Actualización en trasplante de células progenitoras hematopoyéticas en pacientes pediátricos en los últimos 15 años / Updating in transplant of hematopoietic progenitor cells in pediatric patients during the past 15 years

En el pasado año 2010 se conmemoró el 25º aniversario de la introducción en Cuba del trasplante de médula ósea, y su desarrollo ha seguido la secuencia de la historia universal del trasplante hematopoyético. En este trabajo nos referimos a los logros más importantes que se han alcanzado en los últimos 15 años, como ha sido la introducción del trasplante con células movilizadas hacia la sangre periférica. Se exponen los resultados parciales de un estudio comparativo de 2 grupos de pacientes pediátricos, uno que recibió células progenitoras hematopoyéticas obtenidas de médula ósea y otro con células movilizadas hacia la sangre periférica mediante factores de crecimiento hematopoyéticos. Otros avances han sido: la introducción del trasplante no mieloablativo en el año 2002, la aplicación de factores recombinantes producidos en Cuba en el manejo de los pacientes trasplantados, y la introducción de técnicas de quimerismo. Se analizan diferentes aspectos relacionados con la histocompatibilidad y los requerimientos para mejorar los resultados del trasplante. Se señala la contribución que ha tenido la experiencia obtenida con este proceder, para el desarrollo de la medicina regenerativa

In the past year 2010, it was commemorate the 25 Anniversary of introduction in Cuba of the bone marrow transplantation and its development has followed the sequence of the universal history of the hematopoietic transplantation. In present paper authors made reference to more important achievements over the past 15 years including the introduction of the transplantation with mobilized cell to peripheral blood. Partial results of a comparative study of 2 groups of pediatric patients are showed; one received hematopoietic progenitor cells obtained from the bone marrow and other with cells mobilized to the peripheral blood by means of hematopoietic growth factors. Other advances include: the introduction of non-myeloablation transplantation in 2002, the application of recombinant factors produced in Cuba in the management of transplanted patients and the introduction of chimerism. Different features related to histocompatibility are analyzed as well as the requirements to improve the transplantation results. It is indicated the contribution of the experience obtained with this procedure for the development of the regenerative medicine

Have hematopoietic growth factors made an impact on the management of liver disease?

It is clear that the major indication for the use of hematopoietic growth factors in hepatology is to counteract the adverse effects of interferons (neutropenia and thrombocytopenia) and ribavirin (hemolytic anaemia) during the treatment of hepatitis C infection. This is important because the probability of SVR depends on proper adherence to therapy (at least 80% of the requisite dose maintained for at least 80% of the requisite duration) and proper adherence can only be achieved if the side effects are reduced to a minimum. Even though the studies have demonstrated beyond doubt that the use of hematopoietic growth factors does indeed reduce the incidence and severity of these adverse effects and helps the patients to complete the course of therapy, the data on improvement of SVR is still limited. There is only one study of darbepoetin and filgrastim showing the beneficial effect on SVR. Even among the hematological side effects, possibly the only significant effect which limits the use of optimal HCV therapy is the hemolytic anaemia induced by ribavirin. The other two main side effects, i.e. neutropenia and thrombocytopenia are not clinically problematic. The use of such growth factors would be particularly effective if patients who have advanced liver disease or cirrhosis are able to receive adequate anti-viral therapy as has been demonstrated in the study of eltrombopag among HCV cirrhotics. Apart from this, other indications of G-CSF or GM-CSF use are still in the experimental stage. So, as of now, apart from erythropoietic factors, the role played by other hematopoietic growth factors in hepatology is limited. But future research, especially in the areas of immunotherapy of liver cancers and stem cell therapy for endstage liver disease, is surely going to give these factors their due place in hepatology.

Current role of chemotherapy protectors in cancer treatment

The administration of full doses of chemotherapy according to an established schedule improves the response rate and duration of response in cancer patients. However, frequently there are delays in therapy due to dose-limiting side effects and chemotherapy could affect permanently normal tissues. This has led to the development of chemotherapy protectors and of rescue agents in the past years. We will discuss some of these new agents and their use in cancer treatment. Some of these agents include amifostine (Ethyol), dexrazoxane (Zinecard), mesna (Mesnex), leucovorin, G-CSF, GM CSF, recombinant erythropoietin and thrombopoietin. Oncologists must learn the adequate use of different strategies in reducing chemotherapy toxicity in order to improve both the quality and quantity of life of cancer patients

Uso terapeutico dos fatores de crescimento hematopoieticos no periodo neonatal / Therapeutic use of hematopoietic growth factors in the neonatal period

Os fatores de crescimento hematopoietico estäo sendo cada vez mais utilizados na prática clinica. Apresentamos uma análise acerca do uso destes fatores no recém-nascido, mostrando a experiência dentro da Unidade e comparando com a relatada na literatura. Definimos em quais patologias neonatais existe um consenso sobre o seu uso e outras situaçöes em que ainda se questiona esta terapeutica

Emerging concepts in the management of acute lymphoblastic leukaemia.

Modern chemotherapy can cure more than 70 per cent of children with standard risk acute lymphoblastic leukaemia (ALL). Encouraging results are also reported in children with high risk ALL receiving intensive chemotherapy. Results in adults with ALL are less satisfactory, the long term survival is less than 35 per cent. Further dose intensification as possible in the setting of bone marrow transplantation (BMT) has increased the cure rate to 50 per cent in adult ALL. Allogeneic BMT has, however, besides the enhanced antileukaemia activity related to high dose therapy, additional antileukaemia effect related to immune mechanisms. Immune effects may be separated into three elements viz., an antileukaemia effect of graft vs host disease (GvHD), a separate antileukaemia effect of T cells and possibly a specific graft vs leukemia effect (GvL). These immune mediated antileukaemic effects offer a new potential therapeutic modality. For instance, the T cell antileukaemic effect of transplant could be achieved by transfusing radiated T cells or administering lymphokines. Alternatively autologous bone marrow could be manipulated in vitro prior to reinfusion. Manipulation might include activation of natural killer (NK) cells or lymphokine activated killer (LAK) activity. Another newer approach to treat ALL is the use of hemopoietic growth factors. Use of these factors prior to chemotherapy may increase the proportion of proliferating leukaemic stem cells. This would increase the efficacy of many drugs since most are active against proliferating cells. Hemopoietic regulatory factors could also be used to directly inhibit leukemic cell growth or to promote differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Factores de crecimiento hematopoyético: su utilidad en oncología clínica (primera parte) / Hematopoyetic growth factors: its utility in clinical oncology

Los factores de crecimiento hematopoyético (factor estímulante de colonias de granulocitos y macrófagos: GM-CSF; factor estímulante de granulocitos: G-CSF; factor estímnulante de colonias de macrófagos: M-CSF; interleukina 3: IL3) tienen acciones pleiotrópicas sobre la proliferación y diferenciación de las clulas progenitoras hematopoyéticas, y recientemente han ingresado al uso clínico, puesto que ya han demostrado su amplia eficacia y utilidad en diversas situaciones. Pueden mejorar la neutropenia de los síndromes mielodisplásicos y de anemia aplásica. También pueden acelerar la recuperación luego del trasplante de médula ósea y así reducir la morbilidad concomitante a este procedimiento. También pueden incrementar el reclutamiento y cosecha de progenitores de sangre periférica y de ese modo afectar significativamente la posiblilidad de suministar quimioterapía intensiva, con o sin trasplante de médula ósea. Su uso pot6encial más importante se centra en la posibilidad de paliar la neutropenia que sigue a la terapía mielosupresora en pacientes con SIDA y con cáncer que reciben quimioterapía. Los factores de crecimiento hematopoyético han demostrado eficacia en disminución de la duración de la neutropenia, disminución de las infecciones concomitantes y un aumento de la habilidad para suministrar dosis plenas de quimioterapía mielosupresora