with ICU death; production-like was not. The association was substantially stronger in patients with malignancy. The classification requires only the standard blood count and adds no testing burden.

Background/Objectives: The modified Endothelial Activation and Stress Index (mEASIX), derived from routinely available laboratory parameters, has emerged as a potential biomarker reflecting systemic inflammatory and endothelial stress. However, its prognostic value in myelodysplastic syndromes (MDS) remains incompletely defined. This study evaluated the association between the mEASIX and overall survival and explored its time-dependent prognostic pattern. Methods: This retrospective study included 151 patients with MDS. The mEASIX score was calculated using C-reactive protein, lactate dehydrogenase, and platelet count and was log-transformed for regression analyses. Overall survival was estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards models were used to evaluate prognostic factors, including age, IPSS-R risk group, hypomethylating agent (HMA) exposure, and venetoclax exposure. The proportional hazards assumption was assessed, and landmark analyses were performed at the median follow-up time (29 months). Receiver operating characteristic analysis was used to determine the optimal mEASIX cut-off value for mortality prediction. Model comparison, internal validation, and sensitivity analyses were also performed. Results: During a median follow-up of 29 months, 85 deaths occurred. The mEASIX yielded an AUC of 0.767 for mortality prediction (95% CI 0.691–0.844; p < 0.001). Patients with a high mEASIX had inferior overall survival (log-rank p < 0.001). In multivariable Cox regression analysis including age, IPSS-R risk group, HMA exposure, and venetoclax exposure, log(mEASIX) remained independently associated with inferior overall survival (HR 1.325, 95% CI 1.166–1.506; p < 0.001). In landmark analyses, this association persisted during the early follow-up period (≤29 months; HR 1.347, 95% CI 1.172–1.548; p < 0.001) but was attenuated during the late period (>29 months; HR 1.287, 95% CI 0.930–1.782; p = 0.128). Conclusions: The baseline mEASIX was independently associated with overall survival in patients with MDS and appeared most prognostically relevant during early follow-up. These findings suggest that the mEASIX may complement established risk models, although further validation is needed before broader clinical use.

Survival rates of human immunodeficiency virus-positive subjects improved in recent years, especially due to innovations in current lymphoma treatments and the addition of combination antiretroviral therapy (cART). This study presents demographic and clinical characteristics, prognosis, and survival data of acquired immune deficiency syndrome (AIDS)-related lymphoma patients as a single-center experience. This retrospective study included 16 patients with AIDS-related lymphoma treated at our center between August 2010 and March 2022. Demographic data, clinical information, treatment details, and survival analysis of the patients were retrospectively reviewed from the relevant clinical archives. Fifteen out of 16 patients were males with a median age of 46.5 years (range, 24–71 years). The diagnoses were as follows: diffuse large B-cell lymphoma in 6, Burkitt lymphoma in 4, Hodgkin lymphoma in 3, plasmablastic lymphoma in 1, primary central nervous system lymphoma in 1, and chronic lymphocytic leukemia in 1 out of 16 patients. Fifteen patients presented with an advanced stage at diagnosis. Diagnosis of AIDS preceded the onset of lymphoma in 11 patients. The time from human immunodeficiency virus infection to diagnosis of lymphoma was 23.8 months (range, 1–185 months). All patients received cART during lymphoma treatment. The treatment response was evaluated in all patients who completed the initial treatment. Eleven patients (68.8%) are still alive with a complete response. Antitumour treatments administered in conjunction with cART have a favorable impact on survival and response rates in this aggressive group of patients.

Background/Objectives: Early death (ED) remains the primary barrier to long-term survival in acute promyelocytic leukemia (APL). Since current risk stratification models rely solely on static baseline parameters, they fail to capture the high biological volatility during the induction phase. We aimed to evaluate the prognostic value of the dynamic evolution of the endothelial activation and stress index (EASIX). Materials and Methods: This multicenter, retrospective study analyzed 131 newly diagnosed adult APL patients treated with the AIDA protocol. EASIX scores were calculated at admission (D0) and day 7 (D7). ROC, landmark, multivariable logistic and Cox regression analyses were performed to assess the impact of dynamic endothelial changes (ΔEASIX) on mortality and survival. Results: The ED rate was 25.2%. While baseline EASIX successfully predicted very early death ( 0.35) was an independent predictor of early mortality (OR: 12.41, p = 0.007), inferior EFS (HR: 5.70, p = 0.004), and poor OS (HR: 3.69, p = 0.023). Landmark analysis stratified by the kinetic trajectory of ∆EASIX confirmed that patients above the optimal cut-off had significantly inferior 3-year EFS (56.3% vs. 77.8%, p = 0.041) and OS (59.5% vs. 78.0%, p = 0.026). Conclusions: To our knowledge, this is the first study to establish EASIX as a dynamic prognostic marker in APL. Our findings indicate that the “kinetic trajectory” of endothelial stress is a more accurate predictor of survival than static baseline assessment alone. While dynamic EASIX monitoring offers a valuable tool for real-time risk reclassification, these results require validation through prospective studies.

A woman with primary immune thrombocytopenia (ITP) refractory to corticosteroids, intravenous immunoglobulin (IVIG), rituximab, and two thrombopoietin receptor agonists (TPO-RAs) received a new therapy.

Background: Infections are a leading cause of morbidity and mortality in multiple myeloma (MM), particularly during the induction phase. Identifying real-world infection patterns and predictors is crucial for guiding preventive strategies. Methods: This retrospective cohort study included 161 newly diagnosed MM patients who received standard induction therapy at a single tertiary center between 2016 and 2024. Clinical, laboratory, and infection-related parameters were analyzed over the first 12 months. Results: Infections occurred in 50.9% of patients, with the highest incidence within the first 3 months (27.3%, p = 0.004). Pneumonia was the most common type (34.1%), and gram-negative bacteria, particularly Escherichia coli , Klebsiella spp. , and Pseudomonas aeruginosa , were predominant. Antibiotic resistance to TMP-SMX and levofloxacin was observed in E. coli isolates. Multivariate analysis identified advanced ISS stage (OR: 3.83), diabetes mellitus (OR: 3.64), and chronic kidney disease (OR: 6.01) as independent predictors of infection ( p < 0.05). Lymphocyte counts were significantly lower in febrile episodes ( p = 0.040), highlighting a possible early immune marker. Hospitalization was more common in patients with advanced ISS and kidney disease. No significant differences were found between induction regimens. Conclusion: Infections pose a significant burden during the first year of MM treatment, particularly in high-risk patients during early induction. Readily available clinical parameters can aid in early risk stratification. These findings support a risk-adapted approach to prophylaxis, including the selective use of levofloxacin in patients with diabetes or kidney disease during the first 3 months of therapy.