Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up.
Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse.
Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787).
Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.

Objective: Accumulating evidence indicates that miRNAs can negatively influence the expression of their downstream genes, thereby affecting the development of human cancers. The pathogenesis of acute lymphoblastic leukemia (ALL) is complex and more biomarkers and functional molecules need to be found. We attempted to reveal the specific mechanisms and functions of miRNA-181b-5p in ALL and investigated the effects of the miRNA-181b-5p/SSX2IP axis on ALL.
Materials and Methods: Bioinformatics analyses were initially performed to screen out differentially expressed miRNAs in ALL and determine the research subject. qRT-PCR and western blotting were applied to evaluate the expression levels of target genes. Cell function experiments and mouse experiments were conducted to analyze the roles of the target genes in ALL.
Results: miRNA-181b-5p was highly and differentially expressed in ALL and may target SSX2IP. The upregulation of miRNA-181b-5p and downregulation of SSX2IP were observed in ALL cells. miRNA-181b- 5p could control multiple pathological processes of ALL, including cell proliferation, the cell cycle, and apoptosis, and miRNA-181b-5p could also facilitate tumor growth in vivo.
Conclusion: miRNA-181b-5p promoted the malignant progression of ALL by downregulating SSX2IP. The miRNA-181b-5p/SSX2IP axis may be a promising target for intervention against the malignant behaviors of ALL.

Objective: Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL.
Materials and Methods: We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016.
Results: Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and eventfree survival rates were significantly different between the transplant and non-transplant groups (p<0.01, and p=0.033, respectively).
Conclusion: The retrospective analysis of a large volume of real-life data on the Turkish experience regarding non-cutaneous PTCL patients showed consistent results compared to other unselected PTCL cohorts with some minor differences in terms of survival and transplantation outcomes. The long-term outcome of patients who receive autologous hematopoietic cell transplantation as part of upfront consolidation or salvage therapy is favorable compared to patients who are unable to receive high-dose therapy.

Objective: Clinical and pathological differential diagnosis of small B-cell lymphomas (SBCLs) is still controversial and may be difficult due to their overlapping morphology, phenotype, and differentiation to plasma cells. We aimed to examine the expression of the immune receptor translocation-associated protein 1 (IRTA1), myeloid cell nuclear differentiation antigen (MNDA), lymphoid enhancer-binding factor-1 (LEF1), and stathmin 1 (STMN1) markers in SBCL cases involving different sites that may have plasma cell differentiation.
Materials and Methods: We studied 154 tissue samples with lymphoma involvement from 116 patients and evaluated the staining distribution of the markers. Expressions were evaluated in 21 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 7 follicular lymphoma (FL), 14 nodal marginal zone lymphoma, 17 extranodal marginal zone lymphoma, 55 splenic marginal zone lymphoma, 22 marginal zone lymphoma-not otherwise specified, and 18 lymphoplasmacytic lymphoma/Waldenström macroglobulinemia cases by immunohistochemistry.
Results: The results confirmed that LEF1 was the most sensitive and specific marker for CLL/SLL and STMN1 was the most sensitive and specific marker for FL (p<0.001). MNDA and IRTA1 were useful markers to distinguish marginal zone lymphomas.
Conclusion: Our results suggest that LEF1 for CLL/SLL and STMN1 for FL are reliable markers. LEF1, MNDA, STMN1, and IRTA1 are helpful with other routinely used immunohistochemical markers in a diagnostic algorithm considering their limitations.

Objective: Long noncoding RNA small nucleolar RNA host gene 1 (lnc-SNHG1) is involved in leukemogenesis via mediating multiple pathways. The current study aimed to further explore its clinical roles in disease risk, clinical features, and prognosis in patients with acute myeloid leukemia (AML).
Materials and Methods: A total of 161 adult AML patients, 50 patients as a disease control (DC) group, and 50 healthy individuals as a healthy control (HC) group were enrolled and bone marrow mononuclear cells were collected. Subsequently, reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) was performed to measure lnc-SNHG1 expression.
Results: Lnc-SNHG1 expression was higher in AML patients than in the DC and HC groups (both p<0.001), with good value in distinguishing AML patients from DC and HC individuals (area under the curve of 0.726 and 0.884, respectively). Moreover, lnc-SNHG1 expression was positively associated with white blood cell (WBC) count (p=0.008) but was not correlated with other clinical features such as cytogenetics, molecular genetics, and risk stratification (all p>0.05). Lnc-SNHG1 expression was also associated with a lower complete remission (CR) rate (p=0.001). Patients with lnc-SNHG1 expression in the fourth quantile had the worst CR rates compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Furthermore, lnc-SNHG1 expression was correlated with unsatisfactory event-free survival (p<0.001) and overall survival (p=0.002), which were worst in patients with lnc-SNHG1 expression in the fourth quantile compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05).
Conclusion: Lnc-SNHG1 overexpression is associated with elevated WBC count, poor induction treatment response, and poor survival profile in cases of AML and it may serve as a potential indicator for AML.

Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR: : ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR: : ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR: : ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML.
Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR: : ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined.
Results: Of the 40 patients, BCR: : ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR: : ABL1 IS of >10%, whereas it was 6.9% in those with BCR: : ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR: : ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR: : ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others.
Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR: : ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR: : ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.

Objective: Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented.
Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study.
Results: Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/ partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up.
Conclusion: Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.