RESUMO
BACKGROUND: GvHD is one of the major complication after stem cell transplantation affecting transplant-related mortality. Throughout the last years, many serum proteins were been proposed as possible biomarkers for GvHD. AIMS: We studied the trend of five of the most studied serum proteins to evaluate whether a correlation exists between proteins concentration and post-HSCT outcomes. MATERIALS AND METHODS: We measured serum concentration of REG3α, ST2, B-cell activating factor (BAFF), CXCL9 and elafin in a cohort of 77 patients submitted to Hematopoietic allogeneic stem cell transplantation (HSCT) in our department. Blood samples were been collected at baseline, day +30, GvHD onset and GvHD resolution. RESULTS: REG3α levels showed an association only with acute GvHD. Elafin and ST2 levels varied according to both acute and chronic GvHD occurrence. BAFF concentration showed an inverse association with acute GvHD development. Interestingly, baseline BAFF and ST2 levels predicted post-HSCT survival. No associations were found for CXCL9. CONCLUSIONS: Except for CXCL9, the protein levels seem to change according to GvHD development, independently from organ involvement and grading. Pretransplant ST2 and BAFF appeared to be predictors for survival after HSCT.
Assuntos
Proteínas Sanguíneas/metabolismo , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Área Sob a Curva , Fator Ativador de Células B/metabolismo , Biomarcadores/metabolismo , Causas de Morte , Estudos de Coortes , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/fisiopatologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD.
Assuntos
Biomarcadores/metabolismo , Diarreia/metabolismo , Fezes/química , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Complexo Antígeno L1 Leucocitário/metabolismo , Biomarcadores/sangue , Diagnóstico Diferencial , Diarreia/diagnóstico , Diarreia/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Transplante HomólogoRESUMO
BACKGROUND: Human cord blood is a relevant source of CD133+ HPCs. Clinical-scale isolation of human umbilical cord blood (UCB) CD133+ HPCs using immunomagnetic microbeads and the CliniMACS clinical cell isolator is reported. CD133+ HPCs isolated after large-scale processing were functionally characterized. STUDY DESIGN AND METHODS: Closed disposable sets were used to process nine different samples of RBC-reduced UCB nucleated cells. In-vitro hematopoietic assays and human xenografts in NOD/SCID mice were performed to assess the functional properties of isolated CD133+ cells. Different mixtures of human cytokines were tested for the ability to expand nascent CD133+ HPCs. Furthermore, freshly isolated CD133+ cells were conditioned in culture medium specifically tested to support in-vitro myogenesis or osteogenesis. RESULTS: Isolation procedures yielded the recovery of an average of 2.53 x 10(6) CD133+ HPCs with a mean recovery of 96 percent (referred to as RBC-reduced samples) and a final sample purity of 82 percent. Purified CD133+ cells had high cloning efficiency, had relevant long-term activity, and were capable of repopulating irradiated NOD/SCID mice. In 10-day stroma-free cultures, a 2-fold and 8.3-fold expansion of colony-forming cells (CFCs) and extended long-term culture-initiating cells, respectively, was obtained. Freshly isolated CD133+ cells differentiated into large nucleated cells expressing either myosin D or osteopontin (as revealed by RT-PCR and immuno-cytochemistry), with a protein/mRNA expression comparable to or even higher than that observed in UCB CD133- nucleated cells in identical culture conditions. CONCLUSION: Collectively, clinical-scale isolation of UCB CD133+ cells provides a relevant amount of primitive HPCs with high hematopoietic activity and in-vitro mesenchymal potential.