Mehmet Bakırtaş

Background/Objectives: Lymphocyte activation gene-3 (LAG-3) is an inhibitory immune checkpoint molecule that may contribute to immune escape in diffuse large B-cell lymphoma (DLBCL). This study aimed to characterize LAG-3 expression in neoplastic cells and tumor-infiltrating lymphocytes (TILs) and to investigate its associations with clinicopathological features and clinical outcome. Methods: This retrospective, single-center study included 210 patients with DLBCL diagnosed between 2007 and 2019. LAG-3 expression was evaluated immunohistochemically in whole-tissue sections. Tumor-cell expression was assessed according to the percentage and intensity of positive cells, while LAG-3-positive TILs were quantified as the mean number of positive lymphocytes per high-power field (HPF). Associations with clinicopathological parameters, treatment response, overall survival, and progression-free survival (PFS) were analyzed. Results: LAG-3 staining of varying intensity was observed in neoplastic cells in 177 cases (84.3%), and 82 cases (39.0%) were classified as LAG-3 positive using a 10% tumor-cell cut-off. The median number of LAG-3-positive TILs was 5/HPF. Male patients showed a higher percentage of LAG-3-positive tumor cells than female patients (p = 0.039). Moderate-to-strong tumor-cell staining was significantly more frequent in cases with >5 LAG-3-positive TILs/HPF than in those with ≤5 TILs/HPF (p = 0.018). LAG-3 expression parameters were not significantly associated with treatment response or overall survival. Univariate Cox regression analysis also showed no significant association between overall survival and LAG-3-positive TIL count, tumor-cell LAG-3 percentage, or staining intensity. Exploratory PFS analysis in 66 evaluable patients also showed no significant association with LAG-3 expression parameters. Conclusions: LAG-3 expression in DLBCL occurs in both neoplastic cells and TILs. The association between increased LAG-3-positive TILs and stronger tumor-cell expression supports further investigation of LAG-3 across both cellular compartments. No significant association with overall survival was observed in this cohort; however, the limited number of survival events precludes definitive conclusions regarding its prognostic significance. Further studies using standardized assessment methods and larger, clinically well-characterized cohorts are warranted.

Introduction & Objective: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with limited treatment options for steroid-resistant cases. Ruxolitinib, a JAK1/2 inhibitor, has shown promise in treating steroid-resistant acute (aGVHD), chronic (cGVHD), and overlap GVHD (oGVHD), but real-world data remain limited. This study evaluated the real-world efficacy and safety of ruxolitinib in allo-HSCT patients with steroid-resistant GVHD. Materials & Methods: This retrospective, multicenter study included adult patients treated with ruxolitinib for Grade II or higher aGVHD or moderate-to-severe cGVHD at nine centers in Turkey (2017–2024). Clinical characteristics, treatment responses, and adverse events were recorded. Primary outcomes were overall response rate (ORR) and overall survival (OS). Results: Among 80 patients (mean age: 39.3 ± 13.3 years; 60 males), 39 had aGVHD, 68 cGVHD, and 15 oGVHD. The ORR was 72 of 80 patients (90.0%) (complete response: 37 of 80 [46.3%], partial response: 35 of 80 [43.8%]). The 1-year and 2-year OS rates were 91.3% and 82.5%. Severe cGVHD (p < 0.001) and lack of response to ruxolitinib (p = 0.018) were associated with reduced OS. Adverse events included infections in 40 of 80 patients (50.0%), cytopenias in 23 of 80 (28.7%), and cytomegalovirus reactivation in 20 of 80 (25.0%). Conclusion: In this retrospective multicenter cohort, ruxolitinib was associated with high response rates in steroid-refractory GVHD, while disease severity remained a key determinant of survival, and findings should be interpreted as exploratory.

Background: Refractory/relapsed classical Hodgkin’s lymphoma (R/RcHL) poses significant treatment challenges, with limited success rates in achieving long-term remission. Brentuximab Vedotin (BV), an anti-CD30 monoclonal antibody-drug conjugate, has emerged as a promising therapeutic option. This study aims to evaluate the efficacy and safety of BV monotherapy in R/RcHL patients, particularly regarding survival outcomes and adverse events. Methods: This multi-center retrospective study included 82 R/RcHL patients aged 18 and over, treated with BV monotherapy across 14 institutions in Turkey from June 2012 to June 2020. Data on demographics, clinical characteristics, treatment response, adverse events, and overall survival (OS) rates were collected and analyzed. Primary outcomes were overall treatment response rate and OS, while the secondary outcome focused on the adverse event profile of BV treatment. Results: Among the patients (56.1% female, median age 33.5 years), the overall treatment response rate was 76.8%. The median OS was 13.6 months, with patients undergoing hematopoietic stem cell transplantation (HSCT) post-BV treatment exhibiting significantly longer survival (19.6 months) compared to those who did not receive HSCT (7.8 months, p < 0.001). Grade 3 to 5 adverse events were observed in 32.9% of patients, with neutropenia being the most common. Conclusion: BV monotherapy demonstrates substantial efficacy in treating R/RcHL, offering a favorable balance between treatment response and manageable adverse events. Particularly effective as a bridging therapy to HSCT, BV significantly extends survival in R/RcHL patients. These findings underscore the need for prospective studies to further delineate patient subsets most likely to benefit from BV monotherapy.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and p<0.00, respectively). Our study indicated that a high dose (200 mg/m2 ) melphalan could safely be used in the physically fit patients at the ages of 60-69, and a reduced amount (140 mg/m2 ) would be the appropriate dose for the patients over 70. The quantity of infused CD34+ stem cells affect elderly MM patients; mobilization dynamics are also important factors for elderly myeloma. Age itself should not consider a barrier to ASCT, and a comprehensive geriatric evaluation should perform on elderly patients

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and p<0.00, respectively). Our study indicated that a high dose (200 mg/m2 ) melphalan could safely be used in the physically fit patients at the ages of 60-69, and a reduced amount (140 mg/m2 ) would be the appropriate dose for the patients over 70. The quantity of infused CD34+ stem cells affect elderly MM patients; mobilization dynamics are also important factors for elderly myeloma. Age itself should not consider a barrier to ASCT, and a comprehensive geriatric evaluation should perform on elderly patients

GDP (gemcitabine, dexamethasone and cisplatin) is a well-established salvage regimen for relapsed and refractory lymphomas. In this study, we aimed to share our experience with the patients who received GDP/R-GDP (rituximab-gemcitabine, dexamethasone and cisplatin) for stem cell mobilization. Data of 69 relapsed and refractory Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) patients who received GDP/R-GDP as salvage chemotherapy in our center between July 2014 and January 2020 were retrospectively evaluated. After the evaluation of response, 52 patients had a chemosensitive disease and underwent mobilization with GDP/R-GDP plus G-CSF (granulocyte colony-stimulating factor). Collected CD34+ stem cells and related parameters were compared in terms of diagnosis of HL and NHL, early and late stage, patients who did not receive RT and those who received RT, and patients aged under 60 and over 60. On the 15th day on average (range 11?20), median 8.7 × 106 /kg (4.1 - 41.5) CD34+ stem cells were collected in 51 (98%) of our 52 chemosensitive patients and 1 (2%) patients failed to mobilize. We observed acceptable hematological and non-hematological toxicity. The targeted amount of 2 × 106 /kg CD34+ stem cells was attained by 98% (n: 51) patients, and all of them underwent autologous stem cell transplantation. Moreover, low toxicity profiles provide outpatient utilization option clinics with close follow-up and adequate supportive care. We suggest that GDP/R-GDP plus G-CSF can be used as an effective chemotherapy regimen for mobilizing CD34+ stem cells from peripheral blood in relapsed and refractory lymphoma patients due to low toxicity, effective tumor reduction, and successful stem cell mobilization. It can also be assumed that the GDP mobilization regimen may be more effective, especially in patients with early-stage disease and in HL patients.

Introduction / Aim: Melphalan 200 mg/m2 (MEL 200) is known as the standard conditioning regimen for Multiple Myeloma (MM) patients in autologous stem cell transplantation(ASCT). Most of the studies showing the superiority of MEL 200 versus melphalan 140 mg/m2 (MEL 140) were performed in the era of conventional chemotherapies. However, today, several novel agents such as proteasome inhibitors, immunomodulatory agents have been introduced in MM treatment algorithms. There is limited data on the impact of this dose reduction on progression-free survival (PFS) or overall survival (OS). The present study compares MEL 140 and MEL 200 conditioning for ASCT in patients treated with combination therapy of bortezomib‑containing induction. Material and Method: Results of 84 MM patients who underwent ASCT at our center between 2010 and 2018 were analyzed retrospectively. Findings / Results: In the MEL 140 group, PFS was 9 months (%95 CI 2.2-15.8) and OS was 30 months ( %95CI 9.5-50.4), while PFS was 13 months ( %95CI 10.5-15.5) and OS was 34 months( %95CI 6.9-61) in the MEL 200 group. There was no statistically significant difference in PFS and OS between the two groups (p:0.6, p:0.7). Conclusion: Consequently, MEL 140 and MEL 200 were found similar in terms of engraftment duration, transplant-related mortality rate, and survival rates. The idea that similar outcomes in both MEL 140 and MEL 200 group in patients who received combined induction treatment with novel agent suggested that MEL 140 may be used more commonly than the standard approach of MEL 200. ÖZET Giriş: Multipl Myeloma (MM) tedavisinde 200 mg/m2 melfalan (MEL 200) otolog kök hücre nakli (OKHN) için standart hazırlama rejimi olarak kabul edilmiştir. MEL 200’ün 140 mg/m2 melfalan’a (MEL 140) üstünlüğünü gösteren çalışmaların çoğu konvansiyonel kemoterapiler döneminde yapılmıştır. Ancak günümüzde MM tedavisine immünmodulatuvar, proteozome inhibitörü gibi birçok yeni ajan katılmıştır. Bu çalışmada indüksiyon tedavisinde bortezomib içeren kombinasyon tedavisi almış hastaların otolog kök hücre nakli ile konsalidasyonunda MEL 140 ve MEL 200’un karşılaştırılması hedeflendi. Materyal Metot: 2010-2018 yılları arasında merkezimizde OKHN olmuş 84 MM hastasının sonuçları geriye dönük olarak analiz edildi. Bulgular: MEL 140 grubunda progresyonsuz sağkalım (PFS) 9 ay (%95 CI 2.2-15.8), genel sağkalım (OS) 30 ay (%95CI 9.5-50.4) saptanırken MEL 200 grubunda PFS 13 ay ( %95CI 10.5-15.5) , OS 34 ay ( %95CI 6.9-61) saptandı. Her 2 grup arasında PFS ve OS açısından istatistiksel olarak anlamlı bir fark saptanmadı (sırasıyla p:0.6; p:0.7). Sonuç: Sonuç olarak, engraftman süreleri, transplant ilişkili mortalite oranı ve sağkalım oranları açısından MEL 140 ve MEL 200 benzer bulundu. İndüksiyon tedavisinde yeni ajanlar ile kombine tedaviler almış olan hastalarda MEL 140 ve MEL 200 arasında OS ve PFS farkı olmaması, standart yaklaşım olan MEL 200 yerine MEL 140’ın daha yaygın kullanabileceği fikrini doğurmuştur.