Caspian Journal of Internal Medicine

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Background: Central Nervous System (CNS) relapse in acute lymphoblastic leukemia was significantly decreased due to the use of new chemotherapyeutic agents, Intrathecal chemotherapy and cranial irradiation. The purpose of this study was to compare the effectiveness of intrathecal (IT) CNS chemotherapy alone versus combination of IT chemotherapy with cranial irradiation for prevention of CNS relapse.
Methods: From 1998 to 2008 ninety eight cases of acute lymphoblastic leukemia (ALL) admitted in Amirkola Children Hospital were enrolled in this study. The chemotherapy regimen was on the basis of protocol of BFM-79. CNS prophylaxis consisted of intrathecal Cytarabin or Methotrexate, in addition to cranial irradiation for patients more than 3 years old. We assessed the incidence of CNC relapses over 10 years of CNS prophylaxis regimen.
Results: From ninety eight cases, 53 were females and 45 were males. Twenty six were below 3 years old and seventy two were above 3 years old (p<0.05). For 10 years of study for the 72 cases who were more than 3 years old and had received prophylactic cranial irradiation CNS relapse did not happen. Among the 26 cases below 3 years old who didnot receive prophylactic cranial irradiation CNS relapse for one case happened (3.8%) (p<0.05).
Conclusion: The results show that the combination of prophylactic CNS irradiation and intrathecal chemotherapy is effective in prophylaxis of CNS relapse in ALL.

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Background: The treatment of human brucelosis is controversial. The purpose of this study was to search published clinical trial papers to provide a simple and effective treatment in brucellosis.
Methods: Many studies on brucellosis treatment in a twenty- year span from 1993 to 2012 were searched in PubMed, Web of Science (ISI), Scopus, Google Scholar, Magiran, Iranmedex and SID. The studies that were searched and classified in groups according to combination therapy and monotherapy and their results in treatment outcome were compared. Regimens with lower treatment failure or relapse were considered as more suitable for brucellosis treatment.
Results: The comparison of combined doxycycline and rifampicin (DR) with a doxycycline plus streptomycin (DS) favors the latter regimen. The combined doxycycline/co-trimoxazole (DCTM) showed similar effect with DR. The treatment with the combined regimen including quinolones was similar to DR but with higher relapse rates. Higher relapse rate was searched in monotherapy (13% vs. 4.8%) and in short-term (less than 4 weeks) treatment regimen (22% vs. 4.8%), respectively. Although in children, clinical trials were limited but showed cotrimoxazole plus rifampin for six weeks was the best treatment regimen.
Conclusion: In uncomplicated brucellosis in adult patients, doxycycline-aminoglycoside combination is the first choice with doxycycline- rifampin and doxycycline-cotrimoxazole should be the alternative regimens. The other oral regimens including quinolones may be considered as alternatives. Cotrimoxazole plus rifampin for six weeks may be the regimen of choice for the treatment of patients younger than 8 years old. Gentamicin for 5 days plus cotrimoxazole for six weeks may be a suitable alternative regimen.

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Background: Chronic hepatitis B virus infection (HBV) may reactivate during the course of the disease and is called spontaneous relapse. The purpose of this study was to evaluate the incidence of relapse of hepatitis in subjects with inactive HBV carriers.
Methods: This follow-up study was performed on 785 patients with inactive HBV carriers that were followed-up at six month intervals. The presence of serum HBsAg and anti-HBe, without HBeAg, HBV DNA levels <2000 IU/ml with normal alanine aminotransferase (ALT) levels was defined as inactive carriers. Patients who developed ALT ≥80 IU/L with HBV DNA levels ≥2000 IU/ml were considered as spontaneous relapse.
Results: Seven hundred- eighty five cases (441 males, 344 females) of chronic HBV infected individuals were followed-up. The mean age at the entrance of the study was 30.5±11.8 years. The mean follow-up duration was 5.9±5 years. Relapse was seen in 35 (4.5%) cases,  in 27 out of 441 (6.1%) males and in 8 out of 344 (2.3%) females and in 4.2% subjects ≥ 30 years versus in 4.7% cases of under 30 years (p>0.05). The development of relapse in males was higher than females (hazard ratio 2.53, 95% CI 1.2-5.6, p=0.021), but age ≥30 or < 30 years did not have effect (hazard ratio1.21, 95% CI 0.62-2.36, p=0.58).
Conclusions: The results show that spontaneous relapse of hepatitis may develop during the course of chronic HBV infection. We suggest that all patients with chronic hepatitis B, regardless of their age, be examined for the possibility of relapse.

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Background: Rituximab has been used successfully in the recent years for treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a uniform treatment protocol for maintenance therapy and the best interval for evaluation and retreatment have not been postulated. We evaluated the efficacy and safety of rituximab treatment as second line therapy, in Iranian patients with refractory NMOSD, based on annualized relapse rate (ARR) and expanded disability status scale (EDSS).
Methods: In this prospective before-after study, a total of 18 patients were treated with a loading dose of rituximab (375 mg/m² weekly in 4 consecutive weeks). Flow cytometric determination of CD19⁺ B cell in peripheral blood sample was carried every 6 weeks and patients were re-treated based on B cell repopulation with a single dose of 375 mg/m². Wilcoxon signed rank test was used to evaluate the ARR and EDSS before and after treatment. A p-value of <0.05 was considered statistically significant.
Results: Of the 18 patients, 10 (55.5%) were relapse-free during the period of follow up. The EDSS scores were reduced in nine (50%) patients and stable in the remaining nine (50%). The mean EDSS score before and after treatment were 4.1±0.4 and 3.7±0.3, respectively, which was statistically significant. There was also a statistically significant reduction in median ARR after treatment (1.48 (range 0.47-5) vs. 0 (range 0-2)). Rituximab administration did not have significant adverse effect in 94% of patients.
Conclusion: Repeated treatment with Rituximab is an effective and well-tolerated treatment in refractory NMOSD.

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Background: Anti-CD20 are among the high-efficacy DMTs commonly used in treating multiple sclerosis (MS). Long-term safety data on anti-CD20s are limited. There is convincing evidence of hypogammaglobulinemia in the long-term use of anti-CD20s, raising the likelihood of infection. Accordingly, there is an unmet need for de-escalation therapy in stable patients to reduce adverse events. Herein we aimed to describe our experience with ten relapse-remitting MS (RRMS) patients who were switched from anti-CD20s to the low-moderate efficacy DMTs.
Methods: This cohort study was conducted between January 2020 and February 2023 at the MS Research Center of Sina Hospital, Tehran, Iran, to identify the characteristics of RRMS patients who were switched from anti-CD20s to low-moderate efficacy DMTs within 12 months of the last anti-CD20 infusion. Patients were then followed up to 18 months after de-escalation.
Results: All patients were females, with a mean age of 39.3±2.53-year-old and a mean disease duration of 9.7±1.39 years. After a mean of 2.95±0.44 years of treatment with anti-CD20s, patients were de-escalated to INF-β1a (n=5), dimethyl fumarate (DMF) (n=3), fingolimod (n=1), and teriflunomide (n=1). The main reason for anti-CD20 discontinuation was an infectious concern. Within 18 months of follow-up, no patient developed clinical or MRI activity. Additionally, we did not find evidence of disability progression in any patients (P=0.13).
Conclusion: The present study is a real-world experience of de-escalating anti-CD20s to low-moderate efficacy DMTs, which suggests that at short-term follow-up, de-escalating anti-CD20s appeared to be effective and safe in RRMS patients.
 

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Background: COVID-19 could exacerbate the symptoms of autoimmune diseases such as multiple sclerosis (MS). Literature shows an increase in the incidence of relapse in patients with MS after COVID-19. We designed this systematic review and meta-analysis to estimate the pooled incidence of MS-relapse after COVID-19.
Methods: We performed a systematic search in PubMed, Scopus, EMBASE, Web of Science, and Google scholar. Gray literature including references of the references and conference abstracts were also searched to find relevant articles. We extracted data regarding the total number of participants, the name of the first author, publication year, country of origin, mean age, mean disease duration, mean Expanded Disability Status Scale (EDSS), and the number of patients with relapse after COVID.
Results: A literature search revealed 5160 articles, after deleting duplicates, 2270 remained. After careful evaluation of the full texts, twelve studies were included for meta-analysis. Totally, 1595 patients with MS who had a history of COVID-19 were evaluated. Most studies were done in Iran. The mean age of included patients ranged between 35 and 49 years, and mean durations of the disease were between 7and 15.4 years. The incidence of relapse ranged between 2% and 20% in included studies.
The pooled incidence of relapse after COVID-19 was 7% (95%CI:5-10%) (I2=64%, p<0.001).
Conclusions: The results of this systematic review and meta-analysis show that the pooled incidence of MS-related relapse after COVID-19 is 7%.