Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Avelumab is indicated for the management of Merkel cell carcinoma, a rare and aggressive neuroendocrine skin cancer. Its regulatory approval followed the positive outcome of a Phase 2 trial on 88 patients with stage IV disease, which excluded patients with immunodeficiency due to HIV, a risk factor for this cancer type. We report a positive and sustained response to avelumab in an HIV-positive patient with stage IV Merkel cell carcinoma refractory to previous chemotherapy (cisplatin/etoposide) and radiotherapy. Five cycles of avelumab 10 mg/m2 resulted in the resolution of tumor activity visualized using PET-CT scanning in all affected lymph nodes. The only major side effect associated with avelumab was thyroiditis and mild hypothyroidism, a known adverse effect of this treatment, which was well controlled by L-thyroxine treatment. Treatment is ongoing and the positive response has been sustained during 5 further cycles of treatment up to date. This apparently durable response is consistent with the earlier clinical trial experience with avelumab, but seen here in a patient with HIV-associated immunodeficiency as a predisposing factor (an exclusion criterion from the previous trial). Further clinical trials with avelumab in a broader patient population with Merkel cell carcinoma are warranted.
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PMID:Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy. 3014 Feb 9

DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination-mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV-associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered the roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies.
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PMID:Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome. 3056 50

Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95%CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95%CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95%CI = 9.5-130). Mortality associated with birth length below -4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95%CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio = 3.9, 95%CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95%CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95%CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95%CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.
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PMID:A 30-Year Prospective Follow-Up Study Reveals Risk Factors for Early Death in Cartilage-Hair Hypoplasia. 3137 17

Sexual and gender minorities have unique risk factors that may increase their risk of developing skin cancer. In particular, sexual minority men report a higher prevalence of skin cancer (including both keratinocytes carcinomas and melanoma), higher rates of indoor tanning, and overall poorer sun protection behaviors. Sexual and gender minorities also have high rates of alcohol and tobacco use, and infection with human immunodeficiency virus and human papillomavirus, which may increase overall risk of developing skin cancer in these populations. In this review, we discuss the evidence surrounding skin cancer and associated risk factors among sexual and gender minorities.
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PMID:Skin Cancer and Skin Cancer Risk Factors in Sexual and Gender Minorities. 3211 30

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.
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PMID:Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases. 3239 20

The increasing number of hematopoietic stem cell transplantation (HSCT) procedures and lower transplant-related mortality has led to a growing population of survivors facing long-term increased risk of secondary malignancy, including cutaneous neoplasms. In this review, we aim to discuss the incidence, risk factors and preventive strategies for secondary skin neoplasms after autologous and allogeneic HSCT. Cutaneous neoplasms, such as basal cell carcinoma, squamous cell carcinoma and melanoma, are among the most common solid cancers arising in patients after HSCT. Besides risk factors established in the general population, primary disease, chronic graft-versus-host disease (CGvHD), prolonged immunosuppression, especially with the use of cyclosporine and azathioprine, radiation exposure, light skin color, male sex, and young age at transplantation play a role in the development of cutaneous neoplasms in HSCT recipients. Skin cancer development after HSCT may be explained by cumulative effects of chemotherapy and radiotherapy-induced DNA damage, prolonged immunosuppressive conditions and chronic mucosal inflammation, particularly after allogeneic HSCT. Delayed immune recovery and persistent immunodeficiency in patients with graft-versus-host disease (GvHD) may also contribute to carcinogenesis. Regular dermatological surveillance and prompt recognition of precancerous and cancerous lesions is crucial for patient's prognosis and management.
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PMID:Secondary skin neoplasms in patients after autologous and allogeneic hematopoietic stem cell transplantation procedures. 3306 81


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