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Immune reconstitution therapy (IRT) is a relatively new and highly effective treatment option for multiple sclerosis (MS). Uncertainty regarding the development of autoimmune disorders (ADs) after some therapies remains. The aim of this study was to assess new AD development after IRT in MS patients and to describe the nature of those ADs and the time to onset. A total of 179 patients with relapsing multiple sclerosis (37 after autologous haematopoietic stem cell transplantation (AHSCT), 19 after alemtuzumab (ALE) and 123 after cladribine (CLA) treatment) over a ten year period were included in the study. ADs were observed in 6 patients (16.2%) after AHSCT, 8 patients (42.1%) after ALE and 2 patients (1.6%) after CLA treatment. ADs developed earlier after ALE infusions, but later after AHSCT except for cytopenias. Neurologists should be attentive to the development of secondary ADs after ALE and AHSCT in MS patients. [ABSTRACT FROM AUTHOR]

Cladribine indirectly downregulates methylation of DNA, RNA, and histones by blocking the transfer of methyl groups from S -adenosyl-methionine. The cladribine and rituximab combination showed a synergetic effect in treating B-cell lymphomas. Bortezomib (Velcade) is a Food and Drug Administration (FDA)-approved proteasome inhibitor for treating mantle cell lymphoma (MCL). In this single-arm, phase I study, the safety, dose-limiting toxicity, and clinical activity of bortezomib, cladribine, and rituximab (VCR) combination treatment were evaluated in elderly MCL patients. Potential DNA methylation biomarkers for VCR treatment were also proposed. A standard 3 + 3 dose-escalation scheme was designed to determine the maximum tolerated dose of cladribine. The therapy consisted of six 28-day cycles. Most patients tolerated this regimen well. The overall response (OR) rate was 84.6%, and the complete remission (CR) rate was 84.6%. In the newly diagnosed subject cohort, the OR and CR were 100%, the 2-year overall survival rate was 84.6%, and the progression-free survival rate was 76.9%. The median age was 64 (54–81). The median time to first response was 3 (2.1–7.4) months. The median follow-up time was 43 (9–60) months. Low-grade hematological toxicity and mild fatigue were observed. No severe systemic toxicity was observed. Five hypermethylated regions located at gene promoters were identified as potential biomarkers for an effective treatment response. In conclusion, the VCR combination is a well-tolerated, low-toxicity, and highly effective regimen for the elderly with untreated MCL. Clinical Trial Registration: ClinicalTrials.gov , identifier NCT01439750. [ABSTRACT FROM AUTHOR]

Introduction: Cladribine was approved for Multiple Sclerosis (MS) in our country in 2018. A previous study by our group showed that its use among high efficacy therapies options has been increasing along the years. Objective: to analyze the cladribine use trend across time since its approval. Method: A retrospective cohort study was performed. People with MS (pwMS) treated with cladribine were included. Two periods were defined: P1 = 2018 – 2020 and P2 = 2021 – 2023. A comparative analysis was carry out between P1 and P2 to assess the trend of use, clinical/demographic characteristics, and effectiveness. Results: One hundred ninety- seven people with MS (pwMS) were included, mean EDSS: 2.2 ± 3.08, 72.6% female, mean age: 35.2 ± 9 years, mean disease duration: 6.6 ± 5.6 years, mean time lapse under cladribine: 26.1 ± 12.4 months. Regarding patient profile, we found significant differences between P1 and P2 in the MS evolution (p = 0.001) and EDSS (p = 0.018) prior to initiation of cladribine. In the individualized analysis by year, we found a decrease in relapse number in the year prior to starting cladribine (p = 0.02). A higher proportion of No Evidence of Disease Activity (NEDA) was found in patients treated at P2 compared to those treated at P1 (p < 0.001). Conclusion: An earlier use of cladribine achieved a significant increase in reaching NEDA. This learning curve in the use of cladribine allows a better identification of the candidate patient and influences the treatment effectiveness. [ABSTRACT FROM AUTHOR]

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Simple Summary: Cladribine is a chemotherapy used in combination with other chemotherapy drugs in adult patients with acute myeloid leukemia (AML) who relapse or are nonresponsive to treatment. It appeared to work well and is now used for newly diagnosed adult patients. While it is commonly used in adults, it has not been used routinely in children. We looked at medical records of pediatric and adolescent patients treated for AML at MD Anderson to analyze its safety and how well it works against AML. It was found to be safe and well tolerated in these patients and also showed improved survival outcomes. About half of the patients responded to cladribine either by itself or with other chemotherapy agents. This review also highlighted its safety in combination with other agents. We found these combinations to be well tolerated and could provide additional options for pediatric providers who are treating relapsed AML. Background: Cladribine-based combination chemotherapy has demonstrated promising efficacy in patients with relapsed/refractory adult acute myeloid leukemia (AML), prompting its increased utilization in the frontline; in pediatrics, it has been typically reserved for relapsed or refractory cases. While fludarabine has been used more commonly as a purine analog in intensive regimens, cladribine may be an important alternative. Methods: We performed a retrospective study at MD Anderson Cancer Center from January 2015 to July 2023, which included patients aged 1–21 years with refractory or relapsed AML who received cladribine outside of a transplant conditioning. Results: A total of 30 patients were included, with a median age of 20 years (range, 2–21), and 55% being male. Similar to adults, cladribine exhibited good tolerability in pediatric and adolescent patients, with the most common adverse events being febrile neutropenia and myelosuppression. The most common grade 3 or 4 adverse events included febrile neutropenia (55%) and sepsis (26%), and there were no treatment discontinuations due to adverse events. Among patients with a median number of 2 (0–7) prior treatments, the overall response rate (CR/CRi) was 45%, and median event-free and overall survival were 6 and 12 months, respectively. Disease progression resulted in 4 deaths within 30 days of treatment. Conclusions: Cladribine was tolerated in pediatrics. No new safety signals were seen with cladribine regimens in this cohort. Response assessment is limited due to the heavily pretreated cohort. Further prospective studies are warranted on the safety and efficacy of cladribine and establish its role in pediatric, adolescent, and early young adult patients with AML. [ABSTRACT FROM AUTHOR]