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Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry
Ljungman, P., Tridello, G., Piñana, J. L., Ciceri, F., Sengeloev, H., Kulagin, A., Mielke, S., Yegin, Z. A., Collin, M., Einardottir, S., et al
Frontiers in immunology. 2023;14:1125824
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Abstract
INTRODUCTION COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. METHODS This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. RESULTS The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. DISCUSSION Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.
PICO Summary
Population
Adults and children who tested PCR positive to COVID-19 after previous allogeneic transplant, and were reported to the EBMT registry (n=986)
Intervention
Analysis of the outcome of COVID-19 during important phases of the COVID-19.
Comparison
Patients contracting COVID-19 at different time points of the pandemic were compared
Outcome
The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age, worse performance status, contracting COVID-19 within the first 30 days or 30 - 100 days after HCT, ongoing immunosuppression, pre-existing lung disease, and recipient CMV seropositivity had negative impact on overall survival while patients contracting COVID-19 in 2020 or 2021 had worse overall survival than patients with COVID-19 diagnosed in 2022.
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Allogeneic stem cell transplant in relapsed/ refractory Hodgkin lymphoma: A 21 years' experience
Couto, M. E., Vaz, C. P., Branca, R., Leite, L., Brás, G., Roncon, S., Campos, A.
Porto biomedical journal. 2022;7(5):e173
Abstract
Background: Allogenic stem cell transplant (alloSCT) has been used for several decades as a salvage strategy for relapsed/ refractory Hodgkin lymphoma (R/R HL), being a durable disease control method for some patients. Methods: A unicenter retrospective analysis was performed about alloSCT in R/R HL along 21 years. A survival analysis was made in search for prognostic factors with impact in overall survival (OS)/progression free survival (PFS). Results: Thirty-five patients were reviewed: median age 30years [17-46], 57.1% males, 82.9% had an esclero-nodular HL, 54.3% were in stage II of disease, and 42.9% achieved a complete response before the alloSCT. The donor type was matched-related in 54.3% and the stem cell source was peripheral blood in 97.1% of the grafts. All patients did a reduced intensity conditioning regimen. The overall response rate was 85.7% (complete in 68.6%, partial in 17.1%). Acute graft versus host disease grade II-IVwas seen in 45.7%. Transplant related mortality at day 360 was 17.9%. The median OS was 61 months (95% confidente interval: 33.6-88.3). The median PFS was 1Omonths (95% confidente interval: 3.1-16.9). Patients with >3Oyears at the alloSCT time and a previous autologous SCT showed better OS/PFS in the univariate analysis; having a matched donor and absence of infections along the alloSCT also improved PFS. Conclusions: AlloSCT is a feasible procedure in patients with R/R HL, being able to stabilize the disease in a large number of patients. However, it has a relevant toxicity in patients highly pre-treated.
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Acute kidney injury after allogeneic hematopoietic stem cell transplantation - Predictors and survival impact: A single center retrospective study
Menezes, M. D. M., Marques, A. I., Chuva, T., Pinho Vaz, C., Ferreira, H., Branca, R., Paiva, A., Campos, A., Maximino Costa, J.
Nefrologia. 2022;42(6):656-663
Abstract
INTRODUCTION AND OBJECTIVES Acute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting. PATIENTS AND METHODS We performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019. RESULTS AKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p=0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p=0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p<0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p=0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p=0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p=0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p=0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p=0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p=0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival. CONCLUSION Patients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.
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Haplo-identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: results from the Severe Aplastic Anemia Working Party of the EBMT
Zubicaray, J., Pagliara, D., Sevilla, J., Eikema, D. J., Bosman, P., Ayas, M., Zecca, M., Yesilipek, A., Kansoy, S., Renard, C., et al
American journal of hematology. 2021
Abstract
Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n=123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n=33) or T cells depleted in-vivo with some type of graft manipulation ex-vivo (n=59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p 0.22). Event free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p=?0.046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p=0.005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts. This article is protected by copyright. All rights reserved.
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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
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Association of Macroeconomic Factors With Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation for Adults With Acute Lymphoblastic Leukemia: An Analysis From the Acute Leukemia Working Party of the EBMT
Giebel, S., Labopin, M., Ibatici, A., Browne, P., Czerw, T., Socie, G., Unal, A., Kyrcz-Krzemien, S., Bacigalupo, A., Goker, H., et al
Oncologist. 2016;21(3):377-83
Abstract
PURPOSE From a global perspective, the rates of allogeneic hematopoietic cell transplantation (alloHCT) are closely related to the economic status of a country. However, a potential association with outcome has not yet been documented. The goal of this study was to evaluate effects of health care expenditure (HCE), Human Development Index (HDI), team density, and center experience on nonrelapse mortality (NRM) after HLA-matched sibling alloHCT for adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS A total of 983 patients treated with myeloablative alloHCT between 2004 and 2008 in 24 European countries were included. RESULTS In a univariate analysis, the probability of day 100 NRM was increased for countries with lower current HCE (8% vs. 3%; p = .06), countries with lower HDI (8% vs. 3%; p = .02), and centers with less experience (8% vs. 5%; p = .04). In addition, the overall NRM was increased for countries with lower current HCE (21% vs. 17%; p = .09) and HDI (21% vs. 16%; p = .03) and for centers with lower activity (21% vs. 16%; p = .07). In a multivariate analysis, the strongest predictive model for day 100 NRM included current HCE greater than the median (hazard ratio [HR], 0.39; p = .002). The overall NRM was mostly predicted by HDI greater than the median (HR, 0.65; p = .01). Both lower current HCE and HDI were associated with decreased probability of overall survival. CONCLUSION Both macroeconomic factors and the socioeconomic status of a country strongly influence NRM after alloHCT for adults with ALL. Our findings should be considered when clinical studies in the field of alloHCT are interpreted. Copyright ©AlphaMed Press.
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Twenty Years of Autologous Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma: A Single Portuguese Center Experience
Dantas Brito, M., Campilho, F., Branca, R., Vaz, C., Roncon, S., Campos, A.
Acta Medica Portuguesa. 2016;29(3):205-9
Abstract
INTRODUCTION Diffuse large B-cell lymphoma can be cured in 60% - 70% of patients. Autologous stem cell transplantation is the standard treatment for relapsed disease. This high-intensity treatment after first complete remission in patients with high International Prognostic Index remains controversial and was performed in our department during some years. MATERIAL AND METHODS Retrospective study, review of clinical records. RESULTS This study evaluates the outcome of 113 patients transplanted between 1992 and 2012. Considering status before transplantation patients were divided in groups: a) first complete remission after 1 line of chemotherapy (n = 64); b) first complete remission after > two chemotherapy lines (n = 15); c) second complete remission (n = 15); d) more advanced diseased (n = 19). Chemotherapy used in first line therapy was mainly R-CHOP (n = 71) and CHOP (n = 28). The median follow-up of patients still alive was 34 months (1 - 221). At five years, overall survival was 73% (+/- 5) and disease free survival was 75% (+/- 5). CONCLUSION Conventional chemotherapy followed by autologous stem cell transplant is a safe and efficient option for selected patients. In our series 70% high-risk patients were free from disease with this strategy.