Ongoing Immunosuppressive Treatment Research Articles

Differential diagnosis of thyroid orbitopathy - diseases mimicking the presentation or activity of thyroid orbitopathy.

Thyroid orbitopathy (TO) is the most common cause of orbital tissue inflammation, accounting for about 60% of all orbital inflammations. The inflammatory activity and severity of TO should be diagnosed based on personal experience and according to standard diagnostic criteria. Magnetic resonance imaging (MRI) of the orbit is used not only to identify swelling and to differentiate inflammatory active from non-active TO, but also to exclude other pathologies, such as orbital tumours or vascular lesions. However, a group of diseases can mimic the clinical manifestations of TO, leading to serious diagnostic difficulties, especially when the patient has previously been diagnosed with a thyroid disorder. Diagnostic problems can be presented by cases of unilateral TO, unilateral or bilateral TO in patients with no previous or concomitant symptoms of thyroid disorders, lack of symptoms of eyelid retraction, divergent strabismus, diplopia as the only symptom of the disease, and history of increasing diplopia at the end of the day. The lack of visible efficacy of ongoing immunosuppressive treatment should also raise caution and lead to a differential diagnosis of TO. Differential diagnosis of TO and evaluation of its activity includes conditions leading to redness and/or swelling of the conjunctiva and/or eyelids, and other causes of ocular motility disorders and eye-setting disorders. In this paper, the authors review the most common diseases that can mimic TO or falsify the assessment of inflammatory activity of TO.

Agreement between reported questionnaire data and medical records on diagnosis and COVID-19 symptoms at onset

ABSTRACT The aim of this study was to assess whether there was agreement between self-reported data in a survey and medical records regarding diagnoses and symptoms at COVID-19 onset. The impact of sociodemographic factors on agreement between the two data sources was also assessed. Cross-sectional data were extracted from a Swedish longitudinal cohort study. In total, 401 non-hospitalized patients with a polymerase chain reaction-confirmed COVID-19 infection responded to a survey and agreed to a review of their electronic medical records. Agreement, estimated using the kappa statistic, sensitivity, and specificity were calculated for nine diagnoses and eleven symptoms. Differences between subgroups based on sociodemographic factors were assessed. The agreement between the self-reported data and medical records was at a substantial to moderate level for diagnoses such as diabetes mellitus (kappa 0.65, sensitivity 86%) and hypertension (kappa 0.59, sensitivity 56%) and at a fair level for more difficult-to-define conditions such as ongoing immunosuppressive treatment (kappa 0.27, sensitivity 25%). The agreement between the two data sources on symptoms was between fair and poor (kappa 0.36 for fever; kappa 0.05 for fatigue). Agreement for some diagnoses and symptoms varied across some sociodemographic subgroups, e.g. agreement in diabetes mellitus was significantly better in males (kappa 1.0) than females (kappa 0.52, homogeneity tests p = 0.02). In general, kappa values were lower for symptoms than diagnoses. The agreement between the two sources varied with diagnoses and symptoms and was also influenced by sociodemographic factors. This study illustrates that it is important to consider type of data used in the epidemiological studies as different information sources differ with quality and accuracy.

Long-term outcomes of childhood steroid-sensitive nephrotic syndrome

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ2 or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ2=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ2=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.

Ongoing Mycophenolate Treatment Impairs Anti-SARS-CoV-2 Vaccination Response in Patients Affected by Chronic Inflammatory Autoimmune Diseases or Liver Transplantation Recipients: Results of the RIVALSA Prospective Cohort.

Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of “Maggiore della Carità” University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5–53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8–252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6–54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1–99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9–103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4–204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

Real-life vaccination coverage in Slovak children with rheumatic diseases.

BackgroundEvidence-based recommendations for vaccination of patients with pediatric rheumatic diseases (PRDs) are available, their implementation in practice is unknown.ObjectivesTo analyze real-life vaccination coverage in children with PRDs and identify reasons for incomplete vaccination.MethodsUp-to-date information on vaccination status of Slovak children followed at a tertiary pediatric rheumatology center was retrieved from pediatricians over an 18-month period and compared to the standard Slovak Immunization Schedule. Reasons for missed vaccinations were analyzed retrospectively.ResultsVaccination records of 156 patients (median age 10 years, 2–18) with PRDs (JIA n = 108, systemic diseases n = 21, autoinflammatory diseases n = 16, uveitis n = 9, others n = 2) were available for analysis. 117 (75.0%) were completely vaccinated, 2 (1.3%) had not received any vaccine due to reasons unrelated to PRD. 37 (23.7%) remaining patients missed altogether 48 mandatory vaccinations. In 58.3% (n = 28, in 24 patients) no PRD related reasons for missing vaccinations were identified. Only 20 vaccinations (18 live-attenuated and 2 non-live in 19 patients) were missed due to ongoing immunosuppressive treatment or PRD activity. Patients aged 11–14 years were more likely to be incompletely vaccinated than other age groups (48.8% vs. 15.9%, p < 0.001), mainly due to missed MMR booster. Systemic immunosuppressive treatment was a significant predictor for incomplete vaccination status (OR 5.03, 95% CI 1.13–22.31, p = 0.03).ConclusionFull vaccination is possible in a high proportion of PRD patients. In addition to immunosuppressive therapy, reasons unrelated to PRDs are a frequent and possibly inadequate cause of missed vaccinations. Periodic vaccination status assessments are needed in pediatric rheumatology care.

Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults

BackgroundDiffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement.Case presentationPatient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis.ConclusionsWe believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as “idiopathic”. Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

Invasive candidiasis serological diagnosis in solid organ transplant recipients.

Solid organ transplant recipients are at high risk of fungal infections, because of ongoing immunosuppressive treatment. There are three post organ transplant phases: early, intermediate, and late, all of them at risk of Candida infections. Since conventional tests are insufficient, specific secondary diagnostic tests are still being explored. Serological tests are currently the most common choice. The present study was to determine the usefulness of mannan antigen and anti-mannan antibody detection in diagnosing invasive candidiasis in liver or kidney transplant recipients. The levels of mannan and anti-mannan antibodies were assessed with Platelia Candida Ag Plus, and Platelia Candida Ab Plus (Biorad, Marne-la-Coquette, France) commercial tests, according to manufacturer's guidelines. Sixty six serum samples were obtained from 25 patients (9 liver transplant recipients, 7 kidney transplant recipients, and 9 patients prepared for a kidney transplant), 29 serum samples from 15 patients tested positive for mannan antigen. Serum samples were obtained from 14 patients tested positive for anti- mannan antibodies. Fungal antigen detection in blood serum in patients under immunosuppression, especially with neutropenia, suggests that antifungal treatment should be administered. Serological tests, especially mannan and anti-mannan ones, are very useful for confirmation or exclusion of invasive candidiasis in high-risk patients.

Soft tissue infection caused by Legionella bozemanii in a patient with ongoing immunosuppressive treatment

The Legionellaceae family consists of approximately 50 species, of which the most commonly identified species is L. pneumophila, the causative agent of Legionnaires’ disease. Other Legionella ssp. most often cause clinical infections in the immune-compromised patients, in which L. bozemanii has been known to cause both pneumonia and lung abscesses. In the presented case, a soft tissue infection in a patient with ongoing immunosuppression was determined to be due to L. bozemanii. Hence, in immune-deficient patients, L. bozemanii could be considered a possible agent in soft tissue infections when other common pathogens have been ruled out.

Off‐Trial Evaluation of the B cell–Targeting Treatment in the Refractory Cases of Antineutrophil Cytoplasmic Antibodies (ANCA)‐Associated Vasculitis: Long‐Term Follow‐Up from a Single Centre

The aim of the study was to evaluate long-term clinical and immunological effects of anti-B cell treatment in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis refractory to conventional immunosuppressive treatment. Rituximab (RTX) was added to the ongoing immunosuppressive treatment in 29 patients with refractory ANCA-associated vasculitis. The disease activity was measured using Birmingham Vasculitis Activity Score/Wegener's granulomatosis (BVAS/WG score), and clinical laboratory variables were recorded. The median BVAS/WG score before treatment was 6 (IQR 3-8), and 28 patients (97%) had disease flare classified either severe (62%) or limited (34%). Six of 29 patients (21%) achieved a complete remission, and 12 (41%) had a treatment response with ≥50% decrease in BVAS/WG score at 6 months. Fourteen patients (64%) with kidney involvement achieved remission, and in seven patients (50%), no flare was seen during the follow-up period. Three patients had renal flare and were successfully re-treated with RTX. Seventeen patients had disease symptoms from airways and eyes at RTX initiation, whereas only 29% displayed ≥50% treatment response. Limited clinical improvement was seen in patients with endobronchial lesions and trachea-subglottic granulomatous disease. RTX is a potent therapeutic option for ANCA-associated vasculitis refractory to conventional treatment. Best response may be expected in patients with vasculitic manifestations.

Prophylaxis and Treatment of Graft Versus Host Disease After Allogeneic Stem Cell Transplantation: A Survey on Center Strategies by the European Group for Blood and Marrow Transplantation (EBMT)

AbstractAbstract 1261Allogeneic stem cell transplantation is a poorly standardized treatment. Reported outcomes vary markedly, partly due to differences in treatment procedures. The EBMT performed a survey among its member centers about their present strategies in preventing and treating graft versus host disease (GvHD). Seventy-three centers from 23 countries participated in this survey. The main prophylactic regimens used in transplantations with myeloablative conditioning were cyclosporine (CsA) + methotrexate (MTX) in 83%, CsA + mycophenolate mofetil (MMF) in 14 %, tacrolimus (tacro) + MTX in 6%, CsA alone in 8%, and tacro alone, tacro + MMF and ex vivo T-cell depletion (TCD) in 1% of the centers. The administration of CsA was initiated on day -6 (1%), day -3 (13%), day -2 (7%), day -1 (78%) or day 0 (1%). CsA was initially given as short i.v. infusions in 56% (twice daily 91%), continuous infusion in 39% and orally in 5% of the centers. The initial CsA dose was most commonly 3 mg/kg/day (49%); 1–2,5 mg/kg/day was given in 16%, 4–6 mg/kg/day in 31%, and 10–12,5 mg/kg/day in 4% of the centers. Further doses were then usually adjusted according to CsA concentrations (88%), measured from whole blood (81%) or serum (19%). When measured from whole blood, the target CsA concentrations at 1 wk post-Tx ranged from 80 to 400 (mean 230) ng/ml, and at 2–4 wks and 2 mths the ranges (means) were 95–400 (210) and 60–350 (200) ng/ml, respectively. The typical duration of CsA prophylaxis was 60–100 (32%), 120–150 (10%), 180 (54%), or 210–365 (14%) days. In 56% of the centers the estimated risk of relapse affected the length of prophylaxis. MTX was given in the dose of 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, and +11 in 63% and without the last dose in 28% of the centers. There were 6 other variants. Leucovorin rescue was given in 43% of the centers with variable dose and timing. ATG was included in the prophylaxis for one or more subgroups (one center all patients) in 79%, alemtuzumab in 25%, corticosteroids in 10%, and TCD in 24% (one center all patients) of the centers. The main prophylactic regimens in reduced intensity transplantations (RIC) were CsA + MMF (67%), CsA + MTX (33%), CsA (23%), in vivo TCD (19%), tacro + MMF (10%), ex vivo TCD (3%), and tacro alone and tacro + MTX (1% each). ATG was used in some groups of patients in 73% of the centers. The development of chimerism affected the intensity of prophylaxis in 82% of the centers. All centers used corticosteroids as first line treatment of acute GvHD. The treatment was started at first signs likely to be caused by GvHD (17%) or for grade II or higher (83%). The decision to treat was based on clinical signs only in 70% of the centers while in 30% histological documentation was needed. The corticosteroid of choice was methylprednisolone (83%) or prednisolone (17%). The initial daily dose/kg was 1-1, 5 mg (19%), 2 mg (76%), 3 mg (6%), 5–10mg (3%), or 20 mg (1%), given in 1 (16%), 2 (69%), 3 (9%) or 4 (6%) doses, i.v. (79%) or orally (21%). The severity of aGvHD affected the initial dose in 53% and the organ manifestation in 27% of the centers. The dose per kg/day indicating corticosteroid resistance and need for second line treatment was 1mg (3%), 2 mg (72%), 4–5 mg (13%), or 10 mg or more (12%). The minimum time to confirm corticosteroid resistance was 2 (2%), 3 (11%), 4–5 (27%), 6–7 (44%), 10–14 (13%) or 21 (3%) days. The most widely used second line treatments were MMF (33%), anti-TNF antibodies (31%), other monoclonal antibodies (16%), ATG (27%), extracorporeal photopheresis (ECP, 14%), mesenchymal stem cells (7%), alemtuzumab (7%), pentostatin (5%) and “keep going with corticosteroids” (12%). The initial treatment for newly diagnosed chronic GvHD in patients with no ongoing immunosuppressive treatment was corticosteroid (57%), calcineurin inhibitor (CNI) + corticosteroid (38%), or CNI alone (10%). The minimum duration of first line treatment of chronic GvHD to allow the evaluation of efficacy was 2 wks or less (21%), 2–4 wks (12%), 1 mth (42%), 1,5-4 mths (21%), or 9–12 mths (4%). The most commonly used second line treatments were ECP (53%), MMF (36%), rituximab (12%), CNI (12%), mTOR inhibitors (9%), corticosteroids (8%), and tyrosine kinase inhibitors (6%). In conclusion, the present results show marked differences between centers in the prophylaxis and management of GvHD. These findings underline the need for standardization and prospective controlled studies in GvHD prevention and treatment. Disclosures:No relevant conflicts of interest to declare.

Anti-CD20 therapy in patients with refractory systemic lupus erythematosus: a longitudinal analysis of 52 Hispanic patients

The objective of this study was to investigate the efficacy and safety of anti-CD20 treatment in Hispanic patients with refractory systemic lupus erythematosus and to determine whether baseline parameters predict disease flare. Fifty-two patients with systemic lupus erythematosus, 13 with active lupus nephritis, eight with thrombocytopenia, three with leukocytopenia, 25 with severe musculoskeletal involvement and three with skin involvement) refractory to conventional therapy were treated with anti-CD20 treatment (rituximab; MabThera, Roche) plus ongoing immunosuppressive treatment. Disease activity was assessed monthly using the SLEDAI validated for the Mexican population with a follow-up period of 6 months. At 6 months of follow-up, significant clinical improvements were detected, with a reduction in the global SLEDAI validated for the Mexican population score. Five of the 13 patients with lupus nephritis (38.4%) had a complete renal response and five (38.4%) had a partial response. Rituximab was also effective in patients with autoimmune thrombocytopenia, inducing a significant increase in platelet counts (p = 0.012). Nineteen of 25 patients with severe musculoskeletal involvement had remission of arthritis. Only one of the three patients with skin involvement had no lesions at 6 months. Rituximab treatment also allowed a reduction of the oral prednisone dose in the majority of patients. No baseline predictors of flare were found. Treatment was discontinued after the first infusion in two patients due to serum sickness and in another due to pulmonary infection. In conclusion, the addition of rituximab to conventional immunosuppressive therapy may be an effective strategy for lupus nephritis, autoimmune thrombocytopenia and inflammatory polyarthritis in patients with refractory systemic lupus erythematosus.

Causes and consequences of the autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is the first autoimmune hematological disease whose genetic basis has been defined. It is a disorder of apoptosis in which the inability of lymphocytes to die leads to lymphadenopathy, hypersplenism, and autoimmune cytopenias of childhood onset. More than 200 ALPS patients have been studied over the last 15 years and followed by our colleagues and ourselves at the Clinical Center of the National Institutes of Health. Based upon this experience we have determined that patients with germline mutations of the intracellular domain of Fas protein, the most frequent single genetic cause of ALPS, have a significantly increased risk of developing Hodgkin and non-Hodgkin lymphoma (NHL), underscoring the critical role played by cell surface receptor-mediated apoptosis in eliminating redundant proliferating lymphocytes with autoreactive and oncogenic potential. The major determinants of morbidity and mortality in ALPS are the severity of the autoimmune disease, hypersplenism, asplenia-related sepsis, and the risk of lymphoma, which in itself requires long-term surveillance. Though most episodes of cytopenias respond to courses of conventional immunomodulatory agents, some ALPS patients, especially those with massive splenomegaly and hypersplenism, may require splenectomy and/or ongoing immunosuppressive treatment. Thus, ALPS highlights the importance of cell death pathways in health and disease.

Efficacy and safety of vaccination of marrow transplant recipients with a live attenuated measles, mumps, and rubella vaccine.

Long-term immunity to measles, mumps, and rubella viruses was studied in 57 patients after allogeneic bone marrow transplantation. Among patients who were seropositive at the time of transplant, 51% had retained antibodies to measles, 42% had retained antibodies to mumps, and 76% had retained antibodies to rubella 2 y later. There was no difference in the ability to retain antibodies to these viruses between patients with and those without chronic graft-versus-host disease (GVHD). Twenty seronegative patients without active chronic GVHD or ongoing immunosuppressive treatment were vaccinated with a live attenuated trivalent vaccine against measles, mumps, and rubella. No early or late side effects were detected after the vaccinations. The percentages of patients who seroconverted after vaccination were 77%, 64%, and 75% for measles, mumps, and rubella, respectively. Vaccination of transplant recipients with a live attenuated vaccine against measles, mumps, and rubella is safe and usually effective 2 y after transplant if the patients do not have active chronic GVHD or ongoing immunosuppressive treatment at the time of vaccination.