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.

Inmunidad humoral a tétanos, sarampión y rubéola en niños con leucemia linfoblástica aguda luego del tratamiento quimioterápico / Humoral immunity to tetanus, measles and rubella in children with acute lymphoblastic leukemia after chemotherapy

Los regímenes de quimioterapia y los avances en el soporte clínico han mejorado la supervivencia de los niños con leucemia linfoblástica aguda. Son temas de preocupación las secuelas del tratamiento, entre ellas, el daño inmunológico inducido por la terapia inmunosupresora, que se refleja en la pérdida de niveles protectores de anticuerpos provistos por inmunizaciones previas. Nuestro objetivo fue evaluar la presencia de títulos protectores de anticuerpos para sarampión, rubéola y tétanos en pacientes con leucemia linfoblástica aguda luego de haber finalizado el tratamiento quimioterápico. Se incluyeron 61 niños con leucemia linfoblástica aguda asistidos en el Hospital Garrahan, que habían finalizado el tratamiento, como mínimo, 6 meses antes y con vacunación completa previa al diagnóstico. Las tasas de anticuerpos protectores fueron sarampión: 46% (IC 32-59); tétanos: 53% (IC 40-67); rubéola: 60% (IC 47-63). Estos resultados refuerzan la necesidad de reconsiderar la revacunación en este grupo de pacientes.

Chemotherapy regimens and clinical support advances have improved survival in children with acute lymphoblastic leukemia. The after-effects of treatment are a reason for concern, including damage to the immune system induced by immunosuppressive therapy which is reflected in the loss of antibody protection provided by prior immunizations. Our goal was to assess the presence of measles, rubella, and tetanus protective antibody titers among patients with acute lymphoblastic leukemia after completing chemotherapy. Sixty-one children with acute lymphoblastic leukemia seen at the Hospital Garrahan were included; patients had finished their chemotherapy at least 6 months earlier and had a complete immunization schedule before diagnosis. The rates of protective antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60% (CI 47-63) for rubella. These results strengthen the need to reconsider revaccination in this group of patients.

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

Immune status & enzymes activity in blood lymphocytes in adult patients at different stages of acute lymphoblastic leukaemia.

Background & objectives: Pathogenesis acute lymphoblastic leukaemia (ALL) in adults is not well understood, as it is more common in children. We examined the immunological status and the activity of certain enzymes in blood lymphocytes in adult patients of ALL at different stages. Methods: ALL patients (n=71) admitted during 2000-2005 were included in this study. All patients had decreased T-lymphocytes content. At first attack, they had CD4 +-cells decreasing and increasing IgM and IgG concentration. In complete remission all examined parameters were low. The peculiarities of ALL recurrence were high NK-cells content and disbalances of the main immunoglobulin concentrations. Results: In the first attack and recurrence the anaerobe glucose oxidation intensity and the reactions of macromolecular synthesis were lower in lymphocytes compared to control. In remission all these processes restored to normal. In all stages in lymphocytes GR had decreased activity. Interpretation & Conclusions: Our results showed that most of changes in immune status of ALL patients were in a stage of complete remission when patients arrived on its maintenance through the small period from spent before therapy when the immune system of the patient has not been restored. Thus, probably cytostatic action causes immune failure in the future and starts disease again.

Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria) were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years). In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70 percent vs. 1 percent, 54 percent vs. 32 percent, 30 percent vs. 8 percent, and 9 percent vs. 0 percent, respectively). Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88 percent vs. 57 percent, 39 percent vs. 1 percent, 60 percent vs. 1 percent, 77 percent vs. 1 percent, and 56 percent vs. 14 percent, respectively). Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95 percent CI =46.48-6580.42) and thrombocytopenia (OR = 754.13; 95 percent CI =64.57-8806.72) were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study emphasizes the importance of investigating leukemia in patients presenting with musculoskeletal manifestations and, in particular, limb pain associated with thrombocytopenia.

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.

Serum lactate dehydrogenase as a prognostic marker of childhood acute lymphoblastic leukemia.

The estimation of serum lactate dehydrogenase (LDH) is easy, readily available and economic. We can assume the prognosis of childhood acute lymphoblastic leukemia (ALL) through this measurement. This case control prospective study was aimed to evaluate that the level of serum LDH has the prognostic marker of childhood ALL. The study was carried out in the Paediatric Haematology and Oncology unit, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during the period from January to December 2006 on 69 subjects with age ranging from birth to 15 years irrespective of sex. The study subjects were grouped into case (ALL-44) and control (healthy-25). Serum LDH level were performed in ALL patients on admission, day 14 and day 29 of induction and in healthy control when came for check up and found healthy. Haematological parameters were performed in ALL patients and in healthy control along with the measurement of serum LDH. On admission the level of serum LDH was significantly raised in ALL patients than healthy control (p<0.001). After induction, serum LDH level were significantly decreased at day 14 and day 29 of induction from admission (p<0.001). There was significant rise of platelet count were observed at day 29 of induction from admission (p<0.001). A significant decrease of peripheral and bone marrow blast cell percentages were observed at day 29 of induction from admission (p<0.001). The total WBC count was significantly decreased along with serum LDH at day 14 and day 29 of induction from admission (p<0.001). So, the measurement of serum LDH can be accepted as a good and reliable prognostic marker of childhood acute lymphoblastic leukemia.

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.

Homocysteine, vitamin B12 and folate status in pediatric acute lymphoblastic leukemia.

OBJECTIVE: The cause of majority of acute leukemias is unknown, but likely to involve interaction of environment, hematopoitic development and weak susceptibility loci within an individual's genetic constitution. The present study evaluates the association between plasma levels of homocysteine, folate and vitamin B12 and acute lymphoblastic leukemia. METHODS: Plasma levels of homocysteine, folate and vitamin B12 were compared between cases of acute lymphoblastic leukemia and age and sex matched normal controls. Homocysteine levels were measured by solid immunoassay, while folate and vitamin B12 levels were determined by radioassay. RESULTS: Folate levels were significantly among cases as compared to control group (8.56 +/- 4.35) vs (14.04 +/- 2.62) ng/ml, P< 0.001). Although individually vitamin B12 and homocysteine were not significant different between cases and controls, the combined effect of all three parameters was significantly different (P< 0.001), with 83.3% of correct classification of cases and controls was obtained by discriminate function analysis. CONCLUSION: The data provide evidence for the role of folate, vitamin B12 and homocysteine levels in acute lymphoblastic leukemia, suggesting that gene-environment interaction may be an important factor in the development of acute lymphoblastic leukemia.

Serum lactate dehydrogenase level in childhood acute lymphoblastic leukemia.

Serum lactate dehydrogenase (LDH) level was estimated in 44 childhood (age range 1-15 years) acute lymphoblastic leukemia (ALL) on admission, day 14 and day 29 of induction. Another 25 children without ALL were included as control. On admission, the level of serum LDH was significantly high in ALL cases than control (p < 0.001). Total WBC count was significantly decreased along with serum LDH level at day 14 and day 29 of induction (p < 0.001). A significant rise of platelet count was observed at day 29 of induction in relation to significant decrease of serum LDH level (p < 0.001). A significant decrease of peripheral and bone marrow blast cell percentages were also observed at day 29 of induction along with significant decrease level of serum LDH (p < 0.001). So, the measurement of serum LDH level can be accepted as an enzymatic tool for presumption of childhood ALL and the response to chemotherapy during induction of remission.

Haematological and cytomorphological study of acute lymphoblastic leukemia [ALL]

Acute lymphoblastic leukaemia [ALL] has long been recognized to be clinically and morphologically heterogeneous .We tried to study, analyze, and interpret the relationships between age, sex, clinical manifestations, FAB classification, and hematological investigations. Over a period of 6 months, sixty-four, newly diagnosed [Sudan Black B 'negative], cases had been included in this study, from different centers. Clinical study was conducted concentrating on the presence of fever, pallor, bleeding tendency, lymph node enlargement, spleen and liver enlargement, neurological and testicular manifestations, and the presence of mediastinal mass on chest x-rays. Hematological investigations included haemoglobin concentration, initial total white cell count, and platelets count. Bone marrow smears were stained with MGG stain and the FAB classification and the FAB scoring system had been used. Showed that children were 61% of total cases while adults were 39%, with the highest age incidence between 0-5 years. Male: female ratio was 2:1. Age incidence in males was higher than that for females for all age groups. Lymph node enlargement and hepatomegaly were the most common clinical findings. The presence of mediastinal mass on chest x-ray was more in male than female sex [39.5% Vs 9.5%]. L2- morphological subtype was more common in both children and adults 87.2% and 92% respectively] than L1 morphological subtype [12.8% and 8% respectively]. No L3 type had been found in our study. ALL is a disease of children mainly with higher incidence in males than females and, unlike the internationally reported cases where L1 type is more prevalent, L2 type is more prevalent in Iraqi cases

Acute lymphoblastic leukemias; haematologic comparison between two treatment protocols

The present study conducted by the authors showed that in 1st group out of 21 cases, 3 left and remaining total 18 patients of ALL who received conventional treatment 16 [92%] showed complete remission and 2 died showed non-remission. In this group 10 [62%] showed complete remission after 2 months while 6 [38%] showed remission after 3 months. Similarly in 2nd group out of 21 cases, 4 left and in remaining 17 patients who received conventional therapy without L-asnase 16 [94%] showed complete remission and 1 [8%] died. The 16 patients who were in remission and received conventional treatment along with L-asnase enzyme showed complete remission in 14 [87%] cases after 2 months of treatment and 2 [13%] after 3 months of duration. The estimation of various parameters were continued till 6 months which showed maintenance of remission in 15[94%] patients in 1st group and all [100%] patients in 2nd group. This showed that the recommended chemotherapy without any L-asnase is less effective as induction of remission therapy while the addition of L-asnase enzyme in that treatment resulted in intensification of results which are maintained for longer time

Plasma concentrations of lipid peroxidation products in children with acute leukaemia.

Acute leukaemia is the most common childhood malignancy. The cause of leukaemia is not known in most of the cases and of late free radicals have been implicated in the pathogenesis of leukaemia. The degree of lipid peroxidation was studied in the present study as a marker of disease activity in 15 patients of acute lymphoblastic leukaemia and 20 healthy age and sex matched individuals served as control. Serum malonaldehyde (MDA) levels were increased in leukaemia and were higher in the active phase of disease as compared to those in remission, Hence, serum MDA estimation in leukaemia can be of help in diagnosis and to predict the chances of relapse.

Les manifestations cliniques et biologiques des leucemies aigues lymphoblastiques de l'enfant [etude retrospective de 87 cas]

We present in this study the clinical and biological datas of 87 children suffering from acute lymphoblastic leukemia followed between 1985 and 1996. The mean age was 7 years; 37% of the patients were aged under 5 years at diagnosis. The sex ratio was 1.35. the anemic, infection and hemorrhagic syndromes were observed in respectively 65%, 18% and 11% of the patients. Adenopathies were found in 70% splenomegaly and/ or hepatomegaly in 75% Hyperleucocytosis was found in 64%, anemia in 90% and thrombopenia in 85% of the cases. Using the FAB classification we found 72% type 1, 22% type 2 and 6% type 3 acute lymphoblastic leukemia. Cerebro- spinal fluid study revealed meningeal leukemic involvement in 17% of cases

study on copper and zinc in the serum of some cancer patients

Many reposts had suggested that copper and zinc may reflect diseases activity in lymphoma. Also, zinc helps in the function of WBCs in immune system. Whole blood samples were taken from 6 healthy donors and 10 patients suffering from different types of cancer. Serum copper and zinc were measured by using XRF method. Serum copper of cancer patients is higher than that of controls [P < 0.05] while serum zinc concentration is lower in patients than that of controls. Therefore, these two elements can be used as additional tests in diagnosis and managing cancer patients

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.

Transferrin receptor expression by blast cells in acute lymphoblastic leukemia correlates with white cell count & immunophenotype.

Transferrin receptor (TR) expression by blast cells in 127 cases of acute lymphoblastic leukemia (ALL) at presentation and 19 cases at relapse was examined using three anti-TR monoclonal antibodies to find its correlation with prognostic features such as the total leucocyte count (TLC), the morphology of blast cells and their cytochemical and immunophenotypic properties, as well as age and sex of the patients. Blasts in 62 per cent of thymic (T) ALL cases at presentation showed significant TR expression as compared to only 10.9 per cent in common ALL (CALL) (P < 0.001). This differential expression of TR was also observed among cases with > 50 x 10(9)/l TLC, while in cases with < 50 x 10(9)/ l TLC no such pattern was observed (30% TR positivity in T-ALL vs 20% TR positivity in non-T-ALL). Furthermore, the percentage of TR positive blasts was significantly higher (P < 0.005) in cases with > 50 x 10(9)/l TLC as compared to those with < 50 x 10(9)/l (48.3-54.4% vs 24.9-28.8%). In contrast to CALL cases at presentation, those at relapse showed a very high TR positivity (54-66%), similar to the T-ALL cases (53-84%). This suggests a high proliferative rate of blast cells in ALL at relapse, irrespective of its immunophenotype. There was no correlation of TR expression with blast cell morphology (FAB L1 vs L2), their cytochemical properties and sex of the patients. However, a significantly higher incidence of TR positivity was observed in patients above 10 yr of age compared to those below 10 yr (47% vs 15%; P < 0.001). The incidence of T-ALL was also significantly higher in the former group (56%) compared to the latter (33%) (P < 0.005). Our data suggest that by virtue of its association with features of poor prognosis, e.g., age above 10 yr, expression of thymic markers, high leucocyte count and disease relapse, TR expression by blast cells in ALL could serve as a biological marker of poor prognosis.