Hematopoietic stem cell–derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide

Sumii, Yuichi; Kondo, Takumi; Ikegawa, Shuntaro; Fukumi, Takuya; Iwamoto, Miki; Nishimura, M.; Sugiura, Hiroyuki; Sando, Yasuhisa; Nakamura, Makoto; Meguri, Yusuke; Matsushita, T.; Tanimine, Naoki; Kimura, Maiko; Asada, Noboru; Ennishi, Daisuke; Maeda, Yoshinobu; Matsuoka, Ken‐ichi

doi:10.1172/jci.insight.162180

Cited by 3 publications

(1 citation statement)

References 68 publications

(94 reference statements)

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“…As mentioned before, the use of PTCy is increasingly applied to prevent cGVHD and a recent study in murine cGVHD suggests a critical role for Treg-B cell interactions in its effect. In this model PTCy, but not other prophylactic regimens inhibited initial alloreactive T cell responses, which led to increased Tregs and restored bone marrow B cell lymphogenesis ( 111 ).…”

Section: Communication Of Immune Cells In Cgvhd – the Role Of B Cellsmentioning

confidence: 95%

Complex interactions of cellular players in chronic Graft-versus-Host Disease

et al. 2023

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Chronic Graft-versus-Host Disease is a life-threatening inflammatory condition that affects many patients after allogeneic hematopoietic stem cell transplantation. Although we have made substantial progress in understanding disease pathogenesis and the role of specific immune cell subsets, treatment options are still limited. To date, we lack a global understanding of the interplay between the different cellular players involved, in the affected tissues and at different stages of disease development and progression. In this review we summarize our current knowledge on pathogenic and protective mechanisms elicited by the major involved immune subsets, being T cells, B cells, NK cells and antigen presenting cells, as well as the microbiome, with a special focus on intercellular communication of these cell types via extracellular vesicles as up-and-coming fields in chronic Graft-versus-Host Disease research. Lastly, we discuss the importance of understanding systemic and local aberrant cell communication during disease for defining better biomarkers and therapeutic targets, eventually enabling the design of personalized treatment schemes.

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Section: Communication Of Immune Cells In Cgvhd – the Role Of B Cellsmentioning

confidence: 95%

Complex interactions of cellular players in chronic Graft-versus-Host Disease

et al. 2023

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Combination of reduced post‐transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft‐versus‐host disease in human leukocyte antigen‐haploidentical peripheral blood stem‐cell transplantation

Terao,

Kondo,

Nakamura

et al. 2024

eJHaem

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We evaluated the clinical impacts of the concurrent modification of post‐transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)‐initiation timing in 61 patients with human leukocyte antigen‐haploidentical transplantation. Reduced‐dose PTCy (80 mg/kg) was associated with a higher incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) than standard‐dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early‐initiation Tac (day ‐1) increased moderate‐to‐severe chronic GVHD than standard‐initiation Tac (day 5) in the reduced‐dose PTCy group (p = 0.032), whereas Tac‐initiation timing did not impact chronic GVHD in the standard‐dose PTCy group. These data indicate that the combination of reduced‐dose PTCy and early‐initiation Tac can amplify chronic GVHD.

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Posttransplantation cyclophosphamide mediates effective reconstitution of memory B cells after allogeneic hematopoietic cell transplantation

Hayashi,

Nakashima,

Takeda

et al. 2024

European J of Haematology

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ObjectivesImpaired B‐cell reconstitution after allogeneic hematopoietic cell transplantation (allo‐HCT) contributes to the pathogenesis of chronic graft‐versus‐host disease (cGVHD). Therefore, methods to consistently achieve effective B cell lymphogenesis are required. We assessed the long‐term effects of posttransplantation cyclophosphamide (PTCy) use on immune reconstitution in clinical settings, an emerging strategy to suppress allogeneic immunological inflammation early after allo‐HCT and prevent subsequent GVHD.MethodsWe comprehensively analyzed peripheral immune cell subsets and measured serum immunoglobulin G (IgG) or cytokine levels in 39 patients who survived for >1 year after allo‐HCT.ResultsThe absolute counts of B1 and IgM memory B cells were significantly lower in patients with severe cGVHD than in those without. The absolute count and percentage (among total CD19+ B cells) of switched memory B cells and serum IgG levels were significantly higher in patients transplanted with PTCy than in those transplanted with conventional GVHD prophylaxis. Interestingly, increased percentages of switched memory B cells and serum IgG levels were observed only in patients transplanted with PTCy and not in those transplanted with umbilical cord blood.ConclusionsPTCy administration can mediate favorable memory B‐cell reconstitution long after allo‐HCT and may therefore suppress cGVHD.

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Hematopoietic stem cell–derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide

Cited by 3 publications

References 68 publications

Complex interactions of cellular players in chronic Graft-versus-Host Disease

Complex interactions of cellular players in chronic Graft-versus-Host Disease

Combination of reduced post‐transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft‐versus‐host disease in human leukocyte antigen‐haploidentical peripheral blood stem‐cell transplantation

Posttransplantation cyclophosphamide mediates effective reconstitution of memory B cells after allogeneic hematopoietic cell transplantation

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