Pneumonitis in lymphoblastic leukaemia of childhood

In the M.R.C. UKALL VIII study, 35 of 199 (17.6%) patients on protocol developed interstitial pneumonitis within the first 44 weeks of treatment (median 10 weeks). These episodes were carefully documented, and serological investigation for Pneumocystis carinii infection was performed in 33 cases. These 35 patients were divided into two groups, one having either histological or serological evidence of P. carinii infection and the other without such evidence. We saw no false positive serological tests in the nine cases with histological confirmation, but the P. carinii immunofluorescence test was of most help in retrospectively confirming P. carinii infection. High dose trimethoprim-sulphamethoxazole was successful in treating 26 of 33 cases (78%). We did note an improvement in survival in children given steroids and we suggest they may have a role in anti-pneumonitis therapy.     

Early childhood leukemia incidence trends in Brazil

Incidence rates of childhood leukemia vary between different regions of the world. The objective of this study was to test possible trends in incidence rate of early childhood leukemia (children <5 years old at the diagnosis) in Brazil. Data from 18 population-based cancer registries (PBCRs) were analyzed (period 1999–2010). The analysis consisted of frequencies, age-adjusted incidence rates, and joinpoint regression results, including annual average percent change (AAPC) in incidence rates and 95% confidence intervals (CIs). The median age-adjusted incidence rate (AAIR) of overall early childhood leukemia was 61 per million. The AAIR for acute lymphoid leukemia (ALL) was 44 per million and nonlymphoid acute leukemia (NLAL) was 14 per million. The median ALL/NLAL ratio was 3.0, suggesting higher incidence rate of NLAL in these settings. The joinpoint analysis demonstrated increased leukemia incidence rate in João Pessoa (AAPC = 20; 95% CI: 3.5, 39.4) and Salvador (AAPC = 8.68; 95% CI: 1.0, 16.9), respectively, whereas incidence rate in São Paulo PBCR decreased (AAPC = ?4.02%; 95% CI: ?6.1%, ?1.9%). Correlation between ALL AAIR and selected variables of socioeconomic (SES) factors was not observed. Increased AAIR regionally overtime was observed. However, the interpretation for such phenomenon should be cautious because it might reflect the access to health care, diagnosis procedures, and improvement of PBCR´s quality. The observed trend supports the necessity of further ecological studies.     

Physical activity in survivors of childhood acute lymphoblastic leukaemia

Aim: To objectively measure levels of physical activity in children, following treatment for acute lymphoblastic leukaemia (ALL). Methods: Nineteen children who had completed treatment for ALL 6 months–5 years prior to study enrolment wore an accelerometer for 2 weekdays and 2 weekend days. Results: The children spent an average of 141 ± 74 min/day engaged in moderate to vigorous physical activity (MVPA), an amount similar to that previously documented in healthy children. Only three of the 19 subjects averaged less MVPA than the recommended amount (at least 60 min/day). MVPA levels were significantly higher on weekdays than weekend days (P= 0.006). Overall, boys engaged in significantly more MVPA than girls (P= 0.029). MVPA time was negatively correlated with age (r =?0.80) and age at diagnosis (r =?0.87). No trend between MVPA and time off treatment or body mass index was identified. Conclusions: Survivors of childhood ALL appear to be engaging in similar amounts of MVPA as those of the healthy children and are meeting recommended levels of physical activity.     

Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia

The hazards associated with invasive candidiasis and aspergillosis in oncology patients are well recognised. These conditions typically present late in treatment, often after prolonged or recurrent episodes of neutropenia. We report the occurrence of Absidia corymbifera infection causing rhinocerebral zygomycosis in two children with acute lymphoblastic leukaemia, early in the induction phase of treatment and within a 3-month interval, in the same oncology unit. The initial presentation of facial pain was rapidly followed by the development of cranial nerve palsies, cavernous sinus thrombosis, diabetes insipidus, seizures and death within 9 days of symptom onset, despite aggressive management with high-dose liposomal amphotericin (Ambisome), surgical debridement and local instillation of amphotericin solution. These cases highlight the need for awareness of zygomycosis as a potentially lethal fungal infection that can present even with short duration exposure to the usual risk factors. Their occurrence within a limited time period raises questions as to the relative importance of environmental exposure. The failure of medical and surgical intervention to impact on the course illustrates the need to develop appropriate preventative strategies which may have to incorporate measures to reduce the environmental exposure of susceptible patients. Received: 23 February 2000 / Accepted: 11 October 2000     

Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996

In a multinational, population-based study from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2648 children below 15 y of age were diagnosed with acute lymphoblastic leukaemia (ALL) in the years 1981-1996. The annual incidence was 3.9/100 000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification of therapy, based on multidrug chemotherapy including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. For children with non-B-cell ALL ( n = 2602), the event-free survival (p-EFS) increased from 0.53 ± 0.02 (diagnosed 7/81-6/86) to 0.67 ± 0.02 (7/86-12/91) to 0.78 ± 0.02 (1/92-12/96). The corresponding p-EFS values at 5 y were 0.57, 0.70 and 0.78, respectively. The main improvements were seen in the group of children with non-high risk leukaemia, with 5-y p-EFS values increasing from 0.60 to 0.76 and 0.85 for the three periods. In high-risk patients, progress has been moderate, especially in children with high white blood cell values at diagnosis. During the last 5-y period, only 10% of the patients received cranial irradiation in first remission while 90% of the patients received high doses of cytostatic infusions (methotrexate isolated or combined with cytarabinoside) and multiple intrathecal injections of methotrexate as CNS-adjusted treatment without any indication of an increased CNS relapse rate.     

Independent effects of socioeconomic status and place of residence on the incidence of childhood type 1 diabetes in Western Australia

OBJECTIVE: To analyze the incidence of type 1 diabetes in 0- to 14-year olds in Western Australia, from 1985 to 2002, by region and socioeconomic status. METHODS: Primary case ascertainment was from the prospective population-based Western Australian Diabetes Register, and secondary case ascertainment was from the Western Australian Hospital Morbidity Data System. The address at diagnosis was used to categorize cases into urban, rural and remote areas and into five socioeconomic groups using the Index of Relative Socioeconomic Disadvantage. Denominator data were obtained from the Australian Bureau of Statistics. Poisson regression was used to analyze the incidence rates by area and socioeconomic status. RESULTS: There were a total of 1143 cases (904 urban, 190 rural and 49 remote). Case ascertainment was estimated to be 99.8% complete. The mean annual age-standardized incidence from 1985 to 2002 was 18.1 per 100,000 person years in urban (95% CI: 16.3-19.9), 14.3 per 100,000 in rural (95% CI: 11.4-7.3) and 8.0 per 100,000 in remote areas (95% CI: 5.8-10.3). The incidence was significantly higher in urban compared with rural (rate ratio 1.27, p = 0.001) and remote (rate ratio 2.28, p < 0.001) areas. The incidence increased with higher socioeconomic status. The incidence in the highest socioeconomic group was 56% greater than the lowest socioeconomic group (rate ratio 1.56, p < 0.001). These differences in incidence by socioeconomic status and region were independent of each other. CONCLUSIONS: Higher socioeconomic status and residence in the urban area are independently associated with an increased risk of childhood type 1 diabetes in Western Australia.     

Lung function and exercise capacity in survivors of childhood leukaemia

The survival from acute lymphoblastic leukaemia in childhood is now approximately 60–70%, and from acute myeloid leukaemia, up to 50%. However, there is little information on the effects of intensive chemotherapy and radiotherapy used in the treatment of these conditions on lung function and exercise capacity in the long term. Seventy survivors of acute leukaemia from one centre in the UK were studied. Measurements of lung volumes, spirometry and transfer factor were made. Each child also performed a standard, symptom-limited maximal exercise test on a cycle ergometer. Predictive equations for indices of lung function and exercise tolerance were calculated from 146 age- and sex-matched control subjects. The results of the survivors of leukaemia were compared to these. There was a significant reduction of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and transfer for carbon monoxide (DLCO; P < 0.05 for each measurement), in the survivors of leukaemia when compared to the control subjects. In addition, there was a mild but significant reduction of both maximal and submaximal indices of exercise capacity in the leukaemic group. A multivariate analysis was carried out to identify those variables acting independently to reduce lung volumes. For FEV1, FVC and TLC, these were craniospinal irradiation, cyclophosphamide and chest complications during treatment. For a reduction in DLCO, the significant factors were administration of anthracyclines, craniospinal irradiation and bone marrow transplantation. Survivors of acute leukemia have impaired pulmonary function and exercise capacity. Long-term cardiopulmonary follow-up may be necessary and new regimens devised which reduce long-term toxicity without compromising survival rates. © 1995 Wi1ey-Liss Inc.     

Clonal variation in childhood acute lymphoblastic leukaemia at early and late relapse detected by analyses of phenotype and genotype

To increase our knowledge of the clonal relationship of leukaemia relapse, the genotypes and phenotypes of ten children with acute lymphoblastic leukaemia (ALL) were examined at initial diagnosis and relapse. Seven patients were phenotyped as common ALL, two as mixed, and one as T-cell ALL (T-ALL). Comparative analyses of immunoglobulin (Ig) heavy and light chain as well as T-cell receptor -chain (T) sequences revealed clonal variations, i.e. appearance of a novel or an evoluted leukaemic cell clone in five patients coinciding with the loss of common acute lymphoblastic leukaemic antigen (CALLA) in four cases, irrespective of early or late relapse. Conversion of early B- to T-ALL or lymphoblastic to non-lymphoblastic leukaemia was not noted in any of the patients examined. Our results suggest that clonal variation is a frequent event in childhood ALL.Abbreviations Kb kilobase pairs - ALL acute lymphoblastic leukaemia - CALLA common acute lymphoblastic leukaemia antigen - Ig immunoglobulin - TCR T-cell receptor - T T-cell receptor -chain - FAB French-American-British - TdT terminal deoxynucleotidyl transferase - T-ALL T-cell ALL     

Longitudinal growth and final height in long-term survivors of childhood leukaemia

Survival of children with acute lymphoblastic leukaemia (ALL) has increased considerably in recent years and data on the spontaneous growth and final height of these children are conflicting. Therefore, we analysed the longitudinal growth and final height in 52 survivors (33 females, 19 males) of childhood ALL. These children were diagnosed and treated in a single institution, all remained in first remission and were submitted to cranial irradiation with either 2400 or 1800 cGy. None of the patients received testicular or spinal irradiation. Median age at diagnosis was 4.2 (range 1.3–9.6) years in the first group (2400 cGy) and 3.9 (0.8–10.5) years in the second (1800 cGy). Standing height was measured at diagnosis, at the end of treatment (median 3.1 years after diagnosis), 6, 12, 24 months after the end of treatment, and finally at the completion of growth. In girls a significant decrease of mean height standard deviation score (SDS) during treatment and a catch up in growth after the end of therapy was followed by a second period of reduced growth. Mean final height SDS was significantly lower than the value at diagnosis in both groups of girls, but only in males treated with 2400 cGy. Mean overall loss in height SDS from diagnosis to final heigth was higher in females (–1.24) than in males (–0.40) (P=0.009). Females <-4 years of age at diagnosis showed a higher loss in final height than females >4 years. An unchanged or improved final height was evident in 8 cases, the other 44 cases showed a final height decrease between –0.1 and –2 SDS in 36 and >-2 SDS in 8, 6 of whom were females <-4 years at diagnosis and only 1 a female >4 years. Only females treated at a younger age showed a final height lower than midparental height (–5.7±1.8 cm,P<0.01), particularly those treated with 2400 cGy (–7.5±2.5 cm,P<0.05). Menarche occurred earlier than in the normal population (11.5±1.2 years) with no differences between the two radiation dosages.Conclusion Females, notably young girls, treated for ALL show a greater decrease in the final height than treated males. Early sexual maturation may contribute to the decrease in the final height. A better growth pattern seems to be shown by patients irradiated with the lower dosage.     

Meningeal leukaemia in the blastic phase of chronic granulocytic leukaemia

A 51/2-year-old boy is presented with chronic granulocytic leukaemia and blastic transformation whose clinical course is complicated by meningeal leukaemia. In the authors' opinion prophylactic central nervous system therapy should be part of the initial therapy of blastic transformation.Abbreviations CGL chronic granulocytic leukaemia - PAS periodic acid-schiff     

High incidence of childhood type 1 diabetes in Al-Madinah, North West Saudi Arabia (2004-2009)

Habeb AM, Al‐Magamsi MSF, Halabi S, Eid IM, Shalaby S, Bakoush O. High incidence of childhood type 1 diabetes in Al‐Madinah, North West Saudi Arabia (2004–2009). Background: There is a geographical variation in the incidence of childhood type 1 diabetes mellitus (T1DM) with a steady increase reported from some countries. However, data on the incidence of childhood T1DM in Kingdom of Saudi Arabia are limited. Objective: To identify the incidence rate (IR) and epidemiological trends of childhood T1DM in the largest city of northwest Saudi Arabia. Methods: All patients with newly diagnosed T1DM aged 0–12 yr living in the city between 2004 and 2009 were identified from different sources. The data were analyzed according to age, sex, and month of presentation. Results: In total, 419 patients (249 girls) were diagnosed between 2004 and 2009 inclusive. The mean age at diagnosis was 6.9 ± 3.5 yr. The mean annual age‐standardized IR was 29.0 (95% confidence interval 26.0–32.0). The incidence was significantly higher in the 10–12‐yr age group than in younger children (p < 0.001) and higher in girls than in boys (33.0 vs. 22.2 per 100 000; p < 0.001). There was no significant increase in the annual incidence during the 6‐yr period (p = 0.68) and more cases were diagnosed during autumn and winter months (p = 0.002). Conclusions: Al‐Madinah city has the highest reported incidence of childhood T1DM in the Middle East and North Africa region. Further studies to identify the reasons for this high incidence are needed.     

Immunologic monitoring of maintenance therapy for acute lymphoblastic leukaemia in children-preliminary report

BACKGROUND: In the study we evaluated immune reconstitution during maintenance therapy for acute lymphoblastic leukaemia (ALL) in relation to different treatment protocols and response of the immune system to the accompanying infections. PROCEDURE: The study group consisted of 40 children. The BFM protocol'90 was used in the standard risk group, while the New York protocol-in the high risk group. Assessment of the immune system was based on the analysis of peripheral blood mono-nuclear cells by flow cytometry and concentrations of immunoglobulins: G, M, A and IgE. Each patient was examined at 1-3 months' intervals. RESULTS: Following cessation of intensive therapy, the successive months of maintenance treatment showed: (1) a considerable depletion of B lymphocytes, a durable decrease in IgM, IgA and gradually increasing IgG; (2) a correlation between the time passing from the cessation of intensive therapy and increased numbers and percentage of B cells, and the helper/suppressor cell ratio. In the group of children treated according to the high risk protocol, compared to the low-risk group patients, we found lower levels of the following parameters: IgG, % lymphocytes: B and T lymphocytes (including CD4/CD8 ratio and "naive"/"memory" ratio) and NK cells (% and count). During infection: (1) a significant increase was noted in the percentage of T cells with HLA co-expression and monocytes with ICAM-1 co-expression, (2) the percentage of CD3(+)CD45RO(+) "memory" T cells was found to increase. CONCLUSIONS: Our findings indicate quantitative and qualitative changes of the immunity in children with ALL during maintenance therapy.