RESUMEN
PURPOSE OF REVIEW: This review highlights recent advancements in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML). RECENT FINDINGS: Important improvements have been observed throughout the allo-HSCT procedure and patient management. Universal donor availability and reduced risk of graft-versus-host disease (GVHD) have been achieved with the introduction of posttransplant cyclophosphamide for GVHD prophylaxis. It has contributed, together with advances in conditioning regimens, GVHD treatment and supportive care, to a reduced overall toxicity of the procedure. Relapse is now the most frequent cause of transplant failure. With increased knowledge of the biological characterization of AML, better prediction of transplant risks and more profound and standardized minimal residual disease (MRD) monitoring, pharmacological, and immunological strategies to prevent relapse are been developed. SUMMARY: Allo-HSCT remains the standard of care for high-risk AML. Increased access to transplant, reduced toxicity and relapse are improving patient outcomes. Further research is needed to optimize MRD monitoring, refine conditioning regimens, and explore new GVHD management and relapse prevention therapies.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Trasplante Homólogo/métodos , Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Recurrencia , Acondicionamiento Pretrasplante/métodos , Estudios RetrospectivosRESUMEN
It is uncertain whether gastrointestinal (GI) infection caused by viral and bacterial pathogens may predispose to gastrointestinal acute Graft-versus-host disease (aGvHD-GI) in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). We investigated the potential association between detection of enteropathogenic viruses or bacteria in stools and subsequent occurrence of aGvHD-GI in a cohort of 121 allo-HSCT patients. Eighty-six out of 121 patients (71%) had acute diarrhea and underwent screening for primary GI pathogens by molecular diagnostic methods. One or more GI pathogens were detected in 27 out of the 86 patients with diarrhea (31.3%). Specifically, Clostridioides difficile was found in 16 patients (18.6%), enteropathogenic viruses in 11 patients (12.7%) (Astrovirus, n = 4; Norovirus, n = 2; Sapovirus, n = 2; Adenovirus, n = 2; and Rotavirus, n = 1), and Campylobacter spp. in two patients (2.3%). Thirty patients were diagnosed with all grade aGvHD-GI by histopathology. Detection of primary GI pathogens was achieved in 12 out of 30 patients (Clostridium difficile, n = 5; enteric viruses, n = 8; Campylobacter spp., n = 1) who either subsequently developed (n = 9) or previously had (n = 3) grade I-IV IaGvHD (n = 9). Neither the detection of these microorganisms (all combined), enteric viruses, nor C. difficile was significantly associated with subsequent aGvHD-GI development in Cox models (hazard ratio [HR] = 1.11, p = .80; HR = 1.64, p = .62; HR = 0.75, p = .64, respectively). Analogous results were obtained when grade II-IV aGvHD-GI was selected as the clinical outcome. In summary, data in the current study did not support an association between GI infection and subsequent occurrence of aGvHD-GI in an unselected cohort of allo-HSCT recipients.
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Infecciones Bacterianas/complicaciones , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/virología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Virosis/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Anciano , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/patogenicidad , Susceptibilidad a Enfermedades , Heces , Femenino , Enfermedades Gastrointestinales/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Virus/clasificación , Virus/genética , Virus/aislamiento & purificación , Adulto JovenRESUMEN
OBJECTIVE: To compare the efficacy and safety of CD34+ selected ex vivo T-cell depletion (TCD) vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy-Sir-MMF) as graft-vs-host disease (GVHD) prophylaxis. METHODS: We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either TCD (n = 38) or PTCy-Sir-MMF (n = 91). RESULTS: Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P = .06) and 89% vs 97% (P = .3) in TCD and PTCy-Sir-MMF, respectively. Cumulative incidences of aGHVD grade II-IV, III-IV, and moderate to severe cGVHD were 11% vs 19% (P = .2), 3% vs 2% (P = .9), and 3% vs 36% (P < .001) in TCD and PTCy-Sir-MMF, respectively. The 2-year non-relapse mortality, relapse, disease-free and overall survival were 25% vs 8% (P = .01), 20% vs 16% (P = .2), 55% vs 76% (P = .004), 57% vs 83% (P = .004) for TCD and PTCy-Sir-MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein-Barr infection requiring therapy was 76% vs 40% (P < .001) and 32% vs 0% (P < .001) in TCD and PTCy-Sir-MMF, respectively. PTCy-Sir-MMF platform showed faster T-cell reconstitution. CONCLUSIONS: PTCy-Sir-MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD.
Asunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Depleción Linfocítica/efectos adversos , Depleción Linfocítica/métodos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Ciclofosfamida/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Reconstitución Inmune , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Cuidados Posoperatorios , Complicaciones Posoperatorias , Pronóstico , Recurrencia , Índice de Severidad de la Enfermedad , Sirolimus/administración & dosificación , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Torque Teno virus (TTV) DNA load in blood may act as a marker of immune competence after allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Conflicting data have been reported as to the value of this biomarker for anticipating acute Graft versus host disease (aGvHD) occurrence. Here, we hypothesized that quantitation of TTV DNA load in stool specimens early after allo-HSCT could be used to identify patients at high risk of acute intestinal graft versus host disease (aIGvHD). In this prospective two-center study, we recruited a total of 83 nonconsecutive adult patients undergoing allo-HSCT. The study period comprised the first 120 days after allo-HSCT. TTV DNA was quantitated in paired stool samples collected at a median of 2 days prior to cell infusion and at a median of 14 days after allo-HSCT by real-time PCR. Thirty-seven patients developed aGVHD, of whom 25 had aIGVHD (diagnosed at a median of 42 days after allo-HSCT). Median TTV DNA load values in posttransplant stools specimens were comparable (P = .34) in patients with or without subsequent aIGvHD; nevertheless, a falling trajectory (decrease in TTV DNA load >0.5 log10 copies/0.1 g) in paired pretransplant and posttransplant specimens was independently associated with the occurrence of aIGvHD (OR, 5.2; 95% CI, 1.3-21.3; P = .02). Notably, displaying a rising trajectory had a negative predictive value of 87.5% for aIGvHD. In summary, in this hypothesis-generating study, we suggest that the decrease in TTV DNA load from baseline in stool specimens may identify patients at risk of aIGVHD.
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Infecciones por Virus ADN , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Torque teno virus , Adulto , ADN Viral , Humanos , Cinética , Estudios Prospectivos , Carga ViralRESUMEN
Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is on focus of research. We evaluate herein the feasibility of expanding virus-specific T cells (VST) against SARS-CoV-2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS-CoV-2 asymptomatic infection/negative serology, (b) SARS-CoV-2 symptomatic infection/positive serology, and (c) no history of SARS-CoV-2 infection/negative serology. We were able to obtain an expanded VST product from donors 1 and 2 (1.6x and 1.8x increase of baseline VST count, respectively) consisting in CD3 + cells (80.3% and 62.7%, respectively) with CD4 + dominance (60% in both donors). Higher numbers of VST were obtained from the donor 2 as compared to donor 1. T-cell clonality test showed oligoclonal reproducible peaks on a polyclonal background for both donors. In contrast, VST could be neither expanded nor primed in a donor without evidence of prior infection. This proof-of-concept study supports the feasibility of expanding ex vivo SARS-CoV-2-specific VST from blood of convalescent donors. The results raise the question of whether the selection of seropositive donors may be a strategy to obtain cell lines enriched in their SARS-CoV-2-specificity for future adoptive transfer to immunosuppressed patients.
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COVID-19 , SARS-CoV-2 , Traslado Adoptivo , Linfocitos T CD4-Positivos , HumanosRESUMEN
In this prospective randomized study, we compared the outcomes of single-unit umbilical cord blood transplantation (UCBT) and unmanipulated haploidentical stem cell transplantation (haplo-SCT) with post-transplantation cyclophosphamide (PTCy) in adults with hematologic malignancies. All patients received a myeloablative conditioning (MAC) regimen consisting of thiotepa, busulfan, and fludarabine, with antithymocyte globulin (ATG) added for UCBT recipients. Nineteen patients were randomized to UCBT and the other 26 to haplo-HSCT. Four patients (15%) allocated to the haplo-HSCT arm lacked a suitable donor and were crossed over to the UCBT arm. Finally, 23 underwent UCBT and 22 underwent haplo-HSCT. The cumulative incidence of neutrophil recovery was 87% at a median of 19 days (range, 13 to 24 days) in the UCBT arm versus 100% at a median of 17 days (range, 13 to 25 days) in the haplo-SCT arm (P = .04). Platelet recovery was 70% at a median of 40 days (range, 18 to 129 days) in the UCBT arm versus 86% at a median of 24 days (range, 12 to 127 days) in the haplo-HCT arm (P = .02). Rates of acute graft-versus-host disease (GVHD) grade II-IV or grade III-IV, overall chronic GVHD, and extensive chronic GVHD in the UCBT and Haplo-SCT arms were 43% versus 36% (P = .8), 9% versus 9% (P = 1), 66% versus 43% (P = .04), and 41% versus 23% (P = .2), respectively. Two-year nonrelapse mortality and relapse in the 2 arms were 52% versus 23% (P = .06) and 17% versus 23% (P = .5), respectively. Two-year disease-free survival, overall survival, and GVHD/relapse-free survival in the 2 arms were 30% versus 54% (P = .2), 35% versus 59% (P = .1), and 17% versus 40% (P = .04), respectively. Our data show that in the context of an MAC regimen, haplo-SCT with PTCy provides improved outcomes compared with ATG-containing single-unit UCBT.
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Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Adulto , Neoplasias Hematológicas/terapia , Humanos , Recurrencia Local de Neoplasia , Estudios Prospectivos , Acondicionamiento PretrasplanteRESUMEN
We analyzed the outcomes of 26 consecutive patients with acquired severe aplastic anemia (SAA) undergoing peripheral blood stem cell transplantation (PBSCT) with partial ex vivo T cell depletion with a targeted T cell dose from HLA-identical sibling donors. The median patient age was 37 years (range, 3 to 63 years). Four patients with uncontrolled pneumonia at the time of transplantation died, on days +1, +2, +21, and +26. All evaluable patients engrafted, with a median time to neutrophil recovery of 11 days (range, 10 to 14 days) and a median time to platelet recovery of 19 days (range, 8 to 53 days). Two patients had transient grade I acute graft-versus-host disease (GVHD) with skin involvement, but no patients developed grade II-IV acute GVHD. Two patients had mild skin chronic GVHD, and 1 patient had moderate chronic GVHD with ocular involvement. No relapse was observed after a median follow-up of 114 months (range, 4 to 233 months). The overall cumulative incidence of TRM at 10 years was 19%, whereas it was 5% for those with a Karnofsky Performance Status (KPS) score >60 at the time of transplantation. Disease-free survival, overall survival, and GVHD and relapse-free survival at 10 years were 81%, 81%, and 80%, respectively, for all patients and 95%, 95%, and 90%, respectively, for patients with a KPS score >60 at transplantation. Our data indicate that PBSCT with partial ex vivo T cell-depleted targeted cell dose grafts from an HLA-identical sibling donor is a feasible, safe, and effective approach to reduce GVHD and cure patients with SAA.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Depleción Linfocítica , Trasplante de Células Madre de Sangre Periférica , Hermanos , Linfocitos T , Donantes de Tejidos , Enfermedad Aguda , Adolescente , Adulto , Aloinjertos , Anemia Aplásica/sangre , Anemia Aplásica/mortalidad , Anemia Aplásica/terapia , Niño , Preescolar , Supervivencia sin Enfermedad , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Data have been published suggesting a bidirectional interaction between cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGvHD) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we hypothesized that prospective CMV DNA monitoring in stool specimens may be useful for predicting subsequent occurrence of intestinal aGvHD (IaGvHD). METHODS: This two-center study enrolled 121 consecutive adult patients undergoing any modality of allo-HSCT. A total of 1,009 stool specimens were collected (a median of 7 specimens/patient; range, 1-18). CMV DNA monitoring in stools and plasma was performed using real-time PCR assays. RESULTS: CMV DNA was detected in stools in 20 patients (cumulative incidence, 16.9%; 95% CI, 6.3%-31.8%). Median CMV DNA level in stool specimens was 1,258 IU/0.1g (range, 210-4,087 IU/0.1 g). All these patients and their donors were CMV seropositive, and 16 of the 20 patients also had CMV DNAemia, while 4 patients had CMV DNA detected in stools without CMV DNAemia. No correlation was found between CMV DNA loads in plasma and stools (P = .40). Prior CMV DNAemia, aGvHD, or IaGvHD were not associated with presence of CMV DNA in feces. IaGvHD was present in 30 patients, in 5 of whom CMV DNA was detected in stools. Neither detection of CMV DNA in feces nor in plasma was associated with subsequent IaGvHD (OR, 0.67; 95% CI, 0.18-2.52; P = .55 and OR, 0.86; 95% CI, 0.38-1.96; P = .71, respectively). No patient in this cohort had CMV end-organ disease within the study period. CONCLUSION: Our study failed to provide evidence pointing to a reciprocal interaction between GI CMV infection and IaGvHD. CMV DNA monitoring in stools seems of no value to anticipate occurrence of IaGvHD.
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Infecciones por Citomegalovirus , ADN Viral/aislamiento & purificación , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Carga Viral , Adulto , Citomegalovirus/genética , Infecciones por Citomegalovirus/complicaciones , Heces/virología , Enfermedad Injerto contra Huésped/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Enfermedades Intestinales/diagnóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndromes de Inmunodeficiencia/virología , Infecciones por Picornaviridae/inmunología , Infecciones del Sistema Respiratorio/inmunología , Adolescente , Adulto , Anciano , Femenino , Humanos , Síndromes de Inmunodeficiencia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infecciones por Picornaviridae/mortalidad , Estudios Prospectivos , Curva ROC , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Rhinovirus/inmunología , España/epidemiología , Trasplante Homólogo/efectos adversos , Adulto JovenRESUMEN
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be associated with neurologic complications, data on noninfectious etiologies are scanty. Therefore, we analyzed the incidence, clinical characteristics, risk factors, and influence on outcomes of noninfectious neurologic complications (NCs) in 971 consecutive patients with hematologic malignancies undergoing allo-HSCT at our center between January 2000 and December 2016. We evaluated NCs affecting the central nervous system (CNS) and peripheral nervous system (PNS). The median duration of follow-up of survivors was 71 months (range, 11 to 213 months). A total of 467 patients received a matched sibling donor (MSD) transplant, 381 received umbilical cord blood (UCB), 74 received a haploidentical transplant, and 49 received a matched unrelated donor (MUD) transplant. One hundred forty-nine (15.3%) NCs were documented at a median of 78 days after transplantation (range, 5 days before to 3722 days after). The cumulative incidence risk of developing NC was 7.5% (95% confidence interval, 6% to 8.2%) at day +90 and 13% at 5 years. The 5-year cumulative incidence of NCs was 10.8% after MSD allo-HSCT and 15.3% after alternative donor (UCB, MUD, haploidentical) allo-HSCT (Pâ¯=â¯.004). There were 101 (68%) CNS complications, including encephalopathy, n = 46 (31%); headache, n = 20 (13%); stroke, nâ¯=â¯15 (10%); seizures, n = 9 (6%), posterior reversible encephalopathy syndrome, nâ¯=â¯6 (4%), and myelopathy, nâ¯=â¯5 (3%). PNS complications (32%) included neuropathies, nâ¯=â¯25 (17%), and myopathies and neuromuscular junction disorders, nâ¯=â¯23 (17%), with 17% of the total PNS complications being immune-related. In multivariable analysis, donor type other than MSD, age ≥40 years, development of acute graft-versus-host disease (GVHD) grade II-IV (hazard ratio [HR], 3.3; P < .00001), and extensive chronic GVHD (HR, 3.2; Pâ¯=â¯.0002) were independently associated with increased risk of NCs. The 5-year overall survival (OS) was 21% in patients who developed NCs and 41% for those who did not (P < .0001). This difference in OS was observed in patients developing CNS NCs, but not in those developing PNS complications. In conclusion, our study reveals NCs as a frequent and heterogeneous complication that, when affecting CNS, is associated with poor prognosis following allo-HSCT.
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Enfermedades del Sistema Nervioso Central , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades del Sistema Nervioso Periférico , Adolescente , Adulto , Anciano , Aloinjertos , Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/mortalidad , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/mortalidad , Tasa de SupervivenciaRESUMEN
Risk factors (RFs) and mortality data of community-acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co-infections in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo-HSCT recipients diagnosed of CARVs LRTD mono-infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co-infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono-infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveolar lavage (BAL) was significantly higher in group 1, 2, and 4 compared to group 3 (77%, 67%, and 73% vs 35%, respectively, P = .012). Recipients of group 5 showed a trend to better OS compared to those of group 3 (62% vs 35%, P = .1). Multivariate analyses showed bacterial co-infection as a RF for mortality (hazard ratio[HR] 2.65, 95% C.I. 1.2-6.9, P = .017). We identified other 3 RFs for mortality: lymphocyte count <0.5 × 109 /L (HR 2.6, 95% 1.1-6.2, P = .026), the occurrence of and CMV DNAemia requiring antiviral therapy (CMV-DNAemia-RAT) at the time of BAL (HR 2.32, 95% C.I. 1.1-4.9, P = .03), and the need of oxygen support (HR 8.3, 95% C.I. 2.9-35.3, P = .004). CARV LRTD co-infections are frequent and may have a negative effect in the outcome, in particular in the context of bacterial co-infections.
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Líquido del Lavado Bronquioalveolar/microbiología , Coinfección/mortalidad , Infecciones Comunitarias Adquiridas/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones del Sistema Respiratorio/mortalidad , Adulto , Anciano , Antivirales/uso terapéutico , Bacterias/aislamiento & purificación , Lavado Broncoalveolar , Coinfección/microbiología , Coinfección/terapia , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/terapia , Femenino , Hongos/aislamiento & purificación , Humanos , Pulmón/microbiología , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/terapia , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Virus/aislamiento & purificaciónRESUMEN
We analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (CNS) infections in consecutive patients with receiving umbilical cord blood transplantation (UCBT) (n = 343) or HLA-matched sibling donor stem cell transplantation (MST) (n = 366). Thirty-four CNS infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). The cumulative incidence (CI) risk of developing a CNS infection was .6% at day +30, 2.3% at day +90, and 4.9% at 5 years. The 5-year CI of CNS infection was 8.2% after UCBT and 1.7% after MST (P < .001). The causative micro-organisms of CNS infections were fungi (35%), virus (32%), Toxoplasma spp. (12%), and bacteria (12%). Fungal infections occurred in 11 patients after UCBT and 1 after MST and were due to Aspergillus spp. (n = 8), Cryptococcus neoformans (n = 2), Scedosporium prolificans (n = 1), and Mucor (n = 1). Except for 1 patient, all died from CNS fungal infection. Viral infections occurred in 9 patients after UCBT and 1 after MST and were due to human herpes virus 6 (n = 7), cytomegalovirus (n = 2), and varicella zoster virus (n = 1). CNS toxoplasmosis was diagnosed in 3 patients after UCBT and 1 after MST. Other pathogens were Staphylococcus spp, Nocardia spp, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Twenty of the 34 patients (59%) died from the CNS infection. In multivariable analysis, UCBT and disease stage beyond first complete remission were independently associated with the risk of developing CNS infections. The 5-year overall survival was 19% in patients who developed a CNS and 39% for those who did not (P = .006). In conclusion, our study showed that CNS infections are a significant clinical problem after stem cell transplantation associated with poor survival. They were more frequent after UCBT compared to MST.
Asunto(s)
Infecciones del Sistema Nervioso Central/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Antígenos HLA/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Anciano , Infecciones Bacterianas/etiología , Infecciones del Sistema Nervioso Central/microbiología , Infecciones del Sistema Nervioso Central/mortalidad , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Histocompatibilidad , Humanos , Incidencia , Persona de Mediana Edad , Micosis/etiología , Hermanos , Factores de Tiempo , Toxoplasmosis/etiología , Donante no Emparentado , Virosis/etiología , Adulto JovenAsunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades del Pene , Fotoféresis , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Prednisona/administración & dosificación , Enfermedades Testiculares , Adulto , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Humanos , Masculino , Enfermedades del Pene/tratamiento farmacológico , Enfermedades del Pene/etiología , Enfermedades del Pene/patología , Enfermedades Testiculares/tratamiento farmacológico , Enfermedades Testiculares/etiología , Enfermedades Testiculares/patologíaRESUMEN
This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.
RESUMEN
Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.
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Ciclofosfamida , Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Activación Viral , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Activación Viral/efectos de los fármacos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/epidemiología , Trasplante Homólogo/efectos adversos , Citomegalovirus/inmunología , Citomegalovirus/efectos de los fármacos , Anciano , Adulto Joven , Donantes de Tejidos , Adolescente , Trasplante Haploidéntico/efectos adversos , Factores de Riesgo , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Neoplasias Hematológicas/terapia , Donante no Emparentado , Antígenos HLA/inmunología , HermanosRESUMEN
INTRODUCTION: Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution. METHODS: The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009-2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT: 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT). RESULTS: There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017-2020 period. CONCLUSION: despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care.
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Bone marrow (BM) is the recommended stem cell source for hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs) in patients with severe aplastic anemia (SAA) for its superior survival and graft-versus-host disease (GVHD) outcomes compared to recipients of unmanipulated peripheral blood (PB) HSCT. Nevertheless, no studies comparing BM with ex vivo T cell-depleted (TCD) PB have been reported to date. The aim of the present study was to compare the transplantation outcomes of MSD HSCT recipients with SAA using PB (with partial ex vivo TCD targeted cell dose grafts) with those of MSD HSCT recipients with SAA using unmanipulated BM. We performed a matched-pair analysis of MSD-HSCT using TCD PB in a single institution with unmanipulated BM MSD-HSCT in the United States between 2013 and 2019 reported to the Center for International Blood and Marrow Transplant Research. We compared 23 recipients of TCD PB HSCT for SAA (cases) and 69 recipients of unmanipulated BM grafts (controls) matched for age, Karnofsky Performance Status, Hematopoietic Cell Transplantation-Specific Comorbidity Index, time from diagnosis to transplantation, and recipient cytomegalovirus serostatus. We found significantly faster neutrophil and platelet recovery in the TCD PB cohort (P < .001 and P = .03, respectively), as well as a lower incidence of grade II-IV acute GVHD (0% versus 17%; P = .05) and similar overall survival (96% versus 97% at 3 years; P = .8). Our study shows that TCD PB can be considered a safe source for MSD-HSCT in patients with SAA, with potential advantages in engraftment and GVHD that could challenge the standard with BM. These findings provide a basis for future research in a prospective controlled clinical trial.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Humanos , Anemia Aplásica/terapia , Médula Ósea , Estudios Prospectivos , Hermanos , Linfocitos TRESUMEN
Post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is being increasingly used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors (MRDs); however, information regarding the transfusion needs in this setting is lacking. This study compared RBC and platelet units transfused and time to transfusion independence according to the GVHD prophylaxis regimen in MRD HSCT. We performed a matched-pair analysis comparing the transfusion requirements and the clinical outcomes of patients who underwent MRD peripheral blood HSCT using PTCy between January 2017 and June 2021 (n = 100) with historical MRD HSCTs using standard cyclosporine A (CsA)-based prophylaxis (n = 100). Neutrophil engraftment was significantly delayed in the PTCy group compared with the CsA group (16 days versus 13 days; P = .003). PTCy was associated with increased RBC (median, 5 units versus 4 units; P = .04) and platelet (median, 6 units versus 3 units; P = .01) transfusion requirements during the first 30 days after transplantation. The proportion of patients requiring platelet transfusion during days 31 to 90 after transplantation was also higher in the PTCy group (55% versus 25%; P < .0001). In multivariate analysis, PTCy was associated with delayed RBC and platelet transfusion independence (hazard ratio, .61 [P = .007] and .51 [P < .0001], respectively). The cumulative incidence (CuI) of BK polyomavirus-associated hemorrhagic cystitis grade ≥2 at 100 days was higher in the PTCy group (34% versus 12%; P < .0001); however, the PTCy group had lower rates of grade II-IV acute GVHD (100-day CuI, 57% versus 23%; P < .0001) and moderate to severe chronic GVHD (1-year CuI, 49% versus 28%; P = .003), as well as better 2-year overall survival (74% versus 56%; P = .01). Our study shows that although PTCy increases the transfusion burden in MRD HSCT, it is associated with a low incidence of severe GVHD and with encouraging survival outcomes.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Humanos , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Hermanos , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , CiclosporinaRESUMEN
Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are frequently associated with neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, there is a lack of studies comparing the incidence and characteristics of neurologic complications in patients undergoing HSCT based on CNI-free or CNI-based GVHD prophylaxis. This retrospective single-center study analyzed the neurologic complications in 2 cohorts of patients undergoing HSCT with either CNI-based GVHD prophylaxis (n = 523) or CNI-free prophylaxis with post-transplantation cyclophosphamide, sirolimus, and mycophenolate mofetil (n = 371). The latter cohort included older patients and received more reduced-intensity conditioning and transplants from matched unrelated and haploidentical donors. The 2-year cumulative incidence of neurologic complications was significantly lower in the CNI-free cohort (6.9% versus 11.9%; P = .016), and GVHD prophylaxis was the sole statistically significant variable in multivariate analysis (hazard ratio, 2.2; 95% confidence interval [CI], .25 to 3.13; P = .0017). The distribution of neurologic types was similar in the 2 cohorts, with encephalopathy the most prevalent complication, except for headaches and myopathy, which decreased equally from 15% in the CNI-based cohort to 4% in the CNI-free cohort. Neurologic complications had negative impacts on mortality and survival rates, with a significantly higher 2-year cumulative incidence of nonrelapse mortality (NRM) (44% [95% CI, 34% to 54%] versus 16% [95% CI, 13% to 18%]; P < .0001) and inferior overall survival (66% [95% CI, 62% to 69%] versus 46% [95% CI, 37% to 58%]; P < .0001) in patients with neurologic complications. This study suggests that CNI-free GVHD prophylaxis with post-transplantation cyclophosphamide, sirolimus, and mycophenolate mofetil may reduce not only the incidence of GVHD incidence, but also the rates of neurologic complications and NRM, leading to improved survival outcomes in patients undergoing HSCT.
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Extracorporeal photopheresis (ECP) has shown efficacy in treating graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with off-line ECP in our institution, in order to validate this treatment schedule and analyze predictive factors. All consecutive adult patients with steroid-dependent or steroid-refractory GVHD undergoing off-line ECP were included in this single-center retrospective study. ECP was performed with a Spectra Optia device, processing 1 total blood volume, at a twice-weekly frequency for acute GVHD (aGVHD) and once weekly for chronic GVHD (cGVHD), and tapered individually according to clinical response. The cumulative incidence of response, including complete response (CR) and partial response (PR), were compared among patients grouped by different baseline, apheresis, and disease characteristics. Between January 2015 and May 2022, a total of 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of the ECP sessions. GVHD responded in 78% of patients (aGVHD: 57% CR and 4% PR; cGVHD, 39% CR and 48% PR). Overall survival was statistically greater for aGVHD patients who responded to ECP compared to those who did not respond (67.5% versus 26% at 1 year; P = 0.037). Severity was an independent predictor of response in aGVHD, whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in cGVHD. Our findings support the effectiveness of this treatment schedule for GVHD. Further investigation is required to identify ECP-specific predictive factors, given that findings are not homogeneous across studies.