Epstein Barr virus in relation to apoptosis markers and patients' outcome in pediatric B-cell non-Hodgkin lymphoma.

In this study, we investigated Epstein Barr virus (EBV) presence, associated to proliferation and apoptosis proteins in pediatric B-cell Non-Hodgkin lymphoma (B-NHL). EBERs, Ki67, active caspase 3, Bax and Bcl2 were analyzed on B-NHL tissue from 40 patients. Forty percent showed EBV expression, significantly higher among patients ⩽10years (P=0.027), and associated with immunosuppression (P=0.020), but not associated apotosis markers. However, EBV was associated with a worse event-free survival (P=0.016), particularly under immunosuppression. Even though EBV did not seem to alter apoptotic pathways, it exhibited survival disadvantage and could be an important cofactor in B-cell lymphomagenesis in younger children.

Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation.

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein-Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.

A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis.

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.

[Allogeneic hematopoietic transplantation with stem cells extracted from peripheral blood]. / Trasplante hematopoyético alogénico con células progenitoras extraidas de la sangre periférica.

Fifty three patients (pts) received an allogeneic hematopoietic transplant using peripheral blood progenitor cells (PBPC). Diagnosis were acute myeloid leukemia (AML) in 16 pts, acute lymphoblastic leukemia (ALL) in 15, chronic myeloid leukemia (CML) in first chronic phase in 12, aplastic anemia in 4, myelodysplasia in 3 and Hodgkin's disease, major thalasemia and Hunter's syndrome in one each. Mean age was 20 years-old (2-55), 28 males and 25 females. Conditioning regimens were total body irradiation with 1200 cGy and cyclophosphamide 120 mg/kg in 38 pts, busulfan 16 mg/kg and cyclophosphamide 120 mg/kg in 10 pts, total lymphoid irradiation and cyclophosphamide in 3, 2 pts received other chemotherapy based conditionings. PBPC were infused unmanipulated through a central catheter. Graft versus host disease (GVHD) prophylaxis was cyclosporin and short course methotrexate. Donors were 6/6 HLA compatible siblings in 52 cases and 5/6 match in one case. PBPC mobilization was done with G-CSF at a dose of 10 micrograms/kg/day subcutaneously for four days, pheresis started on day 5. Bone marrow harvest was also done in the first thirty cases. Mean cellularities for CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg) were 4.12; 4.59; 2.57; 1.9; 0.55 and 0.68, respectively. Mean recovery of neutrophils > 500/microL was obtained on day +11 and platelets > 20,000/microL on day +13. Patients were hospitalized for a mean period of 26 days (range 18-39) and days with parenteral antibiotics were 12.2 (5-45). Two pts had venoocclusive disease of the liver. Transplant related mortality was 15%. Acute graft versus host disease (GVHD) was observed in 43.4% of pts, only 5 pts had acute GVHD III or IV. Mean time for aGVHD diagnosis was +23 (8-76). Forty three pts were evaluable for chronic GVHD with a mean follow-up of 18 months (4-39). Chronic GVHD was observed in 26.4% by day +240, only 2 pts developed severe cGVHD. The present experience demonstrates an acceptable incidence for cGVHD; however, taking into account recent reports showing an increase of this complication, it seems reasonable not to perform this procedure for non-malignant diseases in which graft versus malignancy effect is not to be expected.

Trasplante hematopoyético alogénico con células progenitoras extraidas de la sangre periférica. / [Allogeneic hematopoietic transplantation with stem cells extracted from peripheral blood]

Fifty three patients (pts) received an allogeneic hematopoietic transplant using peripheral blood progenitor cells (PBPC). Diagnosis were acute myeloid leukemia (AML) in 16 pts, acute lymphoblastic leukemia (ALL) in 15, chronic myeloid leukemia (CML) in first chronic phase in 12, aplastic anemia in 4, myelodysplasia in 3 and Hodgkins disease, major thalasemia and Hunters syndrome in one each. Mean age was 20 years-old (2-55), 28 males and 25 females. Conditioning regimens were total body irradiation with 1200 cGy and cyclophosphamide 120 mg/kg in 38 pts, busulfan 16 mg/kg and cyclophosphamide 120 mg/kg in 10 pts, total lymphoid irradiation and cyclophosphamide in 3, 2 pts received other chemotherapy based conditionings. PBPC were infused unmanipulated through a central catheter. Graft versus host disease (GVHD) prophylaxis was cyclosporin and short course methotrexate. Donors were 6/6 HLA compatible siblings in 52 cases and 5/6 match in one case. PBPC mobilization was done with G-CSF at a dose of 10 micrograms/kg/day subcutaneously for four days, pheresis started on day 5. Bone marrow harvest was also done in the first thirty cases. Mean cellularities for CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg) were 4.12; 4.59; 2.57; 1.9; 0.55 and 0.68, respectively. Mean recovery of neutrophils > 500/microL was obtained on day +11 and platelets > 20,000/microL on day +13. Patients were hospitalized for a mean period of 26 days (range 18-39) and days with parenteral antibiotics were 12.2 (5-45). Two pts had venoocclusive disease of the liver. Transplant related mortality was 15

. Acute graft versus host disease (GVHD) was observed in 43.4

of pts, only 5 pts had acute GVHD III or IV. Mean time for aGVHD diagnosis was +23 (8-76). Forty three pts were evaluable for chronic GVHD with a mean follow-up of 18 months (4-39). Chronic GVHD was observed in 26.4

by day +240, only 2 pts developed severe cGVHD. The present experience demonstrates an acceptable incidence for cGVHD; however, taking into account recent reports showing an increase of this complication, it seems reasonable not to perform this procedure for non-malignant diseases in which graft versus malignancy effect is not to be expected.

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.

Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.

Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.

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.

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