Neutrophil scattering data driven pre-microscopic flagging of acute leukemic cases

ABSTRACT Background: The hematology analyzer, Sysmex XN-1000, generates white blood cell count with varying scattering intensities during a complete blood count (CBC) analysis. Objectives: The objectives of the study were to study the predictive role of median and coefficient of variation of neutrophil scattering items in blood samples for differentiation of leukemic subjects. Methods: We evaluated six neutrophil scattering parameters: neutrophil side scatter mean intensity, neutrophil side fluorescence light (SFL) mean intensity, neutrophil forward scatter mean intensity, neutrophil side scatter area distribution width (NE-WX), neutrophil SFL area distribution width (NE-WY), and neutrophil forward scatter area distribution width (NE-WZ), measured in white blood cell differential scattergram generated by the hematology analyzer (Sysmex XN-1000) at an academic medical center. Results: We collected 433 blood samples from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cases and normal controls. AML group showed highly significant differences in the mean values compared with the control group. Out of six neutrophil scattering items, NE-WX, NE-WY, and NE-WZ showed high efficiency, with area under the curve (AUC) values of 0.764, 0.748, and 0.757, respectively, to differentiate AML from ALL cases and control groups. When comparing combined acute leukemia cases (AML plus ALL) with the control group, NE-WX, NE-WY, and NE-WZ generated highly significant AUC values (0.840, 0.884, and 0.801, respectively). Conclusion: The neutrophil scattering parameters generated during CBC analysis provide a new tool for the prediction of acute leukemia and its lineage.

Recuperación temprana de linfocitos como factor pronóstico en el trasplante hematopoyético / Early lymphocyte recovery as a prognostic factor after hematopoietic stem cell transplantation

Introducción: la recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes sometidos a trasplante hematopoyético. Objetivo: determinar el valor pronóstico del recuento absoluto de linfocitos (RAL). Métodos: se realizó un estudio observacional analítico, transversal, ambispectivo, en pacientes pediátricos con hemopatías malignas trasplantados en el Instituto de Hematología e Inmunología de La Habana, Cuba, entre 1986 y 2008. Se estudiaron 36 pacientes: 15 con leucemia linfoide aguda, 13 con leucemia mieloide aguda, 6 con leucemia mieloide crónica y 2 con linfoma no hodgkiniano. Veintitrés trasplantes fueron autólogos y 13 alogénicos; 22 de médula ósea y 14 de sangre periférica. Resultados : de los trasplantes antólogos, el 60,9 por ciento alcanzó un RAL el día + 15 (RAL-15) = 500 x mm3, mientras en los alogénicos este se alcanzó en el 53,8 por ciento. La sangre periférica tuvo un RAL-15 mayor que la médula ósea y se obtuvo en el 78,6 por ciento y el 45,4 por ciento de los enfermos, respectivamente (p = 0.049). Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis (p <0.001), el RAL-15 < 500 x mm3 ( p= 0.001) y la recaída (p = 0.03). Las curvas de Kapplan-Meier mostraron una mejor supervivencia global y libre de eventos a los cinco años, en los pacientes con RAL-15 = 500 x mm3 (85 por ciento vs 15 por ciento; p <0.001). Conclusiones: el RAL-15 = 500 x mm3 es una herramienta simple y útil para predecir un mejor resultado en pacientes pediátricos sometidos a trasplante hematopoyético

Introduction: early lymphocyte recovery is a prognostic factor related to a higher event-free survival and overall survival in patients who have received hematopoietic transplantation. Objective: eo determine the prognostic value of absolute lymphocyte count (ALC). Method: a study in pediatric patients with hematological malignancies transplanted at the Institute of Hematology and Immunology from 1986 to 2011 was performed. The study group included 36 patients: 15 with acute lymphoid leukemia, 13 with acute myeloid leukemia, 6 with chronic myeloid leukemia and 2 with non Hodgkin lymphoma. Twenty transplants were autologous and 13 allogeneic. As stem cell source, bone marrow was used in 22 patients and peripheral blood in 14. Results : 60,9 percent of the autologous transplants reached an absolute lymphocyte count = 500 x mm3 on day 15 (ALC-15), whereas in the allogeneic this was achieved in 53,8 percent. Peripheral blood had a higher ALC-15 than bone marrow, 78,6 percent and 45,4 percent, respectively (p = 0.049). Prognostic factors associated to worse overall survival were sepsis (p <0.001), ALC-15 <500 x mm3 (p = 0.001) and relapse (p = 0.03). Kapplan-Meier curves showed better overall survival and event-free survival after five years in patients with ALC-15 = 500 x mm3 (85 percent vs. 15 percent, p <0.001). Conclusions: the ALC-15 = 500 x mm3 is a simple and useful tool to predict a better outcome in pediatric patients undergoing hematopoietic transplantation

Leucemia mieloide aguda durante el embarazo: reporte de un caso / Acute myeloid leukemia during pregnancy: case report

Se trata de primigesta de 18 años, etnia wayuu, con amenorrea de 30,5 semanas, quien acude en condiciones clínicas de cuidado por presentar disnea acentuada desde hace una semana. El examen físico demostraba palidez cutánea marcada, hiperplasia gingival, soplo holosistólico grado I, taquisfigmia, murmullo vesicular abolido en ambas bases pulmonares con crepitantes bilaterales, abdomen globoso, útero grávido, AU: 27 cm, feto cefálico activo, tacto sin modificaciones. Presenta anemia, marcada leucocitosis, hipoproteinemia, elevación de LDH, y patrón de consolidación bibasal en radiografía pulmonar. Ingresa con diagnóstico de embarazo simple pretérmino, neumonía bilateral, enfermedad linfoproliferativa, y sepsis (?); durante su evolución presenta alteración en el perfil biofísico fetal y hemodinámico, practicándose cesárea segmentaria debido a oligoamnios y sufrimiento fetal agudo. Se obtiene neonato pretérmino, el cual ingresa por prematuridad, sepsis neonatal y enfermedad de membrana hialina. Frotis de sangre periférica revela leucopenia con predominio de monocitos, trombocitopenia, anisocitosis, hipocromia, y macroplaquetas; mientras que el aspirado de médula ósea presentaba 80 % de infiltración de mieloblastos y alteraciones en la citometría de flujo. Recibe quimioterapia según protocolo BMS y manejo médico de las complicaciones presentadas, fallece durante el puerperio tardío.

Primigravida 18 years, ethnicity Wayuu, with 30.5 weeks of amenorrhea, who went into clinical conditions of care for presenting accentuated dyspnea since a week ago. Physical examination showed marked skin pallor, gingival hyperplasia, holosystolic blow, palpitations, vesicular murmur abolished in lung’s bases with bilateral crackles. Abdomen with graves uterus, height 27cm, and cephalic active fetus; vaginal touch unchanged. Presents anemia, marked leukocytosis, hypoproteinaemia, elevated LDH, and pattern of consolidation at lung’s radiographers. She is admitting with diagnosed of preterm pregnancy, bilateral pneumonia, lymphoproliferative disease, and sepsis (?); during its evolution presents impaired fetal biophysical profile and hemodynamic, practised caesarean operation due to oligoamnios and acute fetal distress. Obtained preterm infant, who was admitted because of prematurity, neonatal sepsis and hyaline membrane disease. Peripheral blood smear reveals predominantly monocytes leukopenia, thrombocytopenia, anisocitosis, hipocromia and macroplaquets. While the bone marrow aspirate showed 80 % of infiltration mieloblasts cells and alterations in the cytometry of flow. Receives chemotherapy by protocol BMS and medical management of complications presented, dies during the late puerperium.

Quantitative estimation of interferon-gamma levels among Egyptian polytransfused haematology cases

This study was designed to estimate interferon-gamma [INF-gamma] levels among polytransfused haematology cases. Cases were selected from the haematology unit of Alexandria main university hospital, Egypt. Complete blood counts, estimation of INF-gamma and hepatitis B and C virus [HBV and HCV] status were conducted on 20 unsplenectomized patients with thalassaemia major and 20 patients with acute myeloid leukaemia [AML] in the maintenance phase and 20 healthy subjects. Mean haemoglobin levels and red blood cell counts were significantly higher in the control group than the AML and thalassaemia groups, while white blood cell counts were significantly lower in the control group than the case groups. Two AML patients [10%] and 1 thalassaemia patient [5%] were HBV-positive, while 5% of both case groups were HCV-positive. Mean values of INF-? were significantly different between AML, thalassaemia major and control groups: 5517 [SD 1142] pg/mL, 1024 [SD 249] pg/mL and 2980 [SD 604] pg/mL respectively

Perfil de metilación de genes supresores de tumores como factor pronóstico en pacientes con leucemia mieloide aguda / Promoter methylation profile in tumor suppressor genes as prognosis factor in patients with acute myeloid leukemia

Existe creciente evidencia que apoya la presencia de un perfil de metilación específico para Leucemia Mieloide Aguda (LMA). La metilación de los islotes CpG en las regiones promotoras de los genes supresores de tumores es un importante mecanismo de control epigenético y participa en el silenciamiento transcripcional. Esto puede contribuir a un nuevo entendimiento de la biología de la enfermedad y vislumbrar nuevas oportunidades terapéuticas. Identificar el perfil de metilación de las áreas promotoras de un grupo de genes supresores de tumores; (p15, p16, ESR1, IGSF4, SOCS1, RARB y DAPK), y relacionar el estatus de metilación gen especifica o combinada con diferentes parámetros clínico patológicos. Se utilizaron muestras de sangre o médula ósea obtenidas al momento del diagnóstico de 33 pacientes con LMA, infantil y del adulto, recolectadas entre los años 1997 y 2008 en el Hospital Hernán Henríquez de Temuco. Se evaluó la presencia de hipermetilación mediante una Reacción de Polimerasa en Cadena Metilación Específica (MSP), previa modificación con bisulfito de sodio. La frecuencia de metilación de los pacientes estudiados fue de 88 por ciento, 27 por ciento, 27 por ciento, 21 por ciento, 15 por ciento, 3 por ciento y 0 por ciento para ESR1, RARb, IGSF4, p15, SOCS1, DAPK, y P16, respectivamente. La hipermetilación de P15 y RARb presentó una asociación significativa para una menor supervivencia en forma individual (p=0,03 y p=0,02), y combinada (p=0,002). No se encontraron diferencias significativas entre metilación y los otros parámetros clínicos analizados. Los pacientes con LMA presentan hipermetilación de la región promotora en algunos genes supresores de tumores, afectando negativamente la supervivencia. Esto pudiese eventualmente contribuir al establecimiento de un patrón de metilación determinado con utilidad clínica.

There is growing evidence than acute myeloid leukemia presents a specific methylation profile. The Methylation of CpG islands within gene promoters is a major epigenetic transcriptional control mechanism and plays a critical role in the transcriptional silencing of tumor suppressor genes. This provides new insights into the biology of the disease and it may offer novel therapeutic opportunities. To identify the promoter methylation profile of tumor suppressor genes (p15, p16, ESR1, IGSF4, SOCS1, RARB y DAPK), and to relate the percentage of methylation with clinicopathological features, as age, gender, white cell count, disease classification and survival rates. Bone marrow and peripheral blood samples were collected at diagnosis from 33 patients with acute myeloid leukemia, infants and adult, between 1997 and 2008 from Hernán Henríquez Aravena Hospital, Temuco, Chile. Methylation in the promoter areas of each tumor suppressor gene was analyzed using the mehylation specific polymerase chain reaction (MSP) technique using sodium bisulfite modification. The frequency of hypermethylation among the patient samples was 88 percent, 27 percent, 27 percent, 21 percent, 15 percent, 3 percent and 0 percent for ESR1, RARb, IGSF4, p15, SOCS1, DAPK, and P16 for each one. Methylation was significantly associated with an inferior overall survival (p=0.03 and p=0.02). When both genes are used, inferior survival is even more significant (p=0.002). There is no significant correlation between methylation and clinicopathological features.Patients with AML have hipermetilation at the promoter region of some tumor supressor genes, with a negative effect in the overall survival. This could eventually become part of establishing a characteristical methilation pattern with clinical utility.

Differential Blast Counts Obtained by Automated Blood Cell Analyzers / 대한진단검사의학회지

BACKGROUND: Automated blood cell analyzers often read leukemic blasts as normal cells. In this study, we evaluated the 5-part differential patterns of blasts using automated analyzers to determine if they can differentiate among blast types. METHODS: Blood samples containing 10% or more blasts were collected from patients with acute leukemia (N=175). The 5-part differential count was conducted using DxH 800 (Beckman Coulter, USA) and XE-2100 analyzers (Sysmex Co., Japan), and the results were compared with manual differential counts, which was used as a reference method. RESULTS: The DxH 800 reported the 5-part white blood cell differential count in 98.9% of the cases. The XE-2100 provided an invalid automated differential count in 72% of the cases. Both analyzers counted most lymphoblasts as lymphocytes and most myeloblasts as monocytes. In 11 cases, the DxH 800 reported a 5-part differential count without a blast flag. CONCLUSIONS: Some automated analyzers are able to recognize and count blasts according to their characteristic cell types. Therefore, complete blood counts obtained automatically can provide valuable data for making provisional decisions regarding the lineage of leukemia cells before further investigation.

Gastrointestinal manifestations as initial presentation of acute leukemias in children and adolescents / Manifestaciones gastrointestinales como presentación de las leucemias agudas en niños y adolescentes

OBJECTIVE: this study aimed to determine the prevalence and characteristics of gastrointestinal manifestations on initial clinical presentation of acute leukemias (AL) in childhood. MATERIAL AND METHODS: this is a retrospective and descriptive study that assessed medical records of 354 patients with AL from January 1995 to December 2004. RESULTS: acute lymphoid leukemia (ALL) was diagnosed in 273 (77.1%) patients and acute non-lymphocytic leukemia (AML) in 81 (22.9%). There were 210 males (59.4%) and 144 females (40.6%). The most common presenting features were: abdominal pain (19.5% in ALL and 11.8% in AML), nausea and vomiting (14.9 in ALL and 14% in AML), abdominal distention (18.5 in ALL and 8.6% in AML; p 0.024), constipation (5% in ALL and 6.5% in AML), diarrhea (3.6% in ALL and 11.8% in AML; p 0.03%), and gastrointestinal bleeding (7.9% in ALL and 9.7% in AML). Ultrasound scanning was made in 61.1% and hepatomegaly was found on 33.6% and esplenomegaly on 28.5% of the patients with AL. Seventy-seven (21.7%) and 15 (4.2%) patients received nonsteroidal anti-inflammatory drugs and glucocorticoids before the diagnostic of AL. An association is well-defined between abdominal symptoms like nausea, vomiting and pain and use of this therapy but this association did not occurred clearly in this study. CONCLUSIONS: gastrointestinal symptoms are not very well-documented as initial manifestation of leukemia in children and should be considered on the differential diagnosis of gastrointestinal symptoms of unknown etiology in children.

Objetivo: el objetivo del estudio fue determinar la prevalencia y las características de las manifestaciones gastrointestinales en la presentación clínica inicial de las leucemias linfoides agudas (LLA) en la infancia. Materialy métodos: se trata de un estudio descriptivo y retrospectivo que evaluó los registros médicos de 354 pacientescon LLA de enero de 1995 a diciembre de 2004. Resultados: la (LLA) ha sido diagnosticada en 273 (77,1%) pacientes y leucemia mieloide aguda (LMA) en 81 (22,9%). Hubo 210 niños (59,4%) y 144 niñas (40,6%). Los síntomas más comunes de presentaciónhan sido los siguientes: dolor abdominal(19,5% en LLA y 11,8% en el LMA), náuseas y vómitos (14,9 en LLA y 14% en LMA, P 0.024), distensión abdominal (18,5 en LLA y 8,6% en LMA, p 0,024), estreñimiento (5% en LLA y 6,5% en LMA), diarrea (3,6% en LLA y 11,8% en LMA, p 0,03%) y hemorragia gastrointestinal (7,9% en LLA y 9,7% enLMA). La ecografía fue realizada en 61,1% de los pacientes encontrándose hepatomegalia en 33,6% y esplenomegalia en 28,5% con LLA. Setenta y siete (21,7%) y 15 (4,2%) pacientes recibieron los fármacos antiinflamatorios no esteroides y glucocorticoides antes del diagnóstico de LLA. Hay una asociación bien definidaentre síntomas abdominales como náuseas, vómitos y dolor y el uso de esta terapia pero esta asociación no seprodujo claramente en este estudio. Conclusiones: las manifestaciones gastrointestinales no están bien documentadas como manifestaciones iniciales de la leucemia en los niños y debe considerarse en el diagnóstico diferencial de los síntomas gastrointestinales de etiología desconocida en estas edades.

Haematologic and immunophenotypic profile of acute myeloid leukemia: an experience of Tata Memorial Hospital.

OBJECTIVES: To study the hematologic and immunophenotypic profile of 260 cases of acute myeloid leukemia at diagnosis. MATERIAL AND METHODS: This is a retrospective analysis of 260 cases of AML diagnosed at our institution between 1998 and 2000. Diagnosis was based on peripheral blood and bone marrow examination for morphology cytochemistry and immunophenotypic studies. SPSS software package, version 10, was used for statistical analysis. RESULTS: Seventy-six percent of our cases were adults. The age of the patients ranged from one year to 78 years with a median age of 27.2 years. There were 187 males and 73 females. The commonest FAB subtype, in both children and adults, was AML-M2. The highest WBC counts were seen in AML-M1 and the lowest in AML-M3 (10-97 x 10(9)/L, mean 53.8 x 10(9)/L). The mean values and range for hemoglobin was 6.8 gm/l (1.8 gm/l to 9.2 gm/l), platelet count 63.3 x 10(9)/L (32-83 x 10(9)/L), peripheral blood blasts 41.4% (5 to 77%) and bone marrow blasts 57.6% (34-96%). Myeloperoxidase positivity was highest in the M1, M2 and M3 subtypes. CD13 and CD33 were the most useful markers in the diagnosis of AML. CD14 and CD36 were most often seen in monocytic (38%) and myelomonocytic (44%) leukemias. Lymphoid antigen expression was seen in 15% of cases. CD7 expression was the commonest (11%). CONCLUSION: AML accounted for 39.8% of all acute leukemias at this institution. The most common subtype was AML-M2. Myeloperoxidase stain was a useful tool in the diagnosis of myeloid leukemias. CD13 and CD33 were the most diagnostic myeloid markers.

Studies on the components of the contact phase system in patients with acute nonlymphoblastic leukemia

The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, Sao Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not elegible, according to the exclusion criteria: infection/septicemia, previous treatment of blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p=0.02) and prealbumin (p=0.03) were significantly decreased, and prothrombin time increased (p=0.003) in the patient group when compared to the control. Significant correlation (r=0.49, critical value=0.43, p<0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r=0.54, critical value=0.44, p<0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by the Willcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.

Monitoring of WT-1 gene expression in peripheral blood of patients with acute leukemia by semiquantitative RT-PCR; possible marker for detection of minimal residual leukemia

The expression of the WT-1 gene which is found exclusively in human leukemic blasts frequently disappears from bone marrow of leukemia patients in complete remission (CR). Using semiquantitative RT-PCR, we investigated the expression of the WT-1 gene in peripheral bloods (PBs) of 33 patients with acute leukemia (AML 26; ALL 7) and monitored its expression after achievement of CR. None of the 6 normal controls expressed detectable levels of WT-1 transcripts (< 10(-4), background level), whereas 31 (93.9%) of 33 patients expressed variable levels of WT-1 transcripts (range, 10(-4) to 10(1)) at diagnosis. The level of WT-1 expression was not different between AML and ALL. By monitoring WT-1 gene expression in PB of 31 patients during CR, 5 patients relapsed (two from the 18 patients with undetectable levels of WT-1 gene expression and three from the 13 with WT-1 gene expression in low levels). Three of the 5 relapsed patients showed preceding reappearance or rise of WT-1 gene expression. From these results, we reconfirmed that the WT-1 gene is a pan-acute leukemic marker, which can be used to monitor minimal residual leukemia (MRL) after chemotherapy or in patients with CR.

Erythrocyte characteristics in childhood acute leuckemia

The percentage of haemoglobin F and A2 were estimated in seventy two cases with acute lymphoblastic leukemia and seven cases with acute myeloblastic leukemia who were attending the Oncology clinic and unit in Al-Mansur Teaching Hospital over a period of one year and five months from May 1993 to the end of Sep. 1994. The majority, 62 cases were evaluated during chemotherapy, 15 cases were off treatment, 2 cases still not given chemotherapy. In addition, the percentage of erythrocytes with "fetal-like" features [F-cells%] were estimated. Both haemoglobin F and haemoglobin A2 were normal in the majority of cases of ALL and AML while the percentage of F-Cells was high. In ALL macrocytosis and/or anisocytosis seen in the majority with normocytosis and/or anisocytosis seen in AML. Sixteen non-leukemic control were studied as well. In the majority haemoglobin F was normal, haemoglobin A2 was high and the percentage of F-cells was also high

Utilidad de la relación cobre/zinc en pacientes con linfoma o leucemias aguda o crónica / Serum copper and zinc levels and Cu/Zn ration in lymphoma and acute and chronic leukemia

Objetivo. Conocer si la relación cobre/zinc (cobre elevado, zinc bajo) se encuentra aumentada en pacientes con neoplasias malignas hematológicas comparada con sujetos controles sanos de edad y sexo similares. Metodología. Se estudiaron 44 pacientes con neoplasias hemato-concológicas de reciente diagnóstico, sin tratamiento previo: 17 linfomas (11 no-Hodgkin), 15 con leucemia aguda (10 mieloblásticas) y 12 con leucemia crónica (8 granulocíticas). También se incluyeron 95 sujetos controles sanos. Se utizó un espectrofotómetro de absorción atómica (Perkin Elmer modelo 2380) para la cuantificación de los niveles séricos de cobre y zinc. Resultados. Los niveles séricos de cobre (µg/dL) fueron significativamente menores en los sujetos controles(54.4 ñ 8.9, p< 0.05), en comparación con los pacientes con linfoma (93.7 ñ 37.5), con leucemia aguda (80.6 ñ 44.6) y con leucemia crónica (95.7 ñ 28.9) mientras que los niveles séricos de zinc (µg/dL) resultaron significativamente mayores en sujetos controles (100.4 ñ 14, p< 0.05) en comparación con los pacientes con linfoma (77.2 ñ 22.6), leucemia aguda (66 ñ 15.6) o leucemia crónica (74.8 ñ 14.7). La relación cobre/zinc resultó ser significativamente más baja en sujetos controles (0.54 ñ 0.13, p< 0.05) que en pacientes con linfoma (1.21 ñ 0.5), leucemia aguda (1.22 ñ 0.7) o leucemia crónica (1.28 ñ 0.4). Veintitrés pacientes falleciron durante el seguimiento (media de 13 meses) observándose que sus niveles séricos de zinc fueron significativamente más bajos (68 ñ 28) que en los pacientes que sobrevivieron (76 ñ 15, p< 0.05). Conclusión. La relación sobre/zinc se encuentra significativamente elevada en pacientes con neoplasias malignas hematológicas

Platelet function in acute leukemias.

Bleeding time, clot retraction, platelet factor 3 availability and platelet aggregation in response to ADP, epinephrine, collagen and ristocetin were studied in 13 cases of acute leukemia which included 5 cases of acute myeloid leukemia, 2 of chronic myeloid leukemia in blast crisis and 6 of acute lymphoblastic leukemia. More than one abnormality was seen in all the patients. Defects in bleeding time, clot retraction and platelet factor 3 availability were encountered in 43% of cases. Platelet aggregation responses to all the reagents were significantly impaired. There was, however, no consistency in the pattern of the defects.

Value of some tumor markers in monitoring childhood acute leukemia and lymphoma in relation to therapy

Plasma fibronectin, fibrinogen; serum copper, zinc and copper to zinc [Cu/Zn] ratio were determined in 17 cases with acute lymphoblastic teukemia [ALL], 10 cases with acute non- lymphoblastic leukemia [ANLL], 23 cases with Non-Hodgkin's lymphoma [NHL] and 5 cases with Hodgkin's lymphoma [HL] as well as 20 controls. The patients were followed up for 128 weeks through which the above mentioned parameters were determined after each stage of therapy. Significantly higher plasma fibronectin, fibrinogen serum copper and CU/Zn ratio values and significantly lower serum zinc values were observed in all groups studied before the start of therapy than controls. After induction of remission and during subsequent stages of therapy plasma fibrinogen, serum copper and Cu/Zn ratio showed significantly lower values, while serum zinc showed significantly higher values than pretherapy levels in cases of NHL. However, plasma fibronectin levels raised significantly after induction of remission than before therapy. This was followed by gradual decrease after each subsequent stage of therapy. In cases with acute leukemias significantly lower plasma fibronectin, fibrinogen; serum copper and Cu/Zn ratio values, while significantly higher serum zinc values were observed after induction of remission and during subsequent stages of therapy than pretherapy levels. During stage of maintenance of remission these parameters were normalized and were comparable to that of controls in all groups studied. Plasma fibronectin, fibrinogen; serum copper and Cu/Zn ratio showed significantly higher levels while serum zinc showed significantly lower levels than controls by a period that ranged from 16 to 40 weeks before clinical and/or hematological relapse in various groups studied. This may be considered as a stage of biochemical relapse. These data suggest the use of plasma fibronectin, fibrinogen; serum copper, zinc and Cu/Zn ratio as useful markers in monitoring acute childhood leukemias and lymphomas therapy. They may be of value in detection of disease activity and early relapse

Blood bioamines, cortisol and aminoacid levels in leukemic patients.

In patients of chronic myeloid leukemia blood adrenaline, noradrenaline, dopamine and glutamate level were significantly elevated. The GABA levels were decreased along with no significant alterations in aspartate levels in these patients. In cases of acute myeloid leukemia only adrenaline and glutamate levels were enhanced with decreased GABA levels. However, plasma cortisol levels were significantly enhanced in both chronic and acute myeloid leukemia patients. These observations suggest that the circulating bioamines, cortisol and certain aminoacids level are considerably altered in chronic and acute myeloid leukemia. All these changes may possibly be attributed to the stress induced by the disease.

Receptores para C3 y para Fc de IgG del sector granulocitico en patologia humana / Receptors for C3 and IgG Fc receptors of the granulocytic sector in human pathologies

Los neutrófilos y sus progenitores medulares tienen receptores para C3 y para Fc de IgG. Con el objeto de estudiar las modificaciones de la expersión de estos receptores en patología se estudiaron: a) sangre de 31 y médula ósea de 9 individuos normales; b) blastos de 29 pacientes de leucemia mieloblástica aguda; c) médula ósea de 8 pacientes con infecciones bacterianas severas. Se trabajó con técnica de rosetas de Saccharomyces-C3 glóbulos rojos de carnero sensibilizados con IgG. Los resultados demuestran que: a) los receptores aparecen gradual y progresivamente en las etapas de diferenciación granulocítica; el receptor de C3 se evidencia en promielocitos y el de Fc en mielocitos; el porcentaje de neutrófilos de médula ósea que expresan estos receptores es inferior al de neutrófilos de la sangre; b) en leucemia mielobástica aguda, a pesar de los signos morfológicos de inmadurez, los blastos expresan frecuentemente receptores que normalmente aparecen en estadios más diferenciados, mostrando otra evidencia de asincronismo núcleocitoplasmático; se observa buena concordancia entre la expresión de receptores y la clasificación FAB; c) en infecciones bacterianas severas aparece desviación izquierda de la expresión de los receptores en la línea de diferenciación de la progenie granulocítica