The prevalence of signs and symptoms of childhood leukemia and lymphoma in Fars Province, Southern Iran

Background: Leukemia and lymphomas are still the common childhood cancers in Iran. This study was undertaken to determine the prevalence of signs and symptoms of these malignancies in children of Fars Province, Southern Iran. Methods: A total of 368 cases of children who were less than 15 years old and diagnosed as acute lymphocytic leukemia (ALL, n = 211), acute myeloid leukemia (AML, n = 64), Burkitt lymphoma (BL, n = 40), chronic myeloid leukemia (CML, n = 5), Hodgkin's disease (HD, n = 33) or non-Burkitt-type, non-Hodgkin's lymphoma (NBNHL, n = 15) referring to the hospitals of Shiraz University of Medical Sciences from April 1997 to March 2002 were enrolled. A questionnaire was provided to record the age, median age at the onset of the disease, sex, type of malignancy and the signs and symptoms at the time of presentation. Results: The common sign or symptoms were fever (74%), in ALL, AML, NHL, and BL patients, hepatosplenomegaly (100%) in CML patients, and lymphadenopathy (54%) and fever (54%) in Hodgkin's disease. Conclusion: Knowledge of signs and symptoms and types of presentations of childhood leukemia and lymphoma may help a physician to improve the patient's outcome. This study revealed that attention to uncommon signs and symptoms in history taking and physical examination together with laboratory tests may increase the physicians’ awareness and better diagnosis of pediatric malignancies and would also be beneficial for the patient.     

Applying Additive Hazards Models for Analyzing Survival in Patients with Colorectal Cancer in Fars Province,Southern Iran

Introduction: Colorectal cancer (CRC) is a commonly fatal cancer that ranks as third worldwide and third and the fifth in Iranian women and men, respectively. There are several methods for analyzing time to event data. Additive hazards regression models take priority over the popular Cox proportional hazards model if the absolute hazard (risk) change instead of hazard ratio is of primary concern, or a proportionality assumption is not made. Methods: This study used data gathered from medical records of 561 colorectal cancer patients who were admitted to Namazi Hospital, Shiraz, Iran, during 2005 to 2010 and followed until December 2015. The nonparametric Aalen’s additive hazards model, semiparametric Lin and Ying’s additive hazards model and Cox proportional hazards model were applied for data analysis. The proportionality assumption for the Cox model was evaluated with a test based on the Schoenfeld residuals and for test goodness of fit in additive models, Cox-Snell residual plots were used. Analyses were performed with SAS 9.2 and R3.2 software. Results: The median follow-up time was 49 months. The five-year survival rate and the mean survival time after cancer diagnosis were 59.6% and 68.1±1.4 months, respectively. Multivariate analyses using Lin and Ying’s additive model and the Cox proportional model indicated that the age of diagnosis, site of tumor, stage, and proportion of positive lymph nodes, lymphovascular invasion and type of treatment were factors affecting survival of the CRC patients. Conclusion: Additive models are suitable alternatives to the Cox proportionality model if there is interest in evaluation of absolute hazard change, or no proportionality assumption is made.     

Modeling of breast cancer prognostic factors using a parametric log-logistic model in Fars province, Southern Iran

In general, breast cancer is the most common malignancy among women in developed as well as some developing countries, often being the second leading cause of cancer mortality after lung cancer. Using a parametric log-logistic model to consider the effects of prognostic factors, the present study focused on the 5-year survival of women with the diagnosis of breast cancer in Southern Iran. A total of 1,148 women who were diagnosed with primary invasive breast cancer from January 2001 to January 2005 were included and divided into three prognosis groups: poor, medium, and good. The survival times as well as the hazard rates of the three different groups were compared. The log-logistic model was employed as the best parametric model which could explain survival times. The hazard rates of the poor and the medium prognosis groups were respectively 13 and 3 times greater than in the good prognosis group. Also, the difference between the overall survival rates of the poor and the medium prognosis groups was highly significant in comparison to the good prognosis group. Use of the parametric log-logistic model - also a proportional odds model - allowed assessment of the natural process of the disease based on hazard and identification of trends.     

Seasonal variations in the onset of childhood leukemia/lymphoma: April 1996 to March 2000, Shiraz,Iran

Infection has long been suspected as a possible factor in the aetiology of leukemia and lymphoma, one of the most common malignancies in children. Since most viral infections have seasonal variations of onset, if seasonal trends in 1 month of diagnosis of leukemia and lymphoma could be proved, this would be supportive evidence for an infectious aetiology. A total of 367 cases in the Hospitals of Shiraz University of Medical Sciences, from April 1996 through March 2000, who were diagnosed as having acute lymphocytic leukemia (ALL), acute myeloblastic leukemia (AML), Burkitt's lymphoma (BL) chronic myeloblastic lymphoma (CML), Hodgkin's disease (HD) or non-Burkitt's type non-Hodgkin's lymphoma (NBNHL) were analysed. The month of appearance of the first symptom and the date of diagnosis were recorded. ALL demonstrated statistically significant monthly variation in the date of appearance of the first symptom (p < 0.05; peak in October) and the date of diagnosis (p < 0.05; peak in November). Seasonal variation was demonstrated in the date of the first appearance of symptoms in BL (p < 0.042), and in the date of diagnosis in AML (p < 0.049). There was no statistically significant seasonal variation in the month of diagnosis for other groups. Analysis based on the date of the first symptoms and the date of diagnosis for ALL patients, using summer-winter ratios, also showed a significant winter excess (p < 0.001). Our data provide modest support for an autumn-winter peak in the diagnosis of childhood ALL, underlying mechanisms that account for these patterns are likely to be complex and need more definitive studies.     

No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.     

Cranial nerve palsy in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

Forty-five children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma had cranial nerve palsy (CNP) as a complication of their disease. Twenty-two of these children had CNP initially and 23, at relapse, with or without previous hematologic relapse. Only one of the 23 patients with CNP at relapse was a long-term survivor. In contrast, 11 of the 22 children who had CNP initially survived in remission for 3+ months to 13+ years. Two factors are associated with an improved outcome for patients with CNP at diagnosis: treatment after 1979 (P less than 0.004) and male gender (P less than 0.01). Patients who received radiation therapy fared better than those for whom radiation was not given (disease-free survival at 2 years 53% versus 29%). The authors conclude that CNP signifies an aggressive or advanced disease requiring intensive systemic chemotherapy and that the role of irradiation should be examined for this group of patients.     

Casitas B-cell lymphoma mutation in childhood T-cell acute lymphoblastic leukemia

Somatic CBL mutations have been reported in a variety of myeloid neoplasms but are rare in acute lymphoblastic leukemia (ALL). We analyzed 77 samples from hematologic malignancies, identifying a somatic mutation in CBL (p.C381R) in one patient with T-ALL that was associated with a uniparental disomy at the CBL locus and a germline heterozygous mutation in one patient with JMML. Two NOTCH1 mutations and homozygous deletions in LEF1 and CDKN2A were identified in T-ALL cells. The activation of the RAS pathway was enhanced, and activation of the NOTCH1 pathway was inhibited in NIH 3T3 cells that expressed p.C381R. This study appears to be the first to identify a CBL mutation in T-ALL.     

The epidemiology of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma in Israel between 1976 and 1981

n epidemiologic survey of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) occurring in Israel, Judea, Samaria and the Gaza Strip between the years 1976 and 1981, revealed 205 cases of ALL and 69 of NHL. The mean annual incidence of lymphatic malignancies was 3.1/10(5) in the Israeli Jews, 2.3/10(5) in the Israeli Arabs and 2.5/10(5) in the Gaza Strip. In the Jewish population there was a peak in the incidence of lymphatic malignancies at the 2-5 years age group, while in the Israeli Arabs this was less prominent. There were no significant differences in the incidence or type of lymphatic malignancies in the various Jewish or Arab groups but there was a trend for a high leukemia to lymphoma ratio (LLR) in the patients from the Gaza Strip. A relatively higher LLR was observed in families of a high socioeconomic status, but it did not reach statistical significance. T-cell ALL comprised about a third of the typed ALL cases. A high proportion of the patients with ALL belonged to the high-risk category: 46% of the Jewish children and 76% of the Gaza Strip children. White blood cell count above 100,000/mm3 were found at presentation in 36.7% of the Gaza Strip patients but only in 9.4% of the Jewish patients. In spite of that, the survival at 4 years of the Jewish and Arab patients was similar. However, the patients with T-cell ALL had a significantly worse survival than the standard risk or the non-T high-risk group: 43.3 +/- 9.7, 66.6 +/- 7.1 and 63.6 +/- 10.4%, respectively. Compared to a previous study conducted in this country in the sixties it appears that the epidemiologic differences that were observed at that time between the various Jewish ethnic groups have practically disappeared.     

Drug monitoring of PEG-asparaginase treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

This is an updated review of the pharmacokinetic profile of PEG-asparaginase (PEG-ASNase) in childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL). In a total of 271 children undergoing ALL/NHL or relapsed ALL treatment according to the Berlin-Frankfurt-Münster (BFM) protocols, drug monitoring of ASNase serum activity was performed after PEG-ASNase infusions. From December 1996 to July 2000, 1667 samples after 362 intravenous administrations of either 500, 750, 1000 or 2500 IU/m2 PEG-ASNase were analyzed. Three weeks after infusion when relating the ASNase activity to the four-dose levels significant differences were not observed. Large interpatient variability was seen at each dose level resulting in a relevant number of patients not achieving adequate treatment intensity. Neither the extent of ASNase pre-treatment nor a prior event of a hypersensitivity reaction against unmodified ASNase had any impact on PEG-ASNase pharmacokinetics. It is concluded that escalation of the dose of PEG-ASNase did not result in a significant prolongation of time with activity values considered therapeutic. Depending on the desired endpoint, a second administration of PEG-ASNase seems to be more favorable than increasing the dose. For a safer recommendation, further investigations assessing the pharmacodynamic profile are required. Drug monitoring is advisable for early detection of patients with rapid elimination in order to ensure maximum treatment intensity.     

Residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia,childhood lymphoma,and childhood nervous system tumors: systematic review,evaluation, and meta-analysis

In 1979, Wertheimer and Leeper reported an increased risk of cancer mortality among children living near electrical wiring configurations, suggestive of high current flow. Since then, numerous, often inconclusively small, investigations with conflicting results have studied the possible asociation between exposure to electric and magnetic fields (EMF) and health effects. The high prevalence of exposure to EMF has drawn attention to the issue of carcinogenesis. We report here the results of a meta-analysis of 13 epidemiologic studies of residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, lymphoma, and nervous system tumors. The combined relative risks for leukemia, lymphoma, and nervous system tumors are 1.49 (95 percent confidence interval [CI]=1.11–2.00); 1.58 (CI=0.91–2.76); and 1.89 (CI=1.34–2.67) respectively. The reports of the primary studies were evaluated for epidemiologic quality and adequacy of exposure assessment. We found no statistically significant relation between combined relative risk estimates and 15 indicators of epidemiologic quality. Assessment of EMF exposure in the primary studies was found to be imperfect and imprecise. Additional high quality epidemiologic research, incorporating comprehensive assessments of EMF exposure collected concurrently with surrogate measures of exposure, is needed to confirm these results.at the time of this researchThis project was supported by a grant from the US National Institute of Environmental Health Sciences, and by a grant from the Agency for Health Care Policy Research.     

Concomitant rearrangements of T-cell beta- and gamma-chain genes in childhood T-lineage leukemia/lymphoma

Similar to the immunoglobulin (Ig) gene rearrangements in B-lineage cells, identification of T-cell receptor (TCR) gene rearrangements is a novel clonal marker and necessary to establish a T-cell lineage. The function of T-cell gamma-chain (T gamma) gene is still unknown, but because of its shared properties with T-cell alpha-chain (T alpha) and T beta genes, we analysed T gamma gene organization in 10 patients with T-lineage leukemia/lymphoma as well as in non-T lineage leukemias. All 10 cases of T-lineage leukemia/lymphoma, whose phenotypes were different, demonstrated T gamma gene rearrangements as well as T beta gene rearrangements. In contrast, among the non-T-lineage leukemias, the emergence of T beta and/or T gamma gene rearrangements was varied. Based on these findings, concomitant rearrangements of T beta and T gamma genes are characteristic in childhood T-lineage leukemia/lymphoma regardless of their phenotypic differences. Furthermore, no obvious developmental hierarchy was observed between T beta and T gamma gene arrangements in these leukemia/lymphoma cells.     

Ambient benzene at the residence and risk for subtypes of childhood leukemia,lymphoma and CNS tumor

Exposure to benzene increases the risk for acute myeloid leukemia and possibly other types of cancer in adults. For children, only limited evidence about benzene and cancer exists. A few studies have indicated that benzene may increase risk for some subtypes of childhood cancer but not for others. We aimed to investigate if outdoor levels of benzene at the residence increase the risk for subtypes of leukemia, lymphoma and CNS tumor in children. We identified 1,989 children diagnosed with leukemia, lymphoma or CNS tumor during 1968–1991 in the Danish Cancer Registry and randomly selected 5,506 control children from the Danish population, matched on sex, age and calendar time. We traced residential history of all children from 9 months before birth to time of diagnosis, calculated outdoor benzene concentration at all addresses and summarized cumulative exposure over fetal and childhood periods separately. We used conditional logistic regression for the statistical analyses. Benzene exposure during childhood above the 90th percentile was associated with relative risks for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) of 1.0 (95% confidence intervals (CI): 0.6–1.7) and 1.9 (95% CI: 0.3–11.1), respectively, when compared with exposure levels below the median. For CNS tumors, there was a tendency of lower risk for ependymoma and higher risk for medulloblastoma in association with higher exposure. In conclusion, benzene was associated with higher risk for childhood AML, but not ALL, which is consistent with the few previous studies.     

The leukemia lymphoma problem in Manipur

Leukemias and lymphomas are the second and fourth commonest malignancies of the entire body respectively in the state of Manipur. The otolaryngological manifestations of these diseases have been emphasized as many of these patients present themselves first in the E.N.T. clinic. The risk factors appear to be yonger age group, male sex, urbanization and the meiteicommunity. Higher incidence of leukemias here than in the rest of India may be due to the racial difference, the local population being Mongoloids.     

Maternal smoking and childhood leukemia and lymphoma risk among 1,440,542 Swedish children.

Possible in utero effects of maternal smoking on hemopoietic cancer in the offspring have been addressed previously, although the results are inconclusive. In this investigation, we take advantage of population-based registers in Sweden to examine maternal smoking during pregnancy and childhood risk of leukemia and lymphoma. Prospective data were available from 1,440,542 Swedish children born between 1983 and 1997. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) controlling for potential confounders. In the study base, 750 hemopoietic cancers occurred across 11 million person-years. Incidence rates per 100,000 person-years were 4.7 for acute lymphocytic leukemia (ALL), 0.45 for acute myelogenous leukemia, and 0.76 for non-Hodgkin's lymphoma. Maternal smoking was associated with a lower risk of ALL (HR, 0.73; 95% CI, 0.58-0.91). On the other hand, there was a higher risk of acute myelogenous leukemia (HR, 1.41; 95% CI, 0.74-2.67) particularly among heavy (> or =10 cigarettes per day) smokers (HR, 2.28; 95% CI, 1.05-4.94). The data also suggested a small excess risk of non-Hodgkin's lymphoma (HR, 1.25; 95% CI, 0.76-2.04). Evidence from this large cohort suggests that maternal smoking affects the risk of childhood leukemia and lymphoma in the offspring. The Swedish registries provide unique opportunities to examine this research question, with a design inherently free of selection and recall biases. The apparent protective effect with ALL needs to be explored further and in no way supports maternal smoking as beneficial, given its adverse association with common pregnancy outcomes.     

Epidemiologic Status of Bladder Cancer in Shiraz,Southern Iran

Background: Bladder cancer is the second most common malignancy of the genitourinary tract worldwideafter prostate cancer. However, in Iran it is the most common cancer of the genitourinary system and the thirdmost common cancer in males. The increasing trend in bladder cancer incidence in recent decades, along with thelack of research on this malignancy in Iran, make epidemiologic research important in light of its preventabilitythrough early recognition and limiting exposure to risk factors. The present study aimed to assess the epidemiologyof bladder cancer in Shiraz, a large city in southern Iran, during a 2-year period. Methods: The data for this studywere obtained from the population-based cancer registry of the Vice-Chancellery for Health Affairs of ShirazUniversity of Medical Sciences and Shiraz hospitals between March 1, 2007 and March 1, 2009. Demographic,clinical and pathological aspects of 216 patients with bladder cancer were investigated through careful reviewof their medical records. Statistical analyses were performed with SPSS software. P values less than 0.05 wereconsidered statistically significant. Results: We analyzed data for 179 (82.9%) men and 37 (17.1%) women (meanage of 65.1±12.7 years). Tobacco and opium use were found in 109 (65.3%) and 44 (34.1%) patients, respectively.Cigarette smokers and water pipe smokers were mostly men (P=0.001 and P=0.04, respectively). The mostcommon type of tumor was transitional cell carcinoma (95.7%) and most tumors were of low malignant potentialgrade (39.7%). Nearly half of the patients suffered recurrence. Conclusion: Comparisons with previous studiesshowed that bladder cancer tends to appear slightly more often in the elderly and that the tumors tend to havea higher grade of malignancy in our region. There is a need for more epidemiologic studies on the trends in theincidence and other epidemiologic indices.