[Cause of death, survival, and prognostic factors in a series of 98 patients with chronic myeloid leukemia]. / Causas de muerte, supervivencia y factores pronósticos en una serie de 98 pacientes con leucemia mieloide crónica.

PURPOSE: To analyse the survival from diagnosis to blastic crisis, as well as the causes of death and the significance of different features in patients diagnosed of chronic myelogenous leukaemia (CML). MATERIAL AND METHODS: The series includes 98 patients who died of CML in Asturias Central Hospital and other nearby hospital between 1970 and 1990. The CML diagnosis had been established according to conventional criteria. The blastic crisis was diagnosed in accordance with morphologic and cytochemical studies, complemented in some cases with the assay of TdT or other markers. The Kaplan-Meier curves and long-rank test were applied to the statistical analysis of survival. The prognostic factors were evaluated by univariate correlation. RESULTS: The series' mean age was 48.57 years (range: 6-90) and the M/F ratio was 56/42. Cytogenetic study had been performed in 35 patients, of whom 33 had the Ph' chromosome. Death occurred in the blastic crisis in 67 cases (72%), in the accelerated phase in 14 cases (15%) and in the chronic phase in 12 cases (13%). The cause of death could be determined in 47 cases; of them, 24 (51%) died of infection, 11 (23.4%) of haemorrhage, and the remaining 12 (25.6%) of different complications. The median survival of the group as a whole was 32 months (range: 4-137). For the blastic crisis this figure was reduced to 2.5 months (range: 1-14), the lymphoid forms doing better, 5 months, than the non-lymphoid ones; 1.5 months (p < 0.03). Out of the data evaluated at diagnosis, only haemoglobin and the percentage of blast cells in peripheral blood showed any correlation with survival (r = +0.28, p < 0.05 for haemoglobin, and r = -0.30, p < 0.01 for blast cells). CONCLUSIONS: (1) Although most patients die from infection or haemorrhage during the blast crisis, CML increases the risk of death in the accelerated and chronic stages as well. (2) Non-lymphoid blastic crisis has poorer prognosis than the lymphoid form. (3) The concentration of blast cells and haemoglobin in peripheral blood at diagnosis acquire prognostic significance in the present study.

[Molecular analysis of glucose-6-dehydrogenase deficiency in Spain]. / Análisis molecular del déficit de glucosa-6-fosfato deshidrogenasa (G6PD) en España.

PURPOSE: G6PD deficiency is the most frequent enzymopathy-producing genetic polymorphism in humans. Up to now, over 400 putative variants of G6PD have been distinguished on the basis of biochemical characterization of the deficient enzyme. Analysis of the G6PD gene has made possible a precise classification of the G6PD molecular variants by identification of about 80 different point mutations causing much of the phenotypic heterogeneity. In the Spanish population, the analysis of G6PD has led to the identification of 15 different point mutations that underlay the phenotypic heterogeneity of G6PD previously reported by biochemical analysis. The purpose of the study has been to identify the genetic mutation responsible of the G6PD deficiency and to improve the knowledge of its genetic homogeneity. PATIENTS AND METHODS: From 50 Spanish males with G6PD deficiency 34 came from out consultation and 16 from the Spanish Study Group on Red Cell Pathology (GEHBTA-Eritropatología) The methods employed included screening of prevalent mutations by ER-PCR, SSCP-PCR, genetic segmentation and biochemical characterization of the deficient enzyme. RESULTS: In 31 cases the mutations were characteristic of the four most frequent polymorphic variants found in Spain (G6PD A-376G/202A, G6PD Mediterranean 563T G6PD Union 1360T and G6PD Seattle 344C). Since these mutations either create or abolish a specific site recognized by a restriction endonuclease (RE), they can be rapidly detected by RE digestion of a PCR-amplified product (PCR-RE). In patients where none of these mutations were present (17 cases), the G6PD gene was subjected to PCR single-strand conformation polymorphism (PCR-SSCP) analysis combined with direct PCR-sequencing. By using this procedure, 9 new mutations have been identified, five of them have been also found in other geographical areas and were associated with favism (G6PD A-376G/968C, G6PD Santamaria 376G/542T, G6PD Aures 143C and G6PD Chatham 1003A) or chronic haemolytic anaemia (G6PD Tomah 1153C). The other four mutations are unique and not reported so far: Three of them are associated with favism (G6PD Málaga 542T, G6PD Murcia 209G and G6PD Valladolid 406T) and one with chronic haemolytic anaemia (G6PD Madrid 1155G). The remaining eight cases are under study. CONCLUSION: The present study confirms the marked genetic heterogeneity of G6PD deficiency in Spain and demonstrate that the PCR-RE analysis is an easy tool for rapid diagnosis of the molecular defect in subjects with the common forms of G6PD deficiency. Furthermore the fact that G6PD A-376G/202A is the most common variant within Spanish population and the finding of G6PD Aures 43C and G6PD Santamaría 76G/542T, who are polymorphic in Algeria is consistent with a significant gene flow from Africa to Europe through Spain.