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1.
Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT
Styczynski, J., Tridello, G., Koster, L., Knelange, N., Wendel, L., van Biezen, A., van der Werf, S., Mikulska, M., Gil, L., Cordonnier, C., et al
Bone marrow transplantation. 2023
Abstract
We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.
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2.
SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination
Piñana, J. L., Martino, R., Vazquez, L., López-Corral, L., Pérez, A., Chorão, P., Avendaño-Pita, A., Pascual, M. J., Sánchez-Salinas, A., Sanz-Linares, G., et al
Bone marrow transplantation. 2023;:1-14
Abstract
The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.
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3.
Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey
Passweg, J. R., Baldomero, H., Ciceri, F., Corbacioglu, S., de la Cámara, R., Dolstra, H., Glass, B., Greco, R., McLornan, D. P., Neven, B., et al
Bone marrow transplantation. 2023;:1-12
Abstract
In 2021, 47,412 HCT (19,806 (42%) allogeneic and 27,606 (58%) autologous) in 43,109 patients were reported by 694 European centers. 3494 patients received advanced cellular therapies, 2524 of which were CAR-T treatments, an additional 3245 received DLI. Changes compared to the previous year were CAR-T treatment (+35%), allogeneic HCT +5.4%, autologous HCT +3.9%, more pronounced in non-malignant disorders. Main indications for allogeneic HCT were myeloid malignancies 10,745 (58%), lymphoid malignancies 5127 (28%) and non-malignant disorders 2501 (13%). Main indications for autologous HCT were lymphoid malignancies 22,129 (90%) and solid tumors 1635 (7%). In allogeneic HCT, use of haploidentical donors decreased by -0.9% while use of unrelated and sibling donors increased by +4.3% and +9%. Cord blood HCT decreased by -5.8%. Pediatric HCT increased overall by +5.6% (+6.9% allogeneic and +1.6% autologous). Increase in the use of CAR-T was mainly restricted to high-income countries. The drop in HCT activity reported in 2020 partially recovered in 2021, the second year of the SARS-CoV-2 pandemic. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual EBMT report reflects current activities useful for health care resource planning.
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4.
Impact of the SARS-CoV-2 pandemic on hematopoietic cell transplantation and cellular therapies in Europe 2020: a report from the EBMT activity survey
Passweg, J. R., Baldomero, H., Chabannon, C., Corbacioglu, S., de la Cámara, R., Dolstra, H., Glass, B., Greco, R., Mohty, M., Neven, B., et al
Bone marrow transplantation. 2022;:1-11
Abstract
In 2020, 45,364 HCT in 41,016 patients, 18,796 (41%) allogeneic and 26,568 (59%) autologous in 690 centers were reported. Changes observed were as follows: total number of HCT -6.5%, allogeneic HCT -5.1%, autologous HCT -7.5%, and were more pronounced in non-malignant disorders for allogeneic HCT and in autoimmune disease for autologous HCT. Main indications were myeloid malignancies 10,441 (25%), lymphoid malignancies 26,120 (64%) and non-malignant disorders 2532 (6%). A continued growth in CAR-T cellular therapies to 1874 (+65%) patients in 2020 was observed. In allogeneic HCT, the use of haploidentical donors increased while use of unrelated and sibling donors decreased. Cord blood HCT increased by 11.7% for the first time since 2012. There was a significant increase in the use of non-myeloablative but a drop in myeloablative conditioning and in use of marrow as stem cell source. We interpreted these changes as being due to the SARS-CoV-2 pandemic starting early in 2020 in Europe and provided additional data reflecting the varying impact of the pandemic across selected countries and larger cities. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual report of the EBMT reflects current activities useful for health care planning.
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5.
SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH-TC)
Piñana, J. L., López-Corral, L., Martino, R., Montoro, J., Vazquez, L., Pérez, A., Martin-Martin, G., Facal-Malvar, A., Ferrer, E., Pascual, M. J., et al
American journal of hematology. 2021
Abstract
This is a multicenter prospective observational study which included a large cohort (n = 397) of allogeneic (allo-HSCT) (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3 to 6?weeks after complete SARS-CoV-2 vaccination from February 1st 2021 to July 20th 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of recipients (93%) were vaccinated more than 1?year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia <1x10(9) /mL [Odds ratio (OR) 0.33, 95% confident interval (95% C.I.) 0.16-0.69, p = 0.003), active graft-vs-host disease (GvHD) (OR 0.51, 95% C.I. 0.27-0.98, p = 0.04) and vaccination within the first year of transplant (OR 0.3, 95% C.I. 0.15-0.9, p = 0.04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL) (OR 0.09, 95% C.I. 0.02-0.44, p = 0.003) and active corticosteroid therapy (OR 0.2, 95% C.I. 0.02-0.87, p = 0.03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, timing of vaccine and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT respectively, to identify candidates for SARS-CoV-2 monitoring. This article is protected by copyright. All rights reserved.
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6.
Risk factors and outcome of COVID-19 in patients with hematological malignancies
Piñana, J. L., Martino, R., García-García, I., Parody, R., Morales, M. D., Benzo, G., Gómez-Catalan, I., Coll, R., De La Fuente, I., Luna, A., et al
Experimental hematology & oncology. 2020;9:21
Abstract
BACKGROUND Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n?=?58) or allogeneic stem cell transplantation (allo-SCT) (n?=?65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p?=?0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age?>?70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p?=?0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p?0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p?=?0.003); neutropenia (0.5?×?10(9)/L) (OR 2.8, 95% CI 1.3-6.1, p?=?0.01); and a C-reactive protein (CRP)?>?20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p?0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p?=?0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P?=?0.1). CONCLUSIONS In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.