Graft-versus-host disease (GVHD), a severe complication of allogeneic stem cell transplantation, arises when donor immune cells attack host tissues, triggering a cytokine storm. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their immunomodulatory, tissue repair, and regenerative properties. Recent studies highlight the fate of MSCs post-administration, revealing their clearance by host macrophages through efferocytosis following apoptosis. This interaction not only modulates the recipient’s immune system but also underscores the role of MSC-derived factors in immune regulation. In addition to mitigating GVHD, MSCs promote engraftment by secreting hematopoietic cytokines and suppressing host immune responses. Despite these advantages, the clinical efficacy of MSCs remains inconsistent, posing a challenge to their widespread application. Notably, MSCs derived from sources such as Wharton’s jelly and adipose tissue exhibit superior immunomodulatory capabilities due to their unique gene signatures that enhance immune regulation. This chapter explores the evolving role of MSCs in GVHD prevention and treatment, emphasizing their mechanistic insights, therapeutic limitations, and the potential of tissue-specific MSCs. It also discusses future strategies for optimizing MSC-based therapies to improve clinical outcomes in stem cell transplantation.

PURPOSE: The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data. MATERIALS AND METHODS: This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India. RESULTS: Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)–based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056). CONCLUSION: This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.