Interleukin-1 beta, transforming growth factor beta 1, prostaglandin E2, and fibronectin levels in the conditioned mediums of bone marrow fibroblast cultures from lung and breast cancer patients.

We analyzed the ability of the bone marrow (BM) stromal cells to achieve confluence and their proliferative capacity in BM primary cultures from 30 untreated lung cancer patients (LCP), 27 breast cancer patients (BCP), and 30 normal controls (NC) when these confluent cells were induced to proliferate following four continuous subcultures. Moreover, we evaluated the production of interleukin-1 beta (IL-1beta), transforming growth factor beta 1 (TGF-beta1), fibronectin, and prostaglandin E2 (PGE2) by pure fibroblasts (fourth passage). A fibroblast colony-forming units (CFU-F) assay was used to investigate the proliferative and confluence capacity. Levels of IL-1beta, TGF-beta1, and fibronectin in conditioned mediums (CM) of fibroblast cultures were measured by enzyme-linked immunosorbent assay (ELISA) kit and PGE(2) by radioimmunoassay (RIA) kit. Confluence was achieved in the 60% of LCP and 78% of BCP primary cultures compared with 100% of NC, and only fibroblasts from seven LCP and six BCP cultures had the capacity to proliferate following four subcultures. Levels of IL-1beta were below 10 pg/ml in both patient groups, while NC had a mean value of 5882.57+/-221.61 pg/ml. Levels of TGF-beta1 in BCP were lower than NC values ( P<0.05). LCP and BCP had significantly decreased levels of fibronectin when compared to NC values ( P<0.05 and P<0.01, respectively). Levels of PGE2 in LCP were higher compared to NC ( P<0.01). In conclusion, BM fibroblasts from LCP and BCP presented a defective proliferative and confluence capacity, and this deficiency may be associated with the alteration of IL-1beta, TGF-beta1, fibronectin, and PGE2 production.

Factor XIII en transplante de médula ósea / Factor XIII in Bone Marrow Transplantation

La subunidad A del Factor XIII (FXIII), parte activa del FXIII, es sintetizada casi exclusivamente por megacariocitos y precursores de monocitos-macrófagos. Determinándose la actividad del FXIII en pacientes sometidos a transplante de médula ósea autólogo (TAMO) y alegeneico (TMO). En 52 pacientes, 30 TAMO y 22 TMO, la actividad del FXIII fue estudiada en días fijos (basal, mitad de régimen condicionante, día 0, día +7, día +15 y día +30). Un descenso del FXIII fue encontrado en todos los casos, cuando se comparó con los niveles basales, alcalzando el nadir de la actividad al día +7. La caída del FXIII fué significativamente más pronunciada en TMO que en TAMO. Se demostró correlación entre la actividad del FXIII y el tiempo de recuperación hematopoyética. Siete de los 52 ptes. (13, 4 porciento) tuvieron niveles de actividad del FXIII inferiores al 10 porciento, sólo 3 sufrieron sangrados asociados. En TMO, los niveles de PAI estaban significativamente aumentados en los días +7, +15 y +30. En conclusión, la actividad del FXIII está siempre desminuída post-trasplante y el restablecimiento de los niveles basales se relaciona directamente con la velocidad de reconstitución hematopoyética. Diferencias en los tiempos de "engraftment" podrían explicar las diferencias encontradas entre TAMO y TMO. Finalmente, la ausencia de sangrado en ptes. con actividad del FXIII por debajo de niveles hemostáticos(<10 porciento) podría deberse a hipofibrinolisis concominante asociada a aumento del PAI

[Bone marrow transplantation for severe aplastic anemia]. / Transplante de Médula osea en anemia aplástica severa.

Severe aplastic anemia is a hematological disease with a high mortality rate, for which bone marrow transplantation is the treatment of choice, specially in children and young adults. The number of transfusions undergone before the transplant is the most important factor to predict the possibility of graft failure. Twenty patients with severe aplastic anemia, most of them already multiple transfused, were transplanted utilizing cyclophosphamide combined with antilymphocyte globulin as a conditioning regiment. All the evaluable patients engrafted and there were no episodes of graft failure. Three patients died, and 17 (85%) are alive with hematopoietic recovery at a median of 27.7 months post-transplant. Bone marrow transplantation was an excellent therapeutic option in this series of patients with severe aplastic anemia and the conditioning regiment appeared to be sufficiently myeloablative and immunosuppressive to avoid early or late graft failure.

Bone marrow fibroblastic progenitors in patients with advanced breast cancer.

Bone marrow fibroblast colony-forming cells (CFU-F) were studied in fifteen consecutive untreated breast cancer patients (BCP) with clinical stages III and IV, and in sixteen normal controls (NC). A decreased number of CFU-F was observed in BCP compared to NC (p < 0.004). Confluence of the adherent cell layer was observed in all normal bone marrow mononuclear cells (MC) cultures, while a lower proportion of cultures from BCP (11/15) showed confluent adherent cell layers. When MC cultures of BCP were treated with indomethacin (Indo, 10(-6)M) 50% of them increased the number of CFU-F compared to the value obtained without treatment. In addition, a significant increase in the release of PGE2 in BCP cultures was observed before Indo treatment. Moreover, after MC were fractionated into adherent and non-adherent progenitors, the CFU-F decreased in both types of fractions of BCP compared to NC value (p < 0.02 and < 0.05, respectively). The number of light density MC per 10 ml of bone marrow aspirate and the number of trypsin-sensitive adherent progenitors were lower than NC in BCP (p < 0.02 and 0.013, respectively). Total MC and fibroblasts (fourth passage) were cultivated to evaluate the production of interleukin-1 beta (IL-1 beta) by ELISA methodology. Results indicated no difference of IL 1 beta spontaneous release when total MC cultures of both groups were compared. However, the levels of this cytokine were lower (< 10 pg/ml) in fibroblast culture supernatants of BCP compared to NC (1,217 +/- 74 pg/ml). Fibroblast cultures from BCP showed low or no release of IL-1 beta after muramyl-dipeptide (MDP. 1 microgram/ml) stimulation. In conclusion, the defective proliferative and confluence capacity of BCP fibroblastic progenitors may be related to the decrease in the production of IL-1 beta by these precursors.

Fibroblastic colony-forming units and levels of tumor necrosis factor and prostaglandin E2 in bone marrow cultures from patients with advanced lung carcinoma.

BACKGROUND: Although alterations of the bone marrow (BM) fibroblast colony-forming cells are involved in the development of diverse hematologic disorders, these progenitors still have not been well characterized in patients with solid tumors. METHODS: The incidence of fibroblast colony-forming units (CFU-F) was evaluated in the cultures of unseparated and fractionated light density BM mononuclear cells (MC) from 25 consecutive untreated lung carcinoma patients (LCP) and 16 normal controls (NC). Unseparated MC also were cultured in the presence of indomethacin (10[-6] M). Finally, the authors evaluated the spontaneous production of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) in culture conditioned mediums of unseparated MC by radioimmunoassay and enzyme-linked immunoadsorbent assay methodology, respectively. RESULTS: A decreased number of CFU-F was observed in unseparated and fractionated (adherent and nonadherent) light density MC cultures from LCP compared with NC. When unseparated MC of LCP were treated with indomethacin, a slightly increase in the number of CFU-F was found. Adherent MC (stromal cells) achieved confluence only in 44% of LCP primary cultures compared with 100% of NC. Overproduction of PGE2 and TNF-alpha was found in the conditioned mediums of LCP compared with the mean values obtained in NC (P < 0.05 and P < 0.02, respectively). CONCLUSIONS: The lack of confluence and suppression of CFU-F in BM of LCP may be related to the increase production of PGE2 and TNF-alpha. Future investigation will allow the determination of how these modifications influence tumor cell growth and will prove if more alterations of the hematopoietic microenvironment imply a worse prognosis.

Total lymphoid irradiation for treatment of drug resistant chronic GVHD.

We report our experience with total lymphoid irradiation (TLI) in three patients with GVHD which had failed to respond to standard drug treatment. The clinical manifestations of GVHD markedly improved with TLI treatment.

[Acute monoarthritis and laryngeal obstruction as extralymphatic manifestations of non-Hodgkin's lymphoma]. / Monoartritis aguda y obstrucción laríngea como manifestaciones extraganglionares de linfoma no Hodgkin.

Joints and larynx are uncommonly involved by non-Hodgkin's lymphoma (NHL). Synovial involvement has been reported in only 7 cases, mainly located in the knees. When this is the first location of NHL it is usually misdiagnosed. The treatment of choice is local radiotherapy followed by systemic chemotherapy. Laryngeal lymphoma can be either primary or forming part of multifocal disease. The prognosis of the primary form is usually good only with radiotherapy, whereas the prognosis of the laryngeal location of advanced disease is rather poor. The symptoms include dysphonia and slowly progressive dyspnea. A case of NHL is presented who showed initial arthritis of the knee, later evolving into severe laryngeal obstruction, an association not previously reported.

Púrpura trombótica trombocitopénica y seropositividad para el virus de la inmunodeficiencia humana adquirida / Thrombotic thrombocytopenic purpura and human acquired immunodeficiency virus seropositivity

La púrpura trombótica trombocitopénica (PTT) es una enfermedad de etiología desconocida,c aracterizad aclínicamene por una péntada diagnóstica (trombocitopenia, anemia hemolítica mciroangiopática, signos y síntomas neurológicos, fiebre y lesión renal). Trabajos recientes describen por primera vez su asociación con el virus dela inmunodeficiencia humana adquirida (HIV). Se comenta el caso clínico de una paciente con diagnóstico de PTT en quien se halló seropositividad para HIV. El daignóstico de PTT fue confirmado con los hallazgos histopatológicos de biopsias y autopsia, en la que se observó la característica microtrombosis sistémica de capilares y arteriolas

[Thrombotic thrombocytopenic purpura and human acquired immunodeficiency virus seropositivity]. / Púrpura trombótica trombocitopénica y seropositividad para el virus de la inmunodeficiencia humana adquirida.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of unknown etiology, clinically characterized by a diagnostic pentad (thrombocytopenia, microangiopathic hemolytic anemia, neurologic signs and symptoms, fever and renal damage). Recent reports in the medical literature have described its association with the human immunodeficiency virus (HIV). We report such a case in a woman admitted with TTP in whom HIV seropositivity was found. The histopathologic findings in biopsies and autopsy confirmed the clinical diagnosis of TTP: disseminated microthrombosis in arterioles and capillaries.

Acute megakaryoblastic leukemia with massive myelofibrosis: complete remission and reversal of marrow fibrosis with allogeneic bone marrow transplantation as the only treatment.

We report results of allogeneic bone marrow transplantation in an 8-year-old boy with acute megakaryoblastic leukemia characterized by intense fibrosis together with 20% blast cells in the bone marrow, who was transplanted without preceding chemotherapy for remission induction. Conditioning comprised cytosine arabinoside, cyclophosphamide and total body irradiation. The donor was his HLA-identical sister. The patient is well with minor chronic graft-versus-host disease and normal hematologic values 670 days post-transplant.

Leucemias de células plasmáticas / Plasma cell leukemias

Comunicamos en este trabajo un paciente con leucemia de células plasmáticas, cuya presentación de novo, pronóstico y evolución difieren del mieloma múltiple. Se mencionan los criterios diagnósticos y se discute esta entidad

Linfopatía angioinmunoblástica con hipogammaglobulinemia / Angioimmunoblastic lymphadenopathy with hypogammaglobulinemia

La linfopatía angioinmunoblástica es una proliferación ganglionar con una histología particular, habiendo numerosos reportes en la literatura desde 1974. Hipergammaglobulinemia policlonal se encontró en el 80% de los casos relatados. La hipogammaglobulinemia ha sido descripta excepcionalmente en esta entidad, y cuando ésta ocurre se debe sospechar transformación linfomatosa. Sin embargo, hay escasas referencias de linfopatía angioinmunoblástica con hipogammaglobulinemia desde el comienzo de la enfermedad (hipogammaglobulinemia total o déficit selectivo de IgA). El mecanismo de la hipogammaglobulinemia en la linfopatía angioinmunoblástica no está aclarado. Probablemente, estos pacientes representen un subgrupo cuyo pronóstico debe ser definido. Presentamos en este trabajo un caso de linfopatía angioinmunoblástica con hipogammaglobulinemia

Linfoma no-Hodgkin de grandes celulas con patron sinusoidal (B inmunoblastico). / Non-Hodgkin lymphoma of large cell with sinusoidal pattern (B immunoblastic)

El linfoma no-Hodgkin de grandes celulas con patron sinusoidal adopta en el ganglio una disposicion particular que en ocasiones puede llevar a error diagnostico, haciendose necesario el uso de tecnicas especiales en algunos casos. Entre estas destacamos la coloracion con verde metilo de pironina, inmunoperoxidasas y microscopia electronica, demostrandose que se trata de un linfoma tipo B celular (inmunoblastico)