Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

Differential diagnostic features between congenital haemangioma, KHE, and congenital fibrosarcoma: a single-centre experience.

Congenital haemangioma (CH) is a rare benign vascular tumour presenting at birth with excellent prognosis. Usually, CH regresses without treatment within the first few months of life. Kaposiform Haemangioendothelioma (KHE) is another type of vascular tumours that has been described as benign with locally aggressive potential. Although the diagnosis of vascular tumours is usually straightforward based on typical clinical presentation, yet some confusing similarities may exist with congenital sarcomas.Conclusion: Data of cases managed at the vascular anomaly clinic during the period 2015 through 2019 were retrospectively analysed. The study included three groups of patients: cases diagnosed as congenital haemangioma (9 cases), cases of Kaposiform Haemangioendothelioma who presented in the neonatal period (7 cases), as well as cases of congenital fibrosarcoma (4 cases) that were referred to the vascular anomaly clinic because of apparent similarity with vascular tumours. The hallmark of the study was to compare clinical and imaging features in the three groups to facilitate differentiation and remove diagnostic confusion when managing these rare cases in the future. What is Known: • Congenital haemangioma is a rare benign vascular tumour presenting at birth. • Kaposiform Haemangioendothelioma is another type of vascular tumours that has been described as benign with locally aggressive potential. What is New: • Confusing similarities may exist between vascular tumours and congenital sarcomas.

Study of the diagnostic criteria for hemophagocytic lymphohistiocytosis in neonatal and pediatric patients with severe sepsis or septic shock.

Septic shock is a major public health concern. However, the clinical and laboratory criteria for sepsis overlap with those for hemophagocytic lymphohistiocytosis (HLH), and their differentiation can be challenging. The aim of this study was to compare HLH criteria among patients diagnosed with neonatal sepsis and childhood sepsis and to study the outcomes in patients fulfilling the diagnostic criteria for HLH. A cross-sectional study included 50 neonates and children with severe sepsis and/or septic shock. Clinical and laboratory data and HLH diagnostic criteria were studied in relation to patients outcome. Of all patients, 18% fulfilled three of the eight HLH diagnostic criteria, 2% fulfilled four criteria, and 4% fulfilled five criteria. All patients who fulfilled three or more of the criteria died. Mortality was higher in the presence of more positive HLH criteria and in pediatric age groups. However, the distributions of the HLH criteria were comparable for pediatric and neonatal patients with severe sepsis/septic shock, and their mortality rates were not significantly different when based on the criteria.

COVID-19 in Children With Cancer: A Single Low-Middle Income Center Experience.

BACKGROUND: Coronavirus disease-2019 (COVID-19) could be associated with morbidity and mortality in immunocompromised children. OBJECTIVE: The objective of this study was to measure the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes. METHODOLOGY: A prospective noninterventional study including all hospitalized children with cancer conducted between mid-April and mid-June 2020 in Ain Shams University Hospital, Egypt. Clinical, laboratory, and radiologic data were collected. SARS-CoV-2 infection was diagnosed by reverse transcription polymerase chain reaction tests in nasopharyngeal swabs. RESULTS: Fifteen of 61 hospitalized children with cancer were diagnosed with SARS-CoV-2. Their mean age was 8.3±3.5 years. Initially, 10 (66.7%) were asymptomatic and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 reverse transcription polymerase chain reaction were not diagnostic; the mean absolute lymphocyte count was 8.7±2.4×109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics as per the febrile neutropenia protocol and local Children Hospital guidance for management of COVID-19 in children. CONCLUSIONS: Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swab in asymptomatic hospitalized cancer patients is recommended.

Inner Ear Complications in Children and Adolescents with Sickle Cell Disease.

Hearing impairment is a reported complication of sickle cell disease, yet inner ear pathology is not fully understood. The study purpose was to examine the patterns of inner ear involvement in patients with sickle cell disease by magnetic resonance imaging (MRI) and to assess its association with auditory functions. A cross-sectional study included 22 children with sickle cell disease examined for inner ear pathology by audiogram, MRI inner ear and transcranial Doppler (TCD) with revision of their hospital records for transfusion, chelation and hydroxyurea (HU) therapy. Abnormal MRI in the form of intrinsic T1 hyperintensity within the lumen of inner ear structures and cochlear neuropathy was found in five (22.7%) patients; left middle cerebral artery (MCA) flow velocity was higher in patients with abnormal MRI (83.4 ± 5.3 cm/sec) compared to normal MRI (68.2 ± 11.1 cm/sec) (p = 0.015), however, none of the patients had TCD of >170 cm/sec. There was no significant difference between patients with normal and abnormal MRI as regards hearing level and speech audiometry. Sensorineural hearing loss (SNHL) was present in two (9.1%) and conductive hearing loss (CHL) in two (9.1%) patients. There was a significant negative correlation between right ear mean hearing level and right MCA flow velocity and significant negative correlation between left ear mean hearing level and basilar artery (BA) flow velocity. We concluded that inner ear pathology is not uncommon in asymptomatic patients with sickle cell anemia, yet it did not correlate with hearing impairment and may occur with normal TCD results.

Egyptian experience in Langerhans cells histiocytosis: frequent multisystem affection and reactivation rates.

Background: Histiocytoses are unique disorders; their clinical presentations vary from self-healing lesions to life-threatening disseminated disease. Objectives: We aimed to evaluate the different clinical presentations, frequency of reactivations, and treatment outcome of Langerhans cell histiocytosis among Egyptian children. Methods: we restrospectively analyzed the data of 37 Langerhans cell histiocytosis patients (LCH) registered at Ain Shams University Children's Hospital for clinicopathological features, treatment modalities and their outcomes. Results: Twenty seven (73%) of the studied patients with LCH had multisystem disease (MS), 24 (88.9%) of them had risk organ involvement (MS RO+) and only 3 without risk organ (MS RO-). Most of the patients received LCH III protocols. Eleven patients (29.7%) had reactivations with median time till reactivation of 17 months (IQR 5-23).Reactivation rates were 40% and 50% in patients with no evidence of active disease (NAD) and those with active disease better (AD better) at week 6 evaluation respectively (p = 0.71).We report 9 deaths (all had MS RO+, two died after reactivation and 7 had progressive disease. The 5 years EFS and OS were 49.4% and 81.2% respectively. Risk stratification did not significantly affect the EFS or OS (p = 0.64 and p = 0.5 respectively). Conclusion: A high reactivation rate was encountered in children with LCH and MS-RO + irrespective of 6 weeks response to induction therapy. A high mortality in patients with progressive disease necessitates a possible earlier aggressive salvage in such group.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.

Determinants of platelet count in pediatric patients with congenital cyanotic heart disease: Role of immature platelet fraction.

OBJECTIVES: Congenital heart defects are common noninfectious causes of mortality in children. Bleeding and thrombosis are both limiting factors in the management of such patients. We assessed the frequency of thrombocytopenia in pediatric patients with congenital cyanotic heart disease (CCHD) and evaluated determinants of platelet count including immature platelet fraction (IPF) and their role in the pathogenesis of thrombocytopenia. METHODS: Forty-six children and adolescents with CCHD during pre-catheter visits were studied; median age was 20.5 months. Complete blood count including IPF as a marker of platelet production and reticulated hemoglobin content (RET-He) as a marker of red cell production and iron status were done on Sysmex XE 2100 (Sysmex, Japan). C-reactive protein, prothrombin time (PT), Activated partial thromboplastin time (APTT) were also assessed. RESULTS: Thrombocytopenia was found in 6 patients (13%). PT was prolonged (P = .016) and IPF was significantly higher in patients with thrombocytopenia compared with patients with normal platelet count (14.15 ± 5.2% vs 6.68 ± 3.39%; P = .003). Platelet count was negatively correlated with IPF while significant positive correlations were found between IPF and hemoglobin, red blood cells (RBCs) count, hematocrit (Hct), PT, reticulocytes count, and immature reticulocyte fraction. CONCLUSIONS: We suggest that elevated IPF in CCHD patients with thrombocytopenia may denote peripheral platelets destruction as an underlying mechanism. Hemoglobin level, RBCs count, Hct, and RET-He were not significant determinants for platelet count in CCHD.

Therapeutic superiority of combined propranolol with short steroids course over propranolol monotherapy in infantile hemangioma.

UNLABELLED: Infantile hemangiomas are the most common benign childhood tumor that may have functional and/or cosmetic complications. We aimed to compare the clinical efficacy of propranolol alone and propranolol primed with systemic corticosteroids on the outcome of infantile hemangioma. A prospective randomized study included 40 infants aged less than 9 months with cutaneous hemangiomas. Patients were randomly assigned into two groups: group A were given oral prednisolone for the initial 2 weeks combined with oral propranolol, while group B were given oral propranolol alone for 6 months. The median age of the studied patients was 4.5 months (ranged 4 weeks-8 months). Sequential determination of the dimensions of the hemangiomas based on direct measurement and photographic analysis were performed. A significant reduction in the size of the lesions was found in group A in the 2-, 4-, and 8-week evaluation compared to group B (p < 0.001) with no statistical difference in the ultimate 6 month response (p = 0.134). Multiple logistic regression showed that early treatment before 6 months of age (OR 9.82, p = 0.007) and combined treatment with propranolol and prednisolone (OR 10.71, p = 0.006) were the predictors of best response. CONCLUSION: Combining propranolol with corticosteroids gives a faster response and should be considered in treating life- or function-threatening hemangiomas.

Alterations of platelet functions in children and adolescents with iron-deficiency anemia and response to therapy.

Several changes in platelets have been reported in patients with iron-deficiency anemia (IDA), so a relationship between iron metabolism and thrombopoiesis should be considered. We aimed to study the alterations of platelet functions in patients with IDA by assessment of platelet aggregation with epinephrine, adenosine diphosphate (ADP) and ristocetin and by measuring platelet function analyzer-100 (PFA-100) closure time together with the effect of iron therapy on the same tests. A follow-up study was conducted in Ain Shams University Children's hospital in the period from June 2011 to June 2012 including 20 patients with confirmed IDA and 20 healthy age- and sex-matched control. Bleeding manifestations were reported. Laboratory analysis included complete blood count, assessment of iron status by measuring serum iron, TIBC and ferritin, assessment of platelet functions by PFA-100 closure time and platelet aggregation with collagen, ADP and ristocetin. Patients with IDA were treated by oral iron therapy 6 mg/kg/day of ferrous sulfate and post-therapeutic re-assessment was done. Mean age of IDA patients was 5.7 ± 4.2 years. Bleeding manifestations were more common in patients group. Mean PFA-100 closure times (with epinephrine) were significantly longer in patients (179.1 ± 86.4 seconds) compared to control group (115 ± 28.5 seconds) (p < 0.05). Platelet aggregation by ADP (38.1 ± 22.2%), epinephrine (19.7 ± 14.2%) and ristocetin (58.8 ± 21.4%) were significantly reduced in patients compared to control (62.7 ± 6.2, 63.3 ± 6.9, 73.8 ± 8.3, respectively; p < 0.001). After treatment platelet aggregation tests induced by ADP (64.78 ± 18.25%), and epinephrine (55.47 ± 24%) were significantly increased in patients with IDA compared to before treatment (39.44 ± 21.85%, 20.33 ± 14.58%; p < 0.001). PFA-100 closure time as well showed significant decreased after treatment (118.4 ± 27.242) compared to before treatment (186.2 ± 90.35; p < 0.05). A negative correlation between platelet aggregation induced by ADP and mean values of serum ferritin before treatment (r = 0.042, p < 0.05) was found. A mutual effect is considered between iron deficiency and platelet functions. Subtle bleeding manifestations can occur in patients with IDA with delay in platelet aggregation and prolongation in PFA-100 closure times which can be reversed by iron therapy.

Outcome of childhood acute Lymphoblastic leukemia in Egyptian children: a challenge for limited health resource countries.

UNLABELLED: In childhood acute lymphoblastic leukemia (ALL) the reported 5-year event-free survival (EFS) rates are as high as 80%. Since 2004, multiple Egyptian centers shifted protocol of therapy of ALL to the CCG 1991 (the single delayed intensification arm) and CCG 1961 protocol for standard risk and high-risk ALL therapy, respectively, being cost effective. We aimed to evaluate the efficacy and safety of the CCG protocol in treatment of childhood ALL in Ain Shams and Menoufeya University hospitals. METHODS: Fifty-two ALL patients, aged 1-17 years, treated according to the modified CCG protocol in both centers and registered from November 2004 to December 2005 were included. They were classified into three risk groups, standard risk (SR), high-risk standard arm (HR-SA), and high-risk augmented arm (HR-AA). RESULTS: The mean age at diagnosis was 5.9 + 3.3 years, male/female ratio of 1.6:1, and central nervous system leukemia represented 6%. The 5-year overall survival (OS) and EFS were 84.6% and 67%, respectively. The 5-year OS and EFS were 92.6% and 70% in SR, 68.8% and 55% in HR-SA, 88.9% and 80% in HR-AA patients, respectively. Six patients had grade 3-4 adverse events. CONCLUSION: The outcome of HR-SA protocol was inferior to the other two groups, necessitating shift to a more intensified arm with double delayed intensification. The use of minimal residual disease for better risk classification of childhood ALL is recommended in our centers.