Hilmi Apak

Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia.

The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.

Retinoblastoma in Turkey: survival and clinical characteristics 1981 - 2004

Background: In this study, the authors aim to describe the survival and clinical characteristics of 141 retinoblastoma cases treated at Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, between 1981 and 2004.

NAD(P)H:quinone oxidoreductase 1 null genotype is not associated with pediatric de novo acute leukemia

NAD(P)H:quinone oxidoreductase1 (NQO1) is a two‐electron reductase that detoxifies quinones derived from the oxidation of phenolic metabolites of benzene. Exposure to benzene metabolites increases the risk of hematotoxicity and leukemia. NQO1 enzyme activity protects the cells against metabolites of benzene. C to T base substitution at nucleotide 609 of NQO1 cDNA (C609T) results in loss of enzyme activity. Low NQO1 activity may play a role in etiology of acute leukemia.

Toxic Epidermal Necrolysis After the Use of High-Dose Cytosine Arabinoside

Abstract: We report a fatal case of toxic epidermal necrolysis (TEN) resulting from a high dose of cytosine arabinoside (ARA‐C). A 13‐year‐old girl with acute lymphocytic leukemia was treated according to the protocol of the BFM Group (BFM‐95, HRG). On the fifth day after administration of a high dose of ARA‐C (2 g/m2 intravenously every 12 hours), she developed bullous lesions on the hands and soles that disseminated, evolving to necrosis, sepsis, and death on the 22nd day. ARA‐C is frequently associated with dermatologic toxicity, but this is only the second case of toxic epidermal necrolysis described in connection with this drug.

Bacteremia in childhood cancer.

Infection-related mortality affects the overall survival rates of children who are receiving treatment for cancer. The leading cause of mortality is bacteremia and sepsis related to it in febrile neutropenic patients. All positive blood cultures of febrile neutropenic patients treated in the Department of Pediatric Hematology-Oncology, Cerrahpasa Medical School, between January 1995 and January 2001 were reviewed. Cultures grew 159 micro-organisms, 95 (60 per cent) of which were Gram-positive bacteria, 56 (35 per cent) were Gram-negative bacteria and eight (5 per cent) were fungi. Coagulase-negative staphylococci (63, 40 per cent) and S. aureus (8, 5 per cent) were the most frequent Gram-positive pathogens. Klebsiella, E. coli, Enterobacter and Pseudomonas infections were the primary Gram-negative pathogens. Twenty cases were lost because of sepsis: in 11 cases (55 per cent) Gram-negative bacteria, in eight cases (40 per cent) Gram-positive bacteria, and in only one case a fungus were the causative organisms. Although vancomycin was not included in the first-line treatment, the mortality rate of Gram-positive bacteremia was 8 per cent. In Gram-negative bacteremia it was 20 per cent. Gram-negative pathogens, which were resistant to multiple antibiotics, caused the mortality. Drug resistance and mortality due to micro-organisms must be taken into consideration while febrile neutropenia protocols are prepared.

ASSOCIATION BETWEEN GENETIC POLYMORPHISM IN DNA REPAIR GENES AND RISK OF B-CELL LYMPHOMA

Objectives: The authors evaluated the possible effect of DNA repair genes, XPD (Xeroderma pigmentosum group D) codon (312 and 751) and XRCC1 (X-ray repair cross-complementing group 1) codon (194 and 399) SNPs (single-nucleotide polymorphisms) on the risk of childhood B-cell lymphoma. Methods: The polymorphisms were analyzed in 33 patients with BL cases and in 52 healthy, age-matched controls using PCR-RFLP method. Results: The authors observed no association between variation in the XPD codon Asp312Asn, Lys751Gln, and XRCC1 codon Arg399Gln polymorphisms and B-cell lymphoma for any parameter. In contrast, tryptophan allele frequency in control and patient groups was 0.10 and 0.03 respectively (p = .04). The frequency of XRCC1 194Arg/Trp genotype in B-cell lymphoma was significantly lower than that in controls (p = .005). No significant relationship was found between genotypes and stage, lactate dehydrogenase, or bone marrow involvement. Conclusions: XRCC1 194Trp allele may be associated with a protective effect against development of childhood B-cell lymphoma. However, these results were based on a small number of case and further studies should be done.

Novel Influenza a (H1N1) Infection in a Pediatric Hematology Oncology Clinic During the 2009–2010 Pandemia

Pandemic influenza A infection (2009 H1N1) was associated with a worldwide outbreak of febrile respiratory infection. Although usually it results in a mild illness, certain patient groups are at increased risk for complications. The authors reviewed their experience in a pediatric hematology-oncology unit to determine the outcome of this disease in children with hematological conditions and solid tumors. During the second outbreak (1 November 2009 to 14 January 2010), a total of 187 children from pediatric clinic were tested for H1N1 influenza A by multiplex polymerase chain reaction (PCR), 63 of them were positive. Patients’ signs and symptoms were recorded prospectively. Ten (35.7%) (5 children with solid tumors, 4 with leukemia, 1 with hereditary spherocytosis) of 28 tested children with hematological conditions were diagnosed with 2009 H1N1 influenza infection. Fever (100%) and cough (90%) were the most common symptoms. Five were neutropenic (neutrophil count <1000/mm3), 4 had severe neutropenia (neutrophil count <500/mm3). Systemic antibiotics were given in 5 patients with the diagnosis of febrile neutropenia. Four were inpatients, others were hospitalized after the diagnosis. One patient required mechanical ventilation; however, he had concomitant invasive fungal infection. Eight patients were treated by oseltamivir, all tolerated the drug well. A total of 4 cases from 9 cancer patients had a delay in their planned chemotherapy for 7 to 15 days. Pandemic H1N1 influenza caused mild symptoms in children with cancer and/or hematological conditions but resulted in delay in anticancer therapy and increase in hospitalization and antibiotic usage.

Antiviral prophylaxis with continuous low dose acyclovir in childhood cancer

Having read the article ‘‘Oral valacyclovir as prophy-laxis against herpes simplex virus reactivation duringhigh dose chemotherapy for leukemia’’ by Orlowskiet al. [1], we wanted to write about our experiencewith acyclovir prophylaxis in children who weretreated for cancer [2]. Although the age of patientsand the medication used for prophylaxis inOrlowski’s and our study were different, an effectiveprophylaxis against reactivation of herpes simplexvirus or new infection in the respective patientpopulations was achieved in both papers.Children on chemotherapy have defects in cellularimmunity which predispose them to severe infectionswith certain viruses, particularly varicella zoster virus(VZV). Except relapse/underlying disease, the lead-ing cause of death in children with cancer is infection[3]. Prophylaxis against infection is a debatablesubject of cancer treatment. Only Pneumocystis cariniiprophylaxis in children receiving chemotherapy andantifungal prophylaxis in bone marrow transplanta-tion (BMT) units is recommended. Prophylaxis withacyclovir is only recommended in case of exposureVZV infections or to prevent the reactivation ofherpes infection in sero-positive patients. To ourknowledge, no pediatric cancer centers give acylovirfor viral prophylaxis, other than BMT. None of ourcases were transplanted, so the novelty of our data isthe critical element of this study.From January 1995 to December 2001, allchildren with cancer or leukemia were evaluated forherpes infections at the Hematology–Oncologydepartment of Cerrahpasa Medical University ofPediatrics. We used high dose acyclovir either in caseof exposure to VZV or for the treatment of varicella(chickenpox) or herpes zoster (shingles) infectionsuntil the end of 1997. From January 1995 to the endof December 1997, a total of 216 patients who werediagnosed with, and treated for, a malignancy havebeen evaluated retrospectively for VZV infections.Since January 1998, prophylactic acyclovir has beenadministered in our department to all patients withleukemia or solid tumor receiving chemotherapy,along with trimethoprim-sulphomethoxazole. Thedose has been determined empirically as 200 mg/day in two divided doses for young children and400 mg/day in two divided doses for older childrenand adolescents, contributing to a dose of approxi-mately 5–10 mg/kg/day. Prophylaxis was continuedfor 3 months after the end of chemotherapy for solidtumors and maintenance therapy of leukemia. Thesetwo periods (with or without prophylaxis) werecompared for frequency, morbidity and mortality ofthe VZV infections.Annually, 75–100 new patients are diagnosed andtreated for their cancer in our department. Duringthe periods with prophylaxis or not, there was nomajor difference in treatment regimens for cancerand supportive care. Before antiviral prophylaxis withcontinuous low dose acyclovir, 2–3 new chickenpoxand 2–4 shingles cases have been documentedyearly. There have even been two fatalities during1985–1990 due to severe varicella infection. Wehave collected the data of thirteen children with VZVinfection diagnosed during a 3-year period beforeprophylaxis. The incidence is 6% (13/216). The pati-ents who were diagnosed with VZV infections beforethe period of prophylaxis are shown in Table Ia. Nota single case of VZV infection has been diagnosed

Varicella-induced hemolytic anemia with hepatitis.

Dear Editor, Chickenpox, one of the most common exanthematous diseases of the childhood, can give rise to various complications, like bacterial superinfections of skin eruptions, encephalitis, cerebellar ataxia, thrombocytopenia, arthritis, and hepatitis [1]. There are many cases previously reported with autoimmune hemolytic anemia related to cold agglutinins during or just after varicella infection [2, 3], but a limited number of cases of hemolytic anemia and hepatitis are reported after varicella infection [4]. Here we report a 7month old boy with hepatitis and autoimmune hemolytic anemia during chickenpox.

A 17-year experience with ALL-BFM protocol in acute lymphoblastic leukemia: prognostic predictors and interruptions during protocol.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and despite the intense combination chemotherapy, cure rates are less than 90%. Several prognostic parameters, including nonneoplastic hematologic cell counts during induction phase, are suggested to predict outcome in ALL. We analyzed 242 ALL patients treated in our center to investigate individual prognostic parameters and the impact of delays on disease outcome. Age at diagnosis, risk groups, extramedullary involvement, t(9;22), prednisone response, bone marrow response at days 15 and 33, day 15 platelet count, day 33 lymphocyte, monocyte, and platelet counts, treatment delay, sepsis, and omission of day 64 cyclophosphamide were valuable predictors of survival in univariate analysis. However only the age, CNS involvement, omission of cyclophosphamide, and total delay during treatment were associated with survival in multivariate analysis. Omission of second cyclophosphamide dose had no impact on survival of standard risk group patients, but adversely affected the long term survival of medium risk group (MRG) patients. The second dose might be given with the first dose on day 36 to MRG patients to prevent delays. Day 15 and 33 platelet counts are promising predictors of survival in low income countries where assessment of minimal residual disease is difficult, but this data needs further consolidation.