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1.
Int J Hematol ; 112(6): 835-840, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32876851

RESUMO

Hematopoietic stem and progenitor cell (HSPC) mobilization regimens in multiple myeloma typically use filgrastim (GCSF) alone or combination of GCSF with plerixafor or high-dose cyclophosphamide. Murine model and human studies have shown HSPC mobilization potential of bortezomib. A total of 37 patients underwent mobilization using bortezomib 1.3 mg/m2 on day 1, 4, 8 and 11, cyclophosphamide 1 g/m2 on day 8 and 9, and GCSF 10 µg/kg from day 10 (B-Cy-GCSF). This regimen was compared with our earlier cohort of patients where cyclophosphamide was given at dose of 1 g/m2 on day 1 and day 2 followed by GCSF 10 µg/kg from day 4 (Cy-GCSF). In B-Cy-GCSF group, median CD34 cells collected were 9.21 × 106/kg (range 4.95-17.1) while in the Cy-GCSF cohort, the median CD34 cell yield was 8.2 × 106/kg (0.4-24.2). Target CD34 cells yield of 5 × 106/kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-GCSF group (p = 0.07). Three patients failed mobilization after Cy-GCSF, while no patients failed mobilization in bortezomib group. Addition of bortezomib to Cy-GCSF mobilization showed a trend towards increased CD34 collection and reduced need for apheresis sessions.


Assuntos
Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos , Feminino , Filgrastim/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
2.
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
3.
Ann Hematol ; 99(6): 1331-1339, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382775

RESUMO

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.


Assuntos
Filgrastim/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Análise Custo-Benefício , Feminino , Filgrastim/economia , Mobilização de Células-Tronco Hematopoéticas/economia , Mobilização de Células-Tronco Hematopoéticas/tendências , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/economia , Polietilenoglicóis/economia , Transplante Autólogo/economia , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Resultado do Tratamento
4.
J Leukoc Biol ; 107(6): 1175-1185, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374077

RESUMO

Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety profile. In this study, we investigated the kinetics of endogenous neutrophils by direct imaging, using confocal intravital microscopy in mouse bone marrow, spleen, and lungs. Neutrophils are observed increasing their velocity and exiting the bone marrow following plerixafor administration, with a concomitant increase in neutrophil numbers in the blood and spleen, while the marginated pool of neutrophils in the lung microvasculature remained unchanged in terms of numbers and cell velocity. Use of autologous radiolabeled neutrophils and SPECT/CT imaging in healthy volunteers showed that plerixafor did not affect GM-CSF-primed neutrophil entrapment or release in the lungs. Taken together, these data suggest that plerixafor causes neutrophil mobilization from the bone marrow but does not impact on lung marginated neutrophil dynamics and thus is unlikely to compromise respiratory host defense both in humans and mice.


Assuntos
Medula Óssea/efeitos dos fármacos , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/farmacologia , Pulmão/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Medula Óssea/diagnóstico por imagem , Medula Óssea/imunologia , Rastreamento de Células/métodos , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/imunologia , Humanos , Contagem de Leucócitos , Pulmão/citologia , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Camundongos Endogâmicos C57BL , Neutrófilos/citologia , Neutrófilos/imunologia , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Baço/citologia , Baço/diagnóstico por imagem , Baço/imunologia , Tecnécio/administração & dosagem
5.
Transfusion ; 60(4): 779-785, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32064638

RESUMO

BACKGROUND: Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals. STUDY DESIGN AND METHODS: Same-day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next-day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14- or 20-hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations. RESULTS: The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change -0.034%; p < 0.01). CONCLUSION: Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results.


Assuntos
Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Leucaférese/métodos , Fatores de Tempo , Esquema de Medicação , Compostos Heterocíclicos/farmacologia , Humanos
6.
Diabetes ; 69(4): 699-712, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31974141

RESUMO

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow-derived CD133+ and CD34+ endothelial progenitor cells and Ym1/2+ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Pé Diabético/fisiopatologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/farmacologia , Tacrolimo/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
7.
Transfus Apher Sci ; 59(1): 102595, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31492570

RESUMO

BACKGROUND AND AIM: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been considered the standard of treatment care for patients with multiple myeloma (MM). Insufficient mobilization and harvest of peripheral stem cells can be a major obstacle for performing ASCT. This is resulting in a lacking opportunity of cure in patients with MM. The aim of this study was to evaluate the factors which influence mobilization failure in patients with MM. MATERIALS AND METHODS: This study has been performed in a retrospective manner. Two hundred and thirty-four patients with diagnosed MM who underwent stem cell mobilization after induction chemotherapy at Hacettepe University Hospital between the years of 2003 and 2018 were evaluated. RESULTS: A total of 234 patients were included in this study. The median age was 54 (32-76) years at the time of diagnosis. In 209 of 234 patients (89.3%) first mobilization trial was successful. At univariate analysis, among parameters identifiable before mobilization, male gender (p = 0.03), number of chemotherapy cycle before stem cell mobilization (p < 0.001), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p < 0.001) predicted mobilization failure. At multivariate analysis, number of chemotherapy cycle before stem cell mobilization (p = 0.03), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p = 0.02) retained independent predictive power. CONCLUSION: Detectable different clinical characteristics of MM patients before initiating mobilization may be predictors of poor mobilization. Therefore, the mobilization protocol should be evaluated on a patient basis. Minimization of exposure to chemotheraputic agents in MM patients, especially immunomodulatory agents, may increase CD34+ cell harvest yields.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Bull Cancer ; 107(1S): S44-S51, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31570213

RESUMO

The modalities of mobilization of hematopoietic stem cells in autologous transplantation have evolved in recent years. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 9th hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2018 in Lille, France, to conduct a review of current practices of the society centers and of international recommendations. The cell dose objectives have been revised. The modalities of mobilization including the use of plerixafor have been specified allowing reaching the objectives of collection while limiting the number of apheresis. Collections failures have become exceptional.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Algoritmos , Antígenos CD34/análise , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Remoção de Componentes Sanguíneos/métodos , Medula Óssea/efeitos dos fármacos , Contagem de Células , Separação Celular/métodos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fatores de Crescimento de Células Hematopoéticas/farmacologia , Mobilização de Células-Tronco Hematopoéticas/normas , Compostos Heterocíclicos/farmacologia , Humanos , Padrões de Prática Médica , Fatores de Risco , Transplante Autólogo
9.
J Oncol Pharm Pract ; 26(1): 23-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30854925

RESUMO

INTRODUCTION: Filgrastim, a granulocyte colony-stimulating factor, is commonly used in autologous hematopoietic stem cell transplants (HSCTs) to assist with peripheral blood progenitor cell (PBPC) collection and to support stem cell engraftment. In the United States, tbo-filgrastim is approved under its own Biologic License Application and is limited to a single indication excluding the HSCT population. METHODS: Approximately one year after a system-wide formulary change to tbo-filgrastim for all on- and off-label indications, our institution conducted an IRB-approved retrospective comparison of tbo-filgrastim to filgrastim in the autologous HSCT setting. The study included 71 patients who received an autologous HSCT from 1 January 2013 to 31 December 2016 with a documented administration of tbo-filgrastim or filgrastim. RESULTS: There were no statistically significant differences noted on CD34 + counts during stem cell mobilization, neutrophil engraftment, infection rates during the engraftment phase, nor duration of hospitalization during the engraftment phase. More patients in the tbo-filgrastim group received plerixafor per protocol resulting in more patients meeting their PBPC collection goal in one day with fewer collection days overall, a result potentially confounded by institutional protocol changes. Utilizing tbo-filgrastim offered an average cost savings per patient of $2664.26 ($1907.33 for PBPC mobilization and $756.93 for stem cell engraftment) when comparing dollars spent on granulocyte colony-stimulating factor products only. CONCLUSION: Tbo-filgrastim demonstrates comparable efficacy with a cost savings benefit compared to filgrastim for autologous PBPC mobilization and stem cell engraftment.


Assuntos
Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Idoso , Feminino , Filgrastim/economia , Rejeição de Enxerto/economia , Rejeição de Enxerto/prevenção & controle , Fármacos Hematológicos/economia , Mobilização de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/economia , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo/economia , Transplante Autólogo/métodos
10.
Ann N Y Acad Sci ; 1466(1): 24-38, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31006885

RESUMO

Peripheral blood hematopoietic stem and progenitor cells (HSPCs), mobilized by granulocyte colony-stimulating factor, are widely used as a source for both autologous and allogeneic stem cell transplantation. The use of mobilized HSPCs has several advantages over traditional bone marrow-derived HSPCs, including a less invasive harvesting process for the donor, higher HSPC yields, and faster hematopoietic reconstitution in the recipient. For years, the mechanisms by which cytokines and other agents mobilize HSPCs from the bone marrow were not fully understood. The field of stem cell mobilization research has advanced significantly over the past decade, with major breakthroughs in the elucidation of the complex mechanisms that underlie stem cell mobilization. In this review, we provide an overview of the events that underlie HSPC mobilization and address the relevant cellular and molecular components of the bone marrow niche. Furthermore, current and future mobilizing agents will be discussed.


Assuntos
Comunicação Celular/fisiologia , Citocinas/fisiologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/fisiologia , Nicho de Células-Tronco/fisiologia , Animais , Medula Óssea/fisiologia , Citocinas/farmacologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Mobilização de Células-Tronco Hematopoéticas/tendências , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos
11.
Semin Hematol ; 56(4): 248-256, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31836031

RESUMO

An essential and influential first step in all cellular therapies is collecting donor or patient cells. In hematopoietic progenitor cell transplantation, autologous or allogeneic hematopoietic progenitor cells (HPCs) are collected from either the bone marrow or the peripheral blood. Peripheral blood collection by apheresis requires mobilization with chemotherapy, granulocyte colony stimulating factor (G-CSF), plerixafor, or a combination. The modalities of mobilization and collection each carry a unique set of risks and benefits for both the donor and the recipient. In other types of cell therapy, most notably chimeric antigen receptor T cells, lymphocytes or monocytes are collected from the peripheral blood. The risks of collecting these cells by apheresis are similar to HPCs, but less is known about the composition, timing and qualitative cell characteristics which contribute to an optimal collection. Here, we review the mobilization and collection of HPCs and the collection of lymphocytes and monocytes. Donor safety is of primary importance when collecting material for any type of cell therapy. Every aspect of mobilization and collection can be studied and potentially optimized to improve patient outcomes.


Assuntos
Fator Estimulador de Colônias de Granulócitos/metabolismo , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfócitos/metabolismo , Monócitos/metabolismo , Feminino , Humanos , Masculino
12.
Cells ; 9(1)2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861319

RESUMO

Albumin, the most abundant plasma protein, not only controls osmotic blood pressure, but also serves as a carrier for various small molecules, including pharmaceuticals. Its impact on pharmacological properties of many drugs has been extensively studied over decades. Here, we focus on its interaction with the following mobilizing agents: Granulocyte-colony stimulating factor (G-CSF) and AMD3100, where such analyses are lacking. These compounds are widely used for hematopoietic stem cell mobilization of healthy donors or patients. Using albumin-deficient (Alb-/-) mice, we studied the contribution of albumin to mobilization outcomes. Mobilization with the bicyclam CXCR4 antagonist AMD3100 was attenuated in Alb-/- mice compared to wild-type littermates. By contrast, mobilization with recombinant human G-CSF (rhG-CSF), administered twice daily over a five-day course, was significantly increased in Alb-/- mice. In terms of a mechanism, we show that rhG-CSF bioavailability in the bone marrow is significantly improved in Alb-/- mice, compared to wild-type (WT) littermates, where rhG-CSF levels dramatically drop within a few hours of the injection. These observations likely explain the favorable mobilization outcomes with split-dose versus single-dose administration of rhG-CSF to healthy donors.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Albumina Sérica Humana/genética , Animais , Disponibilidade Biológica , Feminino , Técnicas de Inativação de Genes , Fator Estimulador de Colônias de Granulócitos/farmacocinética , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Compostos Heterocíclicos/farmacocinética , Masculino , Camundongos
13.
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
14.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625348

RESUMO

BACKGROUND: The aim of this study was to evaluate the efficacy of cyclophosphamide-based (CB) and platinum-based (PB) chemotherapy regimens for hematopoietic stem cell mobilization in patients with Multiple Myeloma (MM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL) and the less well-known IEV (iphosphamide, epirubicin, etoposide) regimen in terms of stem cell harvesting competence, factors affecting stem cell com-petence, and toxicity. METHODS: A retrospective evaluation was made of 203 patients (94 MM, 37 HL, and 72 NHL) with peripheral blood stem cell mobilization in different chemotherapy regimens between 2000 and 2010 at the Department of He-matology, Faculty of Medicine, Akdeniz University. RESULTS: There were no differences between CB or PB mobilization regimens and IEV chemotherapy schema in terms of sufficiency of peripheral stem cell harvest, which was predefined as the collected number of peripheral stem cells ≥ 3 x 106/kg for single hematopoietic stem cell transplantation (HSCT) and ≥ 5 x 106/kg for tandem HSCT. There were also no significant differences between low dose cyclophosphamide, high dose cyclophosphami-de, and HCVAD (cyclophosphamide, vincristine, dexamethasone, methotrexate, cytosine arabinoside [ARA-C]) among the subgroups of cyclophosphamide-based regimens. The number of peripheral blood stem cells collected using ESHAP (ethoposide, methylprednisolone, ARA-C, cisplatin), a platin-based regimen, was significantly higher than the other platin-based regimens including DHAP (dexamethasone, ARA-C, cisplatin), ICE (iphosphamide, carboplatin, ethopocide), and EDAP (etoposide, dexamethasone, ARA-C, cisplatin). The toxicity profiles of CB, PB, and IEV chemotherapies were similar. To determine the independent predictors of the efficacy of the stem cell harvest procedure and collected stem cell count, age, diagnosis, duration of disease, number of treatment sequences before mobilization, and number of rescue regimens were included into multiple logistic regression analysis. However, no correlations were determined. CONCLUSIONS: The results of this study provide information on the effectiveness of different stem cell mobilization regimens. Although no significant difference was determined between the three major chemotherapy regimens, the ESHAP regimen appears to be the preferred treatment regimen for stem cell mobilization in selected lymphomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
15.
J Clin Apher ; 34(6): 686-691, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31566813

RESUMO

The use of granulocyte-colony stimulating factor (G-CSF) with or without chemotherapy to mobilize hematopoietic progenitor cells (HPCs) can result in significant morbidity in light chain (AL) amyloidosis patients. Plerixafor, a strong inducer and mobilizer of HPCs, can be used as an adjunct to G-CSF to improve mobilization efficiency. We describe the outcomes for combined G-CSF/plerixafor mobilized patients with AL amyloidosis. We reviewed data of 53 consecutive AL amyloidosis patients who underwent combined G-CSF/plerixafor HPC mobilization between May 2011 and October 2017 at our institution. We evaluated patients for HPC collection efficiency, perimobilization toxicity and postautologous hematopoietic cell transplantation (autoHCT) outcomes. Median CD34+ cell collection was 12.4 × 106 cells/kg (range 2.5 × 106 to 34.1 × 106 cells/kg) and 45 (85%) patients had collections of ≥5.0 × 106 CD34+ cells/kg. There were no mobilization failures or perimobilization mortality. During mobilization, 37 (70%) patients had weight gain (median 1.3 kg, range 0.1-4) but none >10% body weight, 5 (10%) patients had diarrhea, and one patient each had hypotension and cardiac arrhythmia. Among the 31 patients analyzed for CD34 collection efficiency (CE), the median CD34 CE was 47% (range 36-62). At 5 years follow-up 82% and 84% of patients were progression-free and alive, respectively. Our results suggest that G-CSF/plerixafor mobilization is safe, well tolerated, and effective in AL amyloidosis.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Adulto , Antígenos CD34/sangue , Feminino , Mobilização de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
16.
Transfusion ; 59(12): 3721-3726, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31618456

RESUMO

BACKGROUND: Autologous stem cell transplantation (ASCT) is an effective treatment for patients with relapsing myeloma or lymphoma, diseases associated with unsuccessful peripheral blood stem cell (PBSC) collection. Plerixafor is a potent mobilizing agent, allowing more CD34+ cells to be obtained; however, the main obstacle for its use is its high cost. Our aim was to demonstrate that of the use of reduced doses of plerixafor (RD-plerixafor) can be sufficient to collect at least 2 × 106 /Kg CD34+ PBSC in patients with multiple myeloma (MM) or lymphoma undergoing ASCT. STUDY DESIGN AND METHODS: Twenty patients were mobilized with filgrastim (10 µg/kg/4 days) plus a single dose of plerixafor 0.12 mg/kg in Day 4. Apheresis collection was performed on Day 5. One vial of plerixafor was used for two patients. Clinicaltrials.gov NCT03244930. RESULTS: Cell mobilization and collection was successful in 85% of patients (≥2 × 106 CD34+ cells per kilogram). The median collected CD34+ cell count was 4.62 × 106 /kg (range, 1.27-24.5). A 4.1-fold-increase in the median CD34+ PBSC pre-count was observed (from 10.4/µl to 42.4/µl) after RD-plerixafor administration. Seven patients had mild to moderate adverse events. CONCLUSION: RD-plerixafor is an effective, safe, and affordable strategy to ensure adequate PBSC mobilization in patients with MM or lymphoma who undergo ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Compostos Heterocíclicos/uso terapêutico , Adulto , Idoso , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudo de Prova de Conceito , Transplante Autólogo
17.
Stem Cell Reports ; 13(5): 787-792, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31607567

RESUMO

Hematopoietic stem cell (HSC) transplantation is a curative treatment for a variety of blood and immune disorders. Currently available methods to obtain donor HSCs are suboptimal, and the limited supply of donor HSCs hampers the success and availability of HSC transplantation therapies. We recently showed that manipulation of vascular integrity can be employed to induce HSC mobilization from the bone marrow to the blood stream, facilitating non-invasive collection of HSCs. Here, we tested whether FDA-approved vasodilators are capable of mobilizing HSCs. We found that a rapid, 2-h regimen of a single oral dose of Viagra (sildenafil citrate) combined with a single injection of the CXCR4 antagonist AMD3100 leads to efficient HSC mobilization at levels rivaling the standard-of-care 5-day regimen of granulocyte-colony stimulating factor (G-CSF/Filgrastim/Neupogen). Our findings solidify vascular integrity as an essential regulator of HSC trafficking and provide an attractive, single-day regimen for HSC mobilization using already FDA-approved drugs.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Citrato de Sildenafila/farmacologia , Vasodilatadores/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores CXCR4/antagonistas & inibidores
18.
Neurology ; 93(18): e1732-e1741, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31578302

RESUMO

OBJECTIVE: To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) could be a salvage therapy for neuromyelitis optica spectrum disorder (NMOSD). METHODS: Thirteen patients were enrolled in a prospective open-label cohort study (11 NMOSD aquaporin-4-immunoglobulin G [AQP4-IgG]-positive, 1 NMOSD without AQP4, and 1 NMOSD AQP4-IgG-positive with neuropsychiatric systemic lupus erythematosus [SLE]). Following stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim, patients were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day -5 to day -2, rATG (thymoglobulin) given IV at 0.5 mg/kg on day -5, 1 mg/kg on day -4, and 1.5 mg/kg on days -3, -2, and -1 (total dose 6 mg/kg), and rituximab 500 mg IV on days -6 and +1. Unselected peripheral blood stem cells were infused on day 0. AQP4-IgG antibody status was determined by Clinical Laboratory Improvement Amendments-validated ELISA or flow cytometry assays. Cell-killing activity was measured using a flow cytometry-based complement assay. RESULTS: Median follow-up was 57 months. The patient with coexistent SLE died of complications of active lupus 10 months after HSCT. For the 12 patients with NMOSD without other active coexisting autoimmune diseases, 11 patients are more than 5 years post-transplant, and 80% are relapse-free off all immunosuppression (p < 0.001). At 1 and 5 years after HSCT, Expanded Disability Status Scale score improved from a baseline mean of 4.4 to 3.3 (p < 0.01) at 5 years. The Neurologic Rating Scale score improved after HSCT from a baseline mean of 69.5 to 85.7 at 5 years (p < 0.01). The Short Form-36 health survey for quality of life total score improved from mean 34.2 to 62.1 (p = 0.001) at 5 years. In the 11 patients whose baseline AQP4-IgG serostatus was positive, 9 patients became seronegative by the immunofluorescence or cell-binding assays available at the time; complement activating and cell-killing ability of patient serum was switched off in 6 of 7 patients with before and after HSCT testing. Two patients remained AQP4-IgG-seropositive (with persistent complement activating and cell-killing ability) and relapsed within 2 years of HSCT. No patient with seronegative conversion relapsed. CONCLUSION: Prolonged drug-free remission with AQP4-IgG seroconversion to negative following nonmyeloablative autologous HSCT warrants further investigation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Neuromielite Óptica/terapia , Adulto , Soro Antilinfocitário/uso terapêutico , Aquaporina 4/imunologia , Autoanticorpos/imunologia , Ciclofosfamida/uso terapêutico , Feminino , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/imunologia , Intervalo Livre de Progressão , Recidiva , Rituximab/uso terapêutico , Terapia de Salvação , Transplante Autólogo , Adulto Jovem
19.
Transfusion ; 59(11): 3442-3447, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31625183

RESUMO

BACKGROUND: In a small proportion of cases, hematopoietic function is insufficient after allogeneic hematopoietic stem cell transplantation, as a result of poor graft function or graft failure. These complications are common indications of re-mobilization of the initial donor, either for a second allograft or for an infusion of CD34+ Selected stem Cell Boost (SCB). METHODS AND MATERIALS: We retrospectively reviewed the results of two cycles of CD34+ cell mobilization and collection. CD34+ cells mobilized and collected at each cycle were compared. When CD34+ cell selection from the collected allogeneic mononuclear cells was indicated, it was performed with the Clinimacs Plus® medical device, and results from in-process and final quality checks were analyzed. To assess the efficacy of CD34+ SCB, transfusion needs before and after the infusion of selected CD34+ cells were calculated. RESULTS: The median peripheral blood concentration of CD34+ cells/µL was marginally reduced during the second cycle (35.6 vs 33.8, p < 0.05); results revealed a strong correlation between paired values (r = 0.85). The cumulative number of collected CD34+ cells were similar for both cycles; the total processed blood volume was higher during the second cycle (p = 0.023). For CD34+ immune-selection procedures, CD34+ cell recovery and purity were respectively 57% and 95%, with a median T-cell depletion of 6.7 log. Recipients' needs for platelet and red blood cell transfusions were significantly reduced after CD34+ SCB. CONCLUSION: This study confirms the feasibility of a second cycle of mobilization in healthy related donors and the benefits of CD34+ SCB on hematopoietic reconstitution.


Assuntos
Antígenos CD34/análise , Separação Celular , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco de Sangue Periférico/citologia , Doadores de Tecidos , Adolescente , Adulto , Idoso , Transfusão de Sangue , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Separação Imunomagnética , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Int J Hematol ; 110(6): 648-653, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542851

RESUMO

A "biosimilar" is a biotechnological product with a lower cost profile and equivalent efficacy and safety to the originator, but post-marketing clinical evaluation of biosimilar products has not been adequately conducted. We prospectively investigated the utility of biosimilar filgrastim in 13 peripheral blood stem cell (PBSC) donors from June 2014 to January 2017. In addition, we retrospectively compared these to another 13 PBSC donors mobilized with the originator filgrastim in the same period. Donor characteristics were equivalent between the groups. The median number of CD34+ cells per donor body weight (BW) and blood volume processed (BV) were 4.87 × 106/kg and 25.5 × 103/mL in the biosimilar group and 4.93 × 106/kg and 16.6 × 103/mL in the originator group, respectively. There were no significant differences between the groups in the number of CD34+ cells per donor BW or BV. All adverse events associated with G-CSF were permissive. The total G-CSF cost was significantly lower in the biosimilar group than in the originator group. These findings suggest that biosimilar filgrastim has the same efficacy and short-term safety as originator filgrastim for PBSC mobilization in healthy donors, with economic superiority. Longer follow-up studies are needed to evaluate the incidence of long-term adverse events.


Assuntos
Medicamentos Biossimilares/normas , Filgrastim/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/análise , Mobilização de Células-Tronco Hematopoéticas/métodos , Doadores de Tecidos , Adulto , Antígenos CD34/sangue , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/economia , Feminino , Filgrastim/efeitos adversos , Filgrastim/economia , Filgrastim/normas , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico , Estudos Prospectivos , Estudos Retrospectivos
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