Intervenciones psicológicas en cuidadores primarios de pacientes con trasplante de células hematopoyéticas: Revisión descriptiva / Psychological interventions on primary care healthcare providers of patients with hematopoietic cells transplantation: Descriptive revision / Intervenções psicológicas em cuidadores primários de pacientes com transplante de células hematopoiéticas: Revisão descritiva

Resumen Introducción: El ser cuidador primario informal de un paciente con indicación médica de trasplante de células progenitoras hematopoyéticas puede tener consecuencias negativas en su salud mental y calidad de vida. Objetivo: Describir las intervenciones psicológicas disponibles para el cuidador primario de pacientes sometidos a trasplante de células hematopoyéticas. Metodología: Se realizó una búsqueda sistematizada de los últimos 10 años con los términos MeSH: psychotherapy AND caregive AND stem cell transplantation en las principales bases de datos médicas y de psicología, para su análisis se empleó la estrategia: Problema, Intervención, Comparación y Outcomes (PICO). Resultados: Se identificaron 122 artículos, de ellos diez cumplieron los criterios de inclusión. Las intervenciones provenían de profesionales de enfermería o trabajo social; el 50% incluyó diadas (paciente y cuidador primario), mostraron una tendencia de duración corta, enfocada al periodo posterior al trasplante. Se basan en el entrenamiento en solución de problemas, manejo de estrés, atención plena y expresión emocional. Las intervenciones lograron la disminución de la depresión, ansiedad y estrés en el cuidador; pero no alcanzaron permanencia en la significancia estadística de dichos restablecimientos. Discusión: De acuerdo con lo observado en las publicaciones y por su impacto positivo en la salud mental, se recomienda la implementación de intervenciones psicológicas en cuidadores de pacientes con trasplante de células progenitoras hematopoyéticas. Conclusión: El apoyo psicológico brindado al cuidador generalmente es de profesionales de la salud que no pertenecen al área de la psicología, con resultados clínicos favorables en las etapas más críticas de su estado mental.

Abstract Introduction: Being an informal primary healthcare provider of a patient who undergoes hematopoietic progeny cells transplantation can have adverse consequences on mental health and the quality of life. Objective: To describe the available psychological interventions for the primary healthcare provider of patients undergoing hematopoietic cells transplantations. Methodology: A systematized search of the last 10 years using the MeSH terms psychotherapy AND caregiver AND stem cell transplantation was conducted on the main medical and psychological databases. The analysis strategy followed the PICO scheme (Problem, Intervention, Comparison, Outcomes). Results: 122 articles were identified, and 10 of them fulfilled the inclusion criteria. The interventions were related to nursing or social work professionals. 50% described patient-healthcare provider dyads with short interventions focused on the post-transplantation period. Discussion: According to what has been observed in the publications and due to its positive impact on mental health, the implementation of psychological interventions is recommended in caregivers of patients who underwent hematopoietic stem cell transplantation. Conclusion: The psychological support provided to the caregiver comes mainly from health professionals who do not belong to the area of psychology, with favorable clinical results in the most critical periods for their mental state.

Resumo Introdução: Ser cuidador primário informal de um paciente sometido a transplante de células progenitoras hematopoiéticas pode ter consequências negativas na saúde mental e na qualidade de vida. Objetivo: Descrever as intervenções psicológicas disponíveis para o cuidador primário de pacientes sometidos a transplante de células hematopoiéticas. Metodologia: Realizou-se uma busca sistematizada dos últimos 10 anos com os termos MeSH: psychotherapy AND caregive AND stem cell transplantation nas principais bases de dados médicas e de psicologia, para sua análise realizou-se a estratégia: Problema, Intervenção, Comparação e Outcomes (PICO). Resultados: Identificaram-se 122 artigos, dos quais, dez cumpriram os critérios de inclusão. As intervenções provinham de profissionais em enfermagem ou trabalho social; o 50% incluiu díades (paciente e cuidador primário), mostraram uma tendência de duração curta, focalizada no período posterior ao transplante. Baseiam-se no treinamento em solução de problemas, manejo de estresse, atenção plena e expressão emocional. As intervenções conseguiram melhoras clínicas na diminuição da depressão, ansiedade e estresse no cuidador; mas não alcançaram permanência na significância estatística destes restabelecimentos. Discussão: Conforme o observado nas publicações e por seu impacto positivo na saúde mental, recomenda-se a implementação de intervenções psicológicas em cuidadores de pacientes para quem se indicou transplante de células progenitoras hematopoiéticas. Conclusão: O apoio psicológico oferecido ao cuidador vem de principalmente profissionais da saúde que não pertencem à área da psicologia, com resultados clínicos favoráveis nos períodos mais críticos para seu estado mental.

Hematopoietic progenitor cell mobilization for autologous transplantation - a literature review

ABSTRACT The use of high-dose chemotherapy with autologous support of hematopoietic progenitor cells is an effective strategy to treat various hematologic neoplasms, such as non-Hodgkin lymphomas and multiple myeloma. Mobilized peripheral blood progenitor cells are the main source of support for autologous transplants, and collection of an adequate number of hematopoietic progenitor cells is a critical step in the autologous transplant procedure. Traditional strategies, based on the use of growth factors with or without chemotherapy, have limitations even when remobilizations are performed. Granulocyte colony-stimulating factor is the most widely used agent for progenitor cell mobilization. The association of plerixafor, a C-X-C Chemokine receptor type 4 (CXCR4) inhibitor, to granulocyte colony stimulating factor generates rapid mobilization of hematopoietic progenitor cells. A literature review was performed of randomized studies comparing different mobilization schemes in the treatment of multiple myeloma and lymphomas to analyze their limitations and effectiveness in hematopoietic progenitor cell mobilization for autologous transplant. This analysis showed that the addition of plerixafor to granulocyte colony stimulating factor is well tolerated and results in a greater proportion of patients with non-Hodgkin lymphomas or multiple myeloma reaching optimal CD34+ cell collections with a smaller number of apheresis compared the use of granulocyte colony stimulating factor alone.

The difference in the radiosensitivity between hematopoietic stem and progenitor cells after different doses of 137Csγ-radiation / 天津医药

Objective To observe the different radiosensitivity induced by different doses of 137Csγ-ray irradiation between hematopoietic stem and progenitor cells. Methods Seventy-two C57BL/6 mice were randomly divided into control group and irradiated groups (2, 4 and 6 Csγ-ray irradiation, n=18 for each group). Mice of control group received sham irradiation, and the rest accepted 2, 4 and 6 Gy137Csγtotal body irradiation, respectively. After 14-day, 35-day and 56-day irradiation, the peripheral blood samples were collected by balls enucleation. The number of bone marrow nuclear cells, hematopoietic stem and progenitor cells were counted. Results The peripheral blood of irradiated mice showed significant changes in the number of white blood cells (WBC), red blood cells (RBC), platelets (PLT) and hemoglobin (HGB) in a dose-response relationship. Compared with the control group, the numbers of BMNCs and hematopoietic progenitor cells (HPCs) were significantly lower in irradiated group. At 35 d and 56 d after 6 Gy irradiation the numbers of BMNCs and HPCs were significantly lower than those of control group (P<0.05). There were no significant differences in numbers of BMNCs and HPCs between irradiated groups (2 and 4 Gy) and control group. The number of bone marrow hematopoietic stem cells (HSCs) was significantly lower in irradiated group than that in control group after 14-d and 56-d irradiation (P<0.05). Conclusion 137Csγ-ray irradiation has some damage in mouse hematopoietic system. The damage caused by radiation is persistent to hematopoietic stem cells.

Effects of Astragalus-Angelica compatibility on proliferation of hematopoietic progenitor cells in mice with bone marrow hematopoiesis suppression / 中草药

Objective: To investigate the effects of different proportions of Astragalus and Angelica on the proliferation ability and cell senescence of hematopoietic progenitor cells (HPC) in the mice model of bone marrow hematopoiesis suppression, and to probe the mechanism of Astragalus-Angelica compatibility on promoting hematopoiesis. Methods: ICR male mice were randomly divided into normal group, model group, positive control group of recombinant human granulocyte colony stimulating factor (rhG-CSF), Astragalus group, Angelica group, and different proportion combination groups of Astragalus and Angelica, and the animals in Chinese medicinal herb groups were ig administered, once a day, for 8 d. In the positive control group, rhG-CSF was sc injected on days 6, 7, and 8 of administration. Except for the normal group, the others were received cyclophosphamide (CTX) by ip injection on days 4, 5, and 6 of administration to establish the model of bone marrow hemopoiesis suppression. The mice were killed on day 9 to obtain bone marrow cells for the culture of HPC, and the senescence rate of bone marrow nucleated cell (BMNC) was detected by SA-β-galactosidase staining method. Results: Compared with the model group, Angelica and Astragalus-Angelica with proportions of 5:1, 1:1, and 1:5 could significantly raise colony forming unit-granulocyte (CFU-GM), colony forming unit-megakaryocyte (CFU-MK), colony forming unit-erythroid (CFU-E), and burst forming unit-erythroid (BFU-E) (P < 0.01). Astragalus-Angelica with 10:1 made CFU-MK, CFU-E, BFU-E remarkably increase (P < 0.05, 0.01), and had no effect on CFU-GM. Furthermore, Astragalus-Angelica with 1:1 promoting the formation of HPC was evidently stronger than that of single Astragalus, single Angelica, and other combinations (P < 0.05). Compared with the model group, the senescence positive rate of BMNC was markedly decreased in Astragalus group, Angelica group, and Astragalus-Angelica combination groups (P < 0.01), while being lowest in Astragalus-Angelica with 1:1 proportion (P < 0.05, 0.01). Conclusion: Astragalus, Angelica, Astragalus-Angelica with 10:1, 5:1, 1:1, and 1:5 proportions can prompt the proliferation and differentiation of HPC that bone marrow hematopoiesis is suppressed in mice, inhibit the senescence of bone marrow hematopoietic cell, moreover, the effect of Astragalus-Angelica with 1:1 proportion is the best. It suggests that promoting the proliferation and differentiation of HPC is one of the mechanisms that Astragalus-Angelica prompt hematopoiesis.

Avaliação do valor prognóstico da detecção do status quimérico de pacientes após o transplante alogênico de células progenitoras hematopoéticas / Evaluation of prognostic importance of the detection of chimerical status in post-allogeneic progenitor cell transplantation patients

Este trabalho teve por objetivo correlacionar o status quimérico de pacientes pós -TCPH alogênico com parâmetros clínicos, para avaliar o valor preditivo dos achados laboratorias de quimerismo. Amostras de sangue de 98 pacientes (67 em seguimento e 31 novos casos) foram submetidas à análise do status quimérico pós-TCPH. Os "loci"analisados por biologia molecular foram CS1PO, TPOX, F13A1, FESFPS, HUMTH01, VWA, SE33, HUMARA, HUMD21S11 e Amelogenina. Precocidade da evidência laboratorial de quimerismo misto (QM), em relação ao aparecimento dos sintomas clínicos de recaída, foi observada em 9 dos 12 pacientes nas LA, ou seja, nesses casos, a primeira manifestação de QM foi detectada pelo exame laboratorial antes de qualquer evidência citológica ou clínica de recaída. Em todos eles, houve uma mudança terapêutica relacionada com esse momento do aparecimento do QM. Em 100 por cento dos pacientes com QM na LMC, a detecção do quimerismo pelo exame laboratorial foi anterior a qualquer evidência citológica ou clínica de recaída. De uma maneira geral, o exame laboratorial da avaliação do status quimérico pós-TCPH alogênico pela análise dos "loci"hipervariáveis do genoma, mostrou ser um exame sensível, com detecção de até 1 por cento de QM e precoce, visto que, muitas vezes, foi a primeira manifestação de doença residual antes de qualquer evidência citológica ou clínica da mesma. A associação da existência de QM e a recaída clínica e/ou óbito fica mais evidente nos casos de LA do que nos casos de LMC e AAS.

This study aimed to correlate the chimerical status in post-allogeneic hematopoietic stem cell transplantation (HSCT) patients to clinical patterns in order to evaluate the predictive value of chimerism laboratorial findings. Blood samples from 98 patients (67 current and 31 new cases) were submitted to post-HSCT chimerical status analysis. The CS1PO, TPOX, F13A1, FESFPS, HUMTH01, VWA, SE33, HUMARA, HUMD21S11 and Amelogenian loci were analyzed. Precocity of Mixed Chimerism (MC) laboratorial evidence in relation to recurrent clinical symptom manifestations was observed in 9 out of 12 patients in AL, i.e., in these cases the first MC manifestation was detected in laboratory tests before any cytological or clinical evidence. In all cases, there was a therapeutic change due to MC onset. Chimerism detection through laboratorial examinations was prior to any cytological or clinical evidence in 100 percent of patients presenting MC in CML. Considering that it was the first manifestation of residual disease, before any cytological or clinical manifestation, laboratorial examination to evaluate chimerical status in post-allogeneic hematopoietic stem cell transplantation through analysis of genome hyper-variable loci, turned out to be a more sensitive examination and presented a detection rate of up to 1 percent for early MC. The association of MC to clinical recurrence and/death is more evident in AL cases than in CML and SAA.

Alteraciones renales en el trasplante de células progenitoras hematopoyéticas / Renal alterations in hematopoietic progenitor cell transplantation

Se realizó un estudio retrospectivo y descriptivo de 97 pacientes sometidos a trasplante de células progenitoras hematopoyéticas (TCPH), entre los años 1985 y 2004, para evaluar sus alteraciones renales. Se observó una incidencia de esta complicación del 27,5 % en la muestra analizada. Las alteraciones renales más frecuentes resultaron la disfunción y la insuficiencia renales agudas (51,6 y 22,5 %, respectivamente). Durante los primeros 120 d pos -TCPH predominó la disfunción renal aguda y en el período de más de 120 d, la nefritis radiógena. Predominaron como causas la multifactorial (54,2 %) y la nefrotoxicidad por ciclosporina A (17,1 %): hasta los 30 d, la multifactorial (72,7 %); entre los 31 y 120, la nefrotoxicidad por ciclosporina A (71,4 %) y en el mayor de 120, las radiaciones (50,0 %). Se observaron más alteraciones renales entre los trasplantados alogénicos (61,5 %) que entre los autólogos (15,4 %) y en los sometidos a QMT+RT como régimen condicionante (30,8 %), que los que recibieron solo QMT (11,7 %). La aplicación en el régimen condicionante de las dosis únicas de radioterapia se correlacionó con la aparición de la nefritis radiógena.

A retrospective and descriptive study was conducted among 97 patients that underwent hematopoietic progenitor cell transplantation (HPCT) between 1985 and 2004 to evaluate their renal alterations. An incidence of this complication of 27.5 % was observed in the analysed sample. The most frequent renal alterations were acute renal dysfunction and failure. (51.6 and 22.5 %, respectively). During the first 120 days of the transplantation, there was a predominance of acute renal dysfunction, whereas in the period of more than 120 days there was a prevalence of radiogenic nephritis. The prevailing causes were the multifactorial (54.2 %) and nephrotoxicity due to cyclosporin A (17.1 %): up to 30 days, the multifactorial (72.7 %); between 31 and 120 days, the nephrotoxicity due to cyclosporin A (71.4 %); and in the period over 120 days, the radiations (50 %). More alterations were observed in the allogenous transplant recipients (61.5 %) than in the autologous transplant recipients (15.4 %). Among those who underwent CMT + RT as a conditioning regime (30.8 %) there were also more alterations than among those who received only CMT (11.7 %). The application in the conditioning regime of the unique doses of radiotherapy was correlated with the appearance of radiogenic nephritis.

The Involvement of Multipotential Progenitor Cells in Mooren's Ulcer

The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and alpha-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and yen a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.

Study on the Retrovirus Mediated Transfer of GM-CSF cDNA in Hematopoietic Progenitor Cells / 中国肿瘤生物治疗杂志

In order to investigate the feasibility of granulocyte-macrophage colony stimulating factor (GM-CSF) gene therapy, murine GM-CSF cDNA recombinant retrovirus pLXSN/GM was transfered into retrovirus-packaging cell line PA3 17 by electroporation, and the transfected cells were used to infect hematopoietic progenitor cells rich populations. Transfective efficiency of NeoR gene was detected by G418 resistant CFU-GM test, and the results showed 36% them. In the genome of the infected target cells, integrated NeoR gene and GM-CSF cDNA were identified successfully by PCR and Southern Blot analysis respectively. The recombinant plasmids were showed to be capable of expressing GM-CSF mRNA in hematopoietic cells by in situ hybridization. In Dexter culture system, the present of GM-CSF-producing transduced cells inscreased mature nonadherent cell numbers as compared to controls. These results demonstrated that recombinant plasmids were successfully transfected into hematopoietic progenitor cells, and expressed in the cells. Therefore, it provided a basis for further investigation of gene therapy.

Effect of compounds extracted from spatholobus suberectus dunn on the proliferation of hematopoietic progenitor cell / 中国药理学通报

Aim To study effects of nine compounds extracted from Spatholobus suberectus Dunn (SSD) on proliferation of hematopoietic progenitor cell (HPC) in marrow-depressed mice. Methods Serum pharmacology experiment was used to observe the influence of nine compounds on growth of CFU-E、BFU-E、CFU-GM、CFU-Meg in marrow-depressed mice. Results Compared with the control, all compounds except pyromucic acid and ononin could significantly stimulate the growth of CFU-GM (P