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1.
Br J Haematol ; 201(5): 813-823, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37006158

RESUMEN

Immunocompromised patients, such as those with a haematological malignancy, are at higher risk of SARS-CoV-2 infection, severe outcomes and mortality. Tixagevimab/cilgavimab is a monoclonal antibody combination which binds to the SARS-CoV-2 spike protein. The PROVENT phase III clinical trial reported that tixagevimab/cilgavimab prophylaxis significantly reduced the risk of COVID-19 infection in immunocompromised participants. However, the trial was conducted before the Omicron variant became prevalent. This systematic review and meta-analysis provide an up-to-date summary of the real-world effectiveness of tixagevimab/cilgavimab in immunocompromised patients, including patients with haematological malignancies. Clinical studies from 1 January 2021 to 1 October 2022, which reported breakthrough COVID-19 infections after tixagevimab/cilgavimab, were included. COVID-19-related hospitalisations, intensive care admissions and mortality were also assessed. A meta-analysis was performed to ascertain overall clinical effectiveness. Eighteen studies, with 25 345 immunocompromised participants, including 5438 patients with haematological pathologies, were included in the review. The overall clinical effectiveness of tixagevimab/cilgavimab against COVID-19 breakthrough infection, hospitalisation, intensive care admission and COVID-19-specific mortality was 40.54%, 66.19%, 82.13% and 92.39%, respectively. This review highlights the clinical effectiveness of tixagevimab/cilgavimab at reducing COVID-19 infection and severe outcomes for immunosuppressed individuals, including patients with a haematological malignancy, during the Omicron-predominant era. Real-world studies are important to provide ongoing certainty of the clinical benefit for immunocompromised patients against new SARS-CoV-2 variants.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Humanos , SARS-CoV-2 , Resultado del Tratamiento , Anticuerpos Monoclonales , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Huésped Inmunocomprometido
2.
Br J Haematol ; 198(3): 492-502, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35485402

RESUMEN

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.


Asunto(s)
Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Antígenos CD19/uso terapéutico , Síndrome de Liberación de Citoquinas , Humanos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Estudios Prospectivos , Reino Unido/epidemiología
3.
Br J Cancer ; 125(7): 939-947, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34400804

RESUMEN

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.


Asunto(s)
COVID-19/epidemiología , Neoplasias Hematológicas/epidemiología , Neoplasias/epidemiología , SARS-CoV-2/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/patología , COVID-19/virología , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/virología , Hospitales , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/virología , Factores de Riesgo
4.
Am J Transplant ; 21(2): 864-869, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33037770

RESUMEN

Classical veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication post allogeneic hematopoietic stem cell transplantation (HSCT). Before the recently revised EBMT criteria, the Baltimore and modified Seattle criteria failed to recognize the syndrome of late-onset VOD. We present real-world experience from a large UK transplant center reporting on VOD/SOS in consecutive HSCT adult patients (n = 530), transplanted for hematological cancers. We identified 27 patients treated with Defibrotide for VOD/SOS diagnosis, where detailed data were available for final analysis. Using standard definitions including EBMT criteria, around 30% (n = 8/27) of cases classified as late-onset VOD presenting at median of 46 (22-93) days but with D100 survival (63% vs 58%, Log-rank; P = 0.81) comparable to classical VOD. Hazard ratio for D100 mortality was 2.82 (95% CI: 1.74-4.56, P < .001, Gray test) with all VOD/SOS events. Twenty percent (n = 2/8) of late-onset VOD patients were anicteric and 42% (n = 8) classical VOD patients presented with refractory thrombocytopenia, while less than half met EBMT criteria for classical VOD in adults, highlighting gaps in real-world diagnostic limitations using EBMT criteria. However, challenges remain about underrecognition and difficulties related to early defibrotide access for treatment of late-onset VOD in current treatment guidelines. Our report strongly supports early Defibrotide for the treatment of severe VOD/SOS in adults regardless of time of onset.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Polidesoxirribonucleótidos , Reino Unido
5.
Biol Blood Marrow Transplant ; 26(7): 1342-1349, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32200121

RESUMEN

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT) that is traditionally diagnosed using Baltimore or modified Seattle criteria. Whereas the Baltimore criteria require the presence of hyperbilirubinemia (bilirubin ≥2 mg/dL) for a diagnosis of VOD/SOS, the modified Seattle criteria do not. Before approval by the US Food and Drug Administration, defibrotide was available in the United States through an expanded-access study (T-IND). The T-IND protocol initially required post-HCT diagnosis of VOD/SOS by the Baltimore criteria or biopsy but was later amended to include patients diagnosed using the modified Seattle criteria. This post hoc analysis examined the incidence of VOD/SOS with a bilirubin level <2 mg/dL before and after Day 21 post-HCT in T-IND patients enrolled following the amendment allowing for diagnosis by the modified Seattle criteria. Survival of adult and pediatric patients with or without hyperbilirubinemia and with or without multiorgan dysfunction (MOD) was also evaluated. Of 803 post-HCT patients with VOD/SOS enrolled following the protocol amendment, 181 (23%) had a bilirubin level <2 mg/dL and would not have been diagnosed if hyperbilirubinemia was required. The bilirubin level at diagnosis was <2 mg/dL in 165 of 331 patients (50%) diagnosed by the modified Seattle criteria and in 16 of 23 patients (70%) diagnosed by biopsy. VOD/SOS with a bilirubin level <2 mg/dL was more common in pediatric patients (29%), although it also occurred in adult patients (15%). Patients with hyperbilirubinemia had lower Day 100 survival (54% versus 87% in patients with bilirubin <2 mg/dL) and a higher incidence of MOD (41% versus 26% in patients with bilirubin <2 mg/dL). The incidence of treatment-emergent adverse events and serious adverse events was lower in patients with a bilirubin level <2 mg/dL. These results indicate that anicteric VOD/SOS occurs in both adult and pediatric patients post-HCT and can be diagnosed before and after Day 21 in both groups. The worse survival in patients with bilirubin ≥2 mg/dL suggests that requiring hyperbilirubinemia may result in a progressed disease stage associated with worse outcomes. Taken together, these results highlight the importance of awareness and the possibility of VOD/SOS in the absence of elevated bilirubin level.


Asunto(s)
Fibrinolíticos , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Polidesoxirribonucleótidos , Adulto , Niño , Fibrinolíticos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Incidencia , Polidesoxirribonucleótidos/uso terapéutico , Resultado del Tratamiento
6.
N Engl J Med ; 386(2): 198, 2022 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-35021000
7.
Clin Infect Dis ; 69(10): 1757-1763, 2019 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-30980715

RESUMEN

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG. METHODS: Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records. RESULTS: All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events. CONCLUSION: Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.


Asunto(s)
Suero Antilinfocítico/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/fisiología , Esclerosis Múltiple/terapia , Paraproteinemias/etiología , Acondicionamiento Pretrasplante/efectos adversos , Activación Viral , Adulto , Animales , Suero Antilinfocítico/inmunología , ADN Viral/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conejos/inmunología , Estudios Retrospectivos , Trasplante Autólogo , Carga Viral
8.
Biol Blood Marrow Transplant ; 25(1): 86-93, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30219698

RESUMEN

More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P <.001), whereas relapse incidence and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P = .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for confounders, including sex, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning, confirmed older age as a significant predictor for NRM and OS, but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. In conclusion, our data show that alloHCT in patients age >65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Sistema de Registros , Hermanos , Donante no Emparentado , Adolescente , Adulto , Factores de Edad , Anciano , Aloinjertos , Europa (Continente) , Femenino , Humanos , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Sociedades Médicas , Factores de Tiempo
9.
Biol Blood Marrow Transplant ; 25(3): 443-450, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30935664

RESUMEN

HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplantation (HCT) results in improved survival and fewer post-transplant complications. Limitations in typing technologies used for the hyperpolymorphic HLA genes have meant that variations outside of the antigen recognition domain (ARD) have not been previously characterized in HCT. Our aim was to explore the extent of diversity outside of the ARD and determine the impact of this diversity on transplant outcome. Eight hundred ninety-one VUD-HCT donors and their recipients transplanted for a hematologic malignancy in the United Kingdom were retrospectively HLA typed at an ultra-high resolution (UHR) for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next-generation sequencing technology. Matching was determined at full gene level for HLA class I and at a coding DNA sequence level for HLA class II genes. The HLA matching status changed in 29.1% of pairs after UHR HLA typing. The 12/12 UHR HLA matched patients had significantly improved 5-year overall survival when compared with those believed to be 12/12 HLA matches based on their original HLA typing but were found to be mismatched after UHR HLA typing (54.8% versus 30.1%, P = .022). Survival was also significantly better in 12/12 UHR HLA-matched patients when compared with those with any degree of mismatch at this level of resolution (55.1% versus 40.1%, P = .005). This study shows that better HLA matching, found when typing is done at UHR that includes exons outside of the ARD, introns, and untranslated regions, can significantly improve outcomes for recipients of a VUD-HCT for a hematologic malignancy and should be prospectively performed at donor selection.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad/normas , Histocompatibilidad/inmunología , Análisis de Secuencia de ADN/normas , Adulto , Alelos , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Histocompatibilidad/genética , Prueba de Histocompatibilidad/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Donante no Emparentado
10.
Br J Haematol ; 185(1): 89-92, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30637732

RESUMEN

Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses.


Asunto(s)
Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Adulto , Anciano , Investigación Biomédica , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Adulto Joven
12.
Eur J Haematol ; 101(4): 466-474, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29714032

RESUMEN

OBJECTIVE: Relapse and graft-vs-host disease (GVHD) are still the main complications after allogeneic hematopoietic stem cell transplantation, especially in the setting of reduced intensity regimen (RIC) and unrelated donor. We compared here anti-thymocyte globulin (ATG) or alemtuzumab as GVHD prophylaxis in patients with myeloid disease transplanted after RIC and from an unrelated donor. METHOD: ATG and alemtuzumab patients have been matched by age, gender, HLA matching, comorbidities and cytogenetics risk (119 patients in each group). RESULTS: After matching, we found that ATG decreased the risk of relapse (HR: 0.55, P = .0049) and improved relapse-free survival (RFS, HR: 0.70, P = .042). The improved RFS with ATG was more pronounced in CMV-positive patients but was not influenced by disease risk. Regarding overall survival, GVHD-free relapse-free survival and transplant-related mortality, the risk was similar using ATG or alemtuzumab. CONCLUSION: Even if GVHD risk is lowered by alemtuzumab use, it does not translate in better outcome due to higher risk of relapse.


Asunto(s)
Alemtuzumab/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Donante no Emparentado , Alemtuzumab/farmacología , Suero Antilinfocítico/farmacología , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del Tratamiento
13.
Biol Blood Marrow Transplant ; 23(2): 293-299, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27816648

RESUMEN

Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90.7%. Acute and chronic GVHD each occurred in 6 patients (13.3%), and only 1 case was severe. Mixed T cell chimerism was frequent and persisted after cessation of immunosuppression. T cells were extensively depleted, representing only 11.3% of lymphocytes at day 30 and rising to 43.8% by 1 year, but still significantly below normal levels (67.2%; P = .018), and deficiency persisted after immunosuppressive therapy (IST) withdrawal. Depletion of CD4 T cells was particularly profound, causing inversion of the normal CD4:CD8 T cell ratio. T cell subset composition was also abnormal, with memory and effector T cells predominating for at least 6 months after FCC HSCT. Analysis of T cell subset chimerism showed that CD4 T cells were predominantly donor-derived at 1 year, whereas recipient-derived CD8 T cells shaped mixed chimerism with a notable contribution of recipient effector CD8 T cells. The prolonged mixed T cell chimerism after IST withdrawal and low incidence of GVHD indicates the establishment of mutual tolerance, but the low incidence of viral disease suggests maintenance of antiviral immunity. Our study shows that despite the abnormal T cell profile after allogeneic HSCT for SAA using the FCC regimen, this regimen is conducive to an excellent clinical outcome.


Asunto(s)
Alemtuzumab/farmacología , Anemia Aplásica/terapia , Linfocitos T CD8-positivos/inmunología , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Adolescente , Adulto , Supervivencia Celular , Femenino , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Subgrupos de Linfocitos T/inmunología , Quimera por Trasplante , Resultado del Tratamiento , Irradiación Corporal Total , Adulto Joven
14.
Blood ; 126(8): 1027-32, 2015 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-26160301

RESUMEN

We analyzed 661 adult patients who underwent single-unit (n = 226) or double-unit (n = 435) unrelated cord blood transplantation (UCBT) following a reduced-intensity conditioning (RIC) consisting of low-dose total body irradiation (TBI), cyclophosphamide, and fludarabine (Cy/Flu/TBI200). Eighty-two patients received rabbit antithymocyte globulin (ATG) as part of the conditioning regimen (ATG group), whereas 579 did not (non-ATG group). Median age at UCBT was 54 years, and diagnoses were acute leukemias (51%), myelodysplastic syndrome/myeloproliferative neoplasm (19%), and lymphoproliferative diseases (30%). Forty-four percent of patients were transplanted with advanced disease. All patients received ≥4 antigens HLA-matched UCBT. Median number of collected total nucleated cells was 4.4 × 10(7)/kg. In the ATG group, on 64 evaluable patients, ATG was discontinued 1 (n = 27), 2 (n = 20), or > 2 days before the graft infusion (n = 17). In multivariate analyses, the use of ATG was associated with decreased incidence of acute graft-versus-host disease (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.17-0.55; P < .0001), higher incidence of nonrelapse mortality (HR, 1.68; 95% CI, 1.16-2.43; P = .0009), and decreased overall survival (HR, 1.69; 95% CI, 1.19-2.415; P = .003). Collectively, our results suggest that the use of ATG could be detrimental, especially if given too close to graft infusion in adults undergoing UCBT following Cy/Flu/TBI200 regimen.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Aloinjertos , Ciclofosfamida/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Estimación de Kaplan-Meier , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal Total , Adulto Joven
16.
Mycoses ; 60(2): 79-88, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27562016

RESUMEN

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.


Asunto(s)
Antifúngicos/economía , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras/prevención & control , Adulto , Antifúngicos/uso terapéutico , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Fluconazol/economía , Fluconazol/uso terapéutico , Humanos , Infecciones Fúngicas Invasoras/economía , Infecciones Fúngicas Invasoras/etnología , Infecciones Fúngicas Invasoras/microbiología , Itraconazol/economía , Itraconazol/uso terapéutico , España , Triazoles/economía , Triazoles/uso terapéutico , Voriconazol/uso terapéutico
17.
Biol Blood Marrow Transplant ; 22(10): 1874-1882, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27397724

RESUMEN

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft-versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy resultswere consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose.


Asunto(s)
Ensayos de Uso Compasivo , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Polidesoxirribonucleótidos/administración & dosificación , Adolescente , Adulto , Anciano , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/complicaciones , Enfermedad Veno-Oclusiva Hepática/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Polidesoxirribonucleótidos/efectos adversos , Sepsis/etiología , Adulto Joven
18.
Biol Blood Marrow Transplant ; 22(3): 432-40, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26493563

RESUMEN

The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 2/antagonistas & inhibidores , Mielofibrosis Primaria , Inhibidores de Proteínas Quinasas , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Mielofibrosis Primaria/enzimología , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/terapia , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia
19.
Br J Haematol ; 173(3): 380-93, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27060988

RESUMEN

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom.


Asunto(s)
Neoplasias Hematológicas/complicaciones , Infecciones del Sistema Respiratorio/virología , Trasplante de Células Madre/efectos adversos , Virosis/diagnóstico , Virosis/terapia , Adolescente , Adulto , Niño , Femenino , Neoplasias Hematológicas/terapia , Hematología/normas , Humanos , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/terapia , Factores de Riesgo , Reino Unido , Virosis/prevención & control , Adulto Joven
20.
Br J Haematol ; 193(1): 43-51, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33538335
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