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1.
Cancer Treat Rev ; 89: 102071, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717620

RESUMO

Haplo-identical transplant is being increasingly used in patients who do not have a readily available matched related or unrelated donor. Post-transplant cyclophosphamide's use due to its simplicity and documented efficacy has made this approach readily employable across diverse transplant centres across the globe. The outcomes of regimens used for conditioning in recipients of bone marrow are at times in variance to that from more commonly employed G-CSF mobilised peripheral stem cell (PBSC). This review highlights various conditioning regimens used in PBSC recipients, with emphasis on toxicities, practicalities and transplant related outcomes of relapse, non-relapse mortality and graft versus host disease.


Assuntos
Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Condicionamento Pré-Transplante/métodos , Haplótipos , Mobilização de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Células-Tronco de Sangue Periférico/citologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante Homólogo
2.
Biol Blood Marrow Transplant ; 26(7): e161-e166, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389803

RESUMO

With the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/métodos , Infecções por Coronavirus/epidemiologia , Criopreservação/métodos , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Pneumonia Viral/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Estados Unidos/epidemiologia , Doadores não Relacionados
3.
Leukemia ; 34(10): 2766-2775, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32393841

RESUMO

The ideal stem cell graft source remains unknown in haploidentical haematopietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide (PTCy). This study compared outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for haplo-HCT in acute lymphoblastic leukemia (ALL). A total of 314 patients with ALL (BM-157; PB-157) were included in this study. The cumulative incidence of engraftment at day 30 was higher in the PB group compared with BM (93% vs. 88%, p < 0.01). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were not significantly different between the study cohorts. In the multivariate analysis, there were tendencies toward a higher incidence of grade II-IV acute GVHD (hazard ratio (HR) = 1.52, p = 0.07), chronic GVHD (HR = 1.58, p = 0.05), and nonrelapse mortality (NRM) (HR = 1.66, p = 0.06) in patients receiving PB versus BM graft, respectively. The use of PB grafts was associated with lower leukemia-free survival (LFS) (HR = 1.43, p = 0.05), overall survival (OS) (HR = 1.59, p = 0.02), and GVHD-free, relapse-free survival (GRFS) (HR = 1.42, p = 0.03) compared with BM grafts. There was no difference in relapse incidence (HR = 1.23, p = 0.41) between the study groups. In conclusion, use of BM graft results in better survival after haplo-HCT with PTCy in patients with ALL, compared with PB stem cell graft.


Assuntos
Transplante de Medula Óssea , Mobilização de Células-Tronco Hematopoéticas , Depleção Linfocítica , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante Haploidêntico , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Causas de Morte , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Modelos de Riscos Proporcionais , Linfócitos T , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento
4.
Acta Haematol ; 143(4): 381-387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248194

RESUMO

AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in myeloma. This application has evolved significantly over the past three decades. This review provides a comprehensive assessment of eligibility criteria, stem cell collection, and mobilization strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies as well as long-term outcome with respect to survival, hematologic response and relapse as well as organ responses following stem cell transplantation. Continued efforts to refine patient selection and management, and incorporate novel anti-plasma cell agents in combination or sequentially to further improve outcomes in AL amyloidosis are also discussed.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Melfalan/administração & dosagem , Agonistas Mieloablativos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Terapia Combinada , Gerenciamento Clínico , Mobilização de Células-Tronco Hematopoéticas , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/etiologia , Especificidade de Órgãos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Cuidados Pós-Operatórios , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(14): e19807, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243414

RESUMO

RATIONALE: Very severe aplastic anemia (vSAA) with active infections is always fatal. Adequate infection control before hematopoietic stem cell transplantation is recommended. PATIENT CONCERNS: A 38-year-old woman with vSAA suffered from acute perforated appendicitis and invasive pulmonary fungal infection, and she failed to respond to intense antimicrobial therapies. DIAGNOSIS: She was diagnosed with refractory vSAA with stubborn acute perforated appendicitis and invasive pulmonary fungal infection. INTERVENTIONS: We successfully completed an emergent reduced intensity conditioning-matched unrelated donor (MUD)-peripheral blood stem cell transplantation (PBSCT) as a salvage therapy in the presence of active infections. The conditioning regimens consisted of reduced cyclophosphamide 30 mg/kg/day from day-5 to day-3, fludarabine 30 mg/m/day from day-5 to day-3 and porcine-antilymphocyte immunoglobulin 15 mg/kg/day from day-4 to day-2 without total body irradiation. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Neutrophils and platelets were engrafted on day+15 and day+21. Appendiceal abscess and severe pneumonia developed after neutrophil engraftment, which were successfully managed with intense antimicrobial therapy and surgical intervention. OUTCOMES: Only limited cutaneous chronic GVHD was observed 5 months after transplantation. The patient still lives in a good quality of life 2 years after transplantation. LESSONS: Active infections may be no longer a contraindication to hematopoietic stem cell transplantation for some patients with vSAA.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Doença Aguda , Adulto , Anemia Aplástica/microbiologia , Apendicite/microbiologia , Feminino , Humanos , Pneumopatias Fúngicas/microbiologia , Doadores não Relacionados
6.
Ann Hematol ; 99(4): 877-884, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062742

RESUMO

Autologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006-2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empirical antibiotics), and those in the 2013-2017 period are group 2 (levofloxacin prophylaxis and meropenem as empirical antibiotics). The incidence of febrile neutropenia was 72% in group 1 and 86.2% in group 2 (p = 0.004). The majority of infectious episodes were associated with fever of unknown origin: 55% in group 1 and 59% in group 2. Febrile of unknown origin episodes were 82.6% in group 1 and 80% in group 2. Significant differences between both groups were found in age, hypogammaglobulinemia, and advanced disease at ASCT. No differences were found between groups regarding the most common agent documented in positive blood cultures (Gram+ were 66.6% in group 1 and 69% in group 2 (p = 0.68)). Mortality within 100 days of transplant was low, 1.87%. Regardless of the prophylactic regimen used, most patients experience febrile episodes in the ASCT setting, fever of unknown origin is the most common infection complication, and Gram+ agents are prevalent in both groups. Mortality rates were low. According to our results, ASCT is a safe procedure and there is no clear benefit in favor of levofloxacin versus ciprofloxacin prophylaxis. Both anti-infectious approaches are acceptable, yielding similar outcomes.


Assuntos
Antibioticoprofilaxia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriemia/prevenção & controle , Neutropenia Febril/prevenção & controle , Adolescente , Adulto , Idoso , Amicacina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bacteriemia/etiologia , Ceftazidima/uso terapêutico , Ciprofloxacino/uso terapêutico , Neutropenia Febril/induzido quimicamente , Feminino , Febre de Causa Desconhecida/prevenção & controle , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/terapia , Humanos , Incidência , Levofloxacino/uso terapêutico , Masculino , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Estudos Retrospectivos , Transplante Autólogo , Uruguai , Adulto Jovem
7.
Transfusion ; 60(3): 575-581, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31975416

RESUMO

BACKGROUND: Administering lower total product volumes with high nucleated cell (NC) concentrations may have the potential benefit of decreasing volume- and dimethyl sulfoxide (DMSO)-related patient complications, while maximizing the laboratory's freezer storage capacity. Our study is a retrospective investigation of the effect of HPC(A) products with cell concentrations greater than 3 × 108 NC/mL on clinical and product outcomes in patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. STUDY DESIGN AND METHODS: A total of 113 consecutive patients with hematological malignancies who underwent autologous PBSC transplantation were included in this retrospective analysis. The primary outcomes were days to initial absolute neutrophil count (ANC) recovery and initial platelet recovery. The secondary outcomes included the storage duration, segment thaw viability, and dose of viable CD34+ cells/kg administered. RESULTS: Of 92 patients and 176 apheresis procedures, 81 patients received HPC(A) products with high NC concentration (4.1 × 108 NC/mL), and 11 patients received low NC concentration products (2.4 × 108 NC/mL). There were no observed differences in clinical outcomes with respect to ANC recovery (14 vs. 14 vs. 12 days) and platelet recovery (16 vs. 16 vs. 15 days) when very high NC (5.2 × 108 NC/mL) and high NC (4.1 × 108 NC/mL) groups were compared to the low NC group (2.4 × 108 NC/mL). CONCLUSION: Our retrospective investigation provides further supporting evidence that HPC(A) products with cell concentration greater than 3 × 108 NC/mL did not show detrimental effects on the clinical outcomes in patients undergoing autologous PBSC transplantation.


Assuntos
Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante Autólogo/métodos , Adulto , Idoso , Remoção de Componentes Sanguíneos/métodos , Criopreservação , Feminino , Neoplasias Hematológicas/terapia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Sci Rep ; 9(1): 19938, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882793

RESUMO

A retrospective cohort study was conducted in Singapore General Hospital to study the safety and efficacy of biosimilar granulocyte-colony stimulating factor (G-CSF) Nivestim for chemo-mobilization of stem cells for autologous stem cell transplant (autoSCT). All patients who underwent an autoSCT between January 2011 and December 2016 were screened for eligibility. A total of 194 patients were screened, and 131 were included. Nivestim was used in 65 patients and the originator G-CSF (Neupogen) in 66. Patient characteristics were similar between both arms except for chemo-mobilization regimen used (p < 0.0001). Mobilization success rates were found to be comparable, at 96.9% (Nivestim) and 97% (Neupogen). Adverse events rates were also similar. Median duration of G-CSF use and hospitalization were both found to be shorter in the Nivestim arm. Median drug acquisition cost per mobilization cycle was significantly lower in the Nivestim arm at $533.40 (range $213.40-$1280.20) as compared to $1261.90 (range $574-$2755.20) in the Neupogen arm (p < 0.0001). No difference was observed for neutrophil and platelet engraftment after autoSCT. Nivestim was found to be safe and non-inferior to Neupogen for chemo-mobilization of stem cells for autoSCT, and associated with lower cost and shorter length of hospitalization.


Assuntos
Filgrastim/farmacologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Medicamentos Biossimilares/farmacologia , Estudos de Coortes , Feminino , Neoplasias Hematológicas/terapia , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Células-Tronco de Sangue Periférico/metabolismo , Estudos Retrospectivos , Transplante de Células-Tronco/métodos , Transplante Autólogo/métodos , Resultado do Tratamento
9.
Sci Rep ; 9(1): 15101, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641163

RESUMO

The development and approval of engineered cellular therapies are revolutionizing approaches to treatment of diseases. However, these life-saving therapies require extensive use of inefficient bioprocessing equipment and specialized reagents that can drive up the price of treatment. Integration of new genetic material into the target cells, such as viral transduction, is one of the most costly and labor-intensive steps in the production of cellular therapies. Approaches to reducing the costs associated with gene delivery have been developed using microfluidic devices to increase overall efficiency. However, these microfluidic approaches either require large quantities of virus or pre-concentration of cells with high-titer viral particles. Here, we describe the development of a microfluidic transduction device (MTD) that combines microfluidic spatial confinement with advective flow through a membrane to efficiently colocalize target cells and virus particles. We demonstrate that the MTD can improve the efficiency of lentiviral transduction for both T-cell and hematopoietic stem-cell (HSC) targets by greater than two fold relative to static controls. Furthermore, transduction saturation in the MTD is reached with only half the virus required to reach saturation under static conditions. Moreover, we show that MTD transduction does not adversely affect cell viability or expansion potential.


Assuntos
Lentivirus/genética , Microfluídica/métodos , Células-Tronco de Sangue Periférico/metabolismo , Transdução Genética/métodos , Células Cultivadas , Vetores Genéticos/genética , Humanos , Microfluídica/instrumentação , Transplante de Células-Tronco de Sangue Periférico/métodos , Transdução Genética/instrumentação
10.
Ann Transplant ; 24: 461-471, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395850

RESUMO

BACKGROUND Graft rejection and graft versus host disease (GvHD) have impeded the success of hematopoietic cell transplantation for severe aplastic anemia (SAA) patients. There is no sufficient data to identify the outcomes of peripheral blood stem cell transplantation (PBSCT) in SAA patients, especially for adult SAA patients. The aim of this study was to evaluate the outcomes of adult SAA patients undergoing PBSCT with the FCA regimen. The FCA regimen includes fludarabine, cyclophosphamide, and anti-thymocyte globulin (ATG). MATERIAL AND METHODS We report our experience with 46 adult SAA patients who underwent PBSCT with the FCA regimen. Thirty SAA patients who received only cyclophosphamide and ATG (CA) regimen were used as controls. Complications and survival outcomes were evaluated and compared. RESULTS There was a significantly higher percentage of patients who achieved >95% donor chimerism by day 30 in the FCA group. The 5-year event-free survival (EFS) rate in the FCA group was higher than that in the CA group (95.4% versus 73.3%). In addition, the 5-year rejection rate (RR) in the FCA group was lower than that in the CA group (4.6% versus 23.6%). A multivariable model identified the FCA regimen as an independent factor affecting EFS and RR. However, GvHD and serious infection did not differ between the 2 groups. For patients with an unrelated donor, the FCA regimen had a higher EFS and a lower RR than the CA regimen. CONCLUSIONS The FCA regimen for PBSCT in adult SAA patients compared favorably to the CA regimen. It can improve EFS and reduce graft rejection, especially for unrelated donor PBSCT.


Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Anemia Aplástica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vidarabina/uso terapêutico , Adulto Jovem
11.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269755

RESUMO

Hoyeraal-Hreidarsson syndrome (HHS), caused by several different germline mutations resulting in severe telomeropathy, presents with early-onset growth anomalies and neurologic/developmental disorders including characteristic cerebellar hypoplasia. Early mortalities may arise from immunodeficiency and bone marrow failure if not successfully salvaged by allogeneic hematopoietic stem cell transplantation (HSCT). Few reports have characterized the persistent somatic progression of HHS after successful HSCT. We present an HHS patient with an X-linked recessive DKC1 c.1058C > T; Ala353Val mutation who successfully underwent unrelated HSCT at 5 years of age. After months of early infections and organ toxicities immediately post-transplant, he had more than two years of excellent quality of life with correction of bone marrow failure and immunodeficiency. However, episodic massive variceal bleeding and progressive respiratory insufficiency, which were secondary to non-cirrhotic portal hypertension and pulmonary arteriovenous shunts, respectively, developed over 2 years after HSCT and resulted in his death from respiratory failure 4 years after HSCT. This outcome suggests that while HSCT can correct bone marrow failure and immunodeficiency, it may fail to prevent or even aggravate other fatal processes, such as portal hypertension and pulmonary arteriovenous shunting.


Assuntos
Proteínas de Ciclo Celular/genética , Disceratose Congênita/terapia , Retardo do Crescimento Fetal/terapia , Deficiência Intelectual/terapia , Microcefalia/terapia , Proteínas Nucleares/genética , Transplante de Células-Tronco de Sangue Periférico , Pré-Escolar , Disceratose Congênita/complicações , Disceratose Congênita/genética , Disceratose Congênita/patologia , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/patologia , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Microcefalia/complicações , Microcefalia/genética , Microcefalia/patologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Mutação Puntual
12.
Cytotherapy ; 21(8): 886-894, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31253496

RESUMO

BACKGROUND: Association between low counts of herpesvirus-specific T cells and subsequent relapse of hematologic malignancy has been shown in two retrospective studies. METHODS: Here we present results of a prospective validation study. Multiple subsets of Epstein-Barr virus (EBV)-specific T cells were measured in 69 patients on day 56 and 84, using intracellular flow cytometry after incubation of blood mononuclear cells (MNCs) with EBV peptides or lysate. RESULTS: All EBV T-cell subsets measured, both on day 56 and 84, were lower in patients who did versus did not subsequently relapse. This was most significant for day 56 EBV lysate-stimulated CD8 T cells producing interferon-gamma. Patients with day 56 counts of this subset >5/µL had a significantly lower likelihood of relapse compared with those with ≤5/µL (subhazard ratio, 5.7; P = 0.007). Similar significant associations were shown for a total of seven EBV T-cell subsets on day 56 and nine subsets on day 84. However, sensitivity and specificity of relapse prediction using the count of any subset was low (area under the curve of receiver-operator characteristic curve was <0.8). DISCUSSION: In conclusion, the association between EBV T-cell counts and subsequent relapse is valid. However, its clinical utility appears to be limited.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Subpopulações de Linfócitos T/virologia , Transplante Homólogo/efeitos adversos , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Criopreservação , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Herpesvirus Humano 4/imunologia , Humanos , Incidência , Interferon gama/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Estudos Prospectivos , Curva ROC , Subpopulações de Linfócitos T/imunologia , Doadores de Tecidos , Resultado do Tratamento , Adulto Jovem
13.
Tissue Eng Regen Med ; 16(3): 311-324, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31205859

RESUMO

Background: In recent years, researchers discovered that menstrual blood-derived stem cells (MenSCs) have the potential to differentiate into a wide range of tissues including the chondrogenic lineage. In this study, we aimed to investigate the effect of MenSCs encapsulated in fibrin glue (FG) on healing of osteochondral defect in rabbit model. Methods: We examined the effectiveness of MenSCs encapsulated in FG in comparison with FG alone in the repair of osteochondral defect (OCD) lesions of rabbit knees after 12 and 24 weeks. Results: Macroscopical evaluation revealed that the effectiveness of MenSCs incorporation with FG is much higher than FG alone in repair of OCD defects. Indeed, histopathological evaluation of FG + MenSCs group at 12 weeks post-transplantation demonstrated that defects were filled with hyaline cartilage-like tissue with proper integration, high content of glycosaminoglycan and the existence of collagen fibers especially collagen type II, as well as by passing time (24 weeks post-transplantation), the most regenerated tissue in FG + MenSCs group was similar to hyaline cartilage with relatively good infill and integration. As the same with the result of 12 weeks post-implantation, the total point of microscopical examination in FG + MenSCs group was higher than other experimental groups, however, no significant difference was detected between groups at 24 weeks (p > 0.05). Conclusion: In summary, MenSCs as unique stem cell population, is suitable for in vivo repair of OCD defects and promising for the future clinical application.


Assuntos
Cartilagem Articular/cirurgia , Adesivo Tecidual de Fibrina/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/métodos , Engenharia Tecidual/métodos , Adulto , Animais , Cartilagem Articular/patologia , Condrócitos/transplante , Colágeno Tipo II/farmacologia , Feminino , Glicosaminoglicanos , Humanos , Cartilagem Hialina , Joelho , Pessoa de Meia-Idade , Coelhos , Células-Tronco , Tecidos Suporte , Cicatrização
14.
Ann Transplant ; 24: 367-373, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31221952

RESUMO

BACKGROUND Data about application of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) on patients with high-risk or intermediate-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are lacking. In this study, we report the outcomes of using unmanipulated haploidentical allogeneic peripheral blood stem cell transplantation (haplo-PBSCT) as post-remission therapy for patients with high-risk or intermediate-risk AML in CR1. MATERIAL AND METHODS From January 2008 to July 2016, 33 patients diagnosed as high-risk or intermediate-risk AML in CR1 undergoing haplo-PBSCT in our institution were enrolled for analysis. The cumulative incidence of platelet and neutrophil recovery, the occurrence of acute graft-versus-host-disease (GVHD) and chronic GVHD, relapse and non-relapse mortality were assessed. Patients' survival rates were estimated using the Kaplan-Meier method. RESULTS The cumulative incidence of grade 2-4 acute GVHD, overall and extensive chronic GVHD was 18.2%, 9.1%, and 6.1%, respectively. 2-year probability of relapse was 9.1%. Disease-free survival and overall survival at 2 years were 72.7% and 75.8%, respectively. CONCLUSIONS Our results showed that unmanipulated haploidentical transplantation with G-CSF primed PBSC alone as a graft source could be an acceptable alternative post-remission treatment for high-risk or intermediate-risk AML patients in CR1 lacking a matched donor.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mieloide Aguda/cirurgia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Taxa de Sobrevida , Adulto Jovem
15.
Cytotherapy ; 21(6): 612-618, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31056424

RESUMO

INTRODUCTION: Cell damage inescapably occurs during both the freezing and the thawing graft processes for autologous hematopoietic stem cell (HSC) transplantation. To estimate HSC injury, a quality control is performed including: (i) CD34+ quantification; (ii) percentage of CD34+ viability and (iii) evaluation of HSC functional ability to form colony forming unit-granulocyte macrophage (CFU-GM). Apoptosis involves complex pathways such as caspase enzymes. Here, we assess the extent of apoptosis that is caspase-dependent before and after cryoconservation of CD34+, using a Fluorescent Labeled Inhibitor of CAspases (FLICA). METHODS: Caspase pathway activation status was evaluated in 46 patients (multiple myeloma [n = 24], lymphoma [n = 22]), by flow cytometry, using a 7-aminoactinomycin-D (7AAD)/FLICA staining test, in CD34+, CD3+, CD14+ and CD56+ cells. Viable 7AAD-/FLICA+ cells were then correlated with various parameters. RESULTS: We showed a significant caspase pathway activation, with 23% CD34+/7AAD-/FLICA+ cells after thawing, compared with the 2% described in fresh CD34+ cells (P < 0.0001). Moreover, caspase pathway was significantly activated in thawing CD3+, CD56+ and CD14+ cells. We also report a significant correlation between the rate of CD34+/7AAD-/FLICA+ cells and post-thawing granulocytes count (P = 0.042) and their potential to be differentiated into CFU-GM (P = 0.004). DISCUSSION: Our results show substantial cell death, induced by the increase of caspase pathway activation, secondary to the thawing process, and across all study cell types. This observation may affect the immune response quality during recipient aplasia, without detecting a clinical impact. Moreover, caspase pathway activation through CD3+ and CD56+ subpopulations could modify the therapeutic result of donor lymphocytes infusion (DLI).


Assuntos
Antígenos CD34/metabolismo , Criopreservação/métodos , Granulócitos/fisiologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/citologia , Adolescente , Adulto , Idoso , Apoptose/fisiologia , Autoenxertos , Caspases/metabolismo , Feminino , Citometria de Fluxo , Granulócitos/citologia , Humanos , Linfoma/patologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Células-Tronco de Sangue Periférico/fisiologia , Transplante Autólogo , Adulto Jovem
16.
Stem Cells Transl Med ; 8(8): 822-832, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31037857

RESUMO

We previously demonstrated that intracardiac delivery of autologous peripheral blood-derived CD34+ stem cells (SCs), mobilized by granulocyte-colony stimulating factor (G-CSF) and collected by leukapheresis after myocardial infarction, structurally and functionally repaired the damaged myocardial area. When used for cardiac indication, CD34+ cells are now considered as Advanced Therapy Medicinal Products (ATMPs). We have industrialized their production by developing an automated device for ex vivo CD34+ -SC expansion, starting from a whole blood (WB) sample. Blood samples were collected from healthy donors after G-CSF mobilization. Manufacturing procedures included: (a) isolation of total nuclear cells, (b) CD34+ immunoselection, (c) expansion and cell culture recovery in the device, and (d) expanded CD34+ cell immunoselection and formulation. The assessment of CD34+ cell counts, viability, and immunophenotype and sterility tests were performed as quality tests. We established graft acceptance criteria and performed validation processes in three cell therapy centers. 59.4 × 106 ± 36.8 × 106 viable CD34+ cells were reproducibly generated as the final product from 220 ml WB containing 17.1 × 106 ± 8.1 × 106 viable CD34+ cells. CD34+ identity, genetic stability, and telomere length were consistent with those of basal CD34+ cells. Gram staining and mycoplasma and endotoxin analyses were negative in all cases. We confirmed the therapeutic efficacy of both CD34+ -cell categories in experimental acute myocardial infarct (AMI) in immunodeficient rats during preclinical studies. This reproducible, automated, and standardized expansion process produces high numbers of CD34+ cells corresponding to the approved ATMP and paves the way for a phase I/IIb study in AMI, which is currently recruiting patients. Stem Cells Translational Medicine 2019;8:822&832.


Assuntos
Antígenos CD34/genética , Automação Laboratorial/métodos , Citometria de Fluxo/métodos , Infarto do Miocárdio/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/citologia , Adulto , Animais , Antígenos CD34/metabolismo , Células Cultivadas , Ensaios Clínicos como Assunto , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/metabolismo , Cultura Primária de Células/métodos , Ratos
17.
Transfus Apher Sci ; 58(2): 192-195, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30928229

RESUMO

OBJECTIVE: Reliable and pratique methods are essential for rapid and accurate determination of post thawing viability of peripheral blood stem cell (PBSC) graft before hematopoietic stem cell transplantation. In this study, Trypan Blue (TP) Eosin Y (EO), and Acridine-orange-ethidium bromide (AO/EB), which are of the methods commonly used for the assessment of viability in clinic practice, were compared with the flow cytometry-7AAD (7AAD) method, which is a more sensitive method. The aim of this study is to examine which method evaluates postthawing viability in a more compatible manner with 7AAD. MATERIALS-METHODS: Postthawing viability rates were examined simultaneously by means of four different methods before hematopoietic stem cell transplantation in a total of 20 PBSC graft. The results obtained from the AO/EB, TP, EO methods were evaluated with the flow cytometry-7AAD in terms of concordance. RESULTS: The AO / EB was determined to be the method having the best concordance with the flow cytometry-7AAD method. Although, at a lower level compared to the AO/EB method, the EO method had a statistically significant concordance with the flow cytometry-7AAD method. No statistically significant concordance was detected between the TP method and 7AAD method in terms of viability results. CONCLUSION: The AO/EB method was identified to be the method having the best compatibility with the flow cytometry -7AAD method in showing the viability of the cryopreserved PBSC graft. In the viability assessment of PBCS graft using light microscopy, the EO may be preferred since is more sensitive compared to the TP method.


Assuntos
Criopreservação/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Humanos
18.
Biol Reprod ; 101(1): 91-101, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31034039

RESUMO

Peripheral blood mononuclear cells (PBMCs) are rich in hematopoietic cells and mesenchymal stem cells. Platelet-rich plasma (PRP) is rich in various growth factors. PBMCs and PRP have been suggested, individually, to restore ovarian function by improving the local microenvironment. The current study investigated the effect of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMCs combined with PRP on restoring ovarian function in rats with primary ovarian insufficiency (POI). Thirty adult female rats were randomly subdivided into five groups: normal control (control), cyclophosphamide (CTX) plus subsequent PBS (POI + PBS), CTX plus subsequent PRP (POI + PRP), CTX plus subsequent G-CSF-mobilized PBMCs (POI + PBMCs), and CTX plus subsequent G-CSF-mobilized PBMCs combined with PRP (POI + PBMCs + PRP). CTX exposure induced the typical POI phenotype with increased diestrus; shortened estrus; follicle arrest at all stages; decreased serum levels of estradiol-17ß (E2) and anti-Mullerian hormone (AMH); and increased levels of follicle-stimulating hormone (FSH). Transplantation of mobilized PBMCs with PRP resulted in a much earlier restoration of the estrous cycle, sex hormone levels, and preantral follicle growth in POI rats. Expression of the male-specific Sry gene in the ovarian tissues of POI + PBMCs + PRP female recipient rats was evident at 5, 10, and 20 days posttransplantation along with significant increases in the expression of angiogenesis markers CD34+ and VEGF and folliculogenesis markers AMH and FSHR. Additionally, PBMCs in combination with PRP mitigated granulosa cell apoptosis by downregulating BAX and upregulating BCL-2. These results demonstrate that G-CSF-mobilized PBMCs combined with PRP accelerate the restoration of ovarian function in POI rats by increasing ovarian neovascularization, reducing granulosa cell apoptosis, and promoting folliculogenesis.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucócitos Mononucleares/transplante , Ovário/fisiologia , Plasma Rico em Plaquetas/fisiologia , Insuficiência Ovariana Primária/terapia , Animais , Terapia Combinada , Ciclofosfamida , Feminino , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Transplante de Células-Tronco de Sangue Periférico/métodos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(12): e14786, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896621

RESUMO

RATIONALE: Granulocyte colony-stimulating factor (G-CSF) is most frequently used in healthy donors to mobilize progenitor cells into the peripheral blood for collection. While mild thrombocytopenia is common in allogeneic peripheral blood stem cell transplant donors after G-CSF mobilization, serious thrombocytopenia is rarely reported. Herein, we report a case of severe thrombocytopenia caused by G-CSF in a 14-year-old healthy donor and review the relevant literature. To our knowledge, this is the first reported case of severe thrombocytopenia caused by G-CSF in a healthy adolescent donor. PATIENT CONCERNS: A 14-year-old sister of a girl with T lymphocyte leukemia was selected as a matched donor for transplantation. The donor was healthy with normal blood parameters. DIAGNOSES: The donor received 10 µg/kg/day G-CSF via subcutaneous injection. On day 4 of G-CSF administration, blood tests before stem cell collection indicated that platelets dropped to 51 g/L. Abdominal ultrasound showed that the spleen was mildly enlarged. INTERVENTIONS: In order to prevent blood loss and other effects caused by a too low platelet count after collection, the donor's peripheral blood hematopoietic stem cells were collected after platelet transfusion. OUTCOMES: Checkups for 1 year after G-CSF administration showed normal blood parameters. LESSONS: Due to the rare risk of severe thrombocytopenia in G-CSF mobilization, it is necessary to routinely monitor blood parameters during mobilization to ensure smooth progress of the transplantation process.


Assuntos
Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Doadores Vivos , Irmãos , Trombocitopenia/induzido quimicamente , Adolescente , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Leucemia de Células T/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos
20.
Clin Gastroenterol Hepatol ; 17(6): 1175-1182.e2, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30613001

RESUMO

BACKGROUND & AIMS: Peripheral blood stem cells (PBSCs) mobilized with colony-stimulating factor can promote liver regeneration and increase liver function in patients with liver diseases. However, the long-term effects of stem cell treatments on survival and risk of hepatocellular carcinoma (HCC) in patients with cirrhosis have not been determined. We investigated the long-term effects of autologous stem cell transplantation and risk of HCC in patients with cirrhosis. METHODS: We performed a retrospective analysis of 2 cohorts of patients with decompensated cirrhosis who received transplantations of autologous PBSCs (n = 282) or standard medical treatment (SMT, n = 286) in China from January 1, 2006, through December 31, 2016. Patients were followed up until death or liver transplantation. Mortality data were obtained by case records and confirmed by telephone calls. Survival time was calculated and HCC was confirmed by computed tomography or ultrasound. We used propensity score matching to adjust the differences between the 2 groups. Survival and incidence of HCC were analyzed and Cox proportional hazard regression was used to determine the prognostic factors. RESULTS: After propensity score matching, time of survival was significantly higher in the PBSC group than the SMT group (P = .001). The adjusted rate of 5-year survival was 71.2% in the PBSC group and 52.1% in the SMT group. The overall incidence of HCC did not differ significantly between the PBSC and SMT groups (21.1% vs 20.4%; P = .999). Significant improvement of liver functions was observed at 1 year, 2 years, 3 years, and 5 years after PBSC transplantation compared with the SMT group. CONCLUSIONS: In a long-term analysis of patients with decompensated cirrhosis, autologous transplants of PBSCs significantly improved long-term survival compared with a control group. PBSC transplant did not appear to increase the risk of HCC.


Assuntos
Cirrose Hepática/terapia , Regeneração Hepática/fisiologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Pontuação de Propensão , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Tomografia Computadorizada por Raios X , Transplante Autólogo , Resultado do Tratamento
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