(11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white celi count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z=-1*28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score <-2 had a relapse risk of 8*2 (95Gb confidence interval 3*1 to 21-9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries. (Arch Dis Child 1994; 71: 304-3 10)

either PFS (P ¼ 0.63) or OS (P ¼ 0.52), nor did IgV H mutational status. However, patients with mutated IgV H had a longer treatment-free survival compared with those with unmutated IgV H (Figure 3).The overall response rate of 64% in this cohort of 126 patients with previously untreated B-CLL is comparable to results reported with intravenous fludarabine. Using the same response criteria, Rossi et al. 2 reported an overall response rate of 80% with the same schedule of oral fludarabine in a smaller group of previously untreated B-CLL patients but the proportion of patients in Rai stage III or IV in our study was higher (31% versus 22%) than in the Rossi trial.This study again confirms that the efficacy and toxicity of oral fludarabine are comparable to that of IV fludarabine given on a similar schedule. Although several randomized trials have confirmed a better overall and complete response rate for the combination of fludarabine and cyclophosphamide compared with fludarabine alone, no differences in the OS were observed. 7,8 In the British study, the oral formulation of fludarabine was introduced in both fludarabine arms when the drug became available, and differences in response rates between the two routes of administration did not appear significant. Oral fludarabine is an effective treatment for patients with previously untreated B-CLL, with less health resource utilization compared with IV administration. In an older population, the hematologic toxicity of the combination of fludarabine with cyclophosphamide and the absence of a demonstrable survival advantage, may favor initial therapy with single agent fludarabine and deferring combination therapy. In fludarabine-based combination therapies, the oral formulation should be considered an acceptable alternative. Conflict of interestThe authors declare no conflict of interest.

PURPOSE To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. PATIENTS AND METHODS Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n = 544) were randomly allocated to receive either continuous 6-MP/MTX (group 1, n = 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MTX (200 mg/m(2) every 3 weeks; group 2, n = 272). RESULTS The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P = .28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P = .089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P = .027), while no difference was seen for girls (87.0% v 88.8% SE; P = .78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P = .002), and 772 and 636 for hematologic episodes (P = .005). Deaths on maintenance were: seven (group 1) and one (group 2). CONCLUSION The intermittent use of 6-MP and MTX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Objective: To describe the deaths of children with sickle cell disease (SCD) in Minas Gerais, Brazil, and followed up at the Fundação Hemominas. (March/1998 -February/2005). Deaths were identified by searching for children who did not attend scheduled consultations at hemocenters. Clinical and epidemiological data were abstracted from death certificates, the newborn screening database, individual medical records, and from interviews with families. Methods: Cohort of children diagnosed by the Neonatal Screening Program in Minas GeraisResults: During the period, 1,833,030 newborns were screened; 1,396 had SCD (1:1,300). There were 78 deaths: 63 with SS genotype, 12 with SC genotype, and three with Sß + thalassemia genotype. Fifty-six children (71.8%) died before 2 years of age; 59 died in hospitals and 18 at home or during transportation. Causes of death according to certificates (n = 78): infections, 38.5%; acute splenic sequestration, 16.6%; other causes, 9%; did not receive medical care, 15.4%; and not identified on certificates, 20.5%. According to interviews (n = 52), acute splenic sequestration was responsible for one third of deaths, in contrast with 14% recorded on death certificates. Survival probabilities at 5y (SEM) for children with SS, SC, and Sß + thalassemia were 89.4 (1.4), 97.7 (0.7), and 94.7% (3.0), respectively (SS vs. SC, p < 0.0001). Conclusions:Even with a carefully controlled newborn screening program, the probability of SS children dying was still found to be high. Causes not identified on death certificates may indicate difficulties recognizing SCD and its complications. Educational campaigns directed at health professionals and SCD patients' families should be boosted in order to decrease SCD mortality. Resultados: Foram triadas 1.833.030 crianças no período, sendo 1.396 com DF (1:1.300). Ocorreram 78 óbitos: 63 em crianças com genótipo SS, 12 em crianças com genótipo SC e três em crianças com genótipo S/ß + talassemia. Cinquenta e seis crianças (71,8%) morreram antes dos 2 anos de idade; 59 morreram em hospitais e 18 no domicílio ou trânsito. Causas de óbito pelo atestado (n = 78): 38,5% infecção; 16,6% sequestro esplênico agudo; 9% outras causas; 15,4% sem assistência médica; e 20,5% indeterminada. Segundo as entrevistas (n = 52), o sequestro esplênico foi responsável por quase 1/3 dos óbitos, contrastando com a porcentagem de apenas 14% registrada nos atestados de óbito. As probabilidades de sobrevida aos 5 anos (erro padrão da média) para crianças SS, SC e Sß + talassemia foram: 89,4 (1,4), 97,7 (0,7) e 94,7% (3,0), respectivamente (SS versus SC, p < 0,0001). J Pediatr (Rio J) Conclusões:Mesmo em um programa de triagem neonatal com rigoroso controle do tratamento, a probabilidade de óbito em crianças com genótipo SS ainda é elevada. Os óbitos com causa indeterminada indicam dificuldades no reconhecimento da DF e das suas complicações. Esforços educativos dirigidos a profissionais da saúde e familiares devem ser incrementados para diminuir a mortalidade pela DF. J Pediatr (Ri...

The online version of this article contains a supplementary appendix. BackgroundMinimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and MethodsWe analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. ResultsAt least one marker was detected by polymerase chain reaction in 96.4% of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. ConclusionsThis simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

Erythrocyte thiamin metabolism and transport were investigated in 7 patients from Brazil, Israel and Italy suffering from thiamin-responsive megaloblastic anaemia (TRMA) associated with diabetes mellitus and sensorineural deafness. All patients discontinued thiamin therapy for 4-7 days before the investigation. TRMA patients showed invariably reduced total thiamin levels in erythrocytes (percentage reduction compared with healthy controls, -46.8+3%; mean+SEM). The proportions of individual thiamin compounds, expressed as a percentage of total thiamin content, were within the normal range, whereas their absolute amounts were significantly decreased in the following order: thiamin monophosphate>thiamin pyrophosphate>thiamin. Thiamin pyrophosphokinase activity was also reduced as compared with controls (mean reduction+SEM, -25.9+1%). The saturable, specific component of thiamin uptake, which normally prevails at physiological concentrations of thiamin (< 2/~mol/L), was absent in erythrocytes obtained from TRMA patients, while the non-saturable (diffusive) component of uptake was normally present.These results confirm observations made previously in two patients and demonstrate that TRMA is consistently associated with a state of thiamin deficiency, which is presumably secondary to reduced thiamin cellular transport and absorption (caused by lack of a membrane-specific carrier), and to impaired intracellular pyrophosphorylation.Investigators from our group recently showed that erythrocytes obtained from patients with thiamin-responsive megaloblastic anaemia (TRMA, McKusick 249270), exhibit no saturable, specific component of thiamin transport as well as a reduced thiamin pyrophosphokinase (EC 2.7.6.2; TPK) activity, resulting in decreased red cell total MS received 22.3.94 Accepted 16.5.94

No abstract

The study estimated α-thalassemia (α-thal) prevalence and assessed its associations with clinical and hematological features in a random sample of Brazilian children with sickle cell anemia (208 Hb SS and 13 Hb S-β⁰-thal). α-Thalassemia genotyping was carried out by multiplex polymerase chain reaction (m-PCR) for seven alleles. Clinical and hematological data were retrieved from the 221 children's medical files. Their ages ranged from 2.5 to 10.4 years. Of the Hb SS children, 27.9% carried -α(3.7)/αα and 1.4% -α(3.7)/-α(3.7). The presence of α-thal was significantly associated with reduction in MCV, MCH, WBC values and reticulocyte counts. No significant association with blood transfusion or acute chest syndrome (ACS), was found. α-Thalassemia genotypes were strongly associated with reduction in risk for cerebrovascular disease (CVD) (conditional and abnormal transcranial Doppler or stroke; p = 0.007). The interaction of α-thal with other modulating factors should be investigated in order to define subphenotypes of the disease and to use them as clinical tools in the follow-up care of patients.