How does ocular graft-versus-host disease fit under the dry eye umbrella? A review.

Graft-versus-host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments.

Infectious and Noninfectious Corneal Ulcers in Ocular Graft-Versus-Host Disease: Epidemiology, Clinical Characteristics, and Outcomes.

PURPOSE: To evaluate the incidence, clinical characteristics, microbiological profile, and therapeutic outcomes of corneal ulcers in individuals with chronic ocular graft-vs-host disease (coGVHD). DESIGN: Retrospective clinical cohort study. METHODS: Review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021. Baseline demographics, clinical characteristics, microbiological profile, risk factors for corneal ulceration, and treatment outcomes were collected. Etiology was deemed infectious in individuals with a positive culture or appropriate clinical scenario (presence of stromal infiltrate or hypopyon); otherwise, ulcers were presumed to be noninfectious. Treatment success was defined as reepithelialization with infiltrate resolution, and treatment failure as progression to corneal perforation or keratoplasty. Kaplan-Meier survival analysis estimated the incidence of ulceration. Cox regression analyses examined demographic and risk factors. Infectious and noninfectious ulcer groups were compared using 2-way independent t tests, 1-way analysis of variances, and χ2 tests, as appropriate. RESULTS: 173 individuals were included (53.7±14.4 years old; 59.0% male). Thirty-three individuals developed an ulcer 74.5±54.3 months after HSCT, with estimated 5- and 10-year incidences of 14% and 30%, respectively. Twenty-two (66.6%) ulcers were deemed infectious (15 microbiologically confirmed, 7 clinically) and 11 (33.3%) were deemed noninfectious. Risk factors for corneal ulceration included Black race (hazards ratio [HR] 2.89, 95% CI 1.30-6.42, P < .01), previous ocular surgery (HR 9.16, 95% CI 3.86-21.72, P < .01), eyelid margin abnormalities (HR 3.44, 95% CI 1.69-6.99, P < .01), and topical steroid use (HR 2.74, 95% CI 1.33-5.62, P < .01). Conversely, contact lens use reduced the risk of corneal ulceration (HR 0.29, 95% CI 0.13-0.66, P < .01). Infectious ulcers had a significantly higher frequency of treatment failure than noninfectious ulcers (57.1% vs 20.0%, P = .04). CONCLUSION: Corneal ulceration is a potential complication of coGVHD, with several clinical features identified as risk factors. Infectious ulcers had worse outcomes than noninfectious ulcers.

eHealth mindfulness-based music therapy for patients undergoing allogeneic hematopoietic stem cell transplantation: A pilot randomized controlled trial protocol.

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) is the preferred therapy for patients with high-risk or relapsed hematologic malignancies, but may be complicated by psychological distress (e.g., depression, anxiety) and symptom burden (e.g., fatigue, pain). Mindfulness-based music therapy (MBMT), a relatively novel integrative medicine intervention that draws from mindfulness and music therapy principles, has shown promise in improving psychosocial outcomes and symptom burden in cancer patients. We outline an eHealth-based MBMT (eMBMT) intervention protocol examining: (1) feasibility, acceptability, and intended effects of eMBMT in improving HRQOL, symptom burden, and clinical markers of disease activity (e.g., infections), and (2) the extent to which eMBMT music therapy component-associated improvements in HRQOL, symptom burden, and disease activity are mediated by improvements in psychosocial and physiological (e.g., systemic inflammation, immune recovery) adaptation. METHODS: Participants (n = 60) with a hematologic malignancy undergoing allo-SCT will be randomized to receive eMBMT or an eHealth-based mindfulness meditation (eMM) intervention. eMBMT includes eight 60-min sessions facilitated by a music therapist focusing on mindfulness and music therapy. eMM includes eight 60-min self-led MM practices. RESULTS: Feasibility, acceptability, HRQOL, symptom burden, disease activity, and mediation effects of psychosocial and physiological adaptation will be assessed at baseline, pre-infusion, and post-engraftment with blood collection at baseline and post-engraftment. CONCLUSION: The current pilot RCT is the first eMBMT intervention to address the HRQOL and symptom burden of patients who are undergoing allo-SCT. Results will inform a fully powered RCT to establish preliminary efficacy of eMBMT on improvements in HRQOL, symptom burden, and disease activity.

Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy.

ABSTRACT: Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation.

Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis.

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2-9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4-52.8) and the probability of overall survival was 63.8% (95% CI 54.4-72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5-15.4) and 47.3% (95% CI 38.2-56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS.

Venetoclax monotherapy as front-line therapy for blastic plasmacytoid dendritic cell neoplasm.

Venetoclax is an approved treatment for relapsed/refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). We report a unique case of venetoclax monotherapy used for front-line induction and as a bridge to allogeneic hematopoietic stem cell transplantation (HCT). Venetoclax therapy resulted in rapid complete resolution of skin lesions, however, treatment interruption due to neutropenia led to brisk cancer recurrence. Fortunately, the patient responded to re-challenge and was able to undergo HCT. Venetoclax is active in the first-line treatment setting for BPDCN, however its effect on blood counts and durability of response should be further studied.