Ewing sarkomlu çocuk hastaların klinik özellikleri, prognostik faktörleri ve tedavi sonuçları: Tek merkez deneyimi

Introduction: Ewing sarcoma (ES) is a rare, aggressive, malignant tumor. It is the second most common malignant bone tumor in children. A total of 20-25% of patients are metastatic at the time of diagnosis. The survival rate for localized disease (LD) is approximately 70-74%. For metastatic disease (MD), it is about 30%. The most important prognostic factor affecting survival is the presence of MD at diagnosis. In this study, we investigated the clinical characteristics, treatment outcome, and factors affecting the prognosis and survival of patients followed up with the diagnosis of ES. Materials and Methods: Between 2007 and 2020, a total of 24 ES patients aged 0-18 years were retrospectively analyzed. Results: The most common complaint was pain and swelling in the lesion area (n=9), followed by pain (n=5), swelling (n=3), abdominal pain (n=2), shortness of breath (n=2), facial paralysis (n=1), spinal compression findings (leg pain and walking difficulty) (n=1) and hematuria (n=1). ES was bone-derived in 19 patients (79%). Of these, 14 had LD and 5 had MD at the time of diagnosis. Extraskeletal Ewing sarcomas (EES), was detected in five patients (21%) and derived from the kidney (n=1), rectus abdominis (n=1), left quadriceps femoris muscle (n=1), left upper thoracic region and lumbar region paraspinal muscles (n=2). The rate of MD was 25% (6/24) in the entire patient group. Disease progression was observed in three patients during treatment. Relapse at follow-up was observed in 6 of 19 patients in complete remission. The median time to relapse was 20 months (minimum 13, maximum 34 months) from diagnosis. The median survival of our patients after relapse was 14.5 months (minimum 6-maximum 27 months). Radiological response and histopathological response to induction therapy, presence of relapse or progression, and relapse site were found to be correlated with survival (Fisher’s Exact test p=0.02, 0.0047, [removed]Giriş: Ewing sarkomu nadir görülen, agresif, malign bir tümördür. Çocuklarda görülen ikinci en sık malign kemik tümörüdür ES tanı sırasında lokal (LH) ve metastatik hastalık (MH) olarak karşımıza çıkabilir. %20-25 hasta tanı sırasında metastatiktir. LH’de sağkalım yaklaşık %70-74’tür. MH’de ise %30 civarındadır. Sağkalımı etkileyen en önemli prognostik faktör tanı sırasında MH varlığıdır. Bu çalışmamızda ES tanısı ile takip ettiğimiz hastaların klinik özelliklerini, tedavi yanıtlarını, prognozu etkileyen faktörleri ve sağkalımlarını değerlendirmeyi amaçladık. Gereç ve Yöntem: Hastanemizde 2007-2020 yılları arasında ES tanısı ile tedavi gören 0-18 yaş 24 hasta retrospektif olarak değerlendirildi. Bulgular: Başvuru şikayetleri en sık lezyon bölgesinde ağrı ve şişlik (n=9) iken, ağrı (n=5), şişlik (n=3), karın ağrısı (n=2), nefes darlığı (n=2), yüz felci (n=1), bacaklarda ağrı-yürümede zorluk yakınması ile gelen olgumuzda spinal bası bulguları (n=1) ve hematüri (n=1) hastaneye başvuru nedenleri idi. ES 19 hastada (79%) kemik kaynaklıydı. Bunların 14’ünde tanı sırasında lokal, 5’inde metastatik hastalık mevcuttu. Beş hastada (21%) ise ekstraskeletal saptanmış olup, böbrek (n=1), rektus abdominis (n=1), sol kuadriseps femoris kası (n=1), sol üst torakal bölge ve lomber bölge paraspinal kasları (n=2) kaynaklıydı. Tüm hasta grubunda MH oranı 25% (6/24) idi. Üç hastada tedavi altında progresyon görüldü. Tam remisyona giren 19 hastanın 6’sında (6/19) izlemde relaps gözlendi. Relaps zamanı tanıdan itibaren ise ortanca 20 ay (minimum 13, maksimum 34) idi. Hastalarımızın relaps sonrası yaşam süresi ortanca 14.5 ay (minimum 6-maksimum 27 ay) idi. İndüksiyon tedavisine radyolojik yanıt, indüksiyon tedavisine histopatolojik yanıt, relaps ya da progresyon varlığı ve relaps yeri sağkalım ile ilişkili olarak bulundu (Fisher’s exact test p=0,02, 0,0047, <0,001, 0,001). Sonuç: ES mortalite ve morbiditesi yüksek olan bir kanser türüdür. En sık semptom ağrı ve şişlik olmakla birlikte tümörün kaynaklandığı bölgeye göre semptomlar farklılık gösterebilir. Indüksiyon tedavisine yanıt, relaps-progresyon varlığı prognozu etkileyen faktörlerdir. Sağkalımı artırmak için tedavi kişiselleştirilmelidir

A successful treatment approach in 2 patients with type 1 plasminogen deficiency: Intratracheal application of fresh frozen plasma and tissue plasminogen activator

BACKGROUND: Respiratory system involvement is common in congenital plasminogen deficiency. Although many treatment approaches have been tried, there is still no definitive treatment for respiratory system involvement. OBSERVATIONS: We report 2 congenital plasminogen deficiency cases, who presented with severe respiratory symptoms, for whom a novel treatment modality was tried. After intravenous administration of FFP (fresh frozen plasma), tissue plasminogen activator and FFP were administered intratracheally, and respiratory system findings improved. CONCLUSIONS: Intratracheal administration of tissue plasminogen activator and FFP is an available treatment modality for patients with lung involvement. Fibrin plaques should be carefully removed and new lesion formation should be prevented

Çok Düşük Serum İmmunoglobilin E Seviyesinin Klinik Önemi Var mı?

GİRİŞ: Yüksek serum immünoglobulin (Ig) E seviyeleri alerjik hastalıklar, paraziter enfeksiyonlar ve bazı bağışıklıkyetersizlikleri ile ilişkilidir; bununla birlikte, düşük IgE düzeylerinin insan bağışıklık sistemi üzerindeki potansiyeletkileri ve klinik etkileri iyi bilinmemektedir. Bu çalışma, çocuklarda ve yetişkinlerde çok düşük IgE seviyelerineeşlik eden bozuklukları belirlemeyi amaçlamaktadır.GEREÇ-YÖNTEM: Ocak 2015-Eylül 2020 tarihleri arasında IgE düzeyi belirlenen hastalar incelendi ve IgE düzeyi&lt; 2 IU/mL olan hastalar bu çalışmaya dahil edildi. Hastaların demografik verileri, immünoglobulin düzeyleri,otoantikor sonuçları ve hastaların tanıları hastanemizin elektronik kayıt sisteminden kaydedildi.BULGULAR: 34.809 hastada (21.875 çocuk, 12.934 yetişkin) IgE seviyeleri ölçüldü ve 130 hastanın IgE seviyeleri &lt; 2IU/mL idi. 57 hasta çocuk (%0,26); 73 hasta yetişkin (%0,56) idi. 34’ünde malign bir hastalık vardı (9’u çocuk) (%26),20’si (3’ü çocuk) otoimmün hastalıklar (%15.4) ve 17’si (14’ü çocuk) immünyetmezlik (%13.1) idi. Çocuklarda ensık nedenler diğer hastalıklar, immün yetmezlik ve malignite, yetişkinlerde malignite, otoimmün bozukluklar vediğer hastalıklardı. IgE seviyesi, diğer immünoglobulinlerin seviyeleri ile herhangi bir korelasyon göstermedi.SONUÇ: Nadir olmakla birlikte, düşük bir IgE düzeyinin malignitelere, otoimmün bozukluklara ve immünyetmezliklere eşlik ettiği gösterilmiştir. IgE düzeyleri çok düşük olan hastalar sistemik bozukluklar açısındandikkatle izlenmelidir.</p

Pazopanib maintenance therapy for ewing sarcoma in pediatric patients

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A Neonatal Case of Infantile Malignant Osteopetrosis Presenting with Thrombocytopenia and Hypotonicity: A Novel Mutation in Chloride Voltage-Gated Channel 7 Gene

Autosomal recessive osteopetrosis is also known as infantile malignant osteopetrosis (IMO). The clinical course is often serious andif left untreated, it is fatal in the 1st year of life. Diagnosis is challenging and often delayed or misdiagnosed. Herein, we presentan infant girl who was diagnosed with IMO during evaluations for her hypotonicity and thrombocytopenia. A novel mutation ofthe chloride voltage-gated channel 7 (CLCN7) gene was also reported. A 10-day-old female patient was referred to our hospital forevaluation of hypotonicity. Her physical examination was normal, other than hypotonicity. Laboratory analysis revealed thrombocytopenia and hypocalcemia. In the progress, while she was followed in outpatient clinic, hepatosplenomegaly was detected atthe age of 3 months. IMO was suspected with the findings of hepatosplenomegaly, cytopenia, hypocalcemia, difficulty of obtaining bone marrow, peripheral smear findings, and hearing loss. The X-ray of the bones was consistent with IMO. A novel pathogenichomozygous c.1504&gt;T (p.Arg502Trp) mutation in CLCN7 gene was revealed. IMO is a rare disorder and it is important to differentiate this entity for better clinical outcome. The presence of neurological and hematological findings, organomegaly, hearing loss,and vision disorders must attract attention to IMO.</p

A comparison of hypersensitivity reactions between intravenous and intramuscular applications of native E. coli asparaginase in children with acute lymphoblastic leukemia

Introduction: Asparaginase is an indispensable drug in treating childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions (HSR) are the most common side effects and interfere with the antineoplastic activity of the drug. This study aims to compare the intramuscular (IM) and intravenous (IV) administration routes of Native Escherichia coli Lasparaginase (L-ASNase) in terms of hypersensitive reactions. Methods: L-ASNase was randomly administered IV or IM to newly diagnosed ALL patients and HSR was monitored in all patients for 1 h following the end of the IV infusion and for 2 h following the end of the IM administration of L-ASNase. Based on a retrospective review of clinical charts, reactions were identified. In order to determine the severity of each allergic reaction, we used the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for allergic reactions. Results: A total of 1032 doses of L-ASNase were administered to 85 patients (42 males and 43 females) during the study period. Among 85 patients, 30 reactions were recorded, which means that 35% of the patients reacted. According to the CTCAE, twenty-nine out of 30 reactions (97%) were grade 2, while one (3%) was grade 4. In terms of individual doses, there was a non-significant trend toward increased incidence of reactions with IV administration (3.8% versus 0.9%, p = 0.064). The rate of reactions was higher in patients who received all IV doses (n: 60) as compared to those who received all IM doses (n: 25) (31.7% vs. 3.5%; chi-square= 8.415, p value=0.04). Based on the risk groups and HSR incidence, it was found that high risk group (HRG) patients were significantly more likely to develop HSR compared to the standart risk group (SRG) and intermediate risk group (MRG) patients (chi-square p = 0.003, CI: 95%; odds ratio: 3.12 and 5.91, respectively). Conclusions: In conclusion, IM administration of L-ASNase causes significantly less HSR to L-ASNase than the IV route. Patients with HRGALL have a higher risk of HSR. Since L-ASNase is still used in many developing countries and there are problems in the supply of Erwinia chrysanthemi ASNase (Erwinia), LASNase can be administered IM to reduce the frequency of HSR

Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: A multicentre study

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune-mediated destruction of haematopoietic cell lines. Effective and well-tolerated treatment options for relapsed-refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0–9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow-up and two of them had remission with low-dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed-refractory immune cytopenia

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group

Background: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. Objectives: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. Method: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. Results: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7–340.8; range, 0–3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p:.001) and lymphopenia at diagnosis (OR, 5.21, p:.006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p:.028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p:.003), and LRTD (OR, 10.11, p:.035) were associated with a higher risk for COVID-19-related mortality. Conclusion: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD