RESUMO
BACKGROUND: The kinetics of hematopoietic recovery after autologous stem cell transplantation (ASCT) may be affected by laboratory procedures. The aim of this study was to evaluate the influence of characteristics of the cryopreserved units of peripheral blood stem cells (PBSC) on postthawing cell viability and engraftment outcomes after ASCT. STUDY DESIGN AND METHODS: This was a retrospective cohort study including individuals referred for ASCT. Cryopreservation was conducted at a single processing facility between 2014 and 2019, and patients received clinical care at six transplant centers. Covariates and outcome data were retrieved from participants' records. RESULTS: The study population comprised 619 patients (345 [55.7%] male). Median age was 53 years. Multiple myeloma was the most common diagnosis (62.7%). Higher preapheresis CD34+ cell count, lower nucleated cell (NC) concentration per cryobag, and composition of the cryoprotectant solution (5% dimethyl sulfoxide [DMSO] and 6% hydroxyethyl starch) were statistically significantly associated with higher postthawing cell viability. The linear regression model for time to neutrophil and platelet engraftment included the infused CD34+ cell dose and the composition of the cryoprotectant solution. Patients who had PBSC cryopreserved using 10% DMSO solution presented six times higher odds (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 2.2-21.1; p = .001) of delayed neutrophil engraftment (>14 days) and two times higher odds (OR = 2.3, 95%CI: 1.4-3.7; p = .001) of prolonged hospitalization (>18 days). DISCUSSION: The study showed that mobilization efficacy, NC concentration, and the composition of the cryoprotectant solution significantly affected postthawing cell viability. In addition, the composition of the cryoprotectant solution significantly impacted engraftment outcomes and time of hospitalization after ASCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/fisiologia , Laboratórios , Células-Tronco de Sangue Periférico/fisiologia , Prática Profissional , Adulto , Idoso , Sobrevivência Celular , Estudos de Coortes , Criopreservação/normas , Feminino , Congelamento/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/normas , Células-Tronco Hematopoéticas/citologia , Humanos , Laboratórios/normas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico/citologia , Prática Profissional/normas , Estudos Retrospectivos , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Transplante Autólogo , Resultado do TratamentoRESUMO
OBJECTIVES: We aimed to determine the impact of washout period in patients with multiple myeloma between bortezomib-based induction regimens and the collection of stem cells. METHODS: This was a single-center historical prospective study, including all sequential newly diagnosed patients with myeloma between 2012 and 2017 that were given a first-line bortezomib-based induction therapy (≤6 cycles) followed by stem cell collection (n = 75). RESULTS: We found a statistically significant correlation between the days from last dose of bortezomib and both CD34+ cells/kg yield on the first collection day and the overall collected CD34+ cells/kg (r = .466, P < .001, and r = .341, P = .03, respectively). The optimal receiver operating curve's cutoff point was 8.5 days (79% sensitivity and 71% specificity, P = .001). On multivariate analysis, timing of last dose of bortezomib remained statistically significant (P = .01). Based on this, we developed a model to predict the total collected CD34+ cells/kg = 11.76 + 0.13 (timing in days of last dose of bortezomib) -0.1 (age) -1.39 (if female) -0.01 (≥PR) -1.35 (if prior radiation). CONCLUSIONS: Timing of last dose of bortezomib may predict a successful collection. A washout period of 9 days is associated with a better collection yield. A prospective validation of this novel finding is required.
Assuntos
Antineoplásicos/farmacocinética , Bortezomib/farmacocinética , Mieloma Múltiplo/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Tomada de Decisão Clínica , Gerenciamento Clínico , Mobilização de Células-Tronco Hematopoéticas/métodos , Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Mieloma Múltiplo/diagnóstico , Cuidados Pré-Operatórios , Estudos Prospectivos , Fatores de Tempo , Transplante AutólogoRESUMO
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/normas , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Condicionamento Pré-Transplante , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Transplante AutólogoRESUMO
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 , Benzilaminas , Remoção de Componentes Sanguíneos/métodos , Medula Óssea/efeitos dos fármacos , Contagem de Células , Separação Celular/métodos , Ciclamos , 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 AutólogoRESUMO
INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.
Assuntos
Substituição de Medicamentos/normas , Filgrastim/normas , Mobilização de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Antígenos CD34/análise , Criança , Pré-Escolar , Filgrastim/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/economia , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Lactente , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Mobilization of CD34+ cells by stimulation with G-CSF shows considerable variation across stem cell donors. Upfront prediction of CD34+ cell counts in peripheral blood based on easily available steady-state parameters would be helpful for the planning of apheresis and stem cell transplantation. Commonly accepted steady-state predictors for the mobilization are gender, body mass index and platelet count. The aim of the study was the identification of novel predictors that might influence mobilization efficacy and to create a model for the prediction of stem cell mobilization. METHODS: A total of 333 healthy stem cell donors who donated peripheral stem cells in our institution were retrospectively analysed. All available data before stem cell mobilization with G-CSF were included in the database. Primary end-point was CD34+ cell count before the first apheresis. RESULTS: In this cohort cholinesterase, differential blood cell counts including platelets, gender and body mass index were significantly correlated with CD34+ cell count. G-CSF dose per lean body weight showed a significant correlation with mobilization efficacy in women but not in men. A multivariate analysis identified gender, cholinesterase and platelet and red cell count as main predictors of mobilization. Red cell count showed a strong gender dependence, with higher predictive value in females. CONCLUSION: The counts of eosinophils, platelets, red cells, cholinesterase and gender are the most important predictors of CD34+ cell mobilization in our deduced models. The red cell count as a predictor for mobilization showed a differential gender dependence.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/normas , Células-Tronco de Sangue Periférico/metabolismo , Adulto , Antígenos CD34/metabolismo , Colinesterases/metabolismo , Contagem de Eritrócitos , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/citologia , Contagem de Plaquetas , Fatores Sexuais , Doadores de Tecidos/estatística & dados numéricosRESUMO
BACKGROUND: Poor mobilization results are unexpected after G-CSF-induced peripheral blood stem cell collection in healthy donors. However, 2%-5% of the donors are poor mobilizers. Factors predicting CD34+-cell yield after mobilization in related alternative donors are still poorly known. PATIENTS AND METHODS: Baseline characteristics and efficacy results of G-CSF induced mobilization of 159 adult healthy donors in our institution from 2008 to 2016 were retrospectively analyzed. All donors received 10 µg/kg of G-CSF once a day subcutaneously for 4 days. Leukapheresis started on the 5th day of G-CSF treatment. Donors were classified as poor mobilizers if they had less than 20 000 CD34 + cell/mL peripheral blood count in the 5th day of G-CSF treatment or if they needed three or more leukapheresis for graft collection. RESULTS: Age, weight, and platelet count before and after mobilization were significantly different between poor and good mobilizers. Poor mobilizers (n = 16) were older (50.6 vs 41.7 years, P = 0.002), weight lower (64 vs 75 kg, P = 0.00) and showed a lower platelet count before (199.5 vs 219.0 × 109 /L, P = 0.03) and after (192.5 vs 206 × 109 /L, P = 0.019) mobilization. In the multivariate analysis only the 30% of the variability of mobilization was explained by the model (sensitivity 80%, specificity 70%). CONCLUSION: In this cohort of healthy donors in a single institution, older age, less weight, and lower platelet count was associated with poorer mobilization. With clinical and analytic factors it is not possible to predict more than 30% of the variability. Further studies are needed to investigate new variables.
Assuntos
Antígenos CD34/sangue , Doadores de Sangue , Mobilização de Células-Tronco Hematopoéticas/normas , Células-Tronco de Sangue Periférico/citologia , Adulto , Fatores Etários , Idoso , Peso Corporal , Fator Estimulador de Colônias de Granulócitos/farmacologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos RetrospectivosRESUMO
A randomized, multicenter, open-label study explored the effect of a fixed-dose (FD) of plerixafor versus the approved weight-based (WB) dose for the mobilization of hematopoietic stem cells (HSCs) in patients with non-Hodgkin's lymphoma and a body weight of ≤70 kg. After mobilization with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day for 4 days, patients were randomized 1:1 to either plerixafor FD 20 mg (n = 30) or WB 0.24 mg/kg (n = 31) on the evening of Day 4. Co-primary endpoints were the proportion of patients achieving ≥5 × 106 CD34+ cells/kg in ≤4 days of apheresis, and total systemic exposure to plerixafor (area under the concentration-time curve from 0 to 10 h [AUC0-10]). There was no statistically significant difference between the proportion of patients attaining the primary efficacy endpoint (60% FD arm, 55% WB arm; P = 0.395). Exposure to plerixafor was greater in the FD arm relative to the WB arm; however, there was no appreciable difference regarding fold increases of peripheral blood CD34+ cells. The safety profile was similar between treatment groups. These results suggest there is no statistically significant difference in HSC mobilization with a standard WB dosing regimen of plerixafor plus G-CSF in patients with low body weight compared with an FD regimen.
Assuntos
Peso Corporal , Cálculos da Dosagem de Medicamento , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzilaminas , Ciclamos , Feminino , Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , MagrezaRESUMO
Bortezomib-based induction is often used in transplant-eligible patients with myeloma. The optimal peripheral blood stem cell (PBSC) mobilisation strategy in this context is unclear. We reviewed the efficacy of G-CSF alone (G-alone) vs. G-CSF and cyclophosphamide (G-cyclo: standard dose: 1.5-2 g/m2; high dose: 3-4 g/m2) PBSC mobilisation strategies in 288 patients who only received bortezomib, cyclophosphamide and dexamethasone (VCD) induction prior to autograft across six apheresis centres from November 2012 to June 2017. 'Uncomplicated successful mobilisation' was defined as achieving a PBSC yield of ≥4 × 106/kg within two aphereses, without plerixafor or mobilisation-associated toxicity (predominantly febrile neutropenia, FN). Success rates were 84% in G-cyclo standard dose (6% FN), 64% in G-cyclo high dose (18% FN) and 69% in G-alone (plerixafor successfully salvaged 8/9 patients). Median total stem cell yield was significantly higher with G-cyclo, but not different between the two cyclophosphamide doses. Age greater than the median of 61 years was associated with higher failure rates (22 vs. 11%, p = 0.01) and lower PBSC yield, especially in the G-alone group. Prior radiotherapy exposure did not impact on collection success. Our observations suggest that both G-cyclo standard dose and G-alone are reasonable mobilisation strategies. The former may be preferred if salvage plerixafor is unavailable.
Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Adulto , Fatores Etários , Idoso , Bortezomib/uso terapêutico , Ciclofosfamida/administração & dosagem , Dexametasona/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/citologia , Indução de Remissão/métodosRESUMO
Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We developed a new prediction model from multivariate analysis whose score (pPM-score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score included as risk factors: increasing age, diagnosis of NHL, positive bone marrow biopsy or cytopenias before mobilization, previous mobilization failure, priming strategy with G-CSF alone, or without upfront plerixafor. A simplified version of pPM-score was categorized using a cut-off to maximize positive likelihood ratio (15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7% (95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60-80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM before starting mobilization, allowing changes in clinical management, such as choice of alternative priming strategies, to avoid highly likely mobilization failure.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/normas , Seleção de Pacientes , Valor Preditivo dos Testes , Adolescente , Adulto , Idoso , Área Sob a Curva , Criança , Pré-Escolar , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Successful collection of peripheral blood stem cells (PBSCs) depends on the optimal orchestration of mobilization chemotherapy, granulocyte colony stimulating factor (G-CSF) application, and CD34+ cell number assessment in the peripheral blood (PB). However, determining the optimal timing in accordance to the applied chemomobilization regimen can be challenging. Although most centers apply their own local timing schedules, a reliable timetable including the currently most often used mobilization regimens is lacking. We present a comprehensive analysis of the timing modalities for 11 of the most commonly used chemomobilization regimens. A retrospective analysis was performed on the clinical and PBSC collection parameters (including duration of G-CSF application, time point of CD34+ assessment, PB CD34+ cell count, number of leukapheresis [LP] sessions, processed blood volume, and CD34+ collection results) of 91 representatively selected patients who had undergone stem cell mobilization at 2 collection centers. Six to 10 patients were analyzed per regimen with a variety of diagnoses, including multiple myeloma, malignant lymphoma, and sarcoma. No collection failures (<2 × 106 CD34+ cells/kg body weight) were observed. All analyzed patients successfully reached their individual collection goal in adherence to the given schedule of chemotherapy, application of G-CSF, measurement of CD34+ cells, and subsequent LP. The presented data on the timing of chemomobilization, G-CSF application, and stem cell collection may be helpful in clinical decision making and contribute to a more transparent and predictable treatment process.
Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Adulto , Idoso , Antígenos CD34/sangue , Agendamento de Consultas , Volume Sanguíneo , Feminino , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Leucaférese , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/citologia , Estudos Retrospectivos , Fatores de TempoRESUMO
Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation (AHSCT) worldwide. The collection of PBSCs is the essential step for AHSCT. The limits for minimum and optimum CD34+ cells collected have been accepted as 2 × 106 /kg and ≥4 × 106 /kg for single AHSCT; 4 × 106 /kg and ≥8-10 × 106 /kg for double AHSCT. Despite the success of conventional methods for PBSC mobilization in MM, mobilization failure is still a concern depending on patient age, duration of disease, and the type of induction therapy. By definition, "proven poor mobilizer" is the occurrence of mobilization failure (CD34+ cell peak <20/µL peripheral blood) after adequate preparation (after 6 days of G-CSF 10 µg/kg body weight alone or after 20 days of G-CSF >5 µg/kg body weight following chemotherapy) or a CD34+ cell yield of <2.0 × 106 /kg body weight after three consecutive apheresis. "Predicted poor mobilizer" involves (1) a failure of a previous collection attempt OR (2) a previous history of extensive radiotherapy or full courses of therapy affecting mobilization OR (3) the presence of at least two of the following features: advanced disease (>2 lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity of 30% at the time of mobilization or age >65 years. This article aims at discussing the risk factors for mobilization failure in the era of novel antimyeloma drugs, defining the poor mobilizer concept and summarizing the current and future strategies for the prevention and management of mobilization failures in MM.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/citologia , Fatores de Risco , Transplante Autólogo , Falha de TratamentoRESUMO
High-dose chemotherapy alongside peripheral blood stem cell (PBSC) infusion has become the standard of care in different hematologic malignancies. The goal of PBSC mobilization is to allow collection of sufficient CD34+ cells to proceed to transplantation. The current mobilization regimen with granulocyte colony-stimulating factor (G-CSF), alone or in combination with chemotherapy, still fails in 10-25% of patients. Plerixafor is able to rescue most of these patients from mobilization failure. In this study, we investigated the impact of plerixafor on the cost and time spent on apheresis in patients who were considered poor mobilizers, with <20 × 106/µl peripheral CD34+ cells after mobilization but prior to apheresis. Patient hospital records from ten centers in three European countries were reviewed and compared during two time periods, namely prior and after plerixafor introduction to the market. During the plerixafor period, patients spent less time on apheresis (350 vs. 461 min). Poor mobilizers given plerixafor collected more CD34+ cells during the first apheresis session, leading to a decrease in the average number of apheresis sessions needed. The total apheresis yield was unaffected. This analysis shows that the use of plerixafor lessens the time-effort associated with the management of poor mobilizers and reduces apheresis costs.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/normas , Compostos Heterocíclicos/uso terapêutico , Linfoma não Hodgkin/terapia , Adulto , Idoso , Antígenos CD34/sangue , Benzilaminas , Remoção de Componentes Sanguíneos/economia , Ciclamos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Fatores de Tempo , Falha de TratamentoRESUMO
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France and updated recommendations for indications and follow-up in autologous hematopoietic stem cell transplantation in autoimmune and autoinflammatory diseases, previously published under the auspices of SFGM-TC.
Assuntos
Doenças Autoimunes/terapia , Doença de Crohn/terapia , Escleroderma Sistêmico/terapia , Autoenxertos , Doenças Autoimunes do Sistema Nervoso/terapia , Seguimentos , França , Mobilização de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/terapia , Sociedades Médicas , Condicionamento Pré-Transplante/normasRESUMO
BACKGROUND: CD34 flow cytometry is the gold standard for stem cell enumeration in peripheral blood at the mobilization stage and in the final apheresis product. The new stem cell mode of the Sysmex XN Series analyzer enumerates an immature cell population in the white progenitor and pathological cell (WPC) channel, based on the cell size, internal cellular complexity, and fluorescence intensity. STUDY DESIGN AND METHODS: In this multicenter study we analyzed 147 peripheral blood samples, 22 samples during collection of stem cells, and 45 samples from the apheresis product of 18 healthy allogeneic donors and 84 autologous patients. RESULTS: In this multicenter study we demonstrate that the XN stem cell enumeration method correlates well with viable CD34+ cells determined by flow cytometry during the stem cell mobilization phase to determine apheresis start time, during apheresis for real-time monitoring and adjustment, and for quality control of the final stem cell harvest. CONCLUSION: Our data show that there is an improvement in the correlation of XN stem cells and CD34+ cells in the peripheral blood during stem cell mobilization as well as in stem cell harvests compared to SE or XE Series analyzers. The XN stem cell enumeration method has a number of advantages compared to CD34 flow cytometry: it is fast, simple, reproducible, and less expensive. CE marking for the European market has been obtained, making the stem cell count on the XN analyzer a reportable clinical variable.
Assuntos
Contagem de Células Sanguíneas/instrumentação , Células-Tronco Hematopoéticas/citologia , Antígenos CD34/sangue , Contagem de Células Sanguíneas/economia , Contagem de Células Sanguíneas/métodos , Contagem de Células Sanguíneas/normas , Remoção de Componentes Sanguíneos/normas , Custos e Análise de Custo , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) originators such as filgrastim (Neupogen) and lenograstim (Granocyte) are widely used for peripheral blood stem cell (PBSC) mobilization. In recent years, biosimilar agents have been approved for the same indications. The aim of this retrospective study was to compare the mobilization efficiency of the three G-CSF variants originator filgrastim, lenograstim, and the biosimilar Filgrastim Hexal in a homogeneous group of multiple myeloma (MM) patients in first-line therapy. STUDY DESIGN AND METHODS: Overall mobilization data of 250 patients with MM were included. Of these patients, 74 (30%), 131 (52%), and 45 (18%) were mobilized with originator filgrastim, biosimilar Filgrastim Hexal, or lenograstim, respectively, at a dose of 5 to 10 µg/kg body weight subcutaneously starting from Day 5 after chemomobilization with CAD (cyclophosphamide, doxorubicin, dexamethasone) until completion of PBSC collection. RESULTS: All but one patient reached the collection goal of a minimum of at least 2 × 106 CD34+ cells/kg body weight during a median of one (range, one to three) leukapheresis session. No significant differences in CD34+ mobilization and collection yields between the filgrastim-mobilized (median, 10.5; range, 2.7-40.4), Filgrastim Hexal-mobilized (median, 9.9; range, 0.2-26.0), and lenograstim-mobilized (median, 10.7; range, 3.1-27.9 CD34+ cells × 106 /kg body weight) patients were observed. CONCLUSION: Concerning the clinically relevant efficiencies of PBSC mobilization and in terms of reaching the individual collection target, this retrospective study did not detect any significant differences between the three G-CSF variants in the analyzed patient cohort.
Assuntos
Medicamentos Biossimilares/normas , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/análise , Medicamentos Biossimilares/uso terapêutico , Feminino , Filgrastim/normas , Filgrastim/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/normas , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Lenograstim , Leucaférese , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/normas , Proteínas Recombinantes/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Peripheral blood stem cells mobilized with granulocyte-colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens. STUDY DESIGN AND METHODS: We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40). RESULTS: Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA-CD133+CD34+CD38low ) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p < 0.001), whereas more differentiated subsets clearly prevailed after GP. CONCLUSION: In contrast to the findings of other authors, our study shows a clear shift toward more committed CD34+ subsets after plerixafor in poor mobilizers and elucidates the importance of informative surface markers like CD45RA and CD133 in addition to CD38 to discriminate earlier from more committed CD34+ cells. Further studies are needed to analyze whether these findings have an impact on clinical outcome.
Assuntos
Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/farmacologia , Subpopulações de Linfócitos/citologia , Antígeno AC133/análise , ADP-Ribosil Ciclase 1/análise , Adolescente , Adulto , Idoso , Benzilaminas , Diferenciação Celular/efeitos dos fármacos , Ciclamos , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/normas , Compostos Heterocíclicos/uso terapêutico , Humanos , Antígenos Comuns de Leucócito , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/citologia , Adulto JovemRESUMO
For optimizing CD34+ cell collection, appropriately timing peripheral blood stem cell harvest (PBSCH) initiation is crucial. Automatic cell analyzers with the immature myeloid information channel provide hematopoietic progenitor cell (HPC) count, a surrogate marker of CD34+ cells, which can be obtained within a few minutes without requiring monoclonal antibodies. The final decision on PBSCH initiation can be made using the HPC count obtained on the morning of the harvest day. Herein, we evaluated the impact of the HPC count as an indicator for the optimal timing of PBSCH in clinical practice over 9 years. One hundred and eighteen aphereses from 72 cases had a definite number of CD34+ cells/kg in the PBSC yield. A correlation was found between the HPC count in the PB and the CD34+ cell count (R = 0.563, p ï¼ 0.001), whereas no correlation existed between the white blood cell and CD34+ cell counts (R = 0.0418, p = 0.65). We defined ï¼ 2.0 × 106/kg of CD34+ cells in a single apheresis as good mobilization. Multivariate analysis demonstrated that an HPC count of ï¼ 21/µL, myeloblast count of ï¼ 12/µL, and age at PBSCH of ï¼ 50 years were independently associated with good mobilization (p = 0.001, p ï¼ 0.001, and p = 0.005, respectively). Our findings suggest that the HPC count is a good indicator for the optimal timing of PBSCH.
Assuntos
Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco de Sangue Periférico/citologia , Adulto , Feminino , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Leucaférese/métodos , Leucaférese/normas , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Padrões de Prática Médica/normas , Fatores de TempoRESUMO
Peripheral blood stem cells (PBSCs) used for allogeneic transplantation are collected by apheresis after pre-treatment of donors with G-CSF. Using modern apheresis devices stem cells can be collected more efficiently. It was studied whether collection on the 4th instead of the 5th day after initiation of G-CSF treatment might be feasible. Stem cell yields that could have been collected on day 4 were calculated in two cohorts treated with 10 µg/kg G-CSF once daily (n = 106, cohort I) or 5 µg/kg twice daily schedule (n = 85, cohort II). Harvests were predicted using the median collection efficiency (CE) of the apheresis machine and regarded successful when > 5.0 x106 CD34+/ kg recipient body weight. Successful harvests at day 4 could have been obtained in only 22.6% and 41.2% of donors in cohort I and II respectively, while the expected successful collections on day 5 were 55.7% and 76.5%. Individual donor factors that correlated with a successful harvest on day 4 were weight, BMI, age, ratio donor/recipient weight and total G-CSF dose in cohort I, whereas ratio donor/recipient weight was the only significant predictor in cohort II. Donor weight, BMI and total G-CSF dose correlated positively with CD34+ values in the blood on day 4 in all donors. However, donor characteristics were not able to be used as strong predictors in daily practice. In conclusion, PBSC collection on day 4 will not result in a successful harvest in most stem cell donors, however using a twice daily G-CSF scheme increases the yield.
Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco de Sangue Periférico/citologia , Adolescente , Adulto , Idoso , Antígenos CD34/análise , Doadores de Sangue , Índice de Massa Corporal , Peso Corporal , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Homólogo , Adulto JovemRESUMO
In an otherwise eligible patient with relapsed lymphoma, inadequate mobilization of hematopoietic stem cells (HSCs) is a limiting factor to proceeding with an autologous hematopoietic cell transplantation (auto-HCT). Multiple strategies have been used to mobilize an adequate number of HSCs with no obvious front-line strategy. We report a single institutional experience mobilizing HSCs using four different approaches in lymphoma patients. We prospectively collected mobilization outcomes on patients planned to undergo auto-HCT at Ohio State University. We report results of first mobilization attempts for all relapsed or refractory lymphoma patients between 2008 and 2014. We identified 255 lymphoma patients who underwent mobilization for planned auto-HCT. The 255 lymphoma patients underwent the following front line mobilization strategies: 95 (37%) G-CSF alone, 38 (15%) chemomobilization (G-CSF+chemotherapy), 97 (38%) preemptive day 4 plerixafor, and 25 (10%) rescue day 5 plerixafor. As expected, there were significant differences between cohorts including age, comorbidity indices, histology, and amount of prior chemotherapy. After controlling for differences between groups, the odds of collecting 2 × 106/kg HSCs on the first day of collection and 5 × 106/kg HSCs in total was the highest in the cohort undergoing chemomobilization. In conclusion, our experience highlights the effectiveness of chemomobilization.