CD19+CD21low B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome

In past years, a diagnosis of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant (HCT) conferred nearly universal mortality secondary to lack of consensus for diagnostic criteria, poorly understood disease pathogenesis, and very few studies of therapeutic or supportive care interventions. Recently, however, progress has been made in these areas: revised consensus diagnostic guidelines are now available, supportive care has improved, there is greater understanding of potential mechanisms of disease, and prospective trials are being conducted. This article describes these advances and provides suggestions to optimize therapy for patients with BOS after HCT.

Section: 305253mentioning

confidence: 99%

How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Williams

2017

“…[8][9][10][11] However, the direct evidence in vivo of an increased B-cell replication in patients with cGVHD is still lacking, and it remains to be clarified whether acute GVHD (aGVHD) may have a persistent impact on B-cell neogenesis. It is now possible to measure the bone marrow (BM) B-cell output using real-time polymerase chain reaction (PCR) for quantification of k-deleting recombination excision circles (KRECs), which are generated in the BM during B-cell development.…”

Section: Introductionmentioning

confidence: 99%

Impact of acute and chronic graft-versus-host disease on human B-cell generation and replication

Glauzy

Soret

Fournier

et al. 2014

Key Points• B-cell neogenesis is decreased independently by both aGVHD and cGVHD.• B cells during GVHD undergo a higher number of cell divisions related, in the chronic form, to a higher BAFF/CD19 ratio.Using B-cell rearrangement excision circle measurements, we analyzed B-cell reconstitution in a cohort of 243 patients who underwent allogeneic stem cell transplantation. Acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) transiently increased B-cell replication but decreased overall B-cell neogenesis with a clear difference in terms of kinetics. Moreover, the impact of aGVHD in the absence of cGVHD was transient, recovering at month 6 similar values as in patients who did not suffer from GVHD. Conversely, impact of cGVHD at month 12 in multivariate analysis was independent of the previous aGVHD effect on B-cell output. Finally, we showed in patients affected with cGVHD a higher B-cell division rate that correlates with an elevated BAFF/CD19 1 B-cell ratio, supporting a B-cell hyperactivation state in vivo.( Blood. 2014;124(15):2459-2462

“…46,47 Thus, the continued study of relevant pathologic and protective B-cell subsets in chronic GVHD will likely lead to the development of additional targeted therapeutic agent for affected patients.…”

Section: Cd21mentioning

confidence: 99%

Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial

Cutler¹,

Kim

Bindra³

et al. 2013

108

• Rituximab prevents steroidrequiring chronic graft-vs-host disease when given after peripheral blood stem cell transplantation.• Overall survival is improved with rituximab after allogeneic peripheral blood stem cell transplantation when compared with a control cohort.B cells are implicated in the pathophysiology of chronic graft-vs-host disease (GVHD), and phase 2 trials suggest that B cell depletion can treat established chronic GVHD. We hypothesized that posttransplantation B cell depletion could prevent the occurrence of chronic GVHD. We performed a 65-patient phase 2 trial of rituximab (375 mg/m 2 IV), administered at 3, 6, 9, and 12 months after transplantation. Rituximab administration was safe without severe infusional adverse events. The cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48% and 31%, respectively, both lower than the corresponding rates in a concurrent control cohort (60%, P 5 .1, and 48.5%, P 5 .015). There was no difference in relapse incidence, but treatment-related mortality at 4 years from transplantation was significantly lower in treated subjects when compared with controls (5% vs 19%, P 5 .02), and overall survival was superior at 4 years (71% vs 56%, P 5 .05). At 2 years from transplantation, the B-cell activating factor/B-cell ratio was significantly higher in subjects who developed chronic GVHD in comparison with those without chronic GVHD (P 5 .039). Rituximab can prevent systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell transplantation and should be tested in a prospective randomized trial. This trial was registered at www.clinicaltrials.gov as NCT00379587. (Blood. 2013;122(8):1510-1517