Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS 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. RESULTS: The 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. CONCLUSION: Apparently 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.

Compliance with a protocol for acute lymphoblastic leukemia in childhood

BACKGROUND: Remission 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. OBJECTIVE: The aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol. .... 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. CONCLUSIONS: Compliance 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.