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.

HLA - matched related donor hematopoietic stem cell transplantation in a patient with polynucleotide kinase 3-phosphatase mutation developed acute myeloid leukemia.

BACKGROUND: PNPK gene mutations result in DNA repair disorders and have a spectrum of neurodevelopmental manifestations. To date, cancer predisposition has not been described in patients with PNKP mutations. OBSERVATION: Here, we report a patient with PNKP mutation, who developed AML at age of five and underwent reduced-intensity HSCT. CONCLUSION: Although many DNA repair disorders are known to have increased risk of malignancy, association between PNKP mutations and malignancy is not well-described. This report is the first description of a PNPK mutation patient developing a malignancy and undergoing curative HSCT.

Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation in children: Single-centre experience.

Delayed recovery of thrombocytopenia is a well-known complication after allogeneic HSCT. Eltrombopag (ELT), a thrombopoietin receptor agonist (TRAs), induces platelet maturation and release. Mostly conducted in adults, some of the previous studies have shown that ELT seems to enhance platelet recovery for post-allogeneic HSCT thrombocytopenia, appears efficacious, and offers transfusion independence. To evaluate the safety and efficacy of ELT in pediatric patients with prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) after alloHSCT. Retrospective analysis of childhood patients who received treatment with ELT for persistent thrombocytopenia after alloHSCT between May 2016 and August 2019. We evaluated the safety and efficacy of ELT in 18 childhood patients with PIT or SFPR after alloHSCT. Eltrombopag (50 mg/d) treatment was started in all patients, above 6 years of age and 20 kg weight, who had thrombocytopenia despite neutrophil engraftment on the 30th day of HSCT. Our objective was to decrease the need for platelet transfusion and have a platelet count of more than 50 000/µL. The overall response rate was 77.7%. The median time to achieve a platelet level above 30 000/µL and 50 000/µL was 21 and 44 days, respectively. In four patients, platelet count never reached 30 000/mm3 . In two patients, the treatment was discontinued due to grade 3 hepatotoxicity. Our study supports the efficacy and relative safety of ELT use for the treatment of PIT and SFPR seen after alloHSCT in children.

Clinical Efficacy of Ruxolitinib Monotherapy and Haploidentical Hematopoeitic Stem Cell Transplantation in a Child with Philadelphia Chromosome-like Relapsed/Refractory acute lymphoblastic leukemia.

INTRODUCTION: (Ph-like) ALL is a subset of leukemia which has a gene expression profile similar to Ph+disease, but without the presence of BCR-ABL1 translocation. CASE DESCRIPTION: We reported an exceptional case of a child with relapsed Ph-like ALL with IKZF1 gene deletion treated with high-dose ruxolitinib as monotherapy, after multi-agent chemotherapy. He remains in continued MRD-negative leukemia remission with full donor chimerism at 12 months post-HSCT. DISCUSSION: The circumstance that makes our case featured is the usage of ruxolitinib as monotherapy. This report, we believe, is a pioneering report for a frequent disease with a high risk of failure for the outcome.

Unusual Clinical Presentation of Hodgkin Lymphoma in a Child: Both Spinal Cord Compression and Hydronephrosis.

BACKGROUND: Hodgkin lymphoma (HL) is predominantly a nodal disease with extranodal presentation being uncommon. Presentation with neurological symptoms is not uncommon in adult patients with HL. Subdiaphragmatic involvements are less common especially in childhood. In the literature, there has been no case which presented with both spinal cord compression and bilateral hydronephrosis in pediatric patients with HL. OBSERVATION: We report a 9-year-old boy diagnosed with HL who presented with bilateral hydronephrosis and epidural involvement. CONCLUSION: Differential diagnosis of abdominal mass in patients presenting with spinal cord compression and/or hydronephrosis should include HL. Retrograde J ureteral stenting is the treatment of choice for malignant ureteral obstruction.

Graft-versus-host disease in a child with neuroblastoma after autologous stem cell transplantation.

In the pediatric population, hematopoietic stem cell transplantation (HSCT) is used to treat a wide variety of diseases, both malignant and nonmalignant. For many of these diseases, HSCT is a well-established treatment. Acute graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Graft versus host disease is a common complication of allo-SCT which is induced by donor T cell recognition of recipient alloantigens. The occurrence of autologous GVHD suggests that inappropriate recognition of host self-antigens may occur. GVHD in patients who received autologous HSCT is extremely rare compared to patients who received allogeneic HSCT. We present the case of a 4-year-old girl with metastatic neuroblastoma who spontaneously developed autologous GVHD after autologous HSCT.

Outcome of autologous hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory Hodgkin's lymphoma.

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara-C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.

Invasive fungal infections in children with hematologic and malignant diseases.

BACKGROUND: To evaluate the clinical feature and outcome of invasive fungal infections (IFI) in children with hematologic and malign diseases. PATIENTS AND METHODS: The medical records of children with hematologic and malignant diseases, who were hospitalized at our hospital between January 2010 and December 2011, were reviewed. Proven, probable, and possible IFIs were diagnosed according to the revised definitions of the European Organization for Research and Treatment of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated. RESULTS: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which 10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture of 10 cases with proven IFI yielded yeast and the most common isolated agent was Candida parapsilosis. Seventy percent of cases with fungemia had central venous catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The cases with mold infection had higher median C-reactive protein values, lower neutrophil counts, and longer duration of neutropenia compared with the cases with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone marrow transplantation, total parenteral nutrition, prolonged fever, and proven/probable IFI were detected more often in patients who died, compared with patients who survived. CONCLUSIONS: IFIs are important causes of death in children with hematologic and malignant diseases. Mold infections are seen more frequently in cases with prolonged and profound neutropenia, and invasive yeast infections, especially with non-albicans Candida species, in cases with CVC. Early and effective treatment considering these findings will help to decrease the mortality.

Osteopoikilosis: report of a familial case and review of the literature.

Osteopoikilosis (OPK) is a benign, rare, asymptomatic osteosclerotic bone dysplasia which is inherited as an autosomal dominant trait. It may develop during childhood and persists throughout life. Diagnosis is usually made incidentally according to radiographs. It may be confused with other conditions, such as osteoblastic metastases. OPK must be in differential diagnosis when multiple, small, well-defined, symmetric bone lesions are identified on plain radiograph to avoid alarming the patient with more serious disease and misdiagnosis. Bone scintigraphy is normal and useful for differential diagnosis. Although it is usually asymptomatic, effusion and joint pain can be found in 15-20 % of patients. In this study, we report a 17-year-old boy who suffers from low back pain and has a mother with similar involvement. He was diagnosed OPK radiologically. We also review the clinical manifestation, pathophysiology, diagnosis and treatment of OPK in this paper.

The late effects of anticancer therapy after childhood Wilm's tumor: the role of diastolic function and ambulatory blood pressure monitoring.

OBJECTIVE: Wilms' tumor, or nephroblastoma, is the most common primary malignant renal tumor of childhood. The excellent outcome now expected for most children with this tumor is attributed to the combination of effective adjuvant chemotherapy, improved surgical and anesthetic techniques and also the radiosensitivity of the tumor. The numerous organ systems are subject to the late effects of anticancer therapy. The aim of this study was to investigate the blood pressure profile and ambulatory blood pressure monitoring, and also cardiac diastolic functions and pulmonary venous flow in 25 children with unilateral Wilms' tumor in remission. METHODS: The patient group consists of 25 patients who successfully completed anticancer treatment for unilateral Wilms' tumor. Thirty-three age-, weight- and height-matched healthy children were considered as a control group for an echocardiographic study. Also, 20 age-, weight- and height-matched healthy children were considered as a control group for the ambulatory blood pressure monitoring study. RESULTS: In our study, 24 h, daytime and night-time systolic blood pressure and night-time diastolic blood pressure measurements were found to be significantly increased in the patient group compared with healthy children. We detected diastolic filling pattern abnormalities. We also found increase in pulmonary venous flow (systolic and diastolic) in Wilms' tumor group. CONCLUSIONS: We suggest the regular follow-up of survivors of Wilms' tumor for care and prevention of cardiovascular diseases.

Frequency of obesity and metabolic syndrome in childhood leukemia and lymphoma survivors.

OBJECTIVES: In this study, it was aimed to determine the prevalence and clinical features of obesity and metabolic syndrome, which are long-term effects of survivors after treatment in children with leukemia and lymphoma. PATIENTS AND METHODS: Patients with leukemia and lymphoma, who were diagnosed between 2000 and 2012 (at least 2 two years after remission) were included. Data obtained through reviewing the family history, demographic characteristics, anthropometric measurements, and laboratory parameters (blood glucose, lipid, and insulin levels) were analyzed and compared at the time of diagnosis, after the treatment and at time of the study. RESULTS: Eighty nine patients (45 boys, 44 girls) were included (mean age: 14.7 ± 4.3 years): 77.5% had acute lymphoblastic leukemia, 11.2% had acute myeloid leukemia, and 11.2% had lymphoma. Overall, 46% patients had received radiotherapy, 7% had undergone surgery, and 2.2% had received stem cell transplantation in addition to chemotherapy. The mean duration of treatment was 2.4 years, and the time elapsed after treatment was 4.9 years. While only one had obesity at the diagnosis, a significant increase in obesity (20%), hypertension (15.7%), hyperglycemia (15%), insulin resistance (35%) were observed at the time of study, and family history of hypertension, dyslipidemia, and cardiovascular diseases were significantly higher in this subgroup. CONCLUSION: The prevalence of metabolic syndorme is higher in children with leukemia and lymphoma after treatment, and begins to increase with the initiation of treatment and continues to increase over time. These children should be followed-up for late-effects including metabolic syndrome through life-long period.

Chronic Neutropenia in Childhood: Laboratory and Clinical Features.

OBJECTIVES: To describe the clinical characteristics of patients with chronic neutropenia. METHODS: Data of 36 patients with chronic neutropenia, who were followed up in the authors' clinic between May 2013 and May 2020, were analyzed retrospectively. Patients were diagnosed based on their clinical and laboratory characteristics. RESULTS: A total of 36 patients (23 females, 13 males) were included in the study. The mean age at diagnosis was 9.85 ± 9.17 mo while the mean follow-up time was 21.83 ± 20.03 mo. The mean absolute neutrophil count (ANC) at admission was 462.5 ± 388.8 cells/mm3 (median = 375 cells/mm3), and the lowest and highest ANC mean was 241.2 ± 262.1 cells/mm3 (median = 125 cells/mm3), and 1362.9 ± 1127.9 cells/mm3 (median = 925 cells/mm3), respectively. Idiopathic neutropenia was found in 28 (77.8%) patients, autoimmune neutropenia in 6 (16.7%) patients, and congenital neutropenia in 2 (5.6%) patients. Neutrophil normalization was observed in 19 (52.8%) of the patients. CONCLUSIONS: Chronic neutropenia is a heterogeneous picture that presents with different clinical symptoms in childhood. The cause of neutropoenia in children is usually benign and resolves spontaneously but especially in those with severe neutropoenia genetic examination should be performed.

Clinical, Genetic, and Outcome Characteristics of Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: In this study, we sought to describe the clinical, laboratory, and genetic character- istics of patients diagnosed with primary hemophagocytic lymphohistiocytosis. Thus, we aimed to evaluate the early diagnosis and appropriate treatment options for pediatric hemophago- cytic lymphohistiocytosis patients. MATERIALS AND METHODS: Medical records of 9 patients diagnosed with primary hemophago- cytic lymphohistiocytosis between November 2013 and December 2019 were analyzed retro- spectively. Clinical, genetic, and laboratory characteristics, family histories, initial complaints, physical examination findings, age at diagnosis, treatment choices, and clinical follow-up of all patients were investigated. RESULTS: The mean age at diagnosis was 11 months (range: 1.5 months to 17 years). Genetic analysis was performed in all patients, and a disease-related mutation was detected in 8 (89%) of them. Among clinical features, 6 (66%) patients had fever, 5 (56%) had splenomegaly, 4 (44%) had lymphadenopathy, 4 (44%) had skin rash, and 4 (44%) had neurological findings. Hemophagocytosis was observed in the bone marrow samples of 6 (66%) patients. Disease remission was achieved in 7 (78%) patients. Hematopoietic stem cell transplantation was per- formed in 7 (78%) patients. CONCLUSION: Hemophagocytic lymphohistiocytosis may present with different clinical symptoms that can cause a significant diagnostic delay. The only curative treatment option in primary hemophagocytic lymphohistiocytosis patients is hematopoietic stem cell transplantation. The chemotherapy should be started as early as possible, in order to achieve a disease remission. Patients should be referred to the appropriate bone marrow transplant center for hematopoi- etic stem cell transplantation as soon as they reach the disease remission.

Thalassemia-free and graft-versus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.

18Fluorine-fluorodeoxyglucose PET/CT Imaging in Childhood Malignancies

Objectives: The aim of the study was to evaluate the utility of 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, restaging, and treatment response of childhood malignancies. Methods: This study included 52 patients (32 boys, 20 girls) who were referred to our clinic between November 2008 and December 2018 with the diagnosis of malignancy. The patients were evaluated retrospectively. Median age of the patients was 13 years (range 2-17). 18F-FDG was given to the patients intravenously, and time of flight with PET/16 slice CT was performed 1 hour thereafter. The lowest dose was 2 mCi (74 MBq) and the highest dose was 10 mCi (370 MBq). Fasting blood sugars of all patients were found below 200 mg/dL (11.1 mmol/L). Results: 18F-FDG PET/CT was performed to evaluate the response to treatment in 38 of 52 children, staging in 11 patients (staging and evaluation of the response to treatment in nine of them), restaging in 2 patients, restaging, and evaluation of the response to treatment in 1 patient. 18F-FDG PET/CT examination was reported as normal in 13 patients (5 girls, 8 boys). The pathological 18F-FDG uptake was detected in 39 patients (14 girls, 25 boys), which indicated metastasis and/or recurrence of the primary disease. Total number of deaths was 30 (13 girls, 17 boys). Conclusion: 18F-FDG PET/CT has a significant role for staging, restaging, treatment response, and detection of metastatic disease but it is limited for the early diagnosis of childhood cancers.

Protective effect of vitamin A on ARA-C induced intestinal damage in mice.

BACKGROUND: Cytarabine (ARA-C) has been used for many years in the treatment of patients with leukemia and lymphoma. Gastrointestinal ulceration and mucositis are two of the well-known side effects of ARA-C. We set out to investigate whether vitamin A (VA) can help prevent ARA-C-induced mucosal lesions in mice. MATERIALS AND METHODS: Mice were divided into 5 groups. Group I (control group) received only saline; group II received ARA-C plus saline; group III received ARA-C plus VA; group IV received ARA-C plus a lipid solution, and group V received VA alone. VA (5000 IU/kg) was administered orally to the mice once daily for 7 days. ARA-C (3.6 mg) was administered intraperitoneally for 5 days to groups II, III and IV, starting on the third day of VA treatment. Intestinal segments from the proximal end of the jejunum of treated mice were isolated. RESULTS: There was improved mucosal integrity, less necrosis and increased villus length with advanced mucosal proliferation in crypts in the VA plus ARA-C group when compared to the ARA-C groups without VA. CONCLUSION: We conclude that VA has a protective effect against ARA-C-induced mucosal damage in mice.

Poland syndrome with intracranial germ cell tumor in a child.

Poland syndrome is an uncommon unilateral deformity of chest wall and upper extremity with variable manifestations. Although numerous case reports of Poland syndrome associated with malignancies have been published, intracranial germ cell tumor in Poland syndrome has not been previously reported. The authors describe a 15-year-old male patient with intracranial germ cell tumor and Poland syndrome.

Sacrococygeal teratoma with sarcomatous differentiation in a child.

Most of the extragonadal teratomas are located in the sacrococygeal region. Teratoma with malignant sarcomatous differentiation is a rare form of germ cell tumor. The authors describe a 5-year-old-girl with sacrococygeal teratoma in which sarcomatous elements were observed. The patient was treated with complete surgical excision and adjuvant chemotherapy according to sarcoma protocols.