Evaluación clínica y hematológica de pacientes con drepanocitosis esplenectomizados en el Instituto de Hematología e Inmunología de Cuba: 30 años de experiencia / Clinical and hematological evaluation of patients with splenectomized drepanocytosis at the Hematology and Immunology Institute of Cuba: 30 years of experience

Introducción: Desde 1986 se ha introducido en nuestro país la esplenectomía parcial, que logra prevenir la recurrencia de la crisis de secuestro esplénico y disminuir la incidencia de sepsis sobreaguda postesplenectomía. Objetivo: Comparar desde el punto de vista clínico y de laboratorio los pacientes con esplenectomía total y parcial. Pacientes y métodos: Se estudiaron todos los pacientes con drepanocitosis, seguidos en el Instituto de Hematología e Inmunología, que se hubieran sometido a esplenectomía durante la edad pediátrica. Resultados: Se incluyeron 39 pacientes en cada método de esplenectomía; la mayoría eran varones (60,3%) y predominaba la anemia drepanocítica (69,2%). La edad de aparición de la esplenectomía fue menor en la de tipo parcial (4,7 años; p= 0,009) que en la total (6,7 años), y el tiempo de seguimiento fue de 12,5 años. El grupo de esplenectomía total presentó un mayor aumento de hemoglobina, leucocitos y plaquetas (p= 0,039), así como valores elevados de lactato deshidrogenasa (p= 0,015), hemoglobina plasmática (p= 0,001) y velocidad de regurgitación tricuspídea (p= 0,038). La crisis vasooclusiva dolorosa fue más frecuente tras la esplenectomía total (75,8 ± 14,3 frente a 39,8 ± 10,1; p < 0,001), al igual que las úlceras maleolares (p= 0,04). La crisis hepática y la mortalidad fueron también más frecuentes en la esplenectomía total aunque sin significación estadística (p= 007 y p= 0,305, respectivamente). Conclusiones: La esplenectomía parcial presenta menos complicaciones a largo plazo que la total (AU)

Introduction: Since 1986 has been introduced in our country partial splenectomy, which prevent the recurrence of splenic sequestration crisis and possible reduce the number of overhelming septicemia. Objective: Compare clinical and laboratory aspects in patients with total and partial splenectomy. Patients and methods: All patients with sickle cell disease were studied, followed at the Instituto de Hematología e Inmunología, who have had a splenectomy in childhood. Results: 39 patients were included in each method of splenectomy, where a predominance of males (60.3%) and sickle cell anemia (69.2%). Splenectomy age was lower in the partial, 4.7 years than in total splenectomy, 6.7 years (0.009). Follow-up time was 12.5 years. Total splenectomy group had greater increase in hemoglobin, leucocytes and platelets (p= 0.039), elevated LDH levels (p= 0.015), plasma hemoglobin (p= 0.001) and tricuspid regurgitation velocity (p= 0.038). Vaso-occlusive painful crises was more frequent after total splenectomy (75.8 ± 14.3 vs. 39.8 ± 10.1; p <0.001), as leg ulcer (p= 0.04). Hepatic crisis (p <0.07) and mortality were higher in individuals with complete splenectomy (p= 0.305) but withouth significative statistics. Conclusions: Partial splenectomy has fewer long-term complications that total (AU)

Esplenectomía parcial en pacientes con drepanocitosis / Partial splenectomy in sickle cell disease

INTRODUCCIÓN: La esplenectomía total en la drepanocitosis se relaciona con riesgo de infecciones sobreagudas y con aumento de la incidencia de otros eventos, lo que no se ha comunicado en pacientes con esplenectomía parcial. En este estudio se caracterizó a los pacientes con drepanocitosis y esplenectomía parcial, y se comparó el comportamiento clínico y de laboratorio con los pacientes no esplenectomizados. MATERIAL Y MÉTODOS: Se estudió a 54 pacientes con drepanocitosis sometidos a esplenectomía parcial durante la edad pediátrica, desde 1986 hasta el año 2011, en el Instituto de Hematología e Inmunología. Se compararon con 54 pacientes no esplenectomizados seleccionados por muestreo aleatorio con características similares. RESULTADOS: La esplenectomía parcial se realizó a una edad media de 4,1 años, con una frecuencia mayor en la anemia drepanocítica (70,4%) y su causa más común fue la crisis de secuestro esplénico recurrente. Las complicaciones posoperatorias más frecuentes fueron: fiebre de origen desconocido (14,8%) y síndrome torácico agudo (11,1%). Después de la esplenectomía, aumentaron significativamente los leucocitos, neutrófilos y plaquetas; estos 2 últimos parámetros se mantuvieron elevados de manera significativa cuando se compararon con los pacientes no esplenectomizados. No hubo diferencias en la incidencia de los eventos clínicos, excepto el secuestro hepático, que fue más frecuente en los esplenectomizados. CONCLUSIÓN: La esplenectomía parcial constituyó un proceder seguro en los pacientes con drepanocitosis. No hubo diferencias en el cuadro clínico entre los niños esplenectomizados y los no esplenectomizados, salvo la mayor frecuencia de crisis de secuestro hepático en los primeros

INTRODUCTION: Total splenectomy in sickle cell disease is related to a high risk of fulminant sepsis and increased incidence of other events, which have not been reported in patients with partial splenectomy. In this study we examined the patients with sickle cell disease and partial splenectomy and compared the clinical and laboratory results with non-splenectomized patients. MATERIAL AND METHODS: We studied 54 patients with sickle cell disease who underwent partial splenectomy in childhood from 1986 until 2011 at the Institute of Hematology and Immunology. They were compared with 54 non-splenectomized patients selected by random sampling with similar characteristics. RESULTS: Partial splenectomy was performed at a mean age of 4.1 years, with a higher frequency in homozygous hemoglobin S (70.4%), and the most common cause was recurrent splenic sequestration crisis. The most common postoperative complications were fever of unknown origin (14.8%) and acute chest syndrome (11.1%). After splenectomy there was a significant increase in leukocytes, neutrophils, and platelets, the latter two parameters remained significantly elevated when compared with non-splenectomized patients. There was no difference in the incidence of clinical events, except hepatic sequestration, which was more common in splenectomized patients. CONCLUSION: Partial splenectomy was a safe procedure in patients with sickle cell disease. There were no differences in the clinical picture in children splenectomized and non-splenectomized except the greater frequency of hepatic sequestration crisis in the first group

[Partial splenectomy in sickle cell disease]. / Esplenectomía parcial en pacientes con drepanocitosis.

INTRODUCTION: Total splenectomy in sickle cell disease is related to a high risk of fulminant sepsis and increased incidence of other events, which have not been reported in patients with partial splenectomy. In this study we examined the patients with sickle cell disease and partial splenectomy and compared the clinical and laboratory results with non-splenectomized patients. MATERIAL AND METHODS: We studied 54 patients with sickle cell disease who underwent partial splenectomy in childhood from 1986 until 2011 at the Institute of Hematology and Immunology. They were compared with 54 non-splenectomized patients selected by random sampling with similar characteristics. RESULTS: Partial splenectomy was performed at a mean age of 4.1 years, with a higher frequency in homozygous hemoglobin S (70.4%), and the most common cause was recurrent splenic sequestration crisis. The most common postoperative complications were fever of unknown origin (14.8%) and acute chest syndrome (11.1%). After splenectomy there was a significant increase in leukocytes, neutrophils, and platelets, the latter two parameters remained significantly elevated when compared with non-splenectomized patients. There was no difference in the incidence of clinical events, except hepatic sequestration, which was more common in splenectomized patients. CONCLUSION: Partial splenectomy was a safe procedure in patients with sickle cell disease. There were no differences in the clinical picture in children splenectomized and non-splenectomized except the greater frequency of hepatic sequestration crisis in the first group.

Contaje absoluto de linfocitos como factor pronóstico en la leucemia aguda linfoblástica del niño / Absolute lymphocyte count as a prognostic factor in children with acute lymphoblastic leukemia

Introducción: Estudios recientes sugieren el contaje absoluto de linfocitos (CAL) como un nuevo indicador pronóstico en enfermedades malignas, de forma que aquellos pacientes que posean CAL superiores en determinados momentos del tratamiento, tendrán mayores posibilidades de supervivencia. En particular se ha visto la influencia de las células T y las células naturales asesinas en la inmunidad de pacientes con cáncer. Materiales y métodos: Se realizó un estudio retrospectivo en pacientes pediátricos con leucemia aguda linfoblástica tratados en el Instituto de Hematología e Inmunología entre los años1995 y 2008 (105 pacientes), con el objetivo de evaluar la influencia del conteo absoluto de linfocitos como factor pronóstico en la sobrevida libre de enfermedad (SLE) y la sobrevida global (SG) a los 5 años. Resultados: Evolucionaron desfavorablemente 24,8% y la mediana del CAL determinado los días 15 y 28 de tratamiento de estos pacientes fue de 1.000 células/ l. Los pacientes con CAL el día 15 (CAL-15) y 28 (CAL-28) <1.000 y ≥ 1.000/ l, mostraron una SLE de 51% vs 83% y 55%vs 82% (p = 0,02 y p = 0,04), respectivamente. Igualmente la SG para aquellos con CAL-15 yCAL-28 ≥1.000/ l fue 89% y 86% contra un 59% y 66% para valores <1.000 (p = 0,001 y p = 0,01),respectivamente. Al realizar el análisis multivariado junto a otros factores de riesgo como la edad, el estudio molecular, la respuesta al tratamiento y el contaje inicial de leucocitos, el CAL-15 mostró significación estadística tanto para la SLE (p = 0,006) como para la SG (p = 0,001). Conclusiones: El CAL fue un predictor significativo de supervivencia y recaída. Además tuvo un comportamiento independiente como factor pronóstico (AU)

Introduction: Recent studies have suggested that the absolute lymphocyte count (ALC) may bea prognostic indicator in malignant diseases, in that those patients who have higher ALC at certain times during treatment may have a better chance of survival. The influence of T cellsand natural killer cells in the immune system of the patient with cancer as a response to cancercells is particularly noted. Materials and Method: We prospectively assessed the prognostic value of absolute lymphocytic count (ALC) in 105 pediatric patients with acute lymphoblastic leukemia (ALL), treated in the Cuban Immunology and Hematology Institute from 1995 to 2008. ALC was studied at days 15 (ALC-15) and 28 (ALC-28) of treatment. Results: In our patients, 1000 cells/uL was the median ALC value for patients who relapsed ordied. Using 1000/uL we found that ALL patients with an ALC-15 <1000 cells/ l had a 5-year relapse free survival (RFS) of 51%. In contrast, an ALC-15 >1000 cells/uL showed an excellent prognosis, with a 5-year RFS of 83% (p=0.02). Similarly in our study, an ALC-28 <1000 cells/ lpredicted a 5-year overall survival (OS) of 66%, where as an ALC-28 >1000 cells/ l predicted excellent outcome, with a 5-year OS of 86% (p=0.01). Importantly, ALC is also a strong predictorin multivariate analysis with known prognostic factors. ALC is a simple, statistically powerful measurement for patients with de novo ALL. Conclusions: The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies (AU)

[Absolute lymphocyte count as a prognostic factor in children with acute lymphoblastic leukemia]. / Contaje absoluto de linfocitos como factor pronóstico en la leucemia aguda linfoblástica del niño.

INTRODUCTION: Recent studies have suggested that the absolute lymphocyte count (ALC) may be a prognostic indicator in malignant diseases, in that those patients who have higher ALC at certain times during treatment may have a better chance of survival. The influence of T cells and natural killer cells in the immune system of the patient with cancer as a response to cancer cells is particularly noted. MATERIALS AND METHOD: We prospectively assessed the prognostic value of absolute lymphocytic count (ALC) in 105 pediatric patients with acute lymphoblastic leukemia (ALL), treated in the Cuban Immunology and Hematology Institute from 1995 to 2008. ALC was studied at days 15 (ALC-15) and 28 (ALC-28) of treatment. RESULTS: In our patients, 1000 cells/uL was the median ALC value for patients who relapsed or died. Using 1000/uL we found that ALL patients with an ALC-15 <1000 cells/µl had a 5-year relapse free survival (RFS) of 51%. In contrast, an ALC-15 >1000 cells/uL showed an excellent prognosis, with a 5-year RFS of 83% (p=0.02). Similarly in our study, an ALC-28 <1000 cells/µl predicted a 5-year overall survival (OS) of 66%, whereas an ALC-28 >1000 cells/µl predicted excellent outcome, with a 5-year OS of 86% (p=0.01). Importantly, ALC is also a strong predictor in multivariate analysis with known prognostic factors. ALC is a simple, statistically powerful measurement for patients with de novo ALL. CONCLUSIONS: The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies.

Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba.

Malnutrition has a deleterious effect on the results of therapy for malignant diseases in childhood. The impact of radiotherapy on growth is well known but the impact of cytotoxic drugs on nutritional status is more controversial. The purpose of this study was to determine the nutritional status of a cohort of children treated for acute lymphoblastic leukaemia (ALL) in Cuba. The study involved 49 children admitted to a single center and treated with a Berlin-Frankfurt-Munster-based protocol. Nutritional assessment included measurements of height, weight, body mass index and skin-fold thickness, made at diagnosis, after the intensive phase of treatment and at the end of therapy. Z-scores were used for height and comparison of percentiles for the rest of the variables. All the patients were above the third percentile in all the measurements. There were no statistically significant differences between the results at diagnosis, after intensive therapy and at the end of treatment. Although the sample was small, there was no demonstrable effect of chemotherapy on nutritional status in this Cuban paediatric population, in contrast to that reported in children with ALL in other developing countries.

[Effectiveness of partial splenectomy in the treatment of hereditary spherocytosis]. / Efectividad de la esplenectomía parcial en el tratamiento de la esferocitosis hereditaria.

OBJECTIVES: To evaluate the hematological and clinical response to partial splenectomy in a group of children with hereditary spherocytosis. MATERIAL AND METHODS: We analyzed the main hematological and clinical features in 13 patients with hereditary spherocytosis submitted to partial splenectomy. The diagnosis of the disease and the hematological studies was made according to standard methods. To establish the inheritance pattern we also studied both parents. During the surgical procedure the upper two thirds of the spleen were removed and the lower pole was preserved. We use prophylactic penicillin (250 mg twice a day) during 3 years. RESULTS: The diagnosis of the disease was made during the first year of life in 11 patients, 76.9% had neonatal hyperbilirrubinemia, 53.8% showed hepatomegaly and in 69.2% we observed splenomegaly. 84.6% received blood transfusion. The hemoglobin level was significantly increased (p = 0.04) and the reticulocytes significantly diminished (p = 0.01) after splenectomy. No hemolytic crises, blood cell transfusion requirement neither infection was observed after surgery. CONCLUSIONS: Although the number of patients and the post-surgical follow-up is reduced, the hematological recovery observed in our cases suggest that partial splenectomy is a beneficial surgical procedure for the treatment of the typical and severe form of hereditary spherocytosis.

Successful treatment of acute promyelocytic leukemia using all-trans retinoic acid and erythropoietin in a Jehovah's Witness boy.

A 10-year-old boy with acute promyelocytic leukemia (APL) was treated with all-trans-retinoic acid (ATRA) at a dose of 60 mg/m2/day. Recombinant erythropoietin was also used. The patient parents and other relatives, all Jehova's Witnesses, refused any type of hemotherapy. After 43 days of ATRA treatment complete remission was obtained without the use of hemotherapy. This case exemplifies the advantages provided by ATRA treatment in APL.

Partial splenectomy in children with sickle cell disease and repeated episodes of splenic sequestration.

Twenty-five children with sickle cell disease and repeated episodes of splenic sequestration crises underwent partial splenectomy. They have been followed for 12 to 75 months (median 48 months) after surgery. During this period we have not observed any episode of splenic sequestration and the need for hospitalization and transfusions has been greatly reduced. We believe this is a useful and safe procedure for treating patients with this condition.

[Sickle-cell anemia in the 1st 5 years of life]. / La drepanocitosis en los cinco primeros años de vida.

PURPOSE: A programme for antenatal diagnosis of sickle-cell anaemia (SA) and SC haemoglobinopathy (SC) was started in Cuba in 1983. The purpose of this paper is to report the clinical and haematological data of a group of children diagnosed before birth or in the first few months of life. PATIENTS AND METHODS: Between June 1986 and December 1992, 78 children under 5 years of age were studied at the Haemoglobinpathies Clinic of the Instituto de Hematología e Inmunologia in La Habana; of them, 53 had SA and 25 had SC, there were 41 girls and 37 boys. A comprehensive questionnaire was carried out during the first visit to the clinic, about the onset of the clinical manifestations, as well as a careful physical examination plus peripheral blood study and Hb A2 and Hb F assay. Parents were informed, and folate and prophylactic penicillin were given orally to the children. RESULTS: The yearly average admissions to hospital were 1.6 +/- 3.8 for SA and 0.1 +/- 0.6 for SC. The average number of veno-occlusive crises was 0.2 +/- 0.6 in SA and 0.1 +/- 0.6 in SC (p < 0.04); the average hand-foot crises were 0.3 +/- 1.1. for SA and nil for SC. The average number of infections per year was 0.3 +/- 0.6 in SA and 0.1 +/-0.3 in SC, without any significant difference. Significant differences were found in the haemoglobin rates and reticulocyte counts between both haemoglobinopathies. Hb F rate was 7.80 +/- 4.78% in SA and 2.83 +/- 3.45% in SC. CONCLUSIONS: Admission to hospital, hand-foot crises, infections and splenic sequestration are the commonest clinical events during the first 5 years of life. The number of infections episodes decreases with prophylactic oral penicillin, and overacute pneumococcal infection is suppressed. Parent education allows one to early treat sequestration crises, and partial splenectomy avoids repetition of this complication, while preserving the splenic function.

Leucemia linfoblástica aguda en niños resultados del tratamiento en 24 años

Se realiza un estudio de 186 niños diagnósticados de leucemia linfoblástica aguda de 1972 a 1995 y tratados con distintos esquemas terapéuticos, casi todos incluidos en los protocolos del grupo latinoamericano de tratamiento de homeopatías malignas. Los grupos se clasificaron en bueno, intermedio y malo. Se encontró una diferencia significativa en los porcentaje de sobrevida BIM en los protocolos de la década de los 70, mientras en los esquemas tipo BFM se borran las diferencias entre bueno e intermedio, persistiendo una sobrevida menor en el grupo de pronóstico malo. Los factores pronósticos analizados en forma aislada que tuvieron importancia significativa en los porcentajes de sobrevida fueron: la edad, la esplenomegalia y la cifra de leucocitos suuperior a 50x10/1 (AU)

Sickle cell anemia and beta-gene cluster haplotypes in Cuba.

We have studied 91 patients with SS genotype, 44 children and 47 adults. Excluding the Cameroon and atypical haplotypes, the distribution in the children's sample exhibited 43% Benin, 38% Bantu, and 3% Senegal. In adults, the sample exhibited 46% Benin, 30% Bantu, and 9% Senegal (chi 2: 13.511, 2 df, P = 0.001). When the whole sample of 198 chromosomes (SS, SC, and S/beta thal) is considered, we find that the beta s chromosome is linked 51% to the Benin haplotype, 41% with the Bantu, and 8% with the Senegal. After adjusting for the different frequencies of beta s in Africa, these numbers would predict the port of origin to be 16% from Atlantic West Africa, 37.3% from Central West Africa, and 46% from Bantu-speaking Africa. This is in direct contradiction with the historical record that establishes a higher percentage from Bantu-speaking Africa (55%) and a much lower percentage from Senegal (3.4%). The overall conclusions from these findings is that there is a loss of Bantu haplotypes in sickle cell syndromes in Cuba, particularly among adults, and that there is an excess of Senegal haplotype, also among adults. These differences might reflect the differential survival and severity of the sickle cell disease linked to these haplotypes.

[Treatment of acute lymphoid leukemia (ALL) in the child]. / Tratamiento de la leucemia linfoide aguda (LLA) en el niño.

PURPOSE: To analyse the results of the therapy administered to children with ALL in Cuba. PATIENTS AND METHODS: Four-hundred and twenty-five children (aged below 15 years), diagnosed of ALL in 8 different Cuban hospitals between 1973 and 1991, were evaluated. Five different therapeutic regimes were used: three "classic" GLATHEM protocols in the first period (1973-1981) and two intensive BFM-like protocols in the second period (1982-1991). The Kaplan-Meier method was applied for survival analysis, and the differences were evaluated by the log-rank and Mantel-Cox methods. RESULTS: Two-hundred and sixty-five patients were included in the first period, 81 with low-risk disease, 133 with standard risk and 51 with poor-risk leukaemia. The second period comprised 160 cases, 50 of low-risk, 83 with standard risk and 27 with poor-risk leukaemia. The disease-free survival probability at 60 months was 35% for the first group and 55% for the second (p < 0.0001). The 60-month survival (SV) as a whole was 45% for the "classic" treatments and 60% for the BFM-like protocols (p < 0.01). The disease-free survival (DFS) probability for each prognostic group was as follows: 50% for low-risk, 43% for standard risk, and 25% for poor-risk (p < 0.001) and the probability of survival as a whole was, respectively, 65%, 49% and 28% (p < 0.001). as for this compilation, 172 patients were out of any treatment for periods ranging between 14 and 168 months. CONCLUSIONS: 1) The percentage of remissions was similar for both groups of treatments. 2) The results attained with BFM-like protocols were better than those of the "classic" therapy with regard to the SV and DFS differences. 3) Significant differences can be appreciated between good- and poor-prognosis groups for both types of treatment.