Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status.

BACKGROUND: Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability (MSI) (MSI-H) metastatic colorectal cancer. However, the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI (MSI-L), and microsatellite stable (MSS) metastatic colorectal cancer remains unclear. AIM: To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer, and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months. METHODS: We conducted a retrospective cohort study using the National Cancer Database (NCDB) to evaluate the overall survival (OS) of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy. The study population was stratified by MSI status (MSI-H, MSI-L, and MSS). Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS, adjusting for potential confounders. RESULTS: A total of 21951 patients with metastatic colorectal cancer were included in the analysis, of which 2358 were MSI-H, and 19593 were MSI-L/MSS. In the MSI-H cohort, immunotherapy treatment (n = 142) was associated with a significantly improved median OS compared to chemotherapy (n = 860). After adjusting for potential confounders, immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95%CI): 0.43-0.77, P < 0.001]. In the MSS cohort, no significant difference in median OS was observed between immunotherapy treatment and chemotherapy (aHR: 0.94, 95%CI: 0.69-1.29, P = 0.715). CONCLUSION: In this population-based study using the NCDB, immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer, but not in those with MSI-L/MSS metastatic colorectal cancer. Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Analysis of immune-related adverse events in gastrointestinal malignancy patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors are becoming an increasingly common treatment for advanced gastrointestinal cancer, but the possibility of immune-related adverse events has raised concerns. This study aimed to evaluate the risks of immune-related adverse events between patients who received immune checkpoint inhibitors and those who received chemotherapy among different types of gastrointestinal cancer. The study utilized data from the multicenter TriNetX database in the United States covering the period between 2015 and 2022. Hazard ratios and 95% confidence intervals were used to describe the relative hazard of immune-related adverse events based on comparing time-to-event rates. Our study revealed that the incidence of immune-related adverse events was significantly higher in patients who received immune checkpoint inhibitors and chemotherapy compared to those who received chemotherapy only in treating gastrointestinal cancer. CTLA-4 inhibitors tended to have a higher rate of immune-related adverse events compared to PD-1/PD-L1 inhibitors. Our study found a lower mortality rate among patients who developed immune-related adverse events compared to those who did not after propensity score matching (HR, 0.661; 95% CI 0.620-0.704; p < .01). We provide important real-world data on the incidence and impact of immune-related adverse events in patients with advanced gastrointestinal cancer treated with immune checkpoint inhibitors. Our study's results support clinicians in making informed decisions about the potential benefits and risks of immune checkpoint inhibitor therapy for patients with gastrointestinal cancer.

Therapy-related Acute Myeloid Leukemia in Non-Hodgkin Lymphoma Survivors: Risk, Survival Outcomes and Prognostic Factor Analysis.

BACKGROUND: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. This extensive database study aims to quantify the risk of tAML in NHL and determine the impact of tAML on the overall survival (OS) of patients with NHL. MATERIALS AND METHODS: Patients diagnosed with NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results database. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software were used to calculate SIR and the absolute excess risk of tAML. Overall survival (OS) was evaluated using Kaplan-Meier curves and compared using log-rank tests. Multivariate analysis was used to study the role of each covariate on OS in patients with tAML. RESULTS: The SIR of tAML was 4.89 (95% CI 4.41-5.41), with a higher incidence of tAML observed for age <60 years, NHL prior to 2013 and within 5 years of diagnosis, and those who received chemotherapy. NHL patients with tAML had lower OS than those without tAML (5-year OS 59% vs. 13%, p < 0.001). Patients with tAML showed worse OS than de novo AML in univariate analysis (5-year OS 13% vs. 25%, p = 0.001) but not in multivariate analysis (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years and lack of chemotherapy were associated with poor OS in tAML subcategory. CONCLUSION: Age, time since NHL diagnosis, and receipt of chemotherapy directly influence the risk of development of tAML in NHL survivors.

Outcome of ALL With ALL-BFM-95 Protocol in Nepal.

PURPOSE: Data on survival outcomes in patients with acute lymphoblastic leukemia (ALL) originating from Nepal are limited. We aim to present the real-world data on treatment outcomes of patients with de novo ALL treated with pediatric ALL-Berlin-Frankfurt-Muenster (BFM)-95 protocol in Nepal. PATIENTS AND METHODS: We used the medical records of 103 consecutive patients with ALL treated in our center from 2013 to 2016 to evaluate the overall survival (OS) and relapse-free survival (RFS) and analyzed the effects of clinicopathologic factors on survival outcomes in patients with ALL. RESULTS: The 3-year OS and RFS in the entire cohort was 89.4% (95% CI, 82.1 to 96.7) and 87.3% (95% CI, 79.8 to 94.7), with a mean OS and RFS of 79.4 months (95% CI, 74.2 to 84.5) and 76.6 months (95% CI, 70.8 to 82.4), respectively. Patients with prednisone good response (PGR) showed better mean OS and RFS, whereas complete marrow response on day 33 was associated with better mean OS alone. Patients with Philadelphia (Ph)-positive ALL showed worse mean RFS compared to those with Ph-negative status. On multivariate analysis, PGR (hazard ratio [HR], 0.11; 95% CI, 0.03 to 0.49; P = .004) and sagittal vein thrombosis (SVT; HR, 5.95; 95% CI, 1.30 to 27.18; P = .02) were the only independent predictors of OS and RFS, respectively. Adverse events on BFM-95 protocol included SVT (4.9%), peripheral neuropathy (7.8%), myopathy (20.4%), hyperglycemia (24.3%), intestinal obstruction (7.8%), avascular necrosis of femur (6.8%), and mucositis (46%). CONCLUSION: BFM-95 protocol appears to be a safe and effective strategy in adolescent and young adults and adult Nepalese population with ALL with a low toxicity profile.

Clinical outcomes and prognostic factors in triple-negative invasive lobular carcinoma of the breast.

PURPOSE: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. METHODS: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. RESULTS: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001). CONCLUSION: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Clinical Outcomes and Prognostic Factors in Triple-Negative Invasive Lobular Carcinoma of the Breast.

Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Hemophagocytic Lymphohistiocytosis: an Under-recognized and Life-threatening Condition.

Diagnosis of hemophagocytic lymphohistiocytosis is a challenge in Nepal because of limited resources and the high prevalence of tropical febrile illness mimicking hemophagocytic lymphohistiocytosis. We retrospectively reviewed medical records of 21 patients who were diagnosed with hemophagocytic lymphohistiocytosis from 2010 to 2015 at a single center in Nepal. Two patients had a mutation in their perforin gene and underwent successful haploidentical stem cell transplantation. Marrow hemophagocytosis was found only in 57% of the patients. Five patients had hematological malignancy and were treated with disease-specific chemotherapy. Seven patients developed hemophagocytic lymphohistiocytosis secondary to an infection, including visceral leishmaniasis, scrub typhus, and Epstein Barr virus. EBV-associated hemophagocytic lymphohistiocytosis was refractory to hemophagocytic lymphohistiocytosis 94 protocol, including the addition of rituximab. Malignancy and infection-associated hemophagocytic lymphohistiocytosis was more common. The most common clinical presentations included fever, splenomegaly, hyponatremia, liver function derangement, hyperfibrinogenemia, hyperferritinemia, and cytopenia. With a mortality of 29% in our study cohort, hemophagocytic lymphohistiocytosis should be considered a lethal disease, and clinicians should maintain a high index of suspicion to diagnose this disease. Keywords: Hemophagocytic lymphohistiocytosis; infection; malignancy.

Comorbidity burden and outcomes of older adults with acute promyelocytic leukemia: a National Cancer Database analysis of 2221 patients.

Association between comorbidity burden and patient outcomes has not been adequately investigated in acute promyelocytic leukemia (APL). We utilized the National Cancer Database to evaluate the association of the Charlson-Deyo Comorbidity Index (CCI) with one-month mortality and overall survival (OS) in adults ≥60 years with APL. One-month mortality was 16%, 24%, and 32%, and 3-year OS was 61%, 53%, and 38% for patients with CCI 0, 1, and ≥2, respectively. One-month mortality was higher for patients with CCI 1 (OR 1.67, 95% CI 1.29-2.16, p < .001) and CCI ≥ 2 (OR 2.31, 95% CI 1.70-3.13, p < .001) compared to patients with CCI 0. Patients with CCI 1 (HR 1.27, 95% CI 1.10-1.46, p < .001) and CCI ≥ 2 (HR 1.74, 95% CI 1.48-2.06, p < .001) had worse OS compared to patients with CCI 0. In conclusion, CCI is an independent predictor of survival outcomes in patients with APL.

Risk of second primary malignancy in patients with primary myelofibrosis: a SEER database study.

Prior studies report a greater incidence of second primary malignancy (SPM) among patients with myeloproliferative neoplasms, although the true risk in primary myelofibrosis (PMF) has not been elucidated. We utilized the Surveillance, Epidemiology, and End Results database to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Out of 5273 patients, 385 patients (7.30%) developed SPM. SPM occurred at SIR of 1.95 (95% CI 1.76-2.15) and AER of 149.01 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.76, 95% CI 1.01-2.86), lymphoma (SIR 3.38, 95% CI 2.28-4.83), and leukemia (SIR 27.19, 95% CI 23.09-31.81) was observed. The risk was significantly higher in patients ≤60 years, males, chemotherapy recipients, within 5 years of PMF diagnosis, and for PMF diagnosed after 2009.

Isocitrate dehydrogenase mutation and risk of venous thromboembolism in glioma: A systematic review and meta-analysis.

BACKGROUND: Patients with malignancies including malignant gliomas have a relatively high risk for venous thromboembolism (VTE). Recent evidence has linked isocitrate dehydrogenase (IDH) mutation with reduced VTE risk in malignant glioma. This meta-analysis aims to quantify the association of IDH mutation status with risks of VTE in patients with glioma. METHODS: We searched PubMed, Google Scholar, Medline OVID, Cochrane library, Cumulative Index to Nursing and Allied Health Literature databases to identify relevant studies. The overall odd ratio (OR) was pooled using the random-effects model. We evaluated the statistical heterogeneity using Cochran's Q statistics and I2 tests. We performed subgroup analyses according to age, tumor, study design, and study quality. RESULTS: A total of 2600 patients from 8 studies were included in the meta-analysis. Patients with IDH mutant-type gliomas had a significantly lower risk of VTE (OR: 0.21, 95 % confidence interval [CI]: 0.09-0.46, I2 = 34 %) compared to patients with IDH wild-type gliomas. Among high-grade (III and IV) glioma, VTE events in IDH-mutant gliomas occurred with an OR of 0.28 (95 % CI: 0.14-0.53). No statistically significant decrease in the VTE risk was observed in grade II gliomas with IDH mutation compared to IDH wild-type gliomas, as indicated by the OR of 0.60 (95 % CI: 0.17-2.11). CONCLUSION: IDH mutation is significantly associated with 79 % lower risk of VTE among patients with high-grade glioma compared to IDH wild-type. Our findings suggest the potential utility of IDH mutation status regarding thromboprophylaxis, and the need for further studies to elucidate the mechanism of the association.

Effect of Age and Socioeconomic Factors in the Utilization of Chemotherapy in Acute Lymphoblastic Leukemia (ALL): A SEER Database Study of 16,196 Patients.

INTRODUCTION: The use of multiagent chemotherapy in acute lymphoblastic leukemia (ALL) has resulted in improvement in overall survival (OS), albeit to a different extent across various age groups. This large database study aims to assess the disparity in the utilization of chemotherapy in ALL in the real-world setting. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, patients with ALL diagnosis from 2006 to 2016 were identified. Baseline characteristics were compared between the groups who did vs. did not receive chemotherapy using χ2 test. Multivariable logistic regression was used to evaluate the association between various sociodemographic factors and the receipt of chemotherapy in the entire cohort and in different age groups. RESULTS: Out of 16,196 patients, 1258 patients (8%) did not receive chemotherapy. There was a steady increase in the number of patients who did not receive chemotherapy with advancing age: 2.5% (0-18 years), 5.2% (19-40 years), 9.3% (41-65 years), and 36.2% (>65 years). There was an upward trend in the receipt of chemotherapy in patients >65 years over the last decade. In multivariate analysis, the likelihood of receiving chemotherapy decreased with advancing age, single or widowed status, low income and educational status, and lack of insurance. Insurance status was an independent predictor of receipt of chemotherapy across each age category. CONCLUSION: A significant proportion of patients >65 years do not receive chemotherapy in the United States. Age, marital status, income, education, and insurance status contribute to the disparity in utilization of chemotherapy.

Association of insurance types and outcomes in acute promyelocytic leukemia.

Understanding the association between insurance status and survival in an evolving US healthcare system remains a challenge but is essential to address healthcare disparities. We utilized National Cancer Database to evaluate the effects of insurance type on one-month mortality and overall survival (OS) in patients with acute promyelocytic leukemia. Among patients <65 years, one-month mortality was worse for uninsured patients and patients with Medicare compared to patients with private insurance. OS was similar between patients with private insurance and uninsured patients but worse for patients with Medicare and Medicaid/other government insurance. In multivariate analysis, older age and greater comorbidity burden conferred worse OS. For patients ≥65 years, insurance type did not affect one-month mortality and OS. Older age, greater comorbidity burden, and treatment at non-academic centers conferred worse one-month mortality and OS. Our results highlight healthcare disparities based on insurance types for both younger and older patients.

Characterization of immune profile in an aging multiple sclerosis clinic population.

BACKGROUND: There is limited data regarding adaptive immunity in older persons with Multiple Sclerosis (MS). OBJECTIVE: The aim of the present study was to quantify adaptive immune cells in younger (age less than 50) and older (age greater than 50) with MS in the context of clinical parameters (EDSS, 25-foot walk, SDMT). Subjects were either Untreated (no MS medications in 6 months), taking Injectables (interferons or glatiramer acetate), or Other approved MS treatments. RESULTS: A total of 72 subjects were enrolled (30 younger and 42 older). Older MS patients that were Untreated or taking Injectables had lower CD8 cell counts. Older MS patients demonstrated increased levels of CD4+CD25hi cells and inflammatory serum cytokines (TNF-α, IL-8). There was suggestion that MS treatments modulated IL-10. Cognition as assessed by SDMT was associated with disease duration and IL-10. CONCLUSION: Components of adaptive immunity are influenced by aging in MS which may also impact aspects of cognition as measured by SDMT.

Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer's disease-like pathology in APP/PS1 mice.

Alzheimer's disease (AD) represents the most common form of dementia in the elderly with no available disease modifying treatments. Altered gut microbial composition has been widely acknowledged as a common feature of AD, which potentially contributes to progression or onset of AD. To assess the hypothesis that Candida rugosa lipase (CRL), which has been shown to enhance gut microbiome and metabolite composition, can rebalance the gut microbiome composition and reduce AD pathology, the treatment effects in APPswe/PS1de9 (APP/PS1) mice were investigated. The analysis revealed an increased abundance of Acetatifactor and Clostridiales vadin BB60 genera in the gut; increased lipid hydrolysis in the gut lumen, normalization of peripheral unsaturated fatty acids, and reduction of neuroinflammation and memory deficits post treatment. Finally, we demonstrated that the evoked benefits on memory could be transferred via fecal matter transplant (FMT) into antibiotic-induced microbiome-depleted (AIMD) wildtype mice, ameliorating their memory deficits. The findings herein contributed to improve our understanding of the role of the gut microbiome in AD's complex networks and suggested that targeted modification of the gut could contribute to amelioration of AD neuropathology.

Impact of Insurance on Overall Survival in Acute Lymphoblastic Leukemia: A SEER Database Study.

INTRODUCTION: Insurance status at diagnosis remains an important barrier to health care access and adherence to treatment. Here, we aim to assess the impact of insurance status, and age on overall survival (OS) in patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified all patients younger than 65 years of age diagnosed with ALL from 2010 to 2016. OS was estimated for each group using the Kaplan Meier curves and compared based on insurance type using a log-rank test. Multivariate analysis using Cox proportional hazard regression model was used to assess the effect of insurance status on OS. RESULTS: A total of 9057 patients were included in the analysis. Medicaid beneficiaries had worse 5-year OS than insured patients (HR 1.33, 95% CI 1.08-1.63, P = .006) in 0-18 years age group. Despite chemotherapy, patients older than 18 years showed poor OS in all insurance categories. Patients on Medicaid showed inferior OS compared to insured in 19-40 years (HR 1.46, 95% CI 1.21-1.76, P < .001) and 41-65 years age group (HR 1.27, 95% CI 1.09-1.49, P = .003). Interestingly, no significant difference was observed in the OS between the Medicaid and uninsured groups in each age category. CONCLUSION: Our large database study demonstrates that insured status is associated with better OS in ALL across all age groups. Further studies to develop effective strategies to bridge health care disparities areessential.

Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review.

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1-2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.

Disparity in Utilization of Multiagent Therapy for Acute Promyelocytic Leukemia in the United States.

BACKGROUND: Despite high rate of cure in acute promyelocytic leukemia (APL) in clinical trials, outcomes in real-world practice are dismal. We utilized National Cancer Database (NCDB) to explore utilization of multiagent therapy in APL and identify any disparities in treatment in real-world practices. PATIENTS AND METHODS: NCDB categorizes use of systemic chemotherapy into single agent versus multiagent therapy. Some patients received hormonal therapy, immunotherapy, and unknown therapy; details of these treatments could not be ascertained. We therefore used multiple logistic regression analysis to evaluate effects of covariates on the probability of multiagent therapy use in 6678 patients. RESULTS: Compared to patients >60 years, patients aged 0 to 18 years (hazard ratio[HR] 3.2, 95% confidence interval [CI] 1.8-5.5, P< .0001), 19 to 40 years (HR 1.6, 95% CI 1.03-2.54, P= .03), and 41 to 60 years (HR 1.6, 95% CI 1.3-1.9, P< .0001) were more likely to receive multiagent therapy. Patients with Charlson comorbidity index (CCI) of 0 (HR 1.6, 95% CI 1.2-2.3, P= .001) and CCI of 1 (HR 1.4, 95% CI 1.0-1.9, P= .04) had a higher likelihood of receiving multiagent therapy than patients with CCI ≥ 3. Patients treated at academic cancer centers, compared to those treated at community cancer center (HR 0.5, 95% CI 0.3-0.7, P= .001), comprehensive community cancer center (HR 0.7, 95% CI 0.6-0.8, P< .0001), and integrated network cancer center (HR 0.8, 95% CI 0.6-0.9, P= .02) were more likely to be treated with multiagent therapy. Compared to the patients with private insurance, those with Medicaid had increased likelihood (HR 1.2, 95% CI 1.0-1.4, P= .04) whereas uninsured patients had a lower likelihood of receiving multiagent therapy (HR 0.6, 95% CI 0.5-0.8, P= .0005). CONCLUSION: To our knowledge, this study is the first and the largest scale analysis of treatment practices in APL in real-world practices. Our findings highlight significant disparities in treatment of APL based on age, insurance, and health-system factors.

Adaptive Immune Responses Associated with the Central Nervous System Pathology of Gulf War Illness.

Gulf War Illness is a multisymptomatic condition which affects 30% of veterans from the 1991 Gulf War. While there is evidence for a role of peripheral cellular and humoral adaptive immune responses in Gulf War Illness, a potential role of the adaptive immune system in the central nervous system pathology of this condition remains unknown. Furthermore, many of the clinical features of Gulf War Illness resembles those of autoimmune diseases, but the biological processes are likely different as the etiology of Gulf War Illness is linked to hazardous chemical exposures specific to the Gulf War theatre. This review discusses Gulf War chemical-induced maladaptive immune responses and a potential role of cellular and humoral immune responses that may be relevant to the central nervous system symptoms and pathology of Gulf War Illness. The discussion may stimulate investigations into adaptive immunity for developing novel therapies for Gulf War Illness.