Geographical Distribution and Cluster Detection of Childhood Leukemia in the Metropolitan Area of Guadalajara, Mexico.

BACKGROUND: Acute leukemia is the most common cancer in childhood. Analyzing the spatial distribution of acute leukemia may generate the identification of risk factors. OBJECTIVE: To study the incidence rate of acute leukemia, its geographic distribution, and cluster detection in the metropolitan area of Guadalajara, Mexico. METHODS: We included children under 15 years of age diagnosed with acute leukemia during the period 2010-2014 in the metropolitan area of Guadalajara. Each case was geo-referenced to street level to latitude and longitude coordinates using Quantum Geographic Information System (QGIS). Spatial clusters were found in the location of the acute leukemia cases applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm with R statistical software. RESULTS: A total of 269 cases of leukemia were registered, 227 (84%) were acute lymphoblastic leukemia and 42 (16%) acute myeloblastic leukemia. The mean age was 6 ± 4 years. The mean incidence of acute leukemia was 6.44 cases/100,000 inhabitants: El Salto 10.12/100,000, Guadalajara 7.55/100,000, and Tlaquepaque 6.74/100,000. The DBSCAN found three clusters, all located within the municipality of Guadalajara. CONCLUSIONS: The incidence of acute leukemia in our population is higher than that in Canada and the USA. We found three spatial clusters of childhood acute lymphoblastic leukemia in the municipality of Guadalajara, suggesting the presence of local predisposing factors.

Pediatric donor cell leukemia after allogeneic hematopoietic stem cell transplantation in AML patient from related donor.

Here we present a male patient with acute myeloid leukemia (AML) initially diagnosed as M5 and with karyotype 46,XY. After induction therapy, he underwent a HLA-matched allogeneic hematopoietic stem cell transplantation, and six years later he relapsed as AML M1 with an abnormal karyotype //47,XX,+10[2]/47,XX,+11[3]/48,XX,+10,+11[2]/46,XX[13]. Based on this, we tested the possibility of donor cell origin by FISH and molecular STR analysis. We found no evidence of Y chromosome presence by FISH and STR analysis consistent with the success of the allogeneic hematopoietic stem cell transplantation from the female donor. FISH studies confirmed trisomies and no evidence of MLL translocation either p53 or ATM deletion. Additionally 28 fusion common leukemia transcripts were evaluated by multiplex reverse transcriptase-polymerase chain reaction assay and were not rearranged. STR analysis showed a complete donor chimerism. Thus, donor cell leukemia (DCL) was concluded, being essential the use of cytological and molecular approaches. Pediatric DCL is uncommon, our patient seems to be the sixth case and additionally it presented a late donor cell leukemia appearance. Different extrinsic and intrinsic mechanisms have been considered to explain this uncommon finding as well as the implications to the patient.

A translocation t(5;15)(q15;q11-13) infant case with acute lymphoblastic leukemia and literature review: prognosis implications.

Infant acute lymphoblastic leukemia (ALL) represents poor prognosis despite intensive chemotherapy. Rearrangements of chromosome 11q23 are not observed in 34% of the cases. Infant ALL patients with t(5;15)(p15;q11-13) are rare and sporadic. In large series of infant ALL studies, 6 patients have been reported. We present a new case of an infant ALL patient with t(5;15)(p15;q11-13), and a literature review. Considering the data provided by our case and previous reports, we reinforce that this chromosomal abnormality is characteristic of ALL patients under 12 months of age sharing break point in 5p15 and 15q11-13 and strengthen the existence of an infant ALL subgroup characterized by pre-B L1 ALL, CD10-positive, complete remission (100%), and event-free survival (71%), with a relatively good prognosis and clearly less severe than the 11q23 rearrangement cases. This abnormality can be considered a recurrent abnormality on this nosologic group.

The effect of dexrazoxane for clinical and subclinical cardiotoxicity in children with acute myeloid leukemia.

SUMMARY: Cardiotoxicity is frequently present with anthracycline treatment. Most acute myeloid leukemia (AML) protocols use anthracyclines. Dexrazoxane has cardioprotective activity. The aim of this study was to evaluate cardioprotection of dexrazoxane in a prospective study. Fifty pediatric AML patients were treated with a Medical Research Council AML 10 modified protocol with dexrazoxane previous to any anthracycline dose. Cardiac function was evaluated at diagnosis, before every cycle, and every 6 months after the end of chemotherapy. Accumulative doses of anthracycline reached 424 mg/m (150 to 850 mg/m). Forty-eight patients (96%) received a dose higher than 300 mg/m. Twenty-eight percent had a grade of cardiotoxicity (24% grade 1 and 4% grade 2). Non 3 or 4 grade cardiotoxicity was seen. Cumulated anthracycline doses did not correlated with cardiotoxicity (P=0.815). The event-free survival was 53%, 15.7% died of disease, and 11.8% died free of leukemia. There is still not an agreement for the optimal method to reduce cardiotoxicity in children receiving anthracyclines. In our study, we could conclude that the use of dexrazoxane was effective cardioprotectant to allow a high-dose of anthracycline therapy. A randomized study is necessary to consolidate this asseveration.

Procalcitonin and C-reactive protein serum levels as markers of infection in a pediatric population with febrile neutropenia and cancer.

BACKGROUND: Procalcitonin and C-reactive-protein are inflammatory markers for sepsis. The authors evaluated their sensitivity and specificity in pediatric patients with cancer and febrile neutropenia. PROCEDURE: Serum procalcitonin and C-reactive-protein were evaluated. Patients (n = 54) were divided into 2 groups, with severe infection (n = 18) or without documented infection (n = 36). RESULTS: Procalcitonin and C-reactive protein were significantly higher in the high-risk group. Procalcitonin displayed 72.2% sensitivity and 80.5% specificity. C-reactive-protein had a sensitivity of 77.7% and specificity of 77.2%. CONCLUSIONS: Procalcitonin is an accurate predictor of bacterial infection in neutropenic children, while C-reactive-protein may be a better screening test in emergency settings.

Improved treatment results in Mexican children with acute myeloid leukemia using a Medical Research Council (MRC)-acute myeloid leukemia 10 modified protocol.

We analysed the results of three protocols from 1990 to 2005. Protocol I (1990-1996) consisted of a 2 year VAPA regime. Protocol II (1996-2003) on 1 year daunorubicin/cytarabine alternating with etoposide/cytarabine. Protocol III (2003-2005) on six cycles MRC AML 10 modified. Patients with de novo acute myeloid leukemia 0 to 18 years were included. Demographic and clinical characteristics were analysed. Patients with >100,000 leukocytes, M4 or M5 and primary CNS disease were considered high risk. We compared remission rate, overall and event-free survival. Descriptive statistics, chi square, Kaplan-Meier and long rank tests were used. One hundred forty-five patients were included, 46 in Protocol I; 60 in II and 39 in III. There were no differences in characteristics between groups, except for more low risk patients in Protocol II (61%vs. 43% and 41%. (p = 0.05). Remission rate for Protocol I was 52%, for II 50% and for III 92% (p = 0.0001). Relapse was 18, 30 and 35, respectively (p = 0.141). Five-year event-free survival was 17.9% +/- 6.6%, 15.5% +/- 4.1% and 43.5% +/- 4.1% (s.e) (p = 0.0002). Five-year overall survival was 19.5% +/- 8%, 17.2% +/- 5.9% and 51.2% +/- 4.1% (s.e) (p = 0.0002). The results were superior in the MRC-10 derived protocol.

Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin.

UNLABELLED: Amifostine has emerged as a pancytoprotectant shown protection against nephrotoxicity, neurotoxicity and ototoxicity in preclinical studies. METHODS: We designed a prospective comparative randomized trial to evaluate the cytoprotective effects of amifostine in patients with osteosarcoma receiving cisplatin and doxorrubicin. Patients were evaluated for renal, hearing and cardiac toxicity. RESULTS: We included 28 patients, mean age was 11.6 years, five had metastatic disease. Fifteen patients received amifostine and 13 did not. 20% of patients receiving amifostine developed renal toxicity compared to 30% in the control group (p = 0.318). Grade 1 and 2 audiologic toxicity was present in 100% of the experimental group against 85% of the controls (p = 0.501). Grade 1 cardiac toxicity was present in 2 patients in the control group (p = 0.175). There were no statistical significant differences between the two groups for chemotherapy-related toxicity. Response to chemotherapy was significantly better in the amifostine group. CONCLUSION: amifostine did not reduce the ototoxicity and nephrotoxicity of our treatment regime. It was not well tolerated due to emesis. It is a selective cytoprotectant without reducing the effect of chemotherapy.

Primary central nervous system non-Hodgkin lymphoma in childhood presenting as bilateral optic neuritis.

INTRODUCTION: Primary central nervous system lymphoma is a very rare condition in pediatric patients. CASE REPORT: We describe the case of a 10-year old girl who presented with acute bilateral vision impairment. At the time of presentation, the only positive finding was optic disk swelling, and the brain MRI scan was normal. Seventeen months later, she developed a large-cell non-Hodgkin lymphoma in the brain, with no evidence of neoplasia elsewhere. Immunodeficiencies and Epstein-Barr virus infection could not be demonstrated. The patient was successfully treated with a combination of cyclophosphamide, etoposide, vincristine, methotrexate, and cytarabine, plus intrathecal chemotherapy. Craniospinal irradiation was not used. OUTCOME: The patient's condition is still in remission 68 months after completing the treatment. CONCLUSION: This case is the only non-Hodgkin lymphoma with primary central nervous system location treated in our institution in the last 10 years and represents less than 0.5% of our non-Hodgkin lymphoma series. Due to its rare occurrence, not much is known about the clinical features and treatment outcome of primary central nervous system lymphoma in pediatric patients.

Osteosarcoma como segunda neoplasia de retinoblastoma / Osteosarcoma as a second neoplasm in a children with retinoblastoma

Introducción. Es bien conocido que el osteosarcoma se presenta frecuentemente como segunda neoplasia del retinoblastoma congénito, así como otro tipo de carcinomas, melanomas y tumores neuroepiteliales. Todos los pacientes con retinoblastoma bilateral congéntio presentan una alteración del gen RB1 localizado en el cromosoma 13q14. Caso clínico. Se presenta el caso de una paciente con retinoblastoma bilateral congénito diagnosticado a la edad de 1 año 11 meses, quien recibió tratamiento con ciclofosfamida, epirrubicina y VP 16, entre otros agentes; y que desarrolló osteosarcoma peroneo con metástasis pulmonares tras una latencia de 10 años 6 meses. En esta paciente es conocido el uso de alquilantes, antracíclicos y etopósido, así como los antecedentes familiares de cáncer por ambas ramas. Conclusión. El retinoblastoma bilateral conlleva factores de riesgo para el desarrollo de segundas neoplasias. Los antecedentes familiares constituyen razones suficientes para catalogarlo como un síndrome de cáncer familiar, el uso de agentes alquilantes, antraciclicos y etopósidos, aumentan este riesgo acortando el período de latencia