Chronic graft-versus-host disease. Part II: Disease activity grading and therapeutic management.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 Federal Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of cGVHD. Part II discusses disease grading and therapeutic management.

Chronic graft-versus-host disease. Part I: Epidemiology, pathogenesis, and clinical manifestations.

Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.

Prognostic implications of normal or minimal urinary findings on long-term renal impairment in adults with Henoch-Schönlein purpura.

BACKGROUND: Renal involvement in adult Henoch-Schönlein purpura is a major cause of morbidity and can lead to significant long-term renal impairment. The prognostic significance of normal or minimal urinary abnormalities at diagnosis is unknown. OBJECTIVE: To assess the risk of long-term renal impairment in patients with Henoch-Schönlein purpura who present with normal or minimal urinary abnormalities. METHODS: Retrospective cohort study of adult Henoch-Schönlein purpura patients presenting with normal urinalysis results, microscopic hematuria, or low-grade proteinuria. Patients were followed for development of long-term renal impairment, with adjusting for comorbidities. RESULTS: Forty-seven patients were included, with median follow-up 73.9 months (interquartile range 35 to 98 months). Thirty-nine patients (83.0%) had abnormal urinalysis results, of whom 15 (38.5%) progressed to long-term renal impairment. In contrast, 8 patients (17%) had normal urinalysis results, of whom only 1 (12.5%) developed long-term renal impairment (adjusted hazard ratio 10.58; 95% confidence interval 1.18-94.73). Renal events occurred at a median 36.1 months (interquartile range 17.1 to 61 months) from diagnosis, earlier in patients with comorbidities compared with those with none, and in a constant event rate over time. LIMITATIONS: Small sample size. CONCLUSIONS: Microscopic hematuria and low-grade proteinuria at Henoch-Schönlein purpura diagnosis is a poor prognostic sign for the development of long-term renal impairment. This population should be targeted for prolonged surveillance.

Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis.

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P = .045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P= .044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis.

A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.

BACKGROUND: Herpes zoster (HZ) incidence is linked to immunosuppression. Patients with psoriasis or psoriatic arthritis (PsA) on systemic therapy might be at an increased risk for HZ. OBJECTIVE: To assess HZ risk in patients with psoriasis and PsA by systemic treatment and provide recommendations regarding HZ vaccination. METHODS: A systematic literature search was performed for HZ in patients with psoriasis and PsA. HZ vaccination guidelines were reviewed, and the medical board of the National Psoriasis Foundation made consensus recommendations in psoriasis and PsA patients using graded evidence. RESULTS: In total, 41 studies met inclusion criteria. Systemic corticosteroids (strong, 1), tofacitinib (strong, 1), and combination therapy with biologic and conventional synthetic disease-modifying antirheumatic drugs (weak, 2a) carry increased HZ risk while monotherapy does not. There is insufficient evidence to determine risk with interleukin 12/23, 17, and 23 inhibitors or apremilast (weak, 2a). Recombinant zoster vaccine is recommended for all psoriasis and PsA patients >50 years old and patients <50 years old on tofacitinib, systemic steroids, or combination systemic treatment. Vaccination of patients <50 years old on other systemic therapies may be considered on a case-by-case basis. LIMITATIONS: There was significant heterogeneity between studies. CONCLUSION: HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all psoriasis and PsA patients >50 years old and younger patients at increased risk.

Epidermal barrier function in healthy black South African infants compared with adults.

A cross-sectional observational study of 43 infants and 60 adult women was performed in South Africa to assess skin barrier (SB) function through noninvasive quantification of transepidermal water loss (TEWL) and skin surface hydration (SSH). TEWL and SSH improved with age and in anatomic locations with chronic environmental exposure in keeping with reported trends in other ethnicities.

Chronic Graft-versus-Host Disease-Associated Muscle Cramps: Severity and Response to Immunomodulatory Therapies.

Muscle cramps in patients with chronic graft-versus-host disease (cGVHD) are common and associated with impaired quality of life and symptom burden. Muscle cramps are not currently captured in the 2014 National Institutes of Health (NIH) response criteria, and thus characterization and response to immunomodulatory therapies are lacking. The objective of this study was to characterize muscle cramp frequency, duration, and pain level in patients with steroid-refractory cGVHD undergoing extracorporeal photopheresis (ECP). A single-center cohort of patients who underwent ECP for the indication of steroid-refractory cGVHD with muscle cramps at treatment initiation were followed from April 2021 to April 2023. Of 22 patients receiving ECP for cGVHD during the study period, 9 (41%) had muscle cramps at ECP initiation (6 males [66%]; median age, 59 years; range, 25 to 66 years). Seven of these 9 patients (78%) had multiple organs involved, and 7 (78%) had severe disease by the NIH Global Severity scale. Over a median treatment duration of 28 weeks (range, 10 to 48 weeks), 8 patients (89%) had decreased frequency of muscle cramps from a median of 5 episodes per week (range, 3 per day to 2 per week) to a median of <1 episode per week (range, 1 per month to 3 per week). The pain and duration of muscle cramps were not changed meaningfully. The NIH Global Severity score remained unchanged in 6 patients (67%) and was improved in 3 patients (33%). Muscle cramping is a morbid feature of cGVHD that may be sensitive to change with standard immunomodulatory therapies. Muscle cramp frequency should be further validated as a response measure in cGVHD.

Comparison of treatment response measures in cutaneous sclerosis after allogeneic hematopoietic cell transplantation.

Cutaneous sclerosis, a highly morbid subtype of chronic graft vs. host disease (cGVHD), demonstrates limited treatment response under current NIH Response Measures. We explored novel sclerosis-specific response measures using Chronic GVHD Consortium data. A training cohort included patients with cutaneous sclerosis from a randomized trial of imatinib vs. rituximab, and a Consortium observational study. The validation cohort was a different Consortium observational study. Clinician-reported measures (baseline, and baseline to 6-month change) were examined for association with 6-month clinician-reported response. Patient-reported measures (baseline and baseline to 6-month change) were studied for association with 6-month patient-reported response. A total of 347 subjects were included (training 183, validation 164). While multiple skin and joint measures were associated with clinician-reported response on univariate analysis, PROM total score, PROM total score change, and NIH 0-3 skin change were retained in the final multivariate model (AUC 0.83 training, 0.75 validation). Similarly, many patient-reported measures were associated, but final multivariate analysis retained the HAP AAS, SF36 vitality change, LSS skin, and LSS skin change in the model (AUC 0.86 training, 0.75 validation). We identified which sclerosis measures have greatest association with 6-month clinician- and patient-reported treatment response, a previously unstudied area. However, given the observed performance in the validation cohorts, we conclude that further work is needed. Novel response measures may be needed to optimally assess treatment response in cutaneous sclerosis.

Patient-Reported Outcomes and Mortality in Cutaneous Chronic Graft-vs-Host Disease.

Importance: Chronic graft-vs-host disease (GVHD) is associated with impaired quality of life and symptom burden. The independent association of skin involvement with patient-reported outcomes (PROs) and their utility as a clinical prognostic marker remain unknown. Identification of patients with cutaneous chronic GVHD and impaired PROs could assist in initial risk stratification and treatment selection. Objective: To compare the association of sclerotic and epidermal-type chronic GVHD with longitudinal PROs and to evaluate whether PROs can identify patients with cutaneous chronic GVHD at high risk for death. Design, Setting, and Participants: This multicenter prospective cohort study involved patients from the Chronic GVHD Consortium of 9 US medical centers, enrolled between August 2007 and April 2012, and followed up until December 2020. Participants included adults 18 years and older with a diagnosis of chronic GVHD requiring systemic immunosuppression and with skin involvement during the study period. Main Outcomes and Measures: Patient-reported symptom burden was assessed using the Lee Symptom Scale (LSS) skin subscale with higher scores indicating worse outcomes. Quality of life was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument with lower scores indicating worse outcomes. Nonrelapse mortality, overall survival, and their association with PROs at diagnosis were also assessed. Results: Among 436 patients with cutaneous chronic GVHD (median [IQR] age at transplant, 51 [41.5-56.6] years; 261 [59.9%] male), 229 patients had epidermal-type chronic GVHD (52.5%), followed by 131 with sclerotic chronic GVHD (30.0%), and 76 with combination disease (17.4%). After adjusting for confounders, patients with sclerotic chronic GVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal disease (95% CI, 11.7-0.4; P = .04). Patients with combination disease had mean LSS skin subscale scores 9.0 points worse than those with epidermal disease (95% CI, 4.2-13.8; P < .001). Clinically meaningful differences were defined as at least 7 points lower for FACT-BMT and 11 points higher for LSS skin subscale. At diagnosis, clinically meaningful worsening in FACT-BMT score was associated with an adjusted odds of nonrelapse mortality increased by 9.1% (95% CI, 2.0%-16.7%; P = .01). Similarly, for clinically meaningful worsening in LSS skin subscale score, adjusted odds of nonrelapse mortality increased by 16.4% (95% CI, 5.4%-28.5%; P = .003). These associations held true after adjusting for clinical severity by the National Institutes of Health Skin Score. Conclusions and Relevance: The results of this cohort study demonstrated that skin chronic GVHD was independently associated with long-term PRO impairment, with sclerotic and combination disease carrying the highest morbidity. The degree of impairment at skin chronic GVHD diagnosis was a prognostic marker for mortality. Therefore, PROs could be useful for risk stratification and treatment selection in clinical practice and clinical trials.

Isotretinoin for Acne in Transgender and Gender-Diverse Individuals Receiving Masculinizing Hormone Therapy.

Importance: Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known about its effectiveness and safety among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Objective: To evaluate clinical outcomes of isotretinoin among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Design, Setting, and Participants: This multicenter retrospective case series study was conducted at 4 medical centers: Mass General Brigham, University of Pennsylvania, Emory University, and Fenway Health. It included patients aged between 12 and 49 years who were receiving masculinizing gender-affirming hormonal therapy and prescribed isotretinoin for the management of acne between August 14, 2015, and September 20, 2023. Exposure: Isotretinoin therapy for the management of acne. Main Outcomes and Measures: The percentage of patients experiencing improvement or clearance of acne, as well as rates of acne recurrence. Adverse effects and reasons for treatment discontinuation were also evaluated. Results: Among 55 included patients, the mean (SD) age was 25.4 years; 4 (7.3%) were Asian, 2 (3.6%) were Black, 4 (7.2%) were Hispanic, 1 was (1.8%) multiracial, and 36 (65.5%) were White. The median isotretinoin course duration was 6 months (IQR, 4.0-8.0), with a median cumulative dose of 132.7 mg/kg (IQR, 66.4-168.5); the cumulative dose was less than 90 mg/kg for 16 patients (29.1%) and less than 120 mg/kg for 22 patients (40.0%). Isotretinoin was associated with improvement in 48 patients (87.3%) and clearance in 26 patients (47.3%). For the 33 patients treated with a cumulative dose of 120 mg/kg or more, these rates increased to 32 patients (97.0%) and 21 patients (63.6%), respectively. Among the 20 patients who achieved acne clearance and had any subsequent health care encounters, the risk of recurrence was 20.0% (n = 4). The most frequently reported adverse effects were dryness (n = 44; 80.0%), joint pain (n = 8; 14.5%), and eczema (n = 5; 9.1%). Laboratory abnormalities were uncommon. Reasons for premature treatment discontinuation included cost, pharmacy issues, adverse effects, logistical reasons (scheduling), and wound healing concerns for gender-affirming surgery. Conclusion and Relevance: In this case series study of individuals with acne who were receiving masculinizing gender-affirming hormonal therapy and underwent isotretinoin treatment, isotretinoin was often effective and well tolerated. However, premature treatment discontinuation was common and associated with poorer outcomes. Further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving masculinizing gender-affirming hormonal therapy.

Epidermal Growth Factor Receptor Inhibitor-Induced Symmetrical Drug-Related Intertriginous and Flexural Exanthema: Should You Discontinue the Offending Agent?

Epidermal growth factor receptor (EGFR) inhibitors cause numerous cutaneous adverse events (AEs), including papulopustular eruptions, paronychia, acral fissures, xerosis, alopecia, and trichomegaly. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous reaction that has been uncommonly reported in association with EGFR inhibitors, though the optimal management strategy for this condition is unknown. We present 2 cases of SDRIFE secondary to EGFR inhibitor therapy in which the EGFR inhibitor was successfully continued while topical therapy was administered for effective control of symptoms. We also review the literature on EGFR inhibitor-related SDRIFE to assess the range of approaches to treating this condition. Our analysis suggests that the dermatologist is critical in diagnosing and treating this cutaneous AE, which may be supported with skin-directed therapy and may not require discontinuation of cancer treatment.

Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease.

Importance: Prior studies have demonstrated an association between cutaneous chronic graft-vs-host disease (cGVHD) and mortality. Assessment of the prognostic value of different measures of disease severity would assist in risk stratification. Objective: To compare the prognostic value of body surface area (BSA) and National Institutes of Health (NIH) Skin Score on survival outcomes stratified by erythema and sclerosis subtypes of cGVHD. Design, Setting, and Participants: Multicenter prospective cohort study from the Chronic Graft-vs-Host Disease Consortium including 9 medical centers in the US, enrolled from 2007 through 2012 and followed until 2018. Participants were adults and children with a diagnosis of cGVHD requiring systemic immunosuppression and with skin involvement during the study period, who had longitudinal follow-up. Data analysis was performed from April 2019 to April 2022. Exposures: Patients underwent continuous BSA estimation and categorical NIH Skin Score grading of cutaneous cGVHD at enrollment and every 3 to 6 months thereafter. Main Outcomes and Measures: Nonrelapse mortality (NRM) and overall survival (OS), compared between BSA and NIH Skin Score longitudinal prognostic models, adjusted for age, race, conditioning intensity, patient sex, and donor sex. Results: Of 469 patients with cGVHD, 267 (57%) (105 female [39%]; mean [SD] age, 51 [12] years) had cutaneous cGVHD at enrollment, and 89 (19%) developed skin involvement subsequently. Erythema-type disease had earlier onset and was more responsive to treatment compared with sclerosis-type disease. Most cases (77 of 112 [69%]) of sclerotic disease occurred without prior erythema. Erythema-type cGVHD at first follow-up visit was associated with NRM (hazard ratio, 1.33 per 10% BSA increase; 95% CI, 1.19-1.48; P < .001) and OS (hazard ratio, 1.28 per 10% BSA increase; 95% CI, 1.14-1.44; P < .001), while sclerosis-type cGVHD had no significant association with mortality. The model with erythema BSA collected at baseline and first follow-up visits retained 75% of the total prognostic information (from all covariates including BSA and NIH Skin Score) for NRM and 73% for OS, with no statistical difference between prognostic models (likelihood ratio test χ2, 5.9; P = .05). Conversely, NIH Skin Score collected at the same intervals lost significant prognostic information (likelihood ratio test χ2, 14.7; P < .001). The model incorporating NIH Skin Score instead of erythema BSA accounted for only 38% of the total information for NRM and 58% for OS. Conclusions and Relevance: In this prospective cohort study, erythema-type cutaneous cGVHD was associated with increased risk of mortality. Erythema BSA collected at baseline and follow-up predicted survival more accurately than the NIH Skin Score in patients requiring immunosuppression. Accurate assessment of erythema BSA may assist in identifying patients with cutaneous cGVHD at high risk for mortality.

Detection of novel therapies using a multi-national, multi-institutional registry of cutaneous immune-related adverse events and management.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias. METHODS: Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv. RESULTS: Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated. CONCLUSION: This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made.

Methotrexate Cutaneous Ulceration: A Systematic Review of Cases.

BACKGROUND: Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series. OBJECTIVE: To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration. METHODS: A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases. RESULTS: 114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality. LIMITATIONS: Selection bias present due to abstraction from case reports and case series. CONCLUSION: Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.

Altered adipose tissue macrophage populations in people with HIV on integrase inhibitor-containing antiretroviral therapy.

OBJECTIVE: Antiretroviral therapy (ART) extends the life of people with HIV (PWH), but these individuals are at increased risk for obesity, dyslipidemia, diabetes, and cardiovascular disease. These comorbidities may be a consequence of HIV-related chronic inflammation and/or adverse effects of ART on tissue regulatory adipose tissue macrophages (ATMs). We sought to determine the effects of HIV/ART on metabolically beneficial ATM populations and functions. DESIGN: We examined subcutaneous ATMs from PWH on integrase inhibitor-containing ART ( n  = 5) and uninfected persons ( n  = 9). We complemented these studies with ex vivo and in vitro analyses of peripheral blood mononuclear cell (PBMC) and murine macrophage lipid metabolism and fatty acid oxidation gene expression. METHODS: ATM populations were examined by flow cytometry. Macrophage lipid metabolism and fatty acid oxidation gene expression were examined by Seahorse assay and quantitative PCR. RESULTS: Adipose tissue from PWH had reduced populations of metabolically activated CD9 + ATMs compared to that of uninfected controls ( P  < 0.001). PBMCs of PWH had lower fatty acid metabolism compared to those of uninfected controls ( P  < 0.01). Analysis of murine macrophages revealed that dolutegravir reduced lipid metabolism ( P  < 0.001) and increased expression of the fatty acid beta-oxidation enzyme enoyl-CoA hydratase, short chain 1 ( P  < 0.05). CONCLUSIONS: We report the loss of metabolically beneficial ATM populations in PWH on ART, altered fatty acid metabolism of blood immune cells, and evidence that dolutegravir alters macrophage fatty acid metabolism. Future studies should examine direct or indirect effects and mechanisms of dolutegravir, and other integrase inhibitors and ART classes, on fatty acid beta-oxidation.

Safety and reactogenicity of the recombinant zoster vaccine after allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. A nonlive adjuvanted recombinant zoster vaccine (RZV) has been developed to prevent herpes zoster (HZ), but there are no recommendations for use in this population. In this single-center prospective observational cohort study, we assessed the safety and reactogenicity of RZV, as well as incidence of graft-versus-host disease (GVHD) and confirmed cases of HZ after vaccination. Between December of 2018 and June of 2020, patients aged ≥18 years received 2 doses of RZV between 9 and 24 months after HCT, with the doses separated by ≥8 weeks. One hundred and fifty-eight patients (mean age, 55 years; 42% women) received ≥1 dose (total vaccinated cohort), and 150 patients (95%) received 2 doses (modified total vaccinated cohort). Solicited reactions occurred in 92.1% of patients (grade 3, 32.5%), owing mostly to injection site pain, which occurred in 86% (grade 3, 16%). The cumulative incidence of GVHD in the peri-vaccination period was no different than in historical controls (adjusted incidence rate ratio, 1.05; 95% confidence interval, 0.8-1.38). There were 4 cases of HZ in the total vaccinated cohort (2.5%) and 3 cases in the modified total vaccinated cohort (28.3/1000 person-years). Among recipients of allogeneic HCT, RZV was safe, tolerable, and did not increase rates of GVHD. Future clinical trials are needed to determine the immunogenicity and efficacy of RZV in this population.