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2.
Eur Spine J ; 28(6): 1455-1460, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30406405

RESUMO

INTRODUCTION: Vertebral involvement is found in a high percentage of multiple myeloma (MM) patients, often requiring multilevel surgical treatment to reduce pain and disability and to receive prompt access to oncological care. We describe the clinical use of washout technique for multilevel vertebroplasty in MM patients with diffuse spinal involvement. The aim of this technique is to reduce the risk of pulmonary fat embolism after cement injection and possibly to increment the amount of cement and treated levels in one surgical stage. METHODS: Three patients were treated with the washout technique prior to multilevel vertebroplasty for thoracolumbar diffuse spinal involvement in multiple myeloma. We describe the surgical technique and review the pertinent literature. RESULTS: The technique is clinically safe and effective in reducing pain, without significant complications. Two six-level vertebroplasties were performed in one case, allowing a larger amount of cement injected and a prompt start of the oncological treatment. CONCLUSIONS: Multilevel vertebroplasty in MM patients with diffuse spinal involvement carries the advantages of reducing pain, avoid repeated surgeries and faster return to oncological regimen. Cardiovascular complications, including pulmonary embolism, are rare but can have fatal consequences. It is mainly due to bone marrow mobilization during cement injection and the risk increases with the amount of cement injected and the number of treated levels. Despite multilevel treatment at the same stage, we did not observe any significant complication in our series. Further studies are needed to confirm the preliminary results of this technique. These slides can be retrieved under electronic supplementary material.


Assuntos
Purging da Medula Óssea , Mieloma Múltiplo/terapia , Neoplasias da Coluna Vertebral/terapia , Vertebroplastia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
3.
Tumori ; 101(1): 2-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25702654

RESUMO

High-dose chemotherapy in lymphomas, and mainly non-Hodgkin's lymphomas, has been advancing since the 1970s. This therapeutic strategy is based on the supposed existence of a dose-response curve for cytotoxic agents. However, the available data are contradictory, so high-dose chemotherapy cannot be guaranteed as consolidation treatment for first-remission follicular lymphoma or diffuse large cell lymphoma. The objective of this paper is to review the current knowledge about high-dose chemotherapy followed by hematopoietic stem cell transplantation in follicular non-Hodgkin's lymphoma. The published studies on follicular lymphoma after first remission, recurrent follicular lymphoma, and transformed follicular ­lymphoma were assessed together with the data available on diffuse large cell lymphoma. During analysis of the studies, difficulties were encountered in comparing studies due to the heterogeneous nature of the data. High-dose chemotherapy as consolidation treatment after first remission or in recurrent or refractory disease was also analyzed.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Fatores Imunológicos/uso terapêutico , Linfoma Folicular/terapia , Terapia Neoadjuvante/métodos , Purging da Medula Óssea , Ensaios Clínicos como Assunto , Esquema de Medicação , Medicina Baseada em Evidências , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/cirurgia , Recidiva , Rituximab , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
4.
Vet Clin Pathol ; 44(2): 188-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25627833

RESUMO

BACKGROUND: Volume reduction and RBC depletion of equine bone marrow specimens are necessary processing steps for the immediate therapeutic use of bone marrow (BM)-derived mesenchymal stem cells (MSC), and for MSC expansion in culture. OBJECTIVES: The purpose of the study was to evaluate the ability of the PrepaCyte-CB processing system to reduce volume, deplete RBC, and recover mononuclear cells (MNC) from equine BM specimens. METHODS: One hundred and twenty mL of heparinized BM were obtained from each of 90 horses. A CBC was performed on the BM pre- and post-PrepaCyte-CB processing. Volume and RBC reduction, and total nucleated cell (TNC) and MNC recoveries were determined. RESULTS: Bone marrow volume was reduced from 120 mL to 21 mL with a median RBC depletion of 90.1% (range, 62.0-96.7%). The median preprocessing total TNC count was 2.2 × 10(9) (range, 0.46-7.9 × 10(9)) and the median postprocessing TNC count was 1.7 × 10(9) (range, 0.3-4.4 × 10(9); P < .0001), with a median recovery of 73.5% (range, 22.4-216.7%). The median preprocessing total MNC count was 0.9 × 10(9) (range, 0.1-4.7 × 10(9)) and median postprocessing total MNC count was 0.8 × 10(9) (range, 0.1-2.7 × 10(9); P = .06), with a median recovery of 83.7% (range, 15.4-413.9%). CONCLUSIONS: The PrepaCyte-CB processing system can be used to deplete both volume and RBC, and recover MNC from equine BM specimens. Further studies assessing the viability of MSC and the efficacy of MSC expansion after using the PrepaCyte-CB processing system are warranted.


Assuntos
Purging da Medula Óssea/veterinária , Medula Óssea/química , Separação Celular/veterinária , Eritrócitos/citologia , Cavalos/fisiologia , Leucócitos Mononucleares/citologia , Animais , Purging da Medula Óssea/instrumentação , Separação Celular/instrumentação , Contagem de Eritrócitos/veterinária , Volume de Eritrócitos/veterinária , Eritrócitos/fisiologia , Leucócitos Mononucleares/fisiologia , Manejo de Espécimes
5.
Genet Mol Res ; 14(4): 18287-92, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26782476

RESUMO

We investigated the roles of CD3McAb and rhIL-2 activated bone marrow in the killing and purging of leukemia cells. Cytotoxicity of activated bone marrow was detected with MTT assay. CFU-GM level in activated bone marrow and the destruction of leukemia cells were measured using the semi-solid cell culture. Immune activation markers in activated bone marrow were detected by indirect immunofluorescence assay. Bone marrow activated by CD3McAb and rhIL-2 displayed significantly upregulated the killing and purging abilities on the leukemia cell line K562 and HL-60. Such effects were superior to that of bone marrow activated by rhIL-2 or CD3McAb alone (P < 0.05, P < 0.01). Activation by rhIL-2 and (or) CD3McAb exerted no obvious influence on CFU-GM level in bone marrow. Compared with bone marrow activated by rhIL-2 or CD3McAb alone, the synergistic effect of both CD3McAb+ and hIL-2 caused significant increase of CD3(+), CD8(+), CD19(+), CD25(+), CD38(+), and CD56(+) levels. Our study indicates that CD3McAb enhanced the killing and purging effects of rhIL-2 activated bone marrow on leukemia cells.


Assuntos
Anticorpos Monoclonais/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Purging da Medula Óssea , Interleucina-2/farmacologia , Adolescente , Adulto , Anticorpos Monoclonais/imunologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Purging da Medula Óssea/métodos , Transplante de Medula Óssea , Complexo CD3/imunologia , Complexo CD3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Feminino , Células Progenitoras de Granulócitos e Macrófagos , Células HL-60 , Humanos , Imunofenotipagem , Células K562 , Leucemia/metabolismo , Leucemia/patologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
6.
Strahlenther Onkol ; 190(5): 453-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24595415

RESUMO

PURPOSE: The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome. PATIENTS AND METHODS: A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of 2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported. RESULTS: Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72%, respectively. In all, 29% (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22%, and 60 and 52.7%, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30%). In addition, 15.5% (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28%); 12 of 110 patients (11%) presented with symptoms from osteoporosis, 5 of 110 patients (4.5%) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11% reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented. CONCLUSION: Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic breadth.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Irradiação Corporal Total , Adulto , Purging da Medula Óssea , Terapia Combinada , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Lesões por Radiação/etiologia , Lesões por Radiação/mortalidade , Estudos Retrospectivos
7.
Br J Haematol ; 164(4): 555-64, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24266323

RESUMO

The major limitation of autologous stem cell transplantation (auto-SCT) in non-Hodgkin lymphoma (NHL) is relapse. Although autologous graft contamination may be a potential cause, prior purging of the autograft remains controversial. Therefore, we retrospectively analysed 56 consecutive patients with NHL receiving auto-SCT at complete (n = 41) or partial remission (n = 15). Among them, 24 patients underwent autograft manipulation with positive selection of CD34(+) cells using a CliniMACS device (purged group). Twenty-five patients had received ≥2 previous chemotherapy regimens before auto-SCT. After a median follow-up of 41·4 months, transplant-related mortality was observed only in unpurged group (n = 2; 3·6%). The 3-year overall survival (91·7% vs. 56·1%, P = 0·009) and progression-free survival (78·7% vs. 53·1%, P = 0·034) favoured CD34(+) purification. While neutrophil recovery was similar, platelet recovery was delayed in the purged group. Cytomegalovirus reactivation was predominantly observed in the purged group, although no other clinically unmanageable infectious complications occurred. Although this study has the inevitable limitations of heterogeneity in previous treatment and NHL subtypes, and a small number of patients analysed, the high survival rate in the purged group may suggest the need for prospective randomized trials to determine the role of CD34(+) purification in auto-SCT for NHL.


Assuntos
Antígenos CD34/imunologia , Purging da Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/cirurgia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Antígenos CD34/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
8.
Bone Marrow Transplant ; 49(1): 80-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23974608

RESUMO

Autologous stem cell rescue (ASCT) following high-dose myeloablative chemotherapy is considered to be a therapeutic option for many multiple myeloma (MM) patients; however relapse post ASCT presents a major challenge. The oncolytic potential of reovirus has been previously demonstrated and is currently undergoing phase I monotherapy clinical trials for MM and phase II/III clinical trials for solid tumors. Here we tested the hypothesis that reovirus can successfully purge MM in a murine model that partially recapitulates human MM. RPMI 8226, MM1S, H929 and U266 human myeloma cell lines were exposed to reovirus and oncolysis was assessed. Apheresis product admixed with MM cells was purged with live reovirus (LV) or dead virus (DV) and purging efficacy was monitored via flow cytometry, reverse transcribed-PCR (RT-PCR) and disease relapse in non obese diabetic/severe combined immune deficient (NOD/SCID) mice. Significant LV purging was seen with MM1S, H929 and U266 and the complete ex vivo purging achieved with RPMI 8226 was confirmed by flow cytometry, RT-PCR and absence of disease relapse in vivo. Mice that received LV-purged autografts exhibited 100% survival in comparison to mice that received DV-purged controls. Reovirus's unique ability to kill MM while sparing hematopoietic stem cells places it as an attractive purging agent for MM during ASCT.


Assuntos
Purging da Medula Óssea/métodos , Mieloma Múltiplo/terapia , Terapia Viral Oncolítica , Reoviridae , Animais , Remoção de Componentes Sanguíneos , Linhagem Celular , Linhagem Celular Tumoral , Citometria de Fluxo , Proteínas de Fluorescência Verde/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento
9.
Clin J Pain ; 30(9): 787-99, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24042348

RESUMO

OBJECTIVES: Treatment for childhood leukemia requires frequent lumbar punctures (LP) and bone marrow aspirations (BMA), often described by children and parents as more distressing than the disease itself. Findings in schoolchildren and chronic pain samples indicate that increased parental distress may increase parental protective, pain-attending behavior, which is associated with more child pain and distress. However, in the context of invasive medical procedures, it is unknown which parents are likely to become most distressed and engage in pain-attending behavior, and how this impacts the children's experiences. The present study investigated the impact of parental catastrophic thoughts upon parental distress and pain-attending behavior (verbal and nonverbal). Furthermore, the association between parental responses and the children's pain behavior, pain, and distress was examined. MATERIALS AND METHODS: A total of 46 parents of children with leukemia (range, 0.6 to 15 y) who underwent a LP/BMA procedure participated in this study. Parental catastrophizing was assessed before and parental and child distress was assessed after the LP/BMA procedure. Parental pain-attending behavior and the child's pain behavior were observed before and after the LP/BMA procedure. RESULTS: Findings indicated that heightened parental catastrophic thinking contributed to increased parental distress during LP/BMA and less pain-attending behavior before the LP/BMA procedure, especially in young children. In contrast, heightened distress in parents with high levels of catastrophizing contributed to increased engagement in postprocedural pain-attending behavior. For young children, increased preprocedural pain-attending behavior was related to more child distress, pain, and pain behavior. DISCUSSION: The findings demonstrate the importance of parental catastrophic thinking in understanding their caregiving responses and preparing parents and children for painful invasive medical procedures.


Assuntos
Catastrofização , Leucemia/fisiopatologia , Dor/fisiopatologia , Pais/psicologia , Estresse Psicológico , Adolescente , Adulto , Fatores Etários , Purging da Medula Óssea/efeitos adversos , Purging da Medula Óssea/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia/psicologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/psicologia , Relações Pais-Filho , Punção Espinal/efeitos adversos , Punção Espinal/psicologia , Adulto Jovem
13.
Pediatr Int ; 55(3): e52-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23782379

RESUMO

Bone marrow (BM) transplantation (BMT) is one of the treatment strategies for congenital metabolic disease, but leukemia secondary to intensive cytoreductive treatment is a major concern. Besides BM cells, mesenchymal stem cells (MSC) are also used for transplantation. An 8-month-old girl with hypophosphatasia underwent transplantation of haploidentical BM cells followed by two transplants of MSC obtained from her father to facilitate osteogenesis. Fludarabine(Flu)/cyclophosphamide (CPA)/anti-thymocyte globulin were used for myeloablative conditioning, but the patient developed therapy-related leukemia harboring t(9;22)(q34;q11.2); minor BCR-ABL (t-leukemia with Ph) at the age of 32 months. At the age of 40 months she underwent a second BM and third MSC transplant from the same donor. Thereafter, she achieved complete histological and molecular remission. The present case suggests that the combination of cytotoxic agents (Flu/CPA) and MSC led to t-leukemia with Ph as a consequence of chromosome instability and suppression of host anti-tumor immunity.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Hipofosfatasia/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Purging da Medula Óssea/efeitos adversos , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Retratamento , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados
14.
Pediatr Int ; 55(3): e56-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23782380

RESUMO

Philadelphia chromosome-positive acute lymphoblastic leukemia has a poor prognosis, even in pediatric patients. Although imatinib-containing chemotherapy can reportedly improve early event-free survival, allogeneic hematopoietic stem cell transplantation is still considered to be the main curative treatment option. Dasatinib, a novel abl tyrosine kinase inhibitor, is being used for the treatment of relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia and is reported to have excellent efficacy. We used dasatinib after bone marrow transplantation prior to the anticipated relapse for the purpose of prophylaxis against relapse. After discontinuation of dasatinib administration, molecular remission has lasted for 7 months. Although preventive use of dasatinib is as yet uncommon, we consider that dasatinib may eradicate the minimal residual disease and prevent recurrence, and it is feasible to administer and appears to be safe. Further studies are needed to confirm our experience in this case.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Tiazóis/uso terapêutico , Purging da Medula Óssea , Criança , Dasatinibe , Relação Dose-Resposta a Droga , Esquema de Medicação , Seguimentos , Humanos , Assistência de Longa Duração , Masculino , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Prevenção Secundária , Tiazóis/efeitos adversos
16.
J Clin Oncol ; 31(13): 1624-30, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23547078

RESUMO

PURPOSE: The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma (FL). PATIENTS AND METHODS: Patients with relapsed FL who achieved either complete or very good partial remission with salvage chemotherapy were randomly assigned using a factorial design to rituximab purging (P+; 375 mg/m(2) once per week for 4 weeks) or observation (NP) before HDC-ASCT and to maintenance rituximab (M+; 375 mg/m(2) once every 2 months for four infusions) or observation (NM). RESULTS: From October 1999 to April 2006, 280 patients were enrolled. The median age was 51 years (range, 26 to 70 years), and baseline characteristics were well balanced between groups. On average, patients were 44 months (range, 3 to 464 months) from diagnosis, with 79% having received two lines and 15% three lines of prior therapy. Median follow-up was 8.3 years. In contrast to purging, 10-year progression-free survival (PFS) was 48% for P+ and 42% for NP groups (hazard ratio [HR], 0.80; 95% CI, 0.58 to 1.11; P = .18); maintenance had a significant effect on PFS (10-year PFS, 54% for M+ and 37% for NM; HR, 0.66; 95% CI, 0.47 to 0.91; P = .012). Overall survival (OS) was not improved by either rituximab purging or maintenance. CONCLUSION: Rituximab maintenance after HDC-ASCT is safe and significantly prolongs PFS but not OS in patients undergoing transplantation for relapsed FL. Pretransplantation rituximab in vivo purging, even in rituximab-naive patients, failed to improve PFS or OS.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Purging da Medula Óssea/métodos , Linfoma Folicular/terapia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Linfoma Folicular/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Rituximab , Terapia de Salvação , Transplante Autólogo
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(4): 842-6, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22931639

RESUMO

The objective of this study was to investigate the effect of a novel Zinc phthalocyanine (ZnPcH(1)) based photodynamic therapy (PDT) on acute monocytic leukemia cell lines SHI-1 and its mechanism, so as to provide theory basis for bone marrow purging in vitro for patients with leukemia. The killing effect of ZnPcH(1)-PDT on SHI-1 cells were assessed by MTT method; the SHI-1 cell death patterns were analyzed by AO/EB fluorescence staining, TdT-mediated dUTP nick end labeling (TUNEL), DNA ploidy analysis, and Annexin V-FITC/PI double staining.Cell mixture was established by integrating SHI-1 cells with normal bone marrow MNC (by 1:100-1:10 000). Purging effect of ZnPcH(1)-PDT against SHI-1 mixed into normal MNC was assessed by analyzing the expression of fusion gene MLL/AF6 mRNA using nested RT-PCR. The results showed that ZnPcH(1)-PDT could effectively inhibit SHI-1 cell proliferation in dose-dependent manner, and ZnPcH(1)-PDT could induce cell apoptosis in time-dependent manner. 0.5 µmol/L ZnPcH(1)-PDT could completely photoinactivated kill SHI-1 cells in the simulated remission bone marrow. It concluded that ZnPcH(1)-PDT may be a effective and convenient promising purging technique for leukemia.


Assuntos
Indóis/farmacologia , Leucemia Monocítica Aguda/patologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Purging da Medula Óssea/métodos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/uso terapêutico , Isoindóis , Leucemia Monocítica Aguda/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Compostos de Zinco
18.
Vet Clin Pathol ; 40(4): 444-449, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22092275

RESUMO

BACKGROUND: The therapeutic use of bone marrow-derived mononuclear cells (MNCs) and mesenchymal stem cells for the treatment of soft tissue and orthopedic injuries in equine patients is expanding. After collection, bone marrow must be reduced in volume and depleted of RBCs for immediate therapeutic use or to prepare cells for culture or cryopreservation and storage. The MarrowXpress (MXP) System is an automated, closed, sterile system designed to process human bone marrow samples. OBJECTIVES: The purpose of this study was to evaluate the capacity of the MXP System to process equine bone marrow to reduce volume, deplete RBCs, and enhance recovery of MNCs. METHODS: Bone marrow was collected from 47 horses into 2 60-mL syringes containing heparin and processed using the MXP System. HCT, total nucleated cell (TNC) count, and MNC count were obtained for each sample before and after processing using an Advia 120 hematology analyzer. Volume reduction, RBC depletion, and recovery of TNCs and MNCs were calculated. RESULTS: For equine bone marrow samples, mean values were 73.2% for RBC depletion and 78.0% for volume reduction. TNC count before processing was 2.5 ± 1.2 × 10(7) and after processing was significantly higher at 7.8 ± 3.3 × 10(7) (P < .0001), with a recovery of 68.5 ± 24.5% (mean ± SD). MNC count before processing was 1.1 ± 0.9 × 10(7) and after processing was significantly higher at 3.8 ± 1.9 × 10(7) (P < .0001), with a recovery 73.0 ± 31.5%. CONCLUSIONS: The MXP System can reliably reduce volume and deplete RBCs from aspirates of equine bone marrow aspirates. MNCs can be recovered in a reproducible and sterile manner. Further studies evaluating the effects of the MXP System on cell viability, identification of mesenchymal stem cells (MSCs), and the efficacy of MSC expansion are warranted.


Assuntos
Purging da Medula Óssea/veterinária , Eritrócitos/citologia , Cavalos/sangue , Células-Tronco Mesenquimais/citologia , Monócitos/citologia , Animais , Purging da Medula Óssea/instrumentação , Separação Celular/instrumentação , Separação Celular/veterinária , Contagem de Eritrócitos/veterinária , Volume de Eritrócitos/veterinária , Feminino , Masculino , Reprodutibilidade dos Testes
19.
Cancer Res ; 71(14): 5040-9, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21646477

RESUMO

Autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for selected myeloma patients. However, tumor cells contaminating the apheresis product are a potential source of relapse. Here we report a sequential purging strategy targeting mature and immature clonogenic myeloma cell populations in the autograft. Thawed PBPC products of myeloma patients were treated with rituximab to kill CD138(-)20(+) B cells (highly clonogenic immature cells), and bortezomib to target CD138(+) cells (normal and differentiated myeloma plasma cells), followed by coculture with allogeneic mesenchymal stem cells (MSC) from normal donors. After 7 days of coculture, nonadherent cells were removed and cultured in the absence of MSC for an additional 7 days. Then, efficacy of purging (removal of CD138(-)20(+) and CD138(+) cells) was assessed by flow cytometry and PCR. We used our ex vivo purging strategy to treat frozen aphereses from 16 patients. CD138(+) and CD138(-)20(+)(19(+)) cells present in the initial products were depleted more than 3 and 4 logs, respectively based on 10(6) flow-acquisition events, and to levels below the limit of detection by PCR. In contrast, total nucleated cell (TNC), CD34(+) cell, and colony-forming cell numbers were increased by approximately 12 to 20, 8-, and 23-fold, respectively. Overall, ex vivo treatment of apheresis products with rituximab, bortezomib, and coculture with normal donor MSC depleted mature and immature myeloma cells from clinical aphereses while expanding the normal hematopoietic progenitor cell compartment.


Assuntos
Anticorpos Monoclonais Murinos/farmacologia , Purging da Medula Óssea/métodos , Ácidos Borônicos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Mieloma Múltiplo/cirurgia , Transplante de Células-Tronco de Sangue Periférico/métodos , Pirazinas/farmacologia , Anticorpos Monoclonais Murinos/administração & dosagem , Antígenos CD34/biossíntese , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ácidos Borônicos/administração & dosagem , Bortezomib , Linhagem Celular Tumoral , Separação Celular/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Magnetismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Pirazinas/administração & dosagem , Rituximab , Transplante Autólogo
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