The frequency of allele variants of gene TPMT*2, *3A, *3B, and *3C was estimated in a population of 116 Brazilian children with acute lymphoblastic leukemia. The association between genotype and clinical and laboratory data obtained during chemotherapy maintenance phase and the correlation of intraerythrocyte concentration of 6-mercaptopurine metabolites (6-tioguanine nucleotide nucleotides and methylmercaptopurine) were analyzed. A multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used in DNA amplification. Twelve patients presented TPMT gene mutation, all in heterozygous form. The most frequent allele variation was TPMT*3A (3.9%), followed by *3C (0.9%), *2 (0.4%), and *3B (0%). There was no significant association between clinical and laboratory data and the presence of mutation in TPMT gene. Of the 36 patients who were monitored for 6-mercaptopurine metabolite levels, only 1 had the mutation. In this patient, high 6-tioguanine nucleotide and low methylmercaptopurine concentrations were found. Event-free survival (EFS) for the whole group was 73.4%. There was no significant difference in event-free survival in the comparison between the groups with and without mutation (P = 0.06).

ObjectiveTo characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. MethodsβS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. ResultsThe following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. ConclusionApparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

BackgroundRemission rates achieved after the initial treatment of acute lymphoblastic leukemia may be similar in both developed and developing countries, but relapse rates are much higher in the latter. Thus, other reasons are needed, in addition to biological characteristics of the leukemic cells themselves, to explain the unfavorable evolution of patients living in unfavorable socioeconomic and cultural conditions.ObjectiveThe aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol.MethodsMain abstracted data were: total duration and reasons for interruption of chemotherapy, prescribed doses of 6-mercaptopurine, and median white blood cell and neutrophil counts during the maintenance phase. Interruptions of chemotherapy were considered inappropriate if they did not follow predetermined criteria established in the protocol.ResultsFourteen of 73 patients (19.2%) unduly interrupted chemotherapy by determination of their physicians. The median white blood cell count was higher when compared with the protocol recommendations; the median 6-MP dose was lower than the standard recommended dose. The estimated probability of event-free survival was higher for patients with lower median leukocyte counts and close to those predetermined by the protocol. Event-free survival was also higher for children with a higher percentage of days without chemotherapy due to bone marrow or liver toxicity excluding undue interruptions. In multivariate analysis, both factors remained statistically significant. These results suggest that the intensity of maintenance chemotherapy may not have been enough in some children, to achieve adequate myelosuppression, hence the observation of higher leukocyte counts and none or rare episodes of therapy interruption.ConclusionsCompliance to the therapeutic protocol by both doctors and patients should always be considered in the evaluation of therapeutic failure in acute lymphoblastic leukemia; strict adherence to treatment protocols contributes to better treatment results in acute lymphoblastic leukemia children.

Almost 3 million babies were tested in a newborn screening program in Minas Gerais, Brazil (1998-2008); 128 who have S-like hemoglobins (Hbs) were tested for the β(S) allele and 112 were identified through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequencing. Hb Stanleyville-II [α78(EF7)Asn→Lys (α2); HbA2: c.237C>A] was present in 96 children (85.7%), two in a homozygous state and 94 in a heterozygous state. Its estimated prevalence was 1:11,500. Hbs Hasharon [α47(CE5)Asp→His, GAC>CAC (α2)], Ottawa [α15(A13)Gly→Arg (GGT>CGT) (α2 or α1)], G-Ferrara [β57(E1)Asn→Lys (AAC>AAA or AAG)], St. Luke's [α95(G2)Pro→Arg, C CG>C GG (α1)], Maputo [β47(CD6)Asp→Tyr (GAT>TAT)] and Etobicoke [α84(F5)Ser→Arg (AG C>AG G or CGC or AGA) (α2 or α1)] were also identified. Many children with Hbs Stanleyville-II and Hasharon also co-inherited the -α(3.7) thalassemia gene. African ancestry was recognized by parents of all 31 children with Hb Stanleyville-II who were interviewed. Mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) values were significantly lower in children with α-thalassemia (α-thal). We came to the conclusion that Hb Stanleyville-II is not so uncommon in Brazil and seems to have originated from the African slave trade. This study reinforces the importance of an accurate diagnosis of variants that have electrophoretic mobility similar to Hb S [β6(A3)Glu→Val, GAG>GTG] so that false diagnoses are avoided.

A Leishmaniose Visceral (LV) é uma parasitose com sintomatologia grave, que pode ser fatal, causada por protozoários do gênero Leishmania. Nesse relato, apresentamos um caso suspeito de LV de uma paciente residente em área endêmica para a doença. O quadro de hepatoesplenomegalia, anemia, dor abdominal e plaquetopenia gerou suspeita de LV, apesar de os exames laboratoriais apresentarem resultados negativos. A paciente foi tratada empiricamente com anfotericina B desoxicolato e obteve regressão dos sintomas.

Hemoglobin Rush is an unstable variant generated by a mutation of the β-globin gene which causes amino acid replacement Glu>Gln in the central cavity of hemoglobin (G3). Many members of a Brazilian family of Italian descent have hemoglobin Rush. This is the second report in world literature. Clinical and laboratory features were retrieved and gene mutation was characterized. Hemoglobin electrophoresis, gene sequencing, and restriction fragment length polymorphism with Hpy188I were used to characterize it. In 13 affected members, hemoglobin ranged from 9.3 to 13.0 g/dL and reticulocyte count up to 12.8%. The intensity of hemolysis appeared to be linked to increased stress. The mutation was proved to be HBB:c.304G>C, beta 101(G3) Glu>Gln. Heterozygous hemoglobin Rush should be suspected when alkaline electrophoresis shows three bands, whereas isoelectric focusing and acid electrophoresis show only two. Adequate genetic counseling to avoid intermarriage should be provided because homozygous hemoglobin Rush is predicted to be clinically severe.

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