Purpose: To analyze the long-term outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS) in patients with angioimmunoblastic T-cell lymphoma (AITL) treated with allogeneic stem-cell transplantation (alloSCT). Patients and Methods: Forty-five patients with AITL who had undergone an alloSCT between January 1998 and December 2005 and were registered in the European Group for Blood and Marrow Transplantation database were analyzed. Median age was 48 years (range, 23 to 68 years), 34 patients had received ≥ two lines of chemotherapy before alloSCT, and 11 patients had experienced treatment failure with a prior autologous stem-cell transplantation. Twenty-five patients underwent a myeloablative alloSCT, and 20 underwent a reduced-intensity alloSCT. Donors were HLA-identical siblings in 26 patients. Twenty-seven patients were allografted in chemotherapy-sensitive disease, and 18 were allografted in refractory disease. Results: The cumulative incidence of NRM was 18%, 22%, and 25% at 3, 6, and 12 months, respectively. Patients with poor performance status had a significantly higher NRM (P = .01). RR was estimated as 16% and 20% at 2 and 3 years, respectively, and was lower in patients developing chronic graft-versus-host disease (cGVHD). PFS and OS rates were 62% and 53% and 66% and 64% at 1 and 3 years, respectively, and were significantly better in chemotherapy-sensitive patients. Conclusion: AlloSCT represents a valid therapeutic option for patients with AITL. Both the lower RR after transplantation as well as the decreased RR in patients developing cGVHD after the alloSCT suggests the existence of a clinically relevant graft-versus-lymphoma effect.

Homoeostasis of bone marrow microenvironment depends on a precise balance between cell proliferation and death, which is supported by the cellular-extracellular matrix crosstalk. Multipotent mesenchymal stromal cells (MSC) are the key elements to provide the specialized bone marrow microenvironment by supporting, maintaining, and regulating the functions and fate of haematopoietic stem cells. Despite the great potential of MSC for cell therapy in several diseases due to their regenerative, immunomodulatory, and anti-inflammatory properties, they can also contribute to modulate tumor microenvironment. The extracellular vesicles that comprise exosomes and microvesicles are important mediators of intercellular communication due to their ability to change phenotype and physiology of different cell types. These vesicles may interact not only with neighbouring cells but also with cells from distant tissues to either maintain tissue homoeostasis or participate in disease pathogenesis. This review focuses on the current knowledge about the physiological role of MSC-extracellular vesicles, as well as their deregulation in haematological malignancies and their potential applications as biomarkers for diagnosis, progression, and treatment monitoring of such diseases.

In the context of an allogeneic hematopoietic cell transplantation (HCT), the interplay between host and donor immune cells is considered to be the primary mechanism responsible for graft-versus-leukemia (GVL) reactivity and also able to mediate graft-versus-host disease (GVHD) (Schmid et al. 2021). The tissue specificity of the immune response determines the balance between GVL and GVHD, as well as tropism of GVHD. The main population for success and failure of HCT and DLIs originates from αβT cells. Other subsets are also key modulators of efficacy. For example, NK cells most likely provide acute control of leukemia and of infections like CMV. However, NK cells become rapidly educated over time (Orr and Lanier 2010) and lose their antileukemia activity. Thus, donor transfer of NK cells is obsolete and needs additional, for example, genetic modification to engineer long-term efficacy (Laskowski et al. 2022; Liu et al. 2020). Other subsets, like γδT cells, appear to have a more prolonged antileukemia effect (Handgretinger and Schilbach 2018; Sebestyen et al. 2020) and are also helpful in controlling CMV reactivation (Scheper et al. 2013; de Witte et al. 2018). However, also, donor γδT cells can lose activity over time, and sustainable activity requires, outside the context of an HCT, most likely further modifications (Sebestyen et al. 2020; Li et al. 2023). NKT cells, like regulatory T cells, have been mainly reported to influence GVHD. While an increase in NKT cells in the graft associates with a reduced GVHD incidence (Malard et al. 2016), depletion of regulatory T cells in donor lymphocyte infusions (DLI) improves GVL effects, although it augments the risk of GVHD (Maury et al. 2010). Thus, lymphocyte infusions as part of the graft at the time of transplantation, or delayed as DLI, have multiple effector cells that need to be considered in terms of different alloreactive effects (for review see also (Schmid et al. 2021)).