Immunosuppressive Therapy In Children Research Articles

Comparison of upfront haploidentical hematopoietic stem cell transplantation and salvage haploidentical hematopoietic stem cell transplantation after immunosuppressive therapy in children with acquired severe aplastic anemia - a multicenter study.

For children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients without matched sibling donor (MSD) and matched unrelated donor (MUD), haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) can be chosen as a salvage treatment. This article aims to explore the comparison between upfront Haplo-HSCT and salvage Haplo-HSCT after IST. 29 patients received salvage Haplo-HSCT, and 50 patients received upfront Haplo-HSCT. The two groups received Bu (Busulfan, 3.2mg/kg/d*2d on days -9 to-8), CY (Cyclophosphamide, 60mg/kg/d*2d on days -4 to-3), Flu (fludarabine, 40mg/m2/d*5d on days -9 to -5) and rabbit ATG (Anti-thymocyte globulin, total dose 10mg/kg divided into days -4 to -2). The OS of the salvage Haplo-HSCT group showed no difference to the upfront Haplo-HSCT group (80.2 ± 8.0% vs. 88.7 ± 4.8%, p=0.37). The FFS of the salvage Haplo-HSCT group also showed no difference to the frontline Haplo-HSCT group (75 ± 8.2% vs. 84.9 ± 5.3%, p=0.27). There was no significant difference in the incidence of other complications after transplantation between the two groups, except for thrombotic microangiopathy (TMA). In the grouping analysis by graft source, the incidence of II-IV aGVHD in patients using PBSC ± BM+UCB was lower than that in the PBSC ± BM group (p=0.010). Upfront Haplo-HSCT and salvage Haplo-HSCT after IST in children with acquired severe aplastic anemia have similar survival outcomes. However, the risk of TMA increases after salvage Haplo-HSCT. This article provides some reference value for the treatment selection of patients. In addition, co-transplantation of umbilical cord blood may reduce the incidence of GVHD.

A multi-center interventional study to assess pharmacokinetics, effectiveness, and tolerability of prolonged-release tacrolimus after pediatric kidney transplantation: study protocol for a prospective, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b trial.

Tacrolimus, a calcineurin inhibitor (CNI), is currently the first-line immunosuppressive agent in kidney transplantation. The therapeutic index of tacrolimus is narrow due to due to the substantial impact of minor variations in drug concentration or exposure on clinical outcomes (i.e., nephrotoxicity), and it has a highly variable intra- and inter-individual bioavailability. Non-adherence to immunosuppressants is associated with rejection after kidney transplantation, which is the main cause of long-term graft loss. Once-daily formulations have been shown to significantly improve adherence compared to twice-daily dosing. Envarsus®, the once-daily prolonged-release formulation of tacrolimus, offers the same therapeutic efficacy as the conventional twice-daily immediate-release tacrolimus formulation (Prograf®) with improved bioavailability, a more consistent pharmacokinetic profile, and a reduced peak to trough, which may reduce CNI-related toxicity. Envarsus® has been approved as an immunosuppressive therapy in adults following kidney or liver transplantation but has not yet been approved in children. The objective of this study is to evaluate the pharmacokinetic profile, efficacy, and tolerability of Envarsus® in children and adolescents aged ≥ 8 and ≤ 18 years to assess its potential role as an additional option for immunosuppressive therapy in children after kidney transplantation. The study is designed as a randomized, prospective crossover trial. Each patient undergoes two treatment sequences: sequence 1 includes 4 weeks of Envarsus® and sequence 2 includes 4 weeks of Prograf®. Patients are randomized to either group A (sequence 1, followed by sequence 2) or group B (sequence 2, followed by sequence 1). The primary objective is to assess equivalency between total exposure (of tacrolimus area under the curve concentration (AUC0-24)), immediate-release tacrolimus (Prograf®) therapy, and prolonged-release tacrolimus (Envarsus®) using a daily dose conversion factor of 0.7 for prolonged- versus immediate-release tacrolimus. Secondary objectives are the assessment of pharmacodynamics, pharmacogenetics, adherence, gut microbiome analyses, adverse events (including tacrolimus toxicity and biopsy-proven rejections), biopsy-proven rejections, difference in estimated glomerular filtration rate (eGFR), and occurrence of donor-specific antibodies (DSAs). This study will test the hypothesis that once-daily prolonged-release tacrolimus (Envarsus®) is bioequivalent to twice-daily intermediate-release tacrolimus after pediatric kidney transplantation and may reduce toxicity and facilitate medication adherence. This novel concept may optimize immunosuppressive therapy for more stable graft function and increased graft survival by avoiding T-cell mediated and/or antibody-mediated rejection due to improved adherence. In addition, the study will provide data on the pharmacodynamics and pharmacogenetics of prolonged-release tacrolimus in children and adolescents. EUDRA-CT 2019-003710-13 and ClinicalTrial.gov, identifier NCT06057545.

Efficacy of eltrombopag with immunosuppressive therapy forchildren with acquired aplastic anemia.

Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates. Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

The outcomes of renin-angiotensin-aldosterone system inhibition and immunosuppressive therapy in children with X-linked Alport syndrome.

Alport syndrome (AS) is characterized by progressive kidney disease. There is increasing evidence that renin-angiotensin-aldosterone system (RAAS) inhibition delays chronic kidney disease (CKD) while the effectiveness of immunosuppressive (IS) therapy in AS is still uncertain. In this study, we aimed to analyze the outcomes of pediatric patients with X-linked AS (XLAS) who received RAAS inhibitors and IS therapy. Seventy-four children with XLAS were included in this multicenter study. Demographic features, clinical and laboratory data, treatments, histopathological examinations, and genetic analyses were analyzed retrospectively. Among 74 children, 52 (70.2%) received RAAS inhibitors, 11 (14.9%) received RAAS inhibitors and IS, and 11 (14.9%) were followed up without treatment. During follow-up, glomerular filtration rate (GFR) decreased < 60 ml/min/1.73 m2 in 7 (9.5%) of 74 patients (M/F=6/1). In male patients with XLAS, kidney survival was not different between RAAS and RAAS+IS groups (p=0.42). The rate of progression to CKD was significantly higher in patients with nephrotic range proteinuria and nephrotic syndrome (NS), respectively (p=0.006, p=0.05). The median age at the onset of RAAS inhibitors was significantly higher in male patients who progressed to CKD (13.9 vs 8.1 years, p=0.003). RAAS inhibitors have beneficial effects on proteinuria and early initiation of therapy may delay the progression to CKD in children with XLAS. There was no significant difference between the RAAS and RAAS+IS groups in kidney survival. AS patients presenting with NS or nephrotic range proteinuria should be followed up more carefully considering the risk of early progression to CKD.

Antibody waning after immunosuppressive chemotherapy and immunomodulators, re-immunization considerations in pediatric patients with malignancy and chronic immune thrombocytopenic purpura

IntroductionImmunosuppressive chemotherapy increase the risk of vaccine-preventable infectious diseases in children; nevertheless, chemotherapy may result in delay or miss updated immunization schedules. The predictable antibody waning after incomplete primary immunization series may be intensified at the end of chemotherapy. This study aimed to investigate post-chemotherapy vaccine immunity waning at the end of immunosuppressive therapy in children with malignancy and hematologic disorders.Materials and methodsChildren with malignancies and hematologic disorders including chronic immune thrombocytopenic purpura (ITP) younger than 18 years old were enrolled from September 2015 to August 2019. Eligible patients who completed their treatment protocol for at least 6 months were recruited. The patient information, including sex, age at the date of diagnosis, number of chemotherapy sessions, underlying disease, and vaccination history, was taken by chart review using predefined questionnaires. The patient’s blood samples were obtained, and serum IgG antibody titer checked against diphtheria, tetanus, hepatitis B virus (HBV), mumps, measles, and rubella (MMR) were measured by enzyme-linked immunosorbent assay (ELISA).Results110 children receiving immunosuppressive chemotherapy were recruited. Forty-four (40%) of the children tested were girls and 66 (60%) were boys. The mean age of patients was 5.5 years with a range of 2 to 13 years. Of 110 studied children, 27.3% were seronegative for all antibodies. On average, patients undergo 19 episodes of chemotherapy. The mean chemotherapy sessions were significantly greater in children who were seronegative for all tested antibodies (mean: 36.2, 95% CI 33.16 to 39.24, p-value < 0.001). No statistically significant differences were observed regarding the patient’s sex and age between the seropositive and seronegative groups (p-value 0.513 and 0.060, respectively). Based on Poisson regression model analysis, the female gender was associated with 37% lower odds of seronegativity (incidence rate ratio (IIR): 0.63; [95% conf. interval: 0.39 to 1.01, p-value: 0.55]), while chemotherapy sessions 30 or more was associated with significant odds of seronegativity for all tested vaccines (IIR: 25.41; [95% conf. interval: 6.42 to 100.57, p-value < 0.001]).ConclusionOur results reemphasized planned catchup immunization in children undergoing immunosuppressive chemotherapy for malignancy, especially against tetanus, diphtheria, and hepatitis B at least 6 months after the end of chemotherapy sessions.

Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia.

To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA). A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed. The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05). SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.

Improved outcomes in immunosuppressive therapy in children with severe aplastic anemia with the addition of Eltrombopag

Improved outcomes in immunosuppressive therapy in children with severe aplastic anemia with the addition of Eltrombopag

Study of the Outcome of Pediatric Patients with Aplastic Anemia treated with Immunosuppressive Therapy at Ain Shams University Pediatric Hospital

Abstract Background Aplastic anemia (AA) is life threatening disorder in pediatric age group with an increasing incidence nowadays. Hematopoietic stem cell transplant being the 1st line therapy; immunosuppressive therapy (IST) is the alternative therapy and is the most commonly used modality of treatment especially in the developing countries. Aim of the Work to assess the outcome of IST in children with severe and very severe AA. Patients and Methods Data for 23 children treated with IST from January 201 0 to January 201 9 (10 years) were retrieved from clinic records. IST included rabbit anti thymocyte globulin (ATG) along with cyclosporine A and another group were treated by sandimmune alone. Results Patient characteristics included median age (9) with 73.9% male and 26.1% female. With median interval between diagnosis and start of IST 2(1 -5) months and around 30.4% with hepatitis A associated aplastic anemia. Complete response, and no response were seen in 4 (50%) patients and 4(50%) patients, respectively in patients received ATG and sandimune. While in patients received sandimune alone complete response, partial response and no response were seen in 7(46.7%) patients, 5 (33.3%) patients, and 3 (20%) patients respectively. The median time to best response in the whole cohort was 2 months. There was no difference in outcome related to severity of AA, or higher Hb or platelet level. There was a significantly better rate of response in both groups of patients with higher initial TLC count (p = 0.001) initial ANC (p = 0.002), initial ALC (p = 0.001), and initial ARC (p = 0.014) before start of IST. An overall response rate in both groups around of 43.47% reported a 5-year OS. With 45.5 of patients with complete response had HAAA. A delayed time to complete response with prolonged requirement of cyclosporine therapy was detected in the study. Conclusion In a developing country setting, IST with ATG and cyclosporine seems to be an alternative treatment for children with aplastic anemia lacking MRD.

Study of the Outcome of Pediatric Patients with Aplastic Anemia treated with Immunosuppressive Therapy at Ain Shams University Pediatric Hospital

Abstract Background Aplastic anemia (AA) is life threatening disorder in pediatric age group with an increasing incidence nowadays. Hematopoietic stem cell transplant being the 1st line therapy; immunosuppressive therapy (IST) is the alternative therapy and is the most commonly used modality of treatment especially in the developing countries. Aim of the Work to assess the outcome of IST in children with severe and very severe AA. Patients and Methods Data for 23 children treated with IST from January 201 0 to January 201 9 (10 years) were retrieved from clinic records. IST included rabbit anti thymocyte globulin (ATG) along with cyclosporine A and another group were treated by sandimmune alone. Results Patient characteristics included median age (9) with 73.9% male and 26.1% female. With median interval between diagnosis and start of IST 2(1 -5) months and around 30.4% with hepatitis A associated aplastic anemia. Complete response, and no response were seen in 4 (50%) patients and 4(50%) patients, respectively in patients received ATG and sandimune. While in patients received sandimune alone complete response, partial response and no response were seen in 7(46.7%) patients, 5 (33.3%) patients, and 3 (20%) patients respectively. The median time to best response in the whole cohort was 2 months. There was no difference in outcome related to severity of AA, or higher Hb or platelet level. There was a significantly better rate of response in both groups of patients with higher initial TLC count (p = 0.001) initial ANC (p = 0.002), initial ALC (p = 0.001), and initial ARC (p = 0.014) before start of IST. An overall response rate in both groups around of 43.47% reported a 5-year OS. With 45.5 of patients with complete response had HAAA. A delayed time to complete response with prolonged requirement of cyclosporine therapy was detected in the study. Conclusion In a developing country setting, IST with ATG and cyclosporine seems to be an alternative treatment for children with aplastic anemia lacking MRD.

Safety and efficacy of mycophenolate mofetil as first-line immunosuppressive therapy in children with steroid-dependent nephrotic syndrome

Introduction. More than half of children with idiopathic nephrotic syndrome have relapsed or become steroid-dependent after the disease’s onset. So far they, require long-term therapy with glucocorticosteroids and/or other immunosuppressive treatment to maintain remission. Despite the widespread use of immunosuppressive agents, there is no consensus for appropriate first-line therapy. Materials and methods. A retrospective study included children presenting with steroid-dependent nephrotic syndrome who received treatment with mycophenolate mofetil in the Nephrology department between 2003 and 2018 at the National Medical Research Center for Children’s Health (Moscow). Results. In total, withdrawal of corticosteroids was recorded in 24 (85.7%) patients, while the median remission period was 23 [12; 30] months, after glucocorticosteroids cessation - 19 [10; 24.5] months, the cumulative dose of steroids was reduced from 189 [125.9; 240] to 45.5 [19.5; 68.2] mg/kg per year and relapses rate per year from 1.9 [1.35; 2.35] to 0 during a year. Among children who did not overcome steroid dependence, the treatment failed in 3 patients, and in 1 child, the steroid dosage has been reduced to the lower dose. Conclusion. Mycophenolate mofetil has a favorable efficacy due to the significant reduction of the cumulative dose of steroids and maintenance of long-term remission of nephrotic syndrome after glucocorticosteroid cessation and may be recommended as the first-line therapy in children with steroid-dependent nephrotic syndrome.

Preventive Tuberculosis Services Reduces the Risk of Local Forms of Tuberculosis Development in Children on Immunosuppressive Therapy: Retrospective Cohort Study

Background. Long-term immunosuppressive therapy in children (including genetically engineered biologic drugs, GEBD) is associated with a high risk of local tuberculosis (TB) development. Objective. The aim of the study was to examine efficacy of tuberculosis services in children with high risk of developing tuberculosis associated with immunosuppressive therapy.Methods. The study included children at the age from 0 to 17 years on immunosuppressive therapy due to autoimmune disease and who were referred to phthisiatrician consultation. The incidence of TB was estimated one year after in groups receiving preventive TB services (isoniazid and pyrazinamide for 3–6 months) due to the high risk of TB development (contact with TB patients and/or controversial or positive test results with tubercular recombinant allergen) or not receiving such therapy (no indications for preventive treatment, parents’ refusal). The source of any data was medical documentation.Results. Preventive tuberculosis service was performed in 167 (60%) out of 279 children included in the study, 112 children did not receive such treatment (5 cases — parents’ refusal, 107 cases — lack of indications for preventive treatment). TB was detected in 1 (0.6%) child after one year in the preventive treatment group, and in 14 (12.5%) children (p &lt; 0.001) in the group without preventive treatment. Thoracic lymph nodes tuberculosis was diagnosed in 4 (27%) patients among all who has developed TB, tuberculous primary complex — in 3 (20%) patients, focal tuberculosis in 7 (46%) patients, disseminated tuberculosis in 1 (7%) patient.Conclusion. Preventive tuberculosis service reduces the risk of tuberculosis in children on administration of immunosuppressive drugs, including GEBD.

Pediatric Sympathetic Ophthalmia: 20 Years of Data From a Tertiary Eye Center in India.

To examine the clinical profile of sympathetic ophthalmia among the pediatric age group. Retrospective review of patients 18 years and younger with sympathetic ophthalmia seen in a tertiary eye care center between 1997 and 2017. Of 20 patients included in the study, 70% were male. The most common inciting event for sympathetic ophthalmia was trauma (85%), followed by vitreoretinal surgery (15%). All patients were treated with systemic steroids. Seventeen patients received additional corticosteroid-sparing immunosuppressive agents, and 4 patients (20%) required more than one immunosuppressive agent. Azathioprine was the most commonly used corticosteroid-sparing immunosuppressive agent. The most common complications were cataract (50%) and ocular hypertension (30%). The mean presenting best corrected visual acuity in the sympathizing eye was 1.15 ± 0.99 logarithm of the minimum angle of resolution (logMAR), which improved to 0.54 ± 1.00 logMAR following treatment. Visual outcome was good (6/12 or better) in 70% of the sympathizing eyes, and 3 of the exciting eyes in the current study had good visual outcomes after the treatment. Prompt and effective management with corticosteroid-sparing immunosuppressive therapy in children with sympathetic ophthalmia allows favorable control of the disease and retention of good visual acuity. [J Pediatr Ophthalmol Strabismus. 2020;57(3):154-158.].

Иммуносупрессивная терапия при стероид-зависимом нефротическом синдроме у детей. Обзор литературы

Иммуносупрессивная терапия при стероид-зависимом нефротическом синдроме у детей. Обзор литературы

Immunosuppressive therapy in children with primary nephrotic syndrome: single center experience, Karachi, Pakistan

BackgroundMajority of children with nephrotic syndrome are steroid sensitive, but treatment of difficult to treat nephrotic (frequent relapsing, steroid dependent and steroid resistant) syndrome is challenging. Low dose steroid, levamisole, cyclophosphamide (CPM), mycophenolate mofetil (MMF) and calcineurin inhibitors (CNIs) are the common options of treatment.Objective of the study was to determine the response to steroid and alternative immunosuppressive agents (ISAs) in children with difficult nephrotic syndrome (DNS).MethodsThis is a retrospective cohort study of 176 children with DNS, managed over 12 years at The Kidney Center-Postgraduate Training Institute, Karachi- Pakistan from 2005 to 2017.Initial episode was treated with daily oral prednisolone (OP) for 4–8 weeks followed by alternate day OP for 12–24 weeks. Subsequently low dose OP, levamisole (Leva)and cyclophosphamide was used for frequent relapsing (FR)/ steroid dependent (SD). All with initial steroid resistance and non- responders to leva and or cyclophosphamide were biopsied and treated with CNIs and MMF. Data was analyzed using descriptive statistics.ResultsThere were 130(73.86%) children with FR/SD and 46(26.13%) with SRNS. All children with SR (46) and 86 with FR/SD were biopsied. Minimal change disease (60.60%) and focal segmental glomerulosclerosis (FSGS 23%) were the two common lesions. Majority (73.86%) received single OP whereas divided doses were administered in 26.13% cases. Daily OP was used for 4, 6 and 8 weeks in 61.36,28.4 and10.22% respectively. Steroids were tapered over 3 (31.81%),4 (52.27%) and 6 months (15.90%). Levamisole, CPM, cyclosporin (CS) and MMF were used sequentially in 45, 54.23, 50 and 20% respectively. Combination of MMF and CS was used in 11.29% of cases.Levamisole was effective in 80%, CPM induced complete remission (CR, 57.77%) or partial remission (PR, 22.22%), CS induced CR 46.59% and PR 39.77%. MMF showed PR and CR 69 and 12.82% respectively. At last follow up, 46% were maintaining remission while off treatment, whereas 35% are maintaining remission on therapy,10.23% lost- to-follow, 5.68% progressed to chronic kidney disease. Mortality was 2.84% and it was due to infection and uremia.ConclusionMajority had steroid sensitive MCD. Levamisole and cyclophosphamide were effective in maintaining remission in FR/ SD. FSGS was responsible for resistance to steroid and alternative ISAs. Cyclosporin was effective in inducing remission in SRNS. Mortality was less than 3%.

Aplastic anemia in children: How good is immunosuppressive therapy?

Aplastic anemia (AA) is an uncommon disorder in children, with hematopoietic stem cell transplant being the 1st line therapy; immunosuppressive therapy (IST) is the alternative therapy and is the most commonly used modality of treatment. There is paucity of data from the developing countries regarding treatment outcome with IST. We aimed to assess the outcome of IST in children with AA. Data for 43 children treated with IST from January 2012 to January 2017 (5 years) were retrieved from clinic records. IST included equine antithymocyte globulin (ATG) along with cyclosporine A. Complete response, partial response and nonresponse was seen in 9 (21%), 14 (32.5%) and 20(46.5%) patients, respectively. The median time to best response in the whole cohort was 19.1 months. However, complete response occurred nearly 2-year post-IST. There was no difference in outcome related to severity of AA, the presence of PNH clone, higher ALC or different available brands of ATG. There was a significantly better rate of response (p value: .03) at 6 months in patients who went on to achieve a CR vs patients who achieved a final PR only. An overall response rate, including partial and complete response, of 53.5% was seen in our cohort with a 3-year OS of 63%. This is not at par to the outcome reported from developed nations. The available brands of ATG were similar in terms of response kinetics as well as survival. A delayed time to complete response with prolonged requirement of cyclosporine therapy was seen in the cohort.

Multivariate logistic analysis of predictors of response to immunosuppressive therapy in children with aplastic anemia: a double-center study

ABSTRACTBackgroundImmunosuppressive therapy (IST) composed of antithymocyte globulin (ATG) and cyclosporine A (CSA) is one of the standard therapies in pediatric patients with acquired aplastic anemia (AA), but predictors of IST are lack of consensus.ProceduresNinety-four patients from two pediatric medical centers in China were included between January 2005 and March 2018. Clinical factors associated with the efficacy were analyzed according to multivariate logistic regression model previously established.ResultsWe discovered that overall responsiveness was 77.66%. Five out of 35 factors were statistically significant in univariate analysis. Based on the cutoff point chosen by receiver operating characteristic (ROC) curve, 5 continuous variables were made categorical, among which 3 variables with significance were employed to establish the logistic regression equation. Based on these 3 variables, we found that starting IST within 126 days of the first appearance of symptoms (X1, p = .003), absolute neutrophil count (ANC) higher than 0.435×109/L (X2, p = .012), and rate of decreased actual lymphocyte count (ALC) higher than 59.2% within the 1st week after IST (X3, p = .001) were three independent risk factors for response to IST. The rate of decreased ALC higher than 59.2% after IST was the most significant variable (OR = 9.355, Log (P) = −2.161 + 2.149X1 + 1.662X2 + 2.236X3). The accuracy, sensitivity, and specificity of the model were 86.2%, 94.5% and 57.1%, respectively.ConclusionDuration of AA, ANC and decreased ALC rate after IST might predict the response to IST, among which the rate of decreased ALC after IST is the most important predictive factor.

Elevated Serum Interleukin-6 Predicts Favorable Response to Immunosuppressive Therapy in Children With Aplastic Anemia.

Immunosuppressive therapy (IST) is the standard treatment for aplastic anemia (AA) children who lack a sibling donor, but the clinical response rate to IST varies. Predictors of response to IST are valuable for stratifying AA patients and making clinical decisions. The serum interleukin (IL)-6 levels of 41 AA patients were measured at the time of diagnosis and the response rate of the patients to IST was evaluated at 3, 6, and 12 months after IST. Receiver-operator characteristic (ROC) analysis was used to calculate the predictive value of initial IL-6 levels in determining response at 6 months after IST. The initial IL-6 levels were significant higher in responders than nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8 pg/mL as a threshold, there were 80% sensitivity and 81% specificity for discriminating responders and nonresponders to IST. Patients with initial high IL-6 level (>36.8 pg/mL) have favorable response rates than those with initial low IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). High levels of IL-6 at the time of diagnosis predict a favorable response to IST in children with AA and this may be helpful for patient's stratification and clinical decisions.

Immunosuppressive therapy in children with steroid-resistant, frequently-relapsing, and steroid-dependent idiopathic nephrotic syndrome: a single center experience.

IntroductionImmunosuppressive agents are recommended for the management of children with steroid-resistant (SRNS), frequently-relapsing (FRNS), and steroid-dependent idiopathic nephrotic syndrome (SDNS). This study evaluated the efficacy of immunosuppressive agents in these cases.MethodsThis is a retrospective analysis of the records of 130 pediatric cases recruited from a tertiary-care center over a period of two years. They were divided into two groups: 51 patients with SRNS (Group I) and 79 cases with SDNS and FRNS (Group II). They were treated with immunosuppressive agents in addition to steroids, either as double- or triple-combination therapy. Complete or partial remission was considered a good response.ResultsIn group I, the proportions of good response to cyclophosphamide, cyclosporine A, and mycophenolate mofetil were 48.6, 60, and 80%, respectively (p = 0.162). In group II, the resistance rate was significantly higher with levamisole than with cyclophosphamide and azathioprine (p = 0.046). Leukopenia was reported infrequently after the administration of cyclophosphamide or azathioprine. The most serious adverse reaction was to cyclosporine A, which induced nephrotoxicity (6.4%), while no adverse effects related to levamisole were reported. Histopathological diagnoses were available in only 39 patients.ConclusionThe high potency of cyclosporine with steroids recommends its use in patients with idiopathic SRNS with a normal glomerular filtration rate. Its efficacy is augmented when combined with mycophenolate mofetil. Cyclophosphamide, orally or as intravenous boluses, together with alternate-day steroids, could be a good option outside the peripubertal age. The outcomes of FRNS and SDNS could be improved by encouraging compliance with the use of levamisole.

Markedly High Plasma Thrombopoietin (TPO) Level is a Predictor of Poor Response to Immunosuppressive Therapy in Children With Acquired Severe Aplastic Anemia.

Immunosuppressive therapy (IST) is commonly used for patients with acquired severe aplastic anemia (SAA). Because the clinical response rate and therapeutic outcome for individual patients to IST varies, an in vitro test that identifies potential responders would be desirable. We evaluated the relationship between thrombopoietin (TPO) levels at the time of diagnosis and the response to IST at 6 months in 85 children (median age, 9.0 years; range, 1.0-15.5 years) with acquired SAA using enzyme-linked immunosorbent assay. Thirty-one age-matched healthy individuals were used as controls. All patients received antithymocyte globulin and cyclosporine. Overall, 39 patients (45.9%) responded to IST at 6 months. TPO plasma levels were significantly higher in nonresponders than in responders (1,555.8 vs. 1,284.7 pg/ml, respectively; P = 0.031). Multivariate analysis identified the TPO levels of >1,796.7 pg/ml (TPO-high group, 20 patients; odds ratio (OR), 8.285; 95% confidence interval (CI), 2.114-32.904; P = 0.002) as independent poor predictors of IST response at 6 months. Moreover, the TPO-high group was associated with lower 5-year failure-free survival rates (30% vs. 68%, P = 0.012) compared with the TPO-low group. The measurement of TPO levels at diagnosis is useful for predicting the response to IST in children with SAA and may help in decision making.

Allogeneic Stem Cell Transplantation Is Superior to Immunosuppressive Therapy in Children with Aplastic Anaemia – a Single Centre Analysis from India

Allogeneic Stem Cell Transplantation Is Superior to Immunosuppressive Therapy in Children with Aplastic Anaemia – a Single Centre Analysis from India