A hub-and-spoke model to deliver effective access to chimeric antigen receptor T-cell therapy in a public health network: the Catalan Blood and Tissue Bank experience.

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.

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX.

Leukocytapheresis variables and transit time for allogeneic cryopreserved hpc: better safe than sorry.

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.

Evaluation of Humoral and Cellular Immune Responses to the SARS-CoV-2 Vaccine in Patients With Common Variable Immunodeficiency Phenotype and Patient Receiving B-Cell Depletion Therapy.

Introduction: SARS-CoV-2 vaccines' effectiveness is not yet clearly known in immunocompromised patients. This study aims to assess the humoral and cellular specific immune response to SARS-CoV-2 vaccines and the predictors of poor response in patients with common variable immunodeficiency (CVID) phenotype and in patients treated with B-cell depletion therapies (BCDT), as well as the safety of these vaccines. Methods: From March to September 2021, we performed a prospective study of all adult patients who would receive the SARS-CoV-2 vaccination and were previously diagnosed with (i) a CVID syndrome (CVID phenotype group; n=28) or (ii) multiple sclerosis (MS) treated with B-cell depleting therapies three to six months before vaccination (BCD group; n=24). Participants with prior SARS-CoV-2 infection; or prior SARS-CoV-2 vaccine administration; or use of any immunosuppressant (except BCDT in MS group) were excluded. A group of subjects without any medical condition that confers immunosuppression and who met all study criteria was also assessed (control group; n=14). A chemiluminescence immunoassay was used to determine pre- and post-SARS-CoV-2 vaccine anti-S IgG antibodies. T-cell specific response was assessed by analysis of pre- and post-SARS-CoV-2 vaccination blood samples with an interferon-gamma release assay. The baseline blood sample also included several biochemical, haematological and immunological analyses. Results: SARS-CoV-2 vaccines are safe in immunocompromised patients, although their effectiveness was lower than in healthy individuals. CVID phenotype patients showed impaired humoral (29%) and cellular (29%) response, while BCD patients fundamentally presented humoral failure (54%). Low IgA values, low CD19+ peripheral B cells, low switched memory B cells, and a low CD4+/CD8+ ratio were predictors of inadequate specific antibody response in CVID phenotype patients. No factor was found to predict poor cellular response in CVID phenotype patients, nor a defective humoral or cellular response in BCD patients. Conclusion: The effectiveness of SARS-CoV-2 vaccines in CVID phenotype and BCD patients is lower than in healthy individuals. Knowledge of predictive factors of humoral and cellular response failure in immunocompromised patients could be very useful in clinical practice, and thus, studies in this regard are clearly needed.

Cryopreservation of unrelated donor hematopoietic stem cells: the right answer for transplantations during the COVID-19 pandemic?

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.

Linfoma cutáneo asociado a metotrexato en un paciente con artritis reumatoide / Cutaneous lymphoma associated with methotrexate in a patient with rheumatoid arthritis

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