Laboratory and clinical features of tumor lysis syndrome in children with non-Hodgkin lymphoma and evaluation of long-term renal functions in survivors.

OBJECTIVE: The purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome (TLS) and acute kidney injury (AKI) in childhood non-Hodgkin lymphomas (NHL) and to reveal their impact on long term kidney function in survivors. METHODS: Our single-center retrospective study included 107 patients (0-18 years old) with NHL who were admitted and treated at our hospital between 1998 and 2020. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were assessed. The long-term renal functions of the patients were investigated. RESULTS: 80.3% of the patients were male with a median age of 9.8 years. The most common detected histopathological subgroup was Burkitt lymphoma. Hyperhydration with or without alkalinisation, and allopurinol were used in first-line treatment and prophylaxis of TLS. Laboratory TLS and clinical TLS was observed in 30.8% and 12.1% of patients, respectively. A significant correlation was found between young age, advanced stage, high LDH level at presentation, and TLS. AKI was observed in 12.1% of the patients. When the glomerular filtration rate values of the patients at the first and last admissions were compared after an average of 6.9 years, a mean decrease of 10 mL/min/1.73 m2 was found. It was not, however, found to be statistically significant. CONCLUSION: Lower age, advanced stage, and high LDH level at presentation were found to be risk factors for TLS in our study. Long-term renal function loss was not observed in the survivors who received early and careful prophylaxis/treatment for TLS. The survivors are still being followed up.

Renal Ultrasonographic Abnormalities at Initial Presentation of Children Diagnosed with Acute Lymphoblastic Leukemia and Long-Term Renal Functions and Prognosis in Survivors.

Objectives: The kidney is a vulnerable organ for acute lymphoblastic leukemia (ALL), by the disease, and various associated clinical pictures. This retrospective study aims to document renal ultrasound abnormalities in children with newly diagnosed ALL as well as to investigate the correlation between renal findings and clinical/laboratory/survival data. Methods: All children (age <18 years) with ALL were included in the study. An increase in size/nephromegaly (NM) or hyperechogenicity (HE) of the kidneys at first admission was accepted as a pathological renal abnormality. The clinical/laboratory findings, survival, and long-term renal functions were compared between patients with and without NM/HE. Results: The incidence of NM±HE was 12% in 163 patients. Enlargement of spleen, liver, or both and, hypercreatininemia was independently correlated with the presence of NM/HE. After the induction therapy, ultrasound findings were resolved in all patients, and NM/HE did not influence ALL prognosis. All survivors had normal renal functions in long term. Conclusion: The renal ultrasound abnormalities are not uncommon in children with leukemia at admission, without a negative impact on leukemia prognosis and on long-term renal functions.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Treatment results of modified BFM protocol in pediatric high-risk Burkitt lymphoma.

BACKGROUND: Chemotherapy with high dose methotrexate is the mainstay of treatment for Burkitt lymphoma (BL), especially to manage central nervous system (CNS) disease. However, methotrexate administration requires close drug level monitoring for appropriate folinic acid rescue, which might not be readily available in all centers. In this study, we assessed the long-term treatment outcomes of a modified Non-Hodgkin lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM) 90 regimen in pediatric high-risk BL without CNS involvement. METHODS: Between 1999 and 2011, 42 patients (median age: 7 years) with advanced-stage BL were treated with modified NHL-BFM 90 regimen (methotrexate at a dose of 1 g/m2). Demographic data, stage, lactate dehydrogenase (LDH) and treatment results were retrospectively evaluated. The patients were assessed for toxicity, survival and CNS recurrence. RESULTS: Thirty-six patients had Stage III and six had Stage IV disease, respectively. The median LDH level was 1,432 IU/L. Four patients died of infectious and metabolic complications. One patient had local recurrence at the 48 < sup > th < /sup > month of the follow-up and he is in the second remission for 72 months. In Kaplan-Meier analysis, the overall survival and event-free survival rates at 10 years were found as 90 % and 88 %, respectively. None of our patients died of treatment failure. CONCLUSIONS: The administration of the reduced dose of methotrexate seems to not compromise treatment success nor increase the risk of CNS recurrence in high-risk BL without CNS involvement. The limitation of the study is that it is not randomized. Our treatment scheme might be considered for centers without methotrexate measurement facility.

Hepatitis B Vaccination in Children With Ongoing Cancer Treatment: A Safety and Efficacy Study of Super-Accelerated Vaccination Scheme.

OBJECTIVE: Children with cancer have an increased risk for hepatitis B virus (HBV) infections due to chemotherapy-induced secondary immunodeficiency and frequent blood transfusions. The aim of this study is to evaluate the efficacy and safety of hepatitis B vaccination during the intensive induction chemotherapy in children with cancer found to be seronegative for hepatitis B on admission. MATERIALS AND METHODS: Children newly diagnosed with cancer were evaluated for the presence of hepatitis B surface antigen (HBsAg) and antibody on admission. The children negative for both were included in the study. A super-accelerated vaccination scheme (3 booster doses at days 1-5, 8-12, and 28-33) was administered to these seronegative children concurrently with induction chemotherapy. Antibody response was checked 4-8 weeks after the last vaccination and 6 months after the end of the treatment. RESULTS: Eleven out of 122 children were seronegative for hepatitis B on admission (9%). Acute lymphoblastic leukemia, lymphoma, and solid tumors were diagnosed in 5, 4, and 2 children, respectively. Complete seroconversion was achieved in 4-8 weeks after the last vaccination with high titers of anti-HBs antibody, and all patients remained antibody-positive until 6 months after the completion of chemotherapy. CONCLUSION: The risk of transfusion-related infections increases with a number of transfused products and donor exposures, and it is more significant for immunosuppressed children with hematologic and oncologic malignancies. Hepatitis B vaccination could safely be applied with brisk and sustained responses in this vulnerable population, based on the local epidemiological data.

Posterior Reversible Encephalopathy Syndrome in Childhood Hematological/Oncological Diseases: Multicenter Results.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95±3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.

Cutaneous manifestations in pediatric oncology patients.

BACKGROUND/OBJECTIVES: Oncology patients present with various skin manifestations related to primary disease and treatments. Although these skin toxicities are well described in adults, studies of pediatric oncology patients are limited. The objective of this study was to evaluate the cutaneous findings in pediatric oncology patients receiving chemotherapy. METHODS: In this prospective cohort study conducted from December 2018 to March 2020, all pediatric oncology patients were examined and patients who had a dermatologic finding at any point during their treatments were recorded. Dermatologic examinations were performed by the same dermatologists, and biopsy and microbiologic tests were performed according to clinical need. Patients were grouped according to their oncologic diagnoses and types of chemotherapies. RESULTS: A total of 80 patients with a mean age of 9.1 ± 5.0 years were included in the study. Seventy-five (93.7%) of them developed a dermatologic manifestation during the study period. Most of the patients had hematologic malignancies (n = 48, 60%). Antimetabolites were the most frequently used class of chemotherapeutic agents. Anagen effluvium was the most common dermatologic finding (61.3%, n = 49), followed by inflammatory dermatoses (51.2%, n = 41, most commonly diaper dermatitis in 33 patients), xerosis (35%, n = 28), and nail changes (20%, n = 16, most commonly nail pigmentation in seven patients). Mucositis was seen in 13 (16.2%) patients. Five patients (6.2%) had drug-induced cutaneous hyperpigmentation, and five (6.2%) had toxic erythema of chemotherapy. The highest percentage of xerosis (45.4%) was detected in patients using antitumor antibiotics, whereas inflammatory dermatoses were observed more in patients using antimetabolites (48.6% of patients using antimetabolites), and pigmentation changes were more frequently detected in patients using alkylating agents. CONCLUSION: Identification, diagnosis, and treatment of these reactions are important to dermatologists and oncologists so that appropriate management may be provided to pediatric oncology patients.

Clinical Characteristics of and Cancer Incidence in Children Evaluated for Lymphadenoapthy Referred to Pediatric Oncology Clinics.

OBJECTIVES: In our study, we aimed to investigate the clinical characteristics and cancer frequency in patients referred to our pediatric oncology outpatient clinic for lymphadenopathy. METHODS: The charts of patients admitted to our pediatric oncology outpatient clinics for lymphadenopathy between January 2014, and December 2016 were retrospectively reviewed in this study. Age, gender, duration of complaints, previous therapies, systemic signs and symptoms, lymph node characteristics and laboratory findings were recorded. The frequency of malignancy was calculated. RESULTS: One hundred thirty-four patients (34 girls) with a median age of six years (range four months-17 years) were included in our study. The majority of the patients (98%) had localized lymphadenopathy and the head and neck region was the most common site of involvement (87%). The median long-axis diameter of lymph nodes ranged between 0.5 cm and 5 cm (median 2 cm) by physical examination. Twenty-one patients (15.6%) had lymph node biopsy. Four patients had ruptured epidermal cyst, lymphangioma, pilomatricoma and ectopic thymus. Of the other biopsies, nine patients were diagnosed with reactive LAP, four with lymphadenitis, and four with Hodgkin's disease. The lymphoma patients had lymph node size greater than 2.5 cm and the duration of lymphadenopathy was longer than four weeks. Three out of four patients had systemic clinical findings accompanying lymph node enlargement. CONCLUSION: Three percent of the patients with lymphadenopathy who were referred for suspected malignancy received a cancer diagnosis. This rate, which is too low for a reference center, suggested that the patients might be referred to the pediatric oncology outpatient clinic without a thorough evaluation in primary health care.

Treatment of high-risk neuroblastoma: National protocol results of the Turkish Pediatric Oncology Group.

BACKGROUND: The national protocol aimed to improve the outcome of the high risk neuroblastoma patients by high-dose chemotherapy and stem cell rescue with intensive multimodal therapy. MATERIALS AND METHODS: After the 6 induction chemotherapy cycles, patients without disease progression were nonrandomly (by physicians' and/or parent's choices) allocated into two treatment arms, which were designed to continue the conventional chemotherapy (CCT), or myeloablative therapy with autologous stem cell rescue (ASCR). RESULTS: Fifty-six percent (272 patients) of patients was evaluated as high risk. Response rate to induction chemotherapy was 71%. Overall event-free survival (EFS) and overall survival (OS) at 5 years were 28% and 36%, respectively. "As treated" analysis documented postinduction EFS of 41% in CCT arm (n = 138) and 29% in ASCR group (n = 47) (P = 0.042); whereas, OS was 45% and 39%, respectively (P = 0.05). Thirty-one patients (11%) died of treatment-related complications. CONCLUSION: Survival rates of high-risk neuroblastoma have improved in Turkey. Myeloablative chemotherapy with ASCR has not augmented the therapeutic end point in our country's circumstances. The adequate supportive care and the higher patients' compliance are attained, the better survival rates might be obtained in high-risk neuroblastoma patients received myeloablative chemotherapy and ASCR.

The Incidence of and Factors Associated with Vitamin D Deficiency in Newly Diagnosed Children with Cancer.

This retrospective chart review study aimed to assess vitamin D status and identify risk factors associated with vitamin D deficiency and bone parameters in children with cancer at admission. The data of 86 (50 males and 36 females) patients between April 2013 and June 2015 were analyzed. Calcium, phosphorus, alkaline phosphatase (ALP), 25(OH)D, age, gender, diagnostic category, body mass index, duration of complaints, and season of blood sampling were recorded. Median age was 7.17 years (range 0.31-17.40) in 29 hematological malignancy and 57 solid tumor patients. According to cut-off level of 20 ng/ml, 63% of children with cancer had vitamin D deficiency at diagnosis with a median 25(OH)D of 16.75 ng/ml. The mean vitamin D value of children >10 years was significantly low in comparison to that observed in younger children [11.83, 95% confidence interval (CI) = = 8.85-14.81 ng/ml vs. 19.81, 95% CI = = 17.02-22.60 ng/ml]. Vitamin D measurement between November and May was a risk factor for vitamin D deficiency (P < 0.05). The frequency of hypocalcemia and hypophosphatemia was not different between two groups of vitamin D. Further longitudinal studies are needed to investigate whether monitoring vitamin D status and supplementation in children with cancer might prevent future complications related to vitamin D deficiency.

Chronic hepatitis B in children with or without malignancies: a 13-year follow-up.

AIM: To evaluate the outcome of chronic hepatitis B (CHB) in children with or without malignancies. METHODS: Twenty four children (15 boys and 9 girls) with malignancies, followed up by the pediatric gastroenterology outpatient clinic for CHB between January 2000 and December 2013, were enrolled in the study (Group 1). Group 2 was formed with twenty five children (11 girls and 14 boys) diagnosed with CHB without malignancies. The data from the patients' records were compared between the two groups. RESULTS: Hepatitis B e antigen (HBeAg)/antiHBe seroconversion was observed in 3 patients (12.5%) in group 1 and 15 patients (60%) in group 2, with annual seroconversion rates of 1.61% and 16.6%, respectively, and the difference was significant (P<0.01). One patient (6.6%) in Group 1 and 9 patients (53%) in Group 2 showed HBeAg/antiHBe seroconversion after treatment and the difference between the two groups was significant (P<0.06) Loss of hepatitis B surface antigen was observed in one patient in each of group 1 and 2. No clinical, laboratory and imaging findings of liver disease were observed in any of the patients at the end of the study. CONCLUSION: HBeAg/antiHBe seroconversion rate was lower in patients who had recovered from cancer.

Wilms' tumor: a 24-year retrospective study from a single center.

Medical records of 71 children with Wilms' tumor at Sisli Etfal Education and Research Hospital between 1990 and 2014 were reviewed. Mean age at diagnosis was 3.11 years (2 days-7 years). Male to female ratio was M/F = 6/10. The incidence of associated anomaly was 16.9%. Clinical manifestations included abdominal mass (89%), hematuria (30%), hypertansion (25%), abdominal pain (15%), fever (5%), restlessness (2%), weight loss (2%), varicocele (1%). Ultrasound (USG) was the most often initial study in a child presenting with abdominal mass. Doppler USG was also made to evaluate the inferior vena cava (IVC) for the presence of tumor extension in children with renal mass. The left kidney was affected in 33 patients (46.5%), the right was affected in 31 patients (43.7%). Two patients was extrarenal (2.8%). And 5 patients (7.04%) were bilateral on the presentation. Preoperative chemotheraphy was done in 14 cases. In 63 patients with unilateral Wilm tm, unilateral radical nefrectomy is performed. In one patient with solitary kidney, nephron sparing surgery (NSS) is performed. In 3 patients with bilateral tm NSS is performed and in 2 patients with bilateral Wilms' tm NSS is performed in one side and nefrectomy on the other side. Out of 71 Wilms tumor (WT) patients, 17 of them has been out of our follow. And 4 of them are died. Ten of them has metastases. Forty children are under follow with no metastases. Patients with WT needs a multimodal, multidisiplinary treatment with the cooperation of pediatric oncologist and pediatric surgeon and needs close follow-up.

Comparison of piperacillin tazobactam and cefoperazone sulbactam monotherapy in treatment of febrile neutropenia.

BACKGROUND: Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone-sulbactam (CS) and piperacillin-tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer. PROCEDURE: The study included febrile, neutropenic children hospitalized at our center for cancer. They were randomly selected to receive CS 100 mg/kg/day or PIP/TAZO 360 mg/kg/day. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode. RESULTS: One hundred and two febrile neutropenic episodes were documented in 55 patients with a median age of 4 years. In 50 episodes CS and in 52 episodes PIP/TAZO was used. Duration of fever and neutropenia, neutrophil count, age, sex, and primary disease were not different between two groups. Success rates in the CS and PIP/TAZO groups were respectively 56 and 62% (P > 0.05). Modification rate between two groups showed no significant difference (P > 0.05). No serious adverse effect occurred in either of the groups. CONCLUSION: CS and PIP/TAZO monotherapy are both safe and effective in the initial treatment of febrile neutropenia in children with cancer.

Assessment of hepatitis B immunization status after antineoplastic therapy in children with cancer.

BACKGROUND AND OBJECTIVES: Hepatitis B is a disease that is preventable with vaccination. Antibody levels after vaccination may be affected by suppression of the immune system due to cancer therapy. Children with cancer have a high risk of hepatitis B virus (HBV) infection. We aimed to assess the pretreatment immunization status against HBV infection and the rate of continuity of immunization after therapy in children with cancer. DESIGN AND SETTING: Retrospective case review of patients treated from 2004 to 2008. PATIENTS AND METHODS: We reviewed the medical records of patients treated in the departments of pediatric hematology and oncology and collected data on immunization history and hepatitis B serology. Anti-HBs antibody titers were compared before and after treatment. RESULTS: This study included 159 (99 males, 60 females) children who had a serologic examination. Antineoplastic therapy had been given for acute leukemia (n=66), non-Hodgkin lymphoma (n=27), Hodgkin lymphoma (n=20), and solid tumors (n=46). Fifty-one patients had not been immunized against HBV prior to the therapy; HBV serology was negative in 49 of these patients and HBsAg was positive in 2 patients. Anti-HBs antibody positivity was present in 99 of 108 patients with an immunization history, whereas no vaccination response was present in 9 patients. The titer of anti-HBs antibody was decreased below the protection level in 33 (33%) patients with positive anti-HBs antibody, whereas the protection level was found to be maintained in 66 (67%) patients. The most significant decrease (63.6%) was observed in leukemia patients. Posttreatment HBsAg and HBV DNA positivity was detected in two of the patients with negative pretreatment serology, whereas no HBV infection developed in the group with positive anti-HBs antibody. CONCLUSIONS: This study demonstrated the importance of routine childhood vaccination in reducing the risk of HBV infection in patients with cancer.

Diagnosis in childhood abdominal Burkitt's lymphoma.

BACKGROUND: The role of surgery has changed substantially over the years in abdominal Burkitt's lymphoma. Laparotomy without total excision of the tumor does not have a positive effect on survival, might cause complications, and delays initiation of chemotherapy. Here we present our diagnostic management of patients with abdominal Burkitt's lymphoma. MATERIALS AND METHODS: The diagnostic methods of abdominal Burkitt's lymphoma cases treated between January 1999 and December 2009 were evaluated retrospectively. RESULTS: Of the 48 abdominal Burkitt's lymphoma patients, 13 also had extra-abdominal site involvement. Diagnosis was made with ultrasound-guided tru-cut needle biopsy of the abdominal mass (n = 11), fluid cytology (n = 7), extra-abdominal site biopsy (n = 4), bone marrow aspiration (n = 2), gastroscopy (n = 1), and laparotomy (n = 23). In patients diagnosed with laparotomy, chemotherapy was started in 4-22 days (median 7) compared with patients diagnosed with other diagnostic interventions in 2-4 days (median 2) (P < .001). CONCLUSION: Although the most frequently used technique is laparotomy and open biopsy in our series, other methods provided quicker initiation of chemotherapy and less surgical morbidity. Especially in patients with high stages, cytological evaluation and tru-cut needle biopsy with radiological guidance is a better alternative of laparotomy.

Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile neutropenia.

BACKGROUND: In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases. METHODS: Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as "success" and improvement with modification of the initial treatment and death was defined as "failure". RESULTS: Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group. CONCLUSIONS: Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.