RESUMEN
BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high in Asian countries. Little is known about outcome of leukemia in HBV infected patients in these regions. Hence, we conducted this study in two cohorts of patients. PROCEDURE: We retrospectively evaluated mortality, reduction in dose intensity and duration of therapy (intensive phase and maintenance phase) in children with acute lymphoblastic leukemia (ALL) who developed HBV infection. Sixty-three patients with ALL were included in the retrospective cohort of the study. These were followed up for a minimum of 5 years. We prospectively investigated the prevalence of anti-HBc antibodies in 105 treatment naïve pediatric patients with ALL and negative for HbsAg. RESULTS: Twenty of the 63 patients developed hepatitis, of which 10 were attributed to HBV. All the 10 patients with HBV hepatitis had significantly reduced dose intensity during maintenance therapy with an average delay in completion of therapy of 140 ± 83 days and also a high mortality (40%). In the prospective cohort of the study, 39% of treatment naive patients who were HBsAg negative were anti-HBc positive at presentation, possibly reflecting occult HBV infection. CONCLUSIONS: HBV infection poses a serious problem in patients with ALL. Hence we propose that in India, in addition to screening for HBsAg, patients with leukemia should also be screened for anti-HBc. Improved hepatitis B vaccine coverage in the community under the universal immunization programme and introduction of HBV nucleic acid test (NAT) for blood donations should also help in addressing the problem.
Asunto(s)
Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Hepatitis B/epidemiología , Hepatitis B/mortalidad , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Humanos , India/epidemiología , Lactante , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/virología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Centros de Atención TerciariaRESUMEN
INTRODUCTION: The diagnosis and management of cancer in infantile age group is a significant challenge to pediatric oncologists. Malignancies occurring in infants often have different clinical and biological behavior in comparison to older children. This study was performed with an aim to find out the profile of infantile cancers at a tertiary care cancer center in South India. METHODS: The present study was a retrospective analysis of infants presenting with malignancy between 2003 and 2012 to our center in South India. RESULT: A total of 4588 pediatric patients were registered in the Department of Pediatric Oncology at our institute between 2003 and 2012. Among those, 266 (5.79%) of the patients were infants (0-1 years). There were 65.75% males and 34.25% females. Solid tumors were the most common malignancy in this age group (72.56%). Leukemias were observed in 67 (25.19%) infants. ALL was the most common hematological malignancy (17.29%) followed by AML (5.64%). Common solid tumors in descending orders were neuroblastoma, soft tissue sarcoma, renal tumors, germ cell tumors, retinoblastoma and hepatoblastoma. Thirteen (4.89%) neonates were seen in our study. The most common malignancy in neonates was neuroblastoma. CONCLUSION: The distribution of malignancy in infants is quite different from that which is found in older children. Although neuroblastoma is the most common infantile tumor in western countries, in our study leukemia is the most common infantile malignancy. Embryonal tumors such as neuroblastoma, Wilms tumor, retinoblastoma, and hepatoblastoma were more prevalent in infants. Solid tumors were the most common malignancy in infants which is followed by leukemia.
Asunto(s)
Neoplasias/diagnóstico , Neoplasias/terapia , Factores de Edad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pediatría/métodos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Retinoblastoma (RB) is a prototype of heritable cancers. It is more common in the lower socioeconomic strata. Delayed presentation significantly reduces the overall outcome. We have analyzed the epidemiological and clinical data of children who were diagnosed with RB between the years 2009 and 2014. AIM: RB being a disease of the poor, delayed presentation is common due to lack of awareness. We have analyzed the epidemiological profile of our patients and tried to establish the link between delayed presentation and the presence of high-risk features. High-risk features are associated with higher chance of metastasis and poor rates of vision salvage in RB. METHODOLOGY: Data were collected in a retrospective manner from the patient case files retrieved from the Medical Records Department, Kidwai cancer Institute. The data were analyzed using Excel and SPSS software (IBM Corp. released 2016, IBM SPSS statistics software for Mac OS, version 24, IBM Corp., Armonk, NY). RESULTS: A total of 53 patients were diagnosed with RB in the years 2009-2014. There was a male predominance with 1.2:1 incidence. Bilateral RB was present in 21 cases. The mean age of children with bilateral RB was 2.1 years, against 1.5 years in unilateral cases. High-risk features such as optic nerve invasion, choroidal invasion, intracranial extension, and orbital involvement were found in 12, 6, 5, and 5 eyes, respectively. Bone marrow involvement was detected in 5% and lung metastasis in 2%. Intracranial involvement was found in 10.4% and cerebrospinal fluid positivity in 15%. Children with high-risk features had a significant delay in presentation in comparison to those without high-risk features (P = 0.035). CONCLUSION: Incidence of metastatic disease and delayed presentation is still high in developing countries. Routine eye examination during vaccination visits can ensure early diagnosis and appropriate referral in many of these children.
RESUMEN
Remethylation of homocysteine to methionine is dependent on an adequate supply of one or more of the B vitamins like folate, vitamin B(12) and vitamin B(6). Plasma total homocysteine (tHcy) is also influenced by genetic factors such as polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. MTHFR is a flavo enzyme and a key player in folate metabolism and changes in its activity could modify the susceptibility to Acute Lymphoblastic Leukemia (ALL). In this case - control study we have examined the effect of riboflavin status as measured by erythrocyte glutathione reductase activation coefficient (EGRAC) on homocysteine levels along with vitamin B(12) and folate in pediatric ALL. Folate and B(12) levels were significantly lower among cases as compared to controls while EGRAC and tHcy did not differ significantly among the groups. The multivariate regression analysis revealed that in the ALL group EGRAC significantly influences tHcy levels suggesting that riboflavin availability may be a predictor of tHcy levels in patients with ALL. This finding may have implications for tHcy lowering therapy.
RESUMEN
The production of three ligninolytic enzymes, laccase (LAC), manganese peroxidase (MnP) and lignin peroxidase (LiP) by the white-rot fungus, Stereum ostrea, was significantly more in Koroljova liquid medium in the presence of chlorpyrifos under shaking conditions than under stationary conditions. These enzymes were secreted into the broth to the extent of 214.37, 82.75 and 8.05 U/ml under influence of chlorpyrifos on 10th day of incubation in comparison with 138.06, 51.85 and 6.44 U/ml, respectively, under similar conditions in control. Maximum production of LAC, MnP and LiP on liquid medium with/without chlorpyrifos under stationary conditions did not exceed 80-85, 33-40, 0.6-0.7 U/ml, respectively. Among lignosulfonic acid, veratryl alcohol (VA), gallic acid (GA) and tannic acid tested, GA induced maximum production of LAC (300.53 U/ml) and MnP (181.66 U/ml) after 10 days of growth in the presence of chlorpyriphos, while maximum LiP (1.134 U/ml) was produced when grown with the inducer VA during this period. Our data suggest that chlorpyrifos and inducers interacted positively in producing higher amounts of the ligninolytic enzymes in S. ostrea.
RESUMEN
There have been very few studies focusing on what form of communication patients would find acceptable from a clinic. This study looks at the differences in preferences for various partner notification methods when the respondents were index patients compared with when they had to be contacted because a partner had a sexually transmitted infection (STI). There were 2544 respondents. When the clinic had to notify partners, respondents were more likely to report the method as good when a partner had an STI and they were being contacted compared with when the respondents had an infection and the partner was being contacted. The opposite was true for patient referral partner notification. Therefore, there are variations in the preferences of respondents for partner notification method, which depend on whether they see themselves as index patients or contacts.
Asunto(s)
Trazado de Contacto/métodos , Satisfacción del Paciente , Enfermedades de Transmisión Sexual/psicología , Enfermedades de Transmisión Sexual/transmisión , Instituciones de Atención Ambulatoria , Recolección de Datos , Inglaterra , Humanos , Relaciones Profesional-Paciente , Parejas Sexuales/psicologíaRESUMEN
BACKGROUND: Atypical teratoid rhabdoid tumors (AT/RT) constitute a rare group of pediatric brain tumors. AIM: To study the clinical, histopathological, and immunohistochemical (IHC) profile, management and outcome of children with AT/RT of the central nervous system who presented between the years 2007 and 2015 in a regional tertiary care center in South India. MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case files. Archived slides and tissue blocks were retrieved. All cases had hematoxylin and eosin stained sections. IHC was available in all the cases. RESULTS: There were eight cases with the mean age of presentation being 4 years (range: 4 months to 15 years) and with slight male predominance (male:female = 1.66:1). Most of the presenting complaints were due to raised intra-cranial tension. The median duration of symptoms was 0.75 months. About 62.5% of the tumors were infratentorial in location. The tumors were heterogeneous showing variable expression of cytokeratin, epithelial membrane antigen, glial fibrillary acid protein, and synaptophysin. Loss of integrase interactor-1 expression was demonstrated in seven cases in which it was done. Multimodal treatment comprising surgical resection, radiotherapy and chemotherapy was tailored based on location of tumor, resectability and patient's age. The median overall survival was 2.5 months (range: 1.5-30 months). CONCLUSION: Awareness of this tumor is important as it portends a poor outcome in most patients, in spite of multi-modal treatment. Several new molecules which aim to prolong survival and improve quality of life are being developed to combat this enigmatic tumor.
Asunto(s)
Biomarcadores de Tumor/genética , Tumor Rabdoide/tratamiento farmacológico , Tumor Rabdoide/radioterapia , Tumor Rabdoide/cirugía , Teratoma/tratamiento farmacológico , Teratoma/radioterapia , Teratoma/cirugía , Adolescente , Sistema Nervioso Central/patología , Niño , Preescolar , Terapia Combinada , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/genética , Humanos , India , Lactante , Queratinas/genética , Masculino , Mucina-1/genética , Calidad de Vida , Tumor Rabdoide/patología , Sinaptofisina/genética , Teratoma/patología , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
A 7-year-old boy with mixed exocrine-endocrine pancreatic cancer is presented. This may be the second reported case of such a tumor in childhood.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/epidemiología , Carcinoma de Células Acinares/epidemiología , Neoplasias Pancreáticas/epidemiología , Niño , Humanos , MasculinoRESUMEN
BACKGROUND: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a Tertiary Care Center in South India. MATERIALS AND METHODS: This retrospective descriptive study includes 51 cases of ES in children aged below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic, primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ hybridization (FISH). RESULTS: Fifty-three percent were female and 47% were male with mean age of 10 years. The most common site of involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow-up in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%). All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical histomorphology. CONCLUSION: ESFT had wide histological variation which required confirmation by ancillary studies.
Asunto(s)
Citogenética/métodos , Hibridación Fluorescente in Situ/métodos , Sarcoma de Ewing/patología , Adolescente , Niño , Preescolar , Humanos , India , Masculino , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Sinus histiocytosis with massive lymphadenopathy involving organs other than the lymph nodes is a rare event. A case of SIIML presenting with multiple skin and subcutaneous nodules and multiple osteolytic lesions is described. A search of the Indian literature revealed many cases of nodal SIIML, but none of the reported cases had prominent extranodal involvement.
Asunto(s)
Histiocitosis Sinusal/complicaciones , Enfermedades Linfáticas/complicaciones , Niño , Humanos , MasculinoRESUMEN
Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state coupled with a unique radio imaging appearance. We describe this rare, mostly reversible condition in five cases undergoing similar treatment under preset protocol (MCP-841) for acute lymphoblastic leukemia (ALL) at our centre. Hypertension is a well-known adverse effect of high-dose corticosteroid therapy primarily mediated by its effects on the mineralocorticoid receptor especially in pediatric population and we hypothesize that this may be the etiology of PRES in two of these patients.
RESUMEN
Brain tumors are the second most common cancers after hematological malignancies accounting for approximate 21% of all childhood malignancies in children between ages of 0 and 14 y. The present study was undertaken to determine the spectrum of the brain tumors diagnosed in a tertiary cancer center in South India. A retrospective analysis of the data of pediatric brain tumors diagnosed between 2003 and 2009 was done and data was classified according to the age, gender and histology types. Out of 2,844 pediatric patients, 341 (11.99%) were diagnosed as having brain tumors. Most of the patients were in the age group of >5-14 y. Male to female ratio was 1.58:1. The most common pediatric brain tumor was medulloblastoma followed by astrocytoma and ependymoma. Glioblastoma multiforme was the most common subtype of astrocytoma. Other common tumors were glioma, oligodendroglioma, periphereral neuroectodermal tumor and germ cell tumor. As compared to western data, incidence of brain tumors in children was found to be less in the present study.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Adolescente , Neoplasias Encefálicas/epidemiología , Niño , Preescolar , Femenino , Humanos , India , Lactante , Masculino , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Primary pulmonary rhabdomyosarcoma in children is rare. Three children aged three, nine and three years were evaluated for abnormal shadows on radiological examination with pneumothorax in two cases. Resection and histopathological examination revealed embryonal rhabdomyosarcoma in all and cystic malformation in first case. All the three children were treated with surgery and first two received adjuvant chemotherapy. The disease free duration was 160 months, 19 months and seven months respectively. The literature on primary pulmonary rhabdomyosarcoma in children was reviewed.
RESUMEN
Bleomycin is a chemotherapeutic antibiotic used in various malignancies. Its toxicity is mainly lung and skin with marrow sparing effect. Here we would like to describe a characteristic skin reaction developed because of bleomycin in a case of intracranial germ cell tumor. Flagellate erythema which is a self-limiting toxic reaction can cause residual hyperpigmentation.
RESUMEN
BACKGROUND: Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkin's lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown. OBJECTIVE: To study the clinical, pathologic profile and outcome ALCL. MATERIALS AND METHODS: Fifty patients who had pathologically proven diagnosis of systemic ALCL at our institute from June 2003 to May 2011 were included for retrospective analysis. This included 30 cases of anaplastic lymphoma kinase+ (ALK+), ALCL and 20 cases of anaplastic lymphoma kinase- (ALK-), ALCL. The hospital protocol for treatment of these patients included CHOP chemotherapy regimen in >15 years of age and MCP842 protocol with vinblastine for 1 year in <15 years of age. Event free survival was noted. These outcomes were correlated with ALK status, International Prognostic Index (IPI) score, and stage at presentation. RESULTS: At a median follow-up of 36 months (range: 6-72 months) ALK- ALCL had a poor outcome. The 3 year event free survival in pediatric ALCL was 66.7%. In adults, this was 60% ALK+ ALCL was 60% and 20% in ALK- ALCL. CONCLUSIONS: Systemic ALCL is an aggressive disease. CD3 + positivity is commonly seen in ALK- ALCL and ALK+, epithelial membrane antigen + positivity is seen in ALK+ ALCL. ALK- ALCL, advanced stage III, IV and high IPI score were associated with poor prognosis. The demographic profile and outcome in our study was similar to the world literature. With new drugs like crizotinib and brentuximab vedotin the future looks very promising.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Proteínas Tirosina Quinasas Receptoras/metabolismo , Adolescente , Adulto , Anciano , Quinasa de Linfoma Anaplásico , Biomarcadores de Tumor , Complejo CD3 , Niño , Preescolar , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Humanos , India , Lactante , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: The human papillomavirus (HPV) is an important aetiological agent in cancer but its involvement in retinoblastomas (RBs) is controversial. METHODS: 64 formalin-fixed paraffin-embedded tissue blocks and 19 fresh-frozen specimens were subjected to multiplex PCR using PGMY09/11 primers, HPV genotyping, non-isotopic in situ hybridisation and immunohistochemistry for pRb and p16(INK4a). RESULTS: 24% of RBs contained HPV DNA. 90% of HPV genotypes were of high-risk (HR) type and 10% were of intermediate-risk (IR) type. HR HPVs 45, 59, 68 and 52 were detected for the first time, as were IR HPVs 82 and 73. There was only one HPV 18-positive case. Interestingly, no low-risk genotypes were identified. Nine formalin-fixed paraffin-embedded HPV-positive cases showed nuclear HPV positivity by non-isotopic in situ hybridisation. Immunohistochemistry did not show pRb expression in 67% of cases. 34% expressed nuclear p16(INK4a), of which 20 cases were also positive for HPV by multiplex PCR. A statistically significant association between HPV and pRb expression status was observed (p=0.0001).The association of HPV with p16(INK4a) expression was also statistically significant (p=0.0001). CONCLUSIONS: While the presence of HPV in a subset of RB was demonstrated, its role in carcinogenesis needs further elucidation.
Asunto(s)
Carcinoma de Células Escamosas/virología , ADN Viral/genética , Regulación Neoplásica de la Expresión Génica/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Retinoblastoma/virología , Preescolar , Femenino , Genes p16 , Genotipo , Humanos , Inmunohistoquímica , Masculino , Adhesión en Parafina , Reacción en Cadena de la Polimerasa , PrevalenciaRESUMEN
BACKGROUND: Langerhans cell histiocytosis (LCH) is a disease that primarily affects bone but can be associated with a clinical spectrum that ranges from a solitary bone lesion with a favorable natural history to a multisystem, life-threatening disease process. AIM: We analyzed our single institutional experience of managing children with LCH. SETTINGS AND DESIGN: A total of 40 children of LCH, managed in tertiary cancer center in South India in the period from 2001 to 2005, were evaluated retrospectively. MATERIALS AND METHODS: Clinicopathological features, laboratory findings, treatment modalities and long-term outcome were analyzed. RESULTS: Children were aged between 2 months and 12 years, with a mean of 3 years. Majority of the children were below 5 years of age. Group B constituted a bulk of children. Disseminated cases were less (five patients). Liver function dysfunction was seen in four (10%) children. Pulmonary interstitial infiltrates were seen in two (5%) cases. Diabetes insipidus manifested in three patients. There was one death. CONCLUSION: A better understanding of the etiology and pathogenesis of LCH will result in more directed and efficacious treatment regimens.
RESUMEN
BACKGROUND: The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability. AIMS: We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs. SETTINGS AND DESIGN: Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004. MATERIALS AND METHODS: Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed. RESULTS: There were 9 boys and 3 girls, aged 5-60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications. CONCLUSIONS: Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hepatectomía , Hepatoblastoma/diagnóstico , Hepatoblastoma/terapia , Terapia Neoadyuvante , Centros Médicos Académicos , Preescolar , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Hepatoblastoma/patología , Hepatoblastoma/fisiopatología , Humanos , Lactante , Masculino , Pronóstico , Resultado del TratamientoRESUMEN
INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children. MATERIALS AND METHODS: Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A-->C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48-2.45, p = 0.851) and OR for A1298C was 1.29 (95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p = 0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58-6.52, p = 0.286). CONCLUSION: The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C-->T and 1298 A-->C gene polymorphisms and risk of ALL, which may be due to the small sample size.