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This is a report of three cases of three male patients. One of the patients had myelodysplastic syndrome, and two had aplastic anemia; their ages were 28, 32, and 21 years old, respectively. Two patients underwent sibling allogeneic hematopoietic stem cell transplantation, and one underwent haploidentical hematopoietic stem cell transplantation. All the patients showed elevated hemoglobin and hematocrit at 6, 16, and 9 months after transplantation, with normal white blood cells and platelets and no splenomegaly. All causes of secondary polycythemia were ruled out. Bone marrow morphology showed no erythroid hyperplasia. The PCR result for BCR-ABL (P210, P230, P190, and variants) was negative, and there were no mutations at the amino acid site 617 of JAK2, exon 12 of JAK2, exon 9 of CALR, and amino acid site 515 of MPL. All three patients had hypertension. One patient was treated with amlodipine, and the other two patients were treated with angiotensin receptor blockers. The durations of erythrocytosis for these three patients were 6 years and 3 months, 4 years and 7 months, and 5 years and 3 months, respectively through December 2022. There was no tendency for spontaneous remission. Erythrocytosis after hematopoietic stem cell transplantation is a rare complication. Previous reports in the literature suggest that the mechanism of post-transplant erythrocytosis in recipients of allogeneic hematopoietic stem cell transplantation may be different from that of recipients of other transplants.
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Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the only therapy to cure myelofibrosis(MF) at present. This article gives a review on the following problems: who needs allo-SCT, how to choose allo-SCT in the era of ruxolitinib, the role of Ruxolitinib in the transplantation, whether allo-SCT can cure MF, and how to improve the effect of allo-SCT to guide the allo-SCT, in order for MF patients in clinical work.
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A desnutrição proteica continua sendo um dos principais problemas nutricionais do mundo. Trabalhos de nosso laboratório e de outros autores evidenciam que entre as alterações presentes na desnutrição proteica, está a alteração do tecido hemopoético, com modificações em componentes da matriz extracelular, alterações no ciclo celular da célula tronco/progenitora hemopoética, redução da produção de precursores hemopoéticos, tanto na série eritrocitária como na série leucocitária, levando a anemia e leucopenia. Os mecanismos de participação do Ca2+ nas células da medula óssea são pouco conhecidos, porém, sabe-se que ele atua no processo de hemopoese. Têm sido descrito que elevações da concentração de Ca2+ citoplasmático induzem a proliferação e diferenciação de células mielóides. A ação dessa via em indivíduos desnutridos também é pouco conhecida. Este estudo tem como objetivo avaliar o estabelecimento da celularidade medular in vitro, bem como investigar mecanismos moleculares envolvidos na proliferação e diferenciação dessa celularidade, além de avaliar a ação do cálcio na presença da interleucina-3 em células-tronco hemopoéticas murinas e sua modulação para avaliar alterações na via das MAPKs. Camundongos C57BL/6, machos e adultos foram submetidos à desnutrição proteica e, após a perda de aproximadamente 20% de seu peso corporal, as células da medula óssea foram colhidas. Essas células foram imunofenotipadas, além de reagirem com anticorpos específicos para caracterização da célula-tronco hemopoética e proteínas da via de sinalização de cálcio intracelular. Observamos que a celularidade do estroma medular em cultura de longa duração de animais desnutridos é alterada, principalmente em células de origem mesenquimal, que aparecem em maior número em desnutridos ao longo dos dias de cultura. Além disso, as ondas de cálcio intracelular estavam diminuídas em animais desnutridos, bem como as proteínas p-PKC, p-PLCy, CAMKII, p-AKT e p-STAT5 não respondem ao estímulo de IL-3, levando a uma deficiência da expressão das MAPK: ERK 1/2, JNK e p38. A desnutrição proteica pode causar alterações na celularidade estromal da medula óssea e na diferenciação das células tronco hemopoéticas pela via das MAPKs estimulada por IL-3
Protein malnutrition remains one of the world's major nutritional problems. Studies from our laboratory and others shown that alterations in protein malnutrition include hemopoietic tissue alterations, changes in extracellular matrix components, changes in the hemopoietic stem/progenitor cell tissue, reduction in the production of hemopoietic precursors, in the erythroid series as in the mieloyd series, leading to anemia and leukopenia. Mechanisms of Ca2+ participation in bone marrow cells are poorly understood, but no hemopoiesis has been developed. Elevations of cytoplasmic Ca2+ concentration in proliferation and differentiation of myeloid cells were included. Such an action through malnourished animals is also a little known. This study aims to evaluate the establishment of cellularity in vitro as well as investigate the molecular involvement in cell proliferation and differentiation, as well as to evaluate the action of calcium in the presence of IL-3 in hemopoietic stem cells and its modulation by analytical evaluations in the MAPKs pathway. C57BL/6, male adult mices were subjected to protein restriction and, after loss of approximately 20% of their body weight, bone marrow cells were harvested. These were immunophenotyped in addition to specific activation terms for the hemopoietic stem cell and intracellular signaling pathway proteins. We observed that the bone marrow cells in long-term culture of malnourished animals is altered, mainly in cells of mesenchymal origin, which appears in greater numbers in undernourished throughout the days of culture. In addition, as intracellular calcium waves decreased in malnourished animals, as well as the p-PKC, p-PLC, CAMKII, p-AKT and p-STAT5 proteins did not respond to IL-3, sugesting expression of the expression of MAPK: ERK 1/2, JNK and p38. Protein malnutrition may have changes in bone marrow capacity and differentiation of hemopoietic stem cells through IL-3-stimulated MAPKs
Subject(s)
Animals , Male , Mice , Protein Deficiency/chemically induced , Intracellular Calcium-Sensing Proteins/analysis , Reticulocytes , Blood Cell Count/methods , Bone Marrow , Interleukin-3/analysisABSTRACT
A desnutrição é um dos principais problemas de saúde pública do mundo, que contribui significativamente para o aumento da morbidade e mortalidade. Estima-se um total de 815 milhões de pessoas subnutridas no mundo, e apesar da melhoria dos recursos alimentares o número de pessoas desnutridas ainda é alarmante. Estudos de nosso laboratório tem demonstrado, em modelo murino de desnutrição proteica, hipoplasia medular com evidências histológicas de alterações na matriz extracelular (MEC) e permanência da célula-tronco hemopoética (CTH) na fase G0/G1 do ciclo celular em camundongos desnutridos. Dados deste trabalho evidenciaram alterações nas proteínas Akt /mTOR, que podem contribuir para o aumento da expressão autofágica nas CTHs e CTPHs (célula-tronco progenitora). A literatura demonstra que desequilíbrios nutricionais e metabólicos podem induzir ativação autofágica. Autofagia é um processo catabólico que participa da manutenção da homeostase celular, da MEC e na regulação das CTHs, dados deste trabalho demonstram diminuição da quantidade de CTH e CTPH em camundongos desnutridos sem a presença do gene Atg7, proteína participativa no processo autofágico. Já camundongos com deleção da transglutaminase 2 (TG2) e submetidos a privação de nutrientes por 24 horas , apresentou diminuição da quantidade de CTH e aumento da diferenciação da CTPH. A TG2 tem participação na impulsão e formação do fagóforo (processo inicial autofágico). Considerando que a desnutrição proteica leva a comprometimento da hemopoese, alterações no ciclo celular das CTHs e hipoplasia medular com pancitopenia periférica e que privação e ou jejum prolongado de nutrientes pode aumentar a atividade autofágica, concluímos nesse projeto que autofagia é importante para regulação da CTH e diferenciação da CTPH, entretanto a desnutrição proteica e privação de nutrientes estimula de maneira diversa o mecanismo de diferenciação da CTH
Malnutrition is one of the world's major public health problems, which contributes significantly to increased morbidity and mortality. An estimated 815 million people are undernourished in the world, and despite the improvement in food resources the number of undernourished people is still alarming. Studies of our laboratory have demonstrated in murine model of protein malnutrition, medullary hypoplasia with histological evidence of extracellular matrix (ECM) changes and hemopoietic stem cell (HSC) stay in the G0/ G1 phase of the cell cycle in malnourished mice. Data from this work showed alterations in Akt / mTOR proteins, which may contribute to the increase of autophagic expression in HSC and HPC (progenitor stem cell). The literature demonstrates that nutritional and metabolic imbalances can induce autophagic activation. Autophagy is a catabolic process that participates in the maintenance of cellular homeostasis, ECM and in the regulation of HSC, data from this work demonstrate a decrease in the amount of HSC and HPC in malnourished mice without the presence of the Atg7 gene, a participatory protein in the autophagic process. Mice with transglutaminase 2 deletion (TG2) and submitted to nutrient deprivation for 24 hours showed a decrease in the amount of HSC and an increase in the differentiation of HPC. TG2 plays a role in the uptake and formation of phagophore (autophagic initial process). Considering that protein malnutrition leads to hemopoiesis, alterations in the cell cycle of HSC and spinal cord hypoplasia with peripheral pancytopenia, and that prolonged nutrient starvation or fasting may increase the autophagic activity, we conclude in this project that autophagy is important for regulation of HSC and differentiation of HPC, however, protein malnutrition and nutrient deprivation stimulate in a different way the mechanism of differentiation of HSC
Subject(s)
Animals , Male , Mice , Protein Deficiency/complications , Autophagy , Hematopoietic Stem Cells , Transglutaminases , Extracellular Matrix/classification , Genotyping Techniques/methodsABSTRACT
Objective To establish the index system of nursing quality evaluation for patients with hematopoietic stem cell transplantation. Methods Based on the Donabedian structure-process-result three-dimensional quality management model, the evaluation index system of nursing quality of stem cell transplantation was constructed by combining qualitative and quantitative research of literature inquiry, case review, expert inquiry and analytic hierarchy process. Results Through the second round of expert consultation, the effective recovery rate of the expert questionnaire was 100% , the expert authority coefficient was 0.813, 0.859, and the coordination coefficient was 0.235 and 0.278 respectively (P< 01). Three primary indicators, 14 secondary indicators and 48 tertiary indicators were formed to evaluate the quality of care in stem cell transplantation. The index weight coefficient was established and the consistency test was passed. Conclusion The quality index system of hematopoietic stem cell transplantation nursing is well defined, its weight allocation is reasonable, the index is clear, and it is scientific and operational.
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Objective: To discuss the pathogenesis,clinical manifestations,diagnosis,differential diagnosis, treatment,and prognosis of the patient with rituximab (RTX)-induced interstitial lung disease (ILD) (RTX-ILD).Methods:A male patient aged 19 years old was confirmed as classical Hodgkin's lymphoma more than 2 years ago,and received autologous hemopoietic stem cell transplantation (HSCT)when the disease recurred 1 year ago.Two months after HSCT,the maintenance chemotherapy was given every month with 375 mg· m-2 RTX,but the mediastinal recurrence appeared during the period,then the mediastinal residual lesion radiotherapy was done for 10 times.However,8 d after the third RTX chemotherapy,the patient experienced post-exercising tachypnea,fever,cough,chest congestion,and limb weakness.The chest CT scanning results suggested ground gloss opacity on both lungs,and blood gas analysis suggested a hypoxemia.Neither antibacterial nor antifungal treatment worked well.Afterwards,the sequential etiological examination showed the negative results,and the bronchoscope examination showed the normal results as well.Considering about the possibility of RTX-ILD,RTX was stopped immediately and turned to intravenous infusion of methylprednisolone 40 mg per day.Results:Five d later,the symptoms of the patients were improved,and the follow-up methylprednisolone was changed to oral and gradually reduced to discontinuation.Conclusion:RTX-ILD is relatively rare,and its clinical manifestations lack specificity. Hormonotherapy is the main method in treatment of RTX-ILD. The patients sensitive to hormonotherapy have better prognosis than those insensitive to hormonotherapy.
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Objective To study the radioprotective potential of CBLB502 protein against hemopoiesis injury by irradiat-ion. Methods C57BL/6J mice were assigned to normal irradiation, and CBLB502 0.2mg/kg 30min pre-irradiation group at random before 6.5 Gy 60Co-γray total body irradiation (TBI). The peripheral blood was obtained to assay hemogram pre and post-irradiation. The bone marrow nucleated cell counts were evaluated in mice at 2 h and 24 h after irradiation. Colony-forming unit (CFU) assay was used to analyze the alteration of hemopoietic progenitor cells in bone marrow. Competitive repopulation assay was conducted to observe the implantation ability of bone marrow cells. The percentage of each lineage hemopoietic cells was measured by flow cytometry analysis. Results CBLB502 significantly alleviated the sharp decrease of peripheral blood counts including leukocyte (WBC), erythrocyte (RBC), and platelet, and accelerated recovery. Counts of various hematopoietic progenitor cell colonies of mouse bone marrow in CBLB502 group were significant higher than those of irradiation group (P<0.01). CBLB502 significantly improved the implantation ability of bone marrow cells. Conclusion CBLB502 showed obvious radioprotective effects on haemopoiesis injury by irradiation.
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Objective To study the radioprotective potential of CBLB502 protein against hemopoiesis injury by irradiation. Methods C57BL/6J mice were assigned to normal irradiation, and CBLB502 0.2mg/kg 30min pre-irradiation group at random before 6.5 Gy 60Co-! ray total body irradiation (TBI). The peripheral blood was obtained to assay hemogram pre and post-irradiation. The bone marrow nucleated cell counts were evaluated in mice at 2 h and 24 h after irradiation. Colony-forming unit (CFU) assay was used to analyze the alteration of hemopoietic progenitor cells in bone marrow. Competitive repopulation assay was conducted to observe the implantation ability of bone marrow cells. The percentage of each lineage hemopoietic cells was measured by flow cytometry analysis.
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Objective To evaluate the clinical outcome of autologous hemopoietic stem cell transplantation (AHSCT) for hematological malignancies. Methods Data of 61 patients with hematological malignancies who underwent AHSCT in Xiangya Hospital from April 1994 to August 2008 were retrospectively analyzed. There were 30 acute non-lymphoblastic leukemias (ANLL), 25 non-Hodgkin lymphoma (NHL), 3 Hodgkin lymphoma (HL), and 3 plasmacytoma. Mel 160 mg/m2 + Ara-C 2.0/2.5 g × 2 +Cy 1.8 g/m2 × 2, or TBI 8-10 Gy + Cy 1.8 g/m2 × 2 were mainly included in pretreatment regimens. Results All patients had rapid hemopoietic reconstitution. There was one patient who died of heart failure during the transplantation process. The rate of AHSCT related death was 1.6 %. The median follow up duration was 52(2-211) months. Forty-seven of 61 patients were still alive during the analysis. The probabilities of disease free survival (DFS) at 5 years were significantly different between these two groups: (77.5±5.5) % for AHSCT groups and (31.6±7.3) % for synchronous intensive chemotherapy groups(P ＜0.01). Conclusion AHSCT can be safely performed as an important treatment constituent for hematological malignancies.
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Objective To investigate the curative effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the method of the pretreatment choice on myelodysplastic syndrome (MDS).Methods 13 cases who were undergoing allo-HSCT including 10 HLA-matched, 2 HLA partially matched,and one umbilical cord blood transplanted patients were enrolled in this study. The infusion number of MNC and CD+34 cells is 6.92 (2.65-21.33)×108/kg and 4.47 (1.49-10.22) ×106/kg, respectively. Of the 13 cases,5 adopted TBI, fludarabine(Flud), and cyclophosphamide(Cy) pretreatment, 3 chose BU/Cy pretreatment, and 3 chose TBI and Cy pretreatment, 2 chose Ara-C+BU+Cy+VM26 pretreatment. In order to prevent GVHD, 2cases of HLA partially matched were treated with ATG, cyclosporin A (CsA), MTX and MMF aftertransplantation, while the others were treated with CsA and MTX only. Results 9 out of 13 cases achieved hematopoietic reconstruction completely. 4 died of complications. Conclusion The allogeneic hematopoietic stem cell transplantation is an efficient regimen to cure MDS. The pretreatment should adopt the individuation.
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Granulocyte colony stimulating factor(G-CSF)can mobilize hemopoietic stem cells(HSCs)from bone marrow to peripheral circulation,stimulating HSCs and marrow stromal cells(MSCs)homing to the lesion of cerebral ischemia,contributing to the interactions of HSCs and MSCs with the cells in ischemic penumbra,and promoting the generation of neurotrophic factors.G-CSF also has antiapoptotic effect on neurons and drives neurogenesis.Mobilizing autologous HSCs and MSCs using G-CSF for the treatment of local cerebral ischemic injury may reduce the volume of cerebral infarction,and improve neurological functional recovery.
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Objective To explore the influence of cryopreservation by ladder-style freezing from low temperature refrigerator to liquid nitrogen on hemopoietic stem cell(HSC)transplantation.Methods From April 2001 to April 2006,31 cases treated with HSC transplantation were randomized to controlled-rate freezer-liquid nitrogen group(n=15)and refrigerator-liquid nitrogen group(n=16)in Department of Hematology of 1st People's Hospital of Yunnan Province.The hemopoietic reconstitution time was observed,and the viability of HSC was determined by trypan blue exclusion test in two groups.Results No significant differences were found in transfusion values of mononuclear cells(MNC)and CD34+ cells,rates of trypan blue exclusion and time of ANC0.05).Conclusion Cryopreservation of HSC can produce successful engraftment by ladder-style freezing which has cryoprotectant solution containing final concentrations of 3-percent hydroxyethyl starch,4-percent human serum albumin,and 5-percent DMSO,and its effect is the same as traditional controlled-rate method with 10-percent DMSO cryoprotectant.The new freezing procedure is faster and easier,and freezing cost is reduced.
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OBJECTIVE To study the rate and the risk factors of hospital infection after hemopoietic stem cell transplantation and improve treatment strategy.METHODS The clinical data of 21 cases of hemopoietic stem cell transplantation were analyzed respectively in our hospital.RESULTS Hospital infection was found in 15 cases,the infection rate was 71.4%.Fifteen kinds of bacteria and 4 kinds of fungi were observed.The risk factors were aggressive operation,the abuse of glucocorticoid and antibiotics.CONCLUSIONS The patients have a high rate of hospital infection after hemopoietic stem cell transplantation and a poor prognosis because of hospital infection.To decrease the rate of hospital infection after hemopoietic stem cell transplantation,the whole environmental protection should be carried out except decreased aggressive operation and the correct use of glucocorticoid and antibiotics.
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All types of blood cells are derived from a common precursor:the hematopoietic stem cell.Hematopoietic stem cells can be found in different locations of the developing vertebrate organism. Hematopoiesis is a dynamic process sustained by cytokine induced production and activities of hematopoietic stem and progenitor cells.A number of different cytokines,cells,and cytokine cell interactions are involved in regulating the hematopoiesis. Some cytokines have more than one functions partially due to their actions on different target cells.These actions are mediated through specific receptors transmiting intracellular signals.These signals give the stem and progenitor cells critical information to survive,proliferate, differentiate or to migrate. This paper is to review recent developments in some of the major signal transduction pathways influencing hematopoietic growth and differentiation with a particular emphasis on myeloid cells.
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The prognosis of invasive aspergillosis in allogeneic bone marrow transplantation recipients is grave in the absence of bone marrow recovery in spite of antifungal treatment with amphotericin B. Beneficial role of granulocyte transfusion in neutropenic patients with fungal infection has been re-evaluated since granulocyte colony-stimulating factor made effective collection of granulocyte possible. And Liposomal amphotericin appears to be an effective alternative to conventional amphotericin B with much less toxicity. A 34-year-old patient with acute lymphoblastic leukemia developed invasive pulmonary aspergillosis during very early period of allogeneic hemopoietic stem cell transplantation. We treated the case successfully with liposomal amphotericin and granulocyte transfusion and surgery in spite of known high mortality of invasive aspergillosis in transplantation patients.
Subject(s)
Adult , Humans , Amphotericin B , Aspergillosis , Bone Marrow , Bone Marrow Transplantation , Granulocyte Colony-Stimulating Factor , Granulocytes , Invasive Pulmonary Aspergillosis , Leukemia , Mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Stem Cell Transplantation , Stem CellsABSTRACT
Objective To explore the possibility of cytochrome P-450 3A5 (CYP3A5) genotype as a major factor to guide individualized employment of cyclosporin A(CsA) through a comparative study of CsA concentrations in the peripheral blood of hemopoietic stem cell transplant recipients with different CYP3A5 genotypes. Methods Olymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype CYP3A5 gene, and CsA concentrations were detected by a commercial fluorescence polarization immunoassay. Result There were significant differences in CsA concentrations, including standardized trough concentrations C0 and two h peak concentrations C2 , in the two CYP3A5 genotypes found in our samples, and both C0 and C2 in wild homozygotes were lower than heterozygotes. Conclusion CYP3A5 polymorphism is highly associated with CsA concentrations in hemopoietic stem cell transplant recipients, and CYP3A5 genotype may be a predictor to the dose requirement before clinically employment of CsA.
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Picture of the tongue was observed in 44 cases of malignant hematopathy before and after transplantation of heniopoietic stem cells. Results showed that before transplantation, 28/ 44 cases were thin fur and after transplantation the picture of the tongue had obvious change, at the early stage 29/44 cases were thick and greasy fur, 14/44 cases were dark - purplish proper of tongue, and at the late stage of transplantation 15/ 44 cases were thick and greasy fur, and 14/44 cases were brown, grey or black fur. From the point of view of traditional Chinese medicine, this therapy has effect on the organism in the series of patients and has a certain directive significance for clinical treatment based on differentiation of symptoms and signs.
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Objective:To explore characteristics of TCM syndrome differentiation of graft versus host disease(GVHD)after transplantation of the hemopoietic stem cell,so as to provide basis of clinical syndrome differentiation for further studying on treatment of this disease.Methods:62 cases of GVHD were grouped according to acute or chronic GVHD,and a total of 85 cases-times were investigated for TCM syndrome differentiation.Results:in 50 cases-times of acute GVHD,damp heat type accounted for 68% and 50% have jaundice due to hepatic injury;blood-heat and Yin-deficiency accounted for 32%,with more patients of more severe condition.In 35 cases times of chronic GVHD,damp heat type accounted for 25.7% with more patients companied with Yin- deficiency,blood stasis and Yin-deficiency rate accounted for 74.3%.Conclusion:Commonly-seen basic TCM syndrome types of GVHD are damp-heat and Yin-deficiency types.Damp-heat type was more common in acute GVHD and blood-heat and Yin- deficiency type was.more frequently found in severe patients;chronic GVHD manifest mainly as Yin-deficiency type and with exacerbation of condition and prolongation of disease course,Yin-deficiency type tends to increase.
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Treatment of all the cases were based on differential diagnosis of zheng. Oral medicines were given to the cases in two groups, the damp - heat type and the type of Yin - deficiency blood - heat together with dampness. Of the 15 cases, 14 were markedly effective, a relapsed case was ineffective, the average days of antipyresis was 5 days, demonstrating that the therapy was rather satisfactory and helpful to their convalescence.
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Objective To explore the conditions for construction of human-to-swine hematopoietic chimera and its specific immune tolerance.Methods The human cord blood CD34+ cells (5?105/Kg) were transplanted to neonatal swine through intraperitoneal injections. The experimental swine, injected with human SCF (50ng/Kg.3d) and EPO (100U/Kg. 3d) simultaneously, and swine without injection were defined as transplantation group 1 and group 2, respectively. The swine, injected with saline, were taken as the control group. Peripheral blood (PB) was collected on day 10, 20, 30, 40, 50, and 60 after injection. The human CD71+cells in the chimera PB were quantitated by FACS and the genus-antibodies of PB were detected by blood group gel card. Results The percentage of human CD71+ cells in PB of transplantation group 1 was significantly higher than that of group 2 (P