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BACKGROUND AIMS: To describe and analyze whether a hub-and-spoke organizational model could efficiently provide access to chimeric antigen receptor (CAR) T-cell therapy within a network of academic hospitals and address the growing demands of this complex and specialized activity. METHODS: The authors performed a retrospective evaluation of activity within the Catalan Blood and Tissue Bank network, which was established for hematopoietic stem cell transplantation to serve six CAR T-cell programs in academic hospitals of the Catalan Health Service. Procedures at six hospitals were followed from 2016 to 2021. Collection shipments of starting materials, CAR T-cell returns for storage and infusions for either clinical trials or commercial use were evaluated. RESULTS: A total of 348 leukocytapheresis procedures were performed, 39% of which were delivered fresh and 61% of which were cryopreserved. The network was linked to seven advanced therapy medicinal product manufacturers. After production, 313 CAR T-cell products were shipped back to the central cryogenic medicine warehouse located in the hub. Of the units received, 90% were eventually administered to patients. A total of 281 patients were treated during this period, 45% in clinical trials and the rest with commercially available CAR T-cell therapies. CONCLUSIONS: A hub-and-spoke organizational model based on an existing hematopoietic stem cell transplantation program is efficient in incorporating CAR T-cell therapy into a public health hospital network. Rapid access and support of growing activity enabled 281 patients to receive CAR T cells during the study period.
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Trasplante de Células Madre Hematopoyéticas , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Salud Pública , Estudios Retrospectivos , Receptores de Antígenos de Linfocitos TRESUMEN
BACKGROUND AND OBJECTIVES: Autologous stem cell transplant (ASCT) is a widely used therapy for lymphoma patients and can nowadays be performed on an outpatient basis. This study aimed to describe transfusion support in lymphoma patients undergoing ASCT and identify increased or prolonged transfusion requirement predictors. MATERIALS AND METHODS: A retrospective study of all consecutive lymphoma patients undergoing ASCT between 2010 and 2020. RESULTS: Out of 226 patients, 145 (64%) received red blood cell (RBC) transfusions, whereas all 226 (100%) required platelet transfusion (PT). Transfusions between Day +1 and +30 were higher in patients over 60 (2 [1-4] vs. 2 [0-2] RBC; p = 0.001 and 4 [2-8] vs. 3 [2-4] PT; p < 0.001); patients with pre-transplant anaemia (4 [2.5-6] vs. 2 [0-2] RBC; p < 0.001 and 5 [3-9] vs. 3 [2-4] PT; p = 0.001); pre-transplant thrombocytopenia (2 [1-4] vs. 2 [0-2] RBC; p < 0.001 and 4 [3-8.5] vs. 2 [1-3] PT; p < 0.001) or CD34+ cell dose <4 × 106 /kg (2 [0-4] vs. 2 [0-2] RBC; p = 0.024 and 4 [2-6] vs. 2 [1-3.5] PT; p < 0.001). RBC transfusion independence was reached later in patients receiving carmustine, cytarabine, etoposide and melphalan (BEAM) (hazard ratio [HR] 1.6; confidence interval [CI] 1.1-2.3) and those requiring RBC before infusion and/or with pre-transplant anaemia (HR 2.2; CI 1.4-3.4). Age above 60 (HR 1.4; CI 1.0-1.9), BEAM conditioning (HR 1.4; CI 1.0-2.0) and pre-transplant thrombocytopenia and/or requiring PT before infusion (HR 1.8; CI 1.4-2.5) entailed longer time until PT independence. CONCLUSION: These four factors (age ≥60 years; BEAM conditioning, CD34+ dose <4 × 106 /kg and pre-transplant cytopenia and/or Day -10 to 0 transfusion) allowed dividing patients into three groups with significant differences between them regarding the time until transfusion independence.
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Anemia , Trasplante de Células Madre Hematopoyéticas , Linfoma , Trombocitopenia , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma/terapia , Linfoma/etiología , Trasplante de Células Madre , Trombocitopenia/etiología , Anemia/terapia , Anemia/etiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Bone marrow (BM) harvesting is one of the essential sources of stem cells for haematopoietic stem cell transplantation. In 2019, commercial BM collection kits became unavailable in Europe. Consequently, we created an in-house BM collection kit as an alternative. MATERIALS AND METHODS: We compared two groups of BM collections. The first collections were taken using an in-house kit from June 2022 through February 2023 and the second with a commercial kit from February 2021 through May 2022. These all took place at seven collection centres (CC). We analysed the harvest quality (cell blood count, CD34+ cells, viability, potency and sterility), the incidents occurring with each kit and the time to neutrophil and platelet engraftment in recipients. RESULTS: A total of 23 donors underwent BM harvesting with the in-house kit and 23 with the commercial one. Both cohorts were comparable regarding donor characteristics, CC and time to procedure. No statistical differences were found in harvest quality between the in-house and commercial kits. A new transfusion set was required in three BM harvests (13%) with the in-house kit because of filter clogging. The median time to neutrophil and platelet engraftment was 21 days for both cohorts and 29 days (in-house) and 33 days (commercial), p = 0.284, respectively. CONCLUSION: The in-house BM collection kit offers a real approach to solve the diminished supply of commercial kits. A higher risk of filter clogging was observed compared with commercial kits due to the lack of 850 and 500 µm filters.
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Trasplante de Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Médula Ósea/métodos , Médula Ósea , Trasplante Homólogo , Donantes de TejidosRESUMEN
Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.
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Fármacos Anti-VIH/farmacología , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Activación Viral/inmunología , Latencia del Virus/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Depsipéptidos/farmacología , Diterpenos/farmacología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Carga Viral , Activación Viral/efectos de los fármacos , Latencia del Virus/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: Donor selection criteria (DSC) are a vital link in the chain of supply of Substances of Human Origin (SoHO) but are also subject to controversy and differences of opinion. Traditionally, DSC have been based on application of the precautionary principle. MATERIALS AND METHODS: From 2017 to 2020, TRANSPOSE (TRANSfusion and transplantation PrOtection and SElection of donors), a European research project, aimed to identify discrepancies between current DSC by proposing a standardized risk assessment method for all SoHO (solid organs excluded) and all levels of evidence. RESULTS: The current DSC were assessed using a modified risk assessment method based on the Alliance of Blood Operators' Risk-based decision-making framework for blood safety. It was found that with limited or diverging scientific evidence, it was difficult to reach consensus and an international standardized method for decision-making was lacking. Furthermore, participants found it hard to disregard their local guidelines when providing expert opinion, which resulted in substantial influence on the consensus-based decision-making process. CONCLUSIONS: While the field of donation-safety research is expanding rapidly, there is an urgent need to formalize the decision-making process regarding DSC. This includes the need for standardized methods to increase transparency in the international decision-making process and to ensure that this is performed consistently. Our framework provides an easy-to-implement approach for standardizing risk assessments, especially in the context of limited scientific evidence.
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Donantes de Sangre , Seguridad de la Sangre/métodos , Selección de Donante/normas , Humanos , Medición de RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks. MATERIALS AND METHODS: National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets. Finally, participants rated the risks according to severity, level of evidence and prevalence. RESULTS: Significant discrepancies between anticipated donor risks and the collected data were found. Furthermore, many participants reported that national data on adverse reactions in donors of stem cells, gametes, embryos and tissues were not routinely collected and/or available. CONCLUSIONS: These findings indicate that there is a need to further develop and standardize donor vigilance in Europe and to include long-term risks to donors, which are currently underreported, ensuring donor health and securing the future supply of SoHO.
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Donantes de Sangre , Salud , Seguridad del Paciente , Europa (Continente) , Humanos , Encuestas y Cuestionarios , Donantes de TejidosRESUMEN
BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti-ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain. STUDY DESIGN AND METHODS: A cross-sectional survey was carried out among Spanish hospitals, focused on iTTP patients ≥16 years old attended between 2015 and 2017, and those at follow-up before that interval. Incidence, prevalence, mortality, refractoriness, exacerbations, treatment complications, relapses, and sequelae were estimated. RESULTS: Forty-two hospitals covering roughly 20 million inhabitants answered the survey and reported 203 episodes (138 newly-diagnosed and 65 relapses), of which 193 (95.1%) were treated. Incidence was 2.67 (95% CI 1.90-3.45) patients per million inhabitants per year and prevalence 21.44 (95% CI% 19.10-23.73) patients per million inhabitants. At diagnosis, ADAMTS13 activity and anti-ADAMTS13 autoantibody were measured in 97% and 84.3% of reported episodes, respectively. Fifteen patients (7.4%) died as a direct consequence of iTTP, 6 of them before receiving any iTTP-specific treatment. Thirty-one (16.1%) of the 193 treated episodes were refractory to plasma exchange and corticosteroids, and 51 (26.4%) suffered at least one exacerbation. CONCLUSION: iTTP incidence and prevalence were somewhat higher than those documented in neighboring countries. Together with data on treatments and outcomes, this information will allow us to better estimate what is needed to improve diagnosis and prognosis of iTTP patients in Spain.
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Hematología/organización & administración , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/epidemiología , Púrpura Trombocitopénica Trombótica/terapia , Proteína ADAMTS13/química , Adulto , Autoanticuerpos/química , Estudios Transversales , Hospitalización , Hospitales , Humanos , Incidencia , Evaluación de Resultado en la Atención de Salud , Intercambio Plasmático , Prevalencia , Sistema de Registros , Estudios Retrospectivos , España/epidemiología , Encuestas y Cuestionarios , Resultado del TratamientoAsunto(s)
Hepatitis , Fallo Hepático Agudo , Neoplasias , Humanos , Inmunoterapia , Intercambio PlasmáticoRESUMEN
BACKGROUND: Prematurity is a significant health issue due to its incidence and associated complications. Anemia is common in extremely preterm infants (EPI) and often requires transfusions. Red blood cells (RBC) from adult blood (AB) donors have been linked to oxygen-related complications in EPI, leading to the exploration of cord blood (CB) as an alternative source. However, standardization of CB-RBC manufacturing and comparison with AB-RBC characteristics are necessary before clinical studies can be conducted. MATERIALS AND METHODS: This study investigated the quality and characteristics of leukoreduced, gamma-irradiated CB-RBC obtained using a commercial closed system from CB donations not meeting hematopoietic transplantation criteria. CB-RBC units were compared with AB-RBC units, both stored in saline-adenine-glucose-mannitol (SAGM). Various parameters, including hematological and biochemical characteristics, pH, 2,3-DPG levels, blood gases and potential toxicants, were evaluated during storage. RESULTS: CB-RBC units had acceptable initial quality parameters and a hematocrit (55±2%) comparable to AB-RBC. The main finding during storage was a faster rise in hemolysis compared to AB-RBC. Potassium (K+) significantly increased during storage in both sources. As expected, glucose levels decreased, and conversely, lactate levels increased, indicating similar patterns of anaerobic glycolysis during storage. pH decreased, affecting the oxygen dissociation curve due to reduced 2,3-DPG levels. After irradiation at 14 days of storage, CB-RBC were less stable as hemolysis and K+ significantly increased compared to AB-RBC at 24 hours. Phthalate concentrations, indicative of plasticizers, increased during storage, but significantly less in CB compared to AB-RBC. Most metals measured were within acceptable ranges. DISCUSSION: The quality of CB-RBC during storage is primarily influenced by levels of hemolysis and extracellular K+ content. Based on the analyzed parameters, we suggest that the expiration date for CB-RBC stored with SAGM should be set at 14 days, with transfusion occurring within <24 hours after irradiation.
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BACKGROUND: There is debate whether delayed umbilical cord clamping following delivery, the current gold standard, affects the proportion of cord blood units (CBU) suitable for public cord blood banking. This study was designed to assess the impact of delayed cord clamping on the number of CBU suitable for therapeutic uses. MATERIALS AND METHODS: To minimize variability, data from the four most active collection centers within the Programa Concordia (Spain) were included. Data on CBU collected in utero from mothers following normal vaginal deliveries from July 2018 to December 2021 were analyzed. The weight of the collection bags (as a surrogate of volume) and total nucleated cell (TNC) count were analyzed according to three defined clamping times: 30 s, 60 s and ≥120 s. The CBU were stratified as suitable for stem cell transplantation (≥110 g and ≥1,500×106 TNC/unit) or other clinical applications (≥100 g but TNC count below the threshold). RESULTS: - There were 131 (18%), 548 (76%), and 40 (5%) CBU collected at 30 s, 60 s and ≥120 s, respectively. The median weight of the CBU decreased gradually with time, with a significant difference between units collected when the cord was clamped at 30 s or 60 s (p=0.036), so significantly fewer CBU met the minimal weight criterion (100 g) at 60 s than at 30 s (p=0.002). However, this was not reflected by the TNC available, resulting in non-statistical differences in CBU eligible for banking between these times. The major predictor of collection success was the neonate's birth-weight. DISCUSSION: -Despite decreases in the volume of cord blood collected when cord clamping at 30 s or 60 s, TNC count is maintained resulting in similar numbers of CBU eligible for banking. The different clamping delays investigated in this study are, therefore, compatible with public cord blood banking needs.
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Cryopreservation was recommended to ensure continuity in allogeneic hematopoietic progenitor cells (HPC) transplantation during the COVID-19 pandemic. Several groups have shown no impact on clinical outcomes for patients who underwent HPC transplantation with cryopreserved products during the first months of this pandemic. However, concerns about quality control attributes after cryopreservation have been raised. We investigated, in 155 allogeneic peripheral blood cryopreserved HPC, leukocytapheresis characteristics influencing viable CD34+ and CD3+ cells, and CFU-GM recoveries after thawing. Collection characteristics such as volume, nucleated cells (NC)/mL and hematocrit correlated with viable CD34+ and CD3+ cells recoveries after thawing in univariate analysis but only CD3+ cells remained statistically significant in multivariate analysis (r2 = 0.376; P = < 0.001). Additionally, transit time also showed correlation with viable CD34+ (r2 = 0.186), CD3+ (r2 = 0.376) and CFU-GM recoveries (r2 = 0.212) in multivariate analysis. Thus, diluting leukocytapheresis below 200 × 106 NC/mL, avoiding red cells contamination above 2%, cryopreserving below 250 × 106 NC/mL and minimizing transit time below 36 h, prevented poor viable CD34+ and CD3+ cells, and CFU-GM recoveries. In summary, optimizing leukocytapheresis practices and minimizing transportation time may better preserve the quality attributes of HPC when cryopreservation is indicated.
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COVID-19 , Trasplante de Células Madre Hematopoyéticas , Antígenos CD34/análisis , Supervivencia Celular , Criopreservación , Células Madre Hematopoyéticas , Humanos , Leucaféresis , PandemiasRESUMEN
Cryopreservation was recommended to ensure continuity of unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) during COVID-19 pandemic. However, its impact on clinical outcomes and feasibility was not well known. We compared 32 patients who underwent UD HSCT using cryopreserved peripheral blood stem cells (PBSC) during the COVID-19 pandemic with 32 patients who underwent UD HSCT using fresh PBSC in the previous period. Median neutrophil engraftment was 17.5 and 17.0 days with cryopreserved and fresh grafts, respectively. Non-significant delays were found in platelet recovery days (25.5 versus 19.0; P = 0.192) and full donor chimerism days (35.0 and 31.5; P = 0.872) using cryopreserved PBSC. The rate of acute graft-versus-host disease at 100 days was 41% (95% CI [21-55%]) in cryopreserved group versus 31% (95% CI [13-46%]) in fresh group (P = 0.380). One-hundred days progression-relapse free survival and overall survival did not differ significantly. During COVID-19 pandemic, six frozen UD donations were not transfused and logistical and clinical issues regarding cryopreservation procedure, packaging, and transporting appeared. In summary, UD HSCT with cryopreserved PBSC was safe during this challenging time. More efforts are needed to ensure that all frozen grafts are transplanted and cryopreservation requirements are harmonized.
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COVID-19 , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Criopreservación , Células Madre Hematopoyéticas , Humanos , Pandemias , SARS-CoV-2 , Donante no EmparentadoRESUMEN
BACKGROUND: Bacterial infection remains a frequent complication in patients receiving a hematopoietic stem cell transplantation (HSCT). However, the impact of the antibacterial prophylaxis mortality in these patients is controversial. PATIENTS AND METHODS: Retrospective comparison of 2 consecutive groups of patients undergoing HSCT receiving (n=132) or not (n=107) antibacterial prophylaxis with levofloxacin. RESULTS: 41% of patients receiving prophylaxis with levofloxacin had microbiologically documented infection (MDI) with bacteremia, compared with 40% of those not receiving levofloxacin. The frequency of gram-negative bacteremia was 11 and 38%, the resistance to levofloxacin was 39 and 14%, and the mortality was 8 and 7%, respectively. CONCLUSIONS: In our experience, the use of levofloxacin as prophylaxis in HSCT was associated with a lower frequency of gram-negative bacteremia but was not associated with a decreased rate of MDI and did not influence their outcome. In contrast, there was an increase in quinolone resistance in patients treated with levofloxacin.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Bacteriemia/prevención & control , Infecciones por Bacterias Gramnegativas/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Levofloxacino/uso terapéutico , Adolescente , Adulto , Anciano , Bacteriemia/etiología , Femenino , Infecciones por Bacterias Gramnegativas/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Anemia Refractaria con Exceso de Blastos/complicaciones , Artritis/etiología , Derrame Pericárdico/etiología , Derrame Pleural/etiología , Anemia Refractaria con Exceso de Blastos/diagnóstico , Anemia Refractaria con Exceso de Blastos/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Artritis/tratamiento farmacológico , Azacitidina/uso terapéutico , Citarabina/administración & dosificación , Progresión de la Enfermedad , Etopósido/administración & dosificación , Resultado Fatal , Hepatomegalia/etiología , Humanos , Idarrubicina/administración & dosificación , Inmunosupresores/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Masculino , Persona de Mediana Edad , Derrame Pericárdico/tratamiento farmacológico , Derrame Pleural/tratamiento farmacológico , Serositis/tratamiento farmacológico , Serositis/etiologíaAsunto(s)
Infecciones por Clostridium/sangre , Clostridium perfringens , Hemólisis , Anciano , Humanos , MasculinoRESUMEN
Fundamento: La infección bacteriana continúa siendo una complicación frecuente en pacientes receptores de un trasplante de progenitores hematopoyéticos (TPH). No obstante, el impacto de la profilaxis antibacteriana en la mortalidad de estos pacientes es controvertido. Pacientes y métodos: Comparación retrospectiva de 2 grupos consecutivos de receptores de TPH según recibieran (n = 132) o no (n = 107) profilaxis antibacteriana con levofloxacino. Resultados: En el 41% de los procedimientos de TPH en los que se administró profilaxis con levofloxacino se constató infección microbiológicamente documentada (IMD) con bacteriemia, frente a un 40% de los que no recibieron levofloxacino. La frecuencia de bacteriemia por bacilos gramnegativos fue del 11 y del 38%, la resistencia a levofloxacino fue del 39 y del 14%, y hubo un 8 y 7% de muertes, respectivamente. Conclusiones: En nuestra experiencia, el uso de levofloxacino se asoció a una menor frecuencia de bacteriemia por microorganismos gramnegativos, pero no se asoció a disminución en la tasa de IMD ni influyó en su evolución. En cambio, hubo un aumento de la resistencia a quinolonas en los pacientes tratados con levofloxacino (AU)
Background: Bacterial infection remains a frequent complication in patients receiving a hematopoietic stem cell transplantation (HSCT). However, the impact of the antibacterial prophylaxis mortality in these patients is controversial. Patients and methods: Retrospective comparison of 2 consecutive groups of patients undergoing HSCT receiving (n = 132) or not (n = 107) antibacterial prophylaxis with levofloxacin. Results: 41% of patients receiving prophylaxis with levofloxacin had microbiologically documented infection (MDI) with bacteremia, compared with 40% of those not receiving levofloxacin. The frequency of gram-negative bacteremia was 11 and 38%, the resistance to levofloxacin was 39 and 14%, and the mortality was 8 and 7%, respectively. Conclusions; In our experience, the use of levofloxacin as prophylaxis in HSCT was associated with a lower frequency of gram-negative bacteremia but was not associated with a decreased rate of MDI and did not influence their outcome. In contrast, there was an increase in quinolone resistance in patients treated with levofloxacin (AU
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Humanos , Masculino , Femenino , Receptores del Factor Estimulante de Colonias , Receptores del Factor Estimulante de Colonias/inmunología , Profilaxis Antibiótica/métodos , Levofloxacino/uso terapéutico , Infecciones/tratamiento farmacológico , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Bacteriemia/prevención & control , Control de Infecciones/métodos , Bacilos y Cocos Aerobios Gramnegativos , Bacilos y Cocos Aerobios Gramnegativos/aislamiento & purificación , Resistencia a Medicamentos , Estudios RetrospectivosRESUMEN
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