Glanzmann thrombasthenia in children from Argentina.

PURPOSE: Glanzmann thrombasthenia is a well-defined inherited disorder of platelet function characterized by a decrease or absence of functional platelet glycoprotein (GP) GPIIbIIIa. The diagnosis must be considered in patients presenting with mucocutaneous bleeding, purpura, a normal platelet count, abnormal platelet aggregation, and a prolonged bleeding time. In most of the patients, the presence of small amounts of either GPIIb or GPIIIa was detected in their platelets. These observations could provide a basis for determining the clinical and laboratory heterogeneity of the disease. PATIENTS AND METHODS: We studied 10 patients of seven unrelated families with the usual methods and an immunoalkaline phosphatase technique (APAAP) to analyze the biosynthesis of GP in megakaryocytes. RESULTS: The results allowed us to classify six patients as GT type I, three as type II, and one as a variant. CONCLUSION: The nature and severity of the bleeding manifestations, in our patients, were not predictible by the laboratory findings. These confirm the clinical and laboratory heterogeneity of the disease.

Bleeding time in normal children.

PURPOSE: Because there is little information on bleeding times (BTs) in children we initiated the following study. MATERIALS AND METHODS: Normal children undergoing elective surgery and adult volunteers had their bleeding times measured with a disposable device (Simplate) with a vertical incision in the forearm. Results in children (four age groups) and adults, male and female, were compared. RESULTS: The mean time in children was 270 s with a 95th percentile of 420 s compared with a mean time in adults of 320 s and a 95th percentile of 480 s (p = 0.001). Although the values in the various age groups and sexes were different, only sex had a statistically different value in adults. CONCLUSIONS: The following reference values should be used for children: 0-4 years, 4 +/- 1 min; boys > 4 years, 5 +/- 1 min; girls > 4 years, 5.5 +/- 1 min. We conclude that results obtained in children are significantly shorter than those obtained in normal adult subjects.

[Advances in the treatment of acute myeloid leukemia in children. Experience of the Argentinian Group of Acute Leukemia Treatment and the Latin American Group of Malignant Hemopathies Treatment 1967-1987]. / Progresos en el tratamiento de la leucemia mieloide aguda en niños. Experiencia del GATLA/GLATHEM 1967-1987.

Three hundred and seventy-one children below 16 years, with newly diagnosed acute myeloid leukaemia, were included in six consecutive GATLA/GLATHEM protocols, from November 1967 to December 1987. The study was divided in three periods: 1967 to 1975, 1976 to 1982, and 1983 to 1987. Three induction schedules were used during the first two periods, and different maintenance schemes alternating with monthly consolidations were explored; the value of immunotherapy with C. Parvum and androgen therapy with stanozolol was also tested. Protocol 3-AML-83, representing the third period, included a four-week induction phase with vincristine, adriamycin, cytosine-arabinoside, prednisone and 6-mercaptopurine, followed by a consolidation phase with cyclophosphamide, cytosine-arabinoside and 6-mercaptopurine for four weeks. Maintenance phase included daily, oral 6-mercaptopurine, and monthly cytosine-arabinoside, both during two years, and adriamycin every eighth week, for one year. Complete remission rates for the first two periods of therapy were 40% and 55%, whereas that of the last period was 74%. The overall results of the period 1967-1982, showed actuarial duration rates of complete remission, event-free survival and survival, at 60 months, between 2% and 6%, their median duration being of 9, 8 and 10 months respectively. No significant difference was observed between the first two periods or protocols. Protocol 3-AML-83, activated in March 1983, achieved actuarial rates of continuous complete remission, event-free survival, and survival of 51%, 37% and 39% respectively, at 48 months. The difference between the first two periods and the last one was highly significant (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Alternating pulses of vincristine-prednisone with cytarabine-cyclophosphamide versus vincristine-prednisone in the maintenance therapy of acute lymphoblastic leukemia.

From January 1976 to December 1978, 347 children less than or equal to 15 years of age were entered in a collaborative controlled trial which included: induction (vincristine-daunorubicin-prednisone); intensification (cytarabine-cyclophosphamide); CNS prevention (intrathecal methotrexate-dexamethasone, three doses during induction and three weekly doses during the first month of maintenance, followed by one dose every 3 months for 48 months); and maintenance (6-mercaptopurine daily and methotrexate twice weekly with reinforcement pulse doses of either 1.5 mg/m2 X 1 of vincristine plus 40 mg/m2/day X 7 of prednisone [Arm A] or vincristine-prednisone alternating with 50 mg/m2 of cytarabine sc every 12 hours X 10 plus 600 mg/m2 X 1 of cyclophosphamide [Arm B]). Pulses were performed in both arms at 1, 2, 3, 4, and 6 months and every 3 months thereafter. Randomization was stratified according to age and initial wbc count. A total of 89% (310/347) of patients achieved complete remission. Duration of continuous complete remission was evaluated according to prognostic factor groups. At 5 years, 34.5% of patients with good prognosis, 24.8% with intermediate prognosis, and 12.8% with poor prognosis are in continuous complete remission. There is statistical difference between good versus poor prognosis (P less than 0.0005) and intermediate versus poor prognosis (P less than 0.025). Moreover, 5-year survival is 50.9%, 35.2%, and 18.2% in the good-, intermediate-, and poor-prognosis groups, respectively. Duration of continuous complete remission up to the first event (ie, bone marrow, CNS, or other extramedullary relapse, or death in complete remission), according to prognostic groups, did not differ in relation to reinforcement pulses (Arm A or B). We conclude that there was no benefit in alternating pulses of vincristine-prednisone with cyclophosphamide-cytarabine as used in this study.

Daunorubicin, vincristine, and prednisone for remission induction in patients with acute lymphoblastic leukemia in relapse.

Patients with recurrent acute lymphoblastic leukemia were treated with daunorubicin (40 mg/m2/week X 4), vincristine (1.5 mg/m2/week X 4), and prednisone (40 mg/m2/day x 28). All of the patients had been treated with the same combination during the first induction treatment. Of 266 patients (221 children and 45 adults) treated in first relapse, 141 (53%) achieved complete remission (CR; 55% of the children and 44% of the adults). Of 61 patients who were re-treated with the same combination after the second relapse, 14 (23%) achieved CR. The difference between second and third CR was statistically significant (P less than 0.0005). The median durations of second and third CR were 8 and 6 weeks, respectively. No significant difference was observed when the duration of CR was compared with the initial wbc count, age at diagnosis, or duration of first CR.

Sindrome preleucemico en la infancia. / Preleukemic syndrome in childhood

Se presentan dos ninos con anemia y plaquetopenia (tambien neutropenia en uno) y cuya medula osea (MO) muestra hiperplasia con contenido de mieloblastos no mayor del 10% (7% y10%) y cambios megaloblaticos; en los dos pacientes se detectan anomalias cromosomicas (trisomia 8). En uno de ellos el cultivo de MO muestra disminucion del numero de colonias. Ambos enfermos son tratados con el protocolo 3-LMA-76 del GATLA, sin obtenerse respuesta.De los ninos, uno desarrolla leucemia aguda no linfoblastica, falleciendo a causa de la misma mientras que el otro muere a los 18 meses de evolucion a consecuencia de una hemorragia del SNC, sin llegar a desarrollar cuadro franco de leucemia aguda.Consideramos que la patologia observada en los dos pacientes presentados corresponde a la del sindrome preleucemico, cuyas caracteristicas mas salientes son: citopenia en por lo menos una de las tres series hematopoyeticas; hiperplasia de MO en la mayoria de los casos, con cambios megaloblasticos, diseritropoyesis y aumento del porcentaje de blastos no linfoides (que alcanzan al 5-40%); ademas, alteraciones cromosomicas y disminucion del numero de colonias en el cultivo de MO

Sindrome preleucemico en la infancia. / Preleukemic syndrome in childhood

Se presentan dos ninos con anemia y plaquetopenia (tambien neutropenia en uno) y cuya medula osea (MO) muestra hiperplasia con contenido de mieloblastos no mayor del 10% (7% y10%) y cambios megaloblaticos; en los dos pacientes se detectan anomalias cromosomicas (trisomia 8). En uno de ellos el cultivo de MO muestra disminucion del numero de colonias. Ambos enfermos son tratados con el protocolo 3-LMA-76 del GATLA, sin obtenerse respuesta.De los ninos, uno desarrolla leucemia aguda no linfoblastica, falleciendo a causa de la misma mientras que el otro muere a los 18 meses de evolucion a consecuencia de una hemorragia del SNC, sin llegar a desarrollar cuadro franco de leucemia aguda.Consideramos que la patologia observada en los dos pacientes presentados corresponde a la del sindrome preleucemico, cuyas caracteristicas mas salientes son: citopenia en por lo menos una de las tres series hematopoyeticas; hiperplasia de MO en la mayoria de los casos, con cambios megaloblasticos, diseritropoyesis y aumento del porcentaje de blastos no linfoides (que alcanzan al 5-40%); ademas, alteraciones cromosomicas y disminucion del numero de colonias en el cultivo de MO