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1.
Front Immunol ; 15: 1360275, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510239

RESUMEN

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting antibody-drug conjugate Brentuximab-Vedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable responses in relapsed/refractory (r/r) HL. However, patients with a history of allo-HSCT were frequently excluded from clinical trials due to concerns about the risk of graft-versus-host disease (GVHD). We report the clinical history of a patient with refractory classical HL who underwent two allo-HSCTs (first from matched unrelated and second from haploidentical donor) after relapsing on BV and nivolumab and for whom durable remission was finally obtained using BV-pembrolizumab combination for relapse after haploidentical HSCT. Such treatment was associated with the onset of GVHD after only two cycles which led to treatment discontinuation. However, the side effects were rapidly controlled, and after 2 years of follow-up, the patient is still in remission. Our data support the feasibility and efficacy of combining PD-1 blockade with BV to enhance the graft-versus-lymphoma effect after allo-HSCT.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Humanos , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Recurrencia Local de Neoplasia/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/tratamiento farmacológico
3.
Clin Infect Dis ; 78(2): 423-429, 2024 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-37713176

RESUMEN

BACKGROUND: Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity. METHODS: This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach. RESULTS: Among 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups. CONCLUSIONS: One of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Humanos , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Receptores de Trasplantes , Estudios de Cohortes , Trasplante Homólogo/efectos adversos , Anticuerpos Antivirales/uso terapéutico , Inmunoglobulina G , Estudios Retrospectivos
4.
Open Forum Infect Dis ; 10(12): ofad578, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38088980

RESUMEN

Background: A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations. Methods: We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an allogeneic HCT between 2018 and 2022 in 292 adult (≥18-year-old) consecutive patients. We describe the performance of a TID consultation, arbitrarily defined as major (HCT postponement, procedure, cytomegalovirus [CMV] recipient serology reinterpretation) and minor interventions. Results: Overall, 765 interventions were observed in 257 of 292 (88%) patients: 88 of 765 (11.5%) major and 677 of 765 (88.5%) minor interventions. Among major interventions, HCT was postponed in 8 of 292 (2.7%) patients and a procedure was requested in 18 of 292 (6.2%) patients. The CMV recipient serostatus was changed from indeterminate/low-titer positive to negative in 60 of 292 (20.5%) patients. Among 677 minor interventions, there were 68 (8.8%) additional consultations with other services requested, 260 (33.7%) additional diagnostic tests requested, 102 (13.2%) additional treatments recommended, 60 (7.8%) non-CMV serology reinterpretations performed, 115 (14.9%) deviations from routine anti-infective prophylaxis, and 72 (9.3%) deviations from routine empirical antibiotic treatment recommendations in case of neutropenic fever. Conclusions: We are proposing a structured, clearly defined, and comprehensive pretransplant checklist for an effective assessment of infectious disease risks and complications prior to an allogeneic HCT. Further studies or experiences like ours could help to define a global strategy or new models of care to be implemented in HCT centers in the future.

5.
Open Forum Infect Dis ; 10(12): ofad595, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38094666

RESUMEN

Among 292 recipients of allogeneic hematopoietic cell transplant (2018-2022), 64 (21.9%) tested positive for anti-hepatitis E virus (HEV) immunoglobulin G. Among 208 recipients tested by plasma/serum HEV polymerase chain reaction (2012-2022), 3 (1.4%) primary HEV infections were diagnosed; in 1 patient, plasma HEV polymerase chain reaction relapsed positive for 100 days. HEV infection remains rare albeit associated with persistent viral replication.

6.
Open Forum Infect Dis ; 10(4): ofad169, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37125233

RESUMEN

In this single-center study of 61 allogeneic hematopoietic cell transplant (HCT) recipients receiving letermovir primary cytomegalovirus (CMV) prophylaxis for the first 100 days, we report 23% incidence of clinically significant CMV infection during the first 100 days after letermovir discontinuation, predominately in haploidentical HCT recipients, without any associations with CMV-DNAemia under letermovir.

7.
Front Oncol ; 13: 1095870, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37007116

RESUMEN

Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patients treated with post-allogeneic HSCT sorafenib maintenance therapy for FLT3-ITD AML with a particular focus on tolerability and toxicity-related treatment interruption. We conducted a single-center retrospective study on 30 FLT3-ITD AML patients undergoing allogeneic HSCT in complete remission between 2017 and 2020 and who received sorafenib maintenance. 26 patients (87%) experienced toxicities leading to dose reduction (n=9) or direct interruption (n=17). Average time on sorafenib was 125 days (range 1-765). Most common toxicities were skin, gastrointestinal, and hematologic. Among patients who had a dose reduction, 4 eventually interrupted the drug and 5 were able to continue. Among patients who interrupted sorafenib because of toxicities, 7 were re-challenged with good tolerance in 3 cases. Overall, 18 patients (60% of the entire cohort) definitively discontinued sorafenib because of toxicities. 14 patients were thereafter switched to midostaurin. Importantly, with a median follow-up of 12 months, the median overall survival was not reached suggesting a positive impact of sorafenib maintenance despite the high rates of treatment interruption. In conclusion, our real-world analysis reveals high rates of toxicity-related interruption of sorafenib maintenance after allogeneic HSCT. Interestingly, our results suggest the feasibility of re-challenging with sorafenib and/or of switching to other maintenance approaches in case of intolerance.

8.
Antimicrob Agents Chemother ; 67(4): e0173222, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-36971558

RESUMEN

We present two allogeneic hematopoietic cell transplantation recipients (HCTr) treated with pritelivir for acyclovir-resistant/refractory (r/r) HSV infection based on the expanded access program of the pritelivir manufacturer. Outpatient treatment with pritelivir was administered, with partial response by week 1 of treatment and complete response by week 4 of treatment in both patients. No adverse events were noted. Pritelivir appears to be an effective and safe option for the management of acyclovir-r/r HSV infections in highly immunocompromised patients in an outpatient setting.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Herpes Simple , Humanos , Antivirales , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia Recuperativa , Receptores de Trasplantes , Herpes Simple/tratamiento farmacológico , Herpes Simple/inducido químicamente , Aciclovir/uso terapéutico
9.
Am J Transplant ; 23(6): 844-847, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36972802

RESUMEN

Peripheral allogeneic hematopoietic stem cell transplant recipients are the most vulnerable patients to community-acquired respiratory viruses such as respiratory syncytial virus, influenza virus, or others. These patients are likely to develop severe acute viral infections; community-acquired respiratory viruses have also been identified as triggers of bronchiolitis obliterans (BO). BO is a manifestation of pulmonary graft-versus-host disease, most often leading to irreversible ventilatory impairment. To date, there are no data on whether Severe acute respiratory syndrome â€‹coronavirus 2 (SARS-CoV-2) could be a trigger for BO. Here, we report the first report of a case of bronchiolitis obliterans syndrome following SARS-CoV-2 infection occurring 10 months after allogeneic hematopoietic stem cell transplant with a flare of underlying extra thoracic graft-versus-host disease. This observation provides a new perspective and should be of particular interest to clinicians, suggesting the need for close monitoring of pulmonary function test (PFTs) after SARS-CoV-2 infection. The mechanisms leading to bronchiolitis obliterans syndrome after SARS-CoV-2 infection require further investigation.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Bronquiolitis Obliterante , COVID-19 , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , SARS-CoV-2 , Bronquiolitis Obliterante/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos
10.
Bull Cancer ; 110(2S): S67-S78, 2023 Feb.
Artículo en Francés | MEDLINE | ID: mdl-36307323

RESUMEN

In this article, we discuss again the definition, the risk factor and guideline to treat the graft failure, the poor graft function and erythrobalstopenia. Graft failure is a severe but rare complication after hematopoietic cell transplantation (HCT). Despite disparity in the literature, we defined this complication and discussed the factor risks and recommendation for treatment based on new studies. Poor graft function is also a more frequent complication after HCT. New studies will soon be available to prove or not the current recommendation suggested in this article based on therapeutics medicine or cellular therapy. Erythroblastopenia, is a rarer complication post HCT. Despite anticipation for a better choice of compatibility donor/recipient, some patients still suffer from this complication.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de Riesgo , Enfermedad Injerto contra Huésped/complicaciones
11.
Transplant Cell Ther ; 28(11): 765.e1-765.e9, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35953029

RESUMEN

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a well-known complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with a mortality rate of up to 85%.  Defibrotide has shown efficacy in treatment of SOS/VOD. Moreover, evidence exists supporting the efficacy of defibrotide as SOS/VOD prophylaxis. We have previously reported our single center experience on 52 HSCT recipients receiving defibrotide as SOS/VOD prophylaxis, which has shown that the patients did not develop any SOS/VOD under this prophylaxis. The aim of the present study was to see if we can confirm the previous results, mainly on the decrease incidence of SOS/VOD, as well as improve event-free survival (EFS) on a larger study population. We extended our previous study in a single-center retrospective analysis to include 237 consecutive patients (248 transplantations) who underwent transplantation between 1999 and 2009 for hematological diseases and receiving intravenous defibrotide as prophylaxis. This cohort was compared to 241 patients (248 transplantations) treated before 1999 or after 2009 when defibrotide prophylaxis was not routinely used in our center. Median follow-up for the study group was 10 (range 2-16) years and for the control group 2.7 (range 1-18) years. None of the 237 patients in the defibrotide group developed SOS/VOD. The cumulative incidence (CI) of SOS/VOD was 0% in the defibrotide group as compared to 4.8% (95% confidence interval [CI], 2.6-8%; P= .00046) in the control group. There was also a better 1-year EFS with 38% (95% CI, 32%-44%) in the defibrotide group versus 28% (95% CI, 22%-34%) (P= .00969) and decreased cumulative incidence of acute graft-versus-host disease (GvHD) in the defibrotide group 31% (95% CI, 25%-37%) versus 42% (95% CI, 36%-48%) (P= .026). The 1-year overall survival, relapse incidence, and non-relapse mortality were not statistically different. Multivariable analysis, performed taking into account clinical factors known to influence the risk of SOS/VOD, confirmed the favorable impact of defibrotide on SOS/VOD (HR 1.38e-08 [95% CI, 3.28e-09-5.80e-08]; P< .00001). Conversely, multivariable analysis failed to confirm the impact of defibrotide on 1-year EFS or acute GvHD. This large retrospective study on SOS/VOD-prophylaxis with defibrotide suggests that this approach may be of benefit. These results need to be confirmed in a prospective randomized trial.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Humanos , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Estudios Retrospectivos , Estudios Prospectivos , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos
12.
Mycoses ; 65(11): 1061-1067, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35815918

RESUMEN

BACKGROUND: Limited data exist to describe end-of-treatment (EOT) parameters of antifungal therapy for invasive mould infections (IMI). METHODS: In a 10-year cohort of consecutive adult allogeneic haematopoietic cell transplant recipients with proven/probable IMI, we describe treatment duration and patient profile at EOT. RESULTS: There were 61 patients with 66 proven/probable IMI identified: 47/66 (71%) invasive aspergillosis (IA), 11/66 (17%) mucormycosis, and 8/66 (12%) other-IMI. Excluding 5 (8%) patients lost to follow-up, treatment was prematurely discontinued due to death or palliative care in 29/56 (51.8%) patients. Antifungal treatment was completed in 27 (48.2%) patients, for a median duration of 280 days (IQR: 110, 809): 258 (IQR: 110, 1905) and 307.5 (99, 809) days in IA and non-IA IMI, respectively. Treatment was continued after 90 and 180 days in 43/56 (76.8%) and 30/56 (53.6%) patients, respectively. At EOT, most patients were not neutropenic (ANC: 2.12 G/L, IQR: 0.04, 5.3), with CD4+ counts at 99 cells/µl (IQR: 0, 759) and immunoglobulins at 5.6 g/L (IQR: 2.3, 10.6). Most patients (16/27, 59.3%) were not receiving steroids at EOT, while 14/27 (53.9%) were on another type of immunosuppression. Amongst 15 patients with imaging at EOT, 12 (80%) had complete/partial radiologic response. Any chart documentation or an infectious disease consultation on treatment discontinuation was observed in 12/56 (21%) and 11/56 (20%) patients, respectively. CONCLUSIONS: Long treatment courses are observed in patients with IMI, due to prolonged immunosuppression. Although immune reconstitution and radiological response were frequently observed at EOT, consistent documentation of treatment discontinuation based on well-defined parameters is lacking.


Asunto(s)
Aspergilosis , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Adulto , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Hongos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones Fúngicas Invasoras/microbiología , Receptores de Trasplantes
13.
Open Forum Infect Dis ; 9(1): ofab596, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34993259

RESUMEN

BACKGROUND: Despite progress in diagnostic, prevention, and treatment strategies, invasive mold infections (IMIs) remain the leading cause of mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. METHODS: We describe the incidence, risk factors, and mortality of allo-HCT recipients with proven/probable IMI in a retrospective single-center 10-year (01/01/2010-01/01/2020) cohort study. RESULTS: Among 515 allo-HCT recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%), and other molds (8/51, 15%). Overall, 35/51 (68.6%) breakthrough IMIs (bIMIs) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31-180, and >180 days post-HCT, respectively. Risk factors for IMI included prior allo-HCT (sub hazard ratio [SHR], 4.06; P = .004) and grade ≥2 acute graft-vs-host disease (aGvHD; SHR, 3.52; P < .001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI (P = .02). Mortality predictors included disease relapse (hazard ratio [HR], 7.47; P < .001), aGvHD (HR, 1.51; P = .001), CMV serology-positive recipients (HR, 1.47; P = .03), and IMI (HR, 3.94; P < .001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (log-rank P = .47). At 1 year post-IMI diagnosis, 70.8% (34/48) of the patients were dead. CONCLUSIONS: IA mortality has remained relatively unchanged during the last 2 decades. More than two-thirds of allo-HCT recipients with IMI die by 1 year post-IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.

14.
G Ital Cardiol (Rome) ; 23(1): 4-9, 2022 01.
Artículo en Italiano | MEDLINE | ID: mdl-34985454

RESUMEN

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has greatly modified outpatient follow-ups. The aim of this retrospective study was to evaluate the organizational modalities and clinical effects of rearrangements of pacemaker (PM) and implantable cardioverter-defibrillator (ICD) outpatient visits performed in our centers at Ravenna and Lugo Hospitals, Italy, during the pandemic outbreak in 2020. METHODS: All scheduled in-person device follow-up visits in March-December 2020 have been considered. On the basis of documented past functioning of each device and of remote monitoring (RM) capabilities, in-person visits were either performed or postponed at variable times. The characteristics of the follow-ups and the device-related clinically relevant events were analyzed, the latter being further divided into serious malfunction and problems to be corrected by device reprogramming. RESULTS: Overall, 27% of in-person visits were postponed (n = 576) (36% of ICDs and 25% of PMs), peaking 62% in March-May 2020. RM compensated nearly all hold-ups in ICDs and just 63% of postponements in PMs. The postponement-caused delay between in-person visits was 5.6 ± 1.1 months for ICDs and 4.7 ± 1.2 months for PMs; in 24% of ICDs the time interval between in-person visits was ≥18 months. Clinically relevant events were 56 (18 [4.4%] in ICDs, 38 [2.1%] in PMs), with no deaths and 21 serious malfunctions (4 [1%] in ICDs, 15 [0.8%] in PMs). RM identified all ICD malfunctions, while it was not available in the affected PMs. In comparison with the year 2019, serious malfunctions increased, though the difference was not significant. Monthly RM transmissions increased by 2.3 fold. CONCLUSIONS: In our single-center experience during the COVID-19 pandemic, numerous in-person PM/ICD follow-up visits were postponed, and delays were well beyond the previously recommended time limits. However, device-related malfunctions did not increase, notably, when RM capabilities were used.


Asunto(s)
COVID-19 , Desfibriladores Implantables , Marcapaso Artificial , Electrónica , Estudios de Seguimiento , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2
15.
Mycoses ; 65(2): 199-210, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34936143

RESUMEN

BACKGROUND: Antifungal treatment duration and changes for invasive mould infections (IMI) have been poorly described. METHODS: We performed a 10-year cohort study of adult (≥18-year-old) allogeneic haematopoietic cell transplant recipients with proven/probable IMI to describe the duration and changes of antifungal treatment. All-cause-12-week mortality was described. RESULTS: Sixty-one patients with 66 IMI were identified. Overall treatment duration was 157 days (IQR: 14-675) and 213 (IQR: 90-675) days for patients still alive by Day 84 post-IMI diagnosis. There was at least one treatment change in 57/66 (86.4%) cases: median 2, (IQR: 0-6, range:0-8). There were 179 antifungal treatment changes due to 193 reasons: clinical efficacy (104/193, 53.9%), toxicity (55/193, 28.5%), toxicity or drug interactions resolution (15/193, 7.8%) and logistical reasons (11/193, 5.7%) and 15/193 (7.8%) changes due to unknown reasons. Clinical efficacy reasons included lack of improvement (34/104, 32.7%), targeted treatment (30/104, 28.8%), subtherapeutic drug levels (14/104, 13.5%) and other (26/104, 25%). Toxicity reasons included hepatotoxicity, nephrotoxicity, drug interactions, neurotoxicity and other in 24 (43.6%), 12 (21.8%), 12 (21.8%), 4 (7.4%) and 3 (5.5%) cases respectively. All-cause 12-week mortality was 31% (19/61), higher in patients whose antifungal treatment (logrank 0.04) or appropriate antifungal treatment (logrank 0.01) was started >7 days post-IMI diagnosis. All-cause 1-year mortality was higher in patients with ≥2 changes of treatment during the first 6 weeks post-IMI diagnosis (logrank 0.008) with an OR: 4.00 (p = .04). CONCLUSIONS: Patients with IMI require long treatment courses with multiple changes for variable reasons and potential effects on clinical outcomes, demonstrating the need more effective and safer treatment options. Early initiation of appropriate antifungal treatment is associated with improved outcomes.


Asunto(s)
Antifúngicos/uso terapéutico , Sustitución de Medicamentos , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Receptores de Trasplantes , Adulto , Antifúngicos/clasificación , Estudios de Cohortes , Hongos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones Fúngicas Invasoras/tratamiento farmacológico
16.
J Fungi (Basel) ; 7(10)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34682233

RESUMEN

BACKGROUND: Antifungal combination treatment is frequently administered for invasive mold infections (IMIs) after allogeneic hematopoietic cell transplantation (HCT). Here, we describe the indications, timing, and outcomes of combination antifungal therapy in post-HCT IMI. METHODS: A single-center, 10-year, retrospective cohort study including all adult HCT recipients with proven/probable IMI between 1 January 2010 and 1 January 2020 was conducted. RESULTS: During the study period, 515 patients underwent HCT, of whom 47 (9.1%) presented 48 IMI episodes (46 patients with one IMI episode and 1 patient with two separate IMI episodes): 33 invasive aspergillosis (IA) and 15 non-IA IMIs. Almost half (51%) of the patients received at least one course of an antifungal combination (median: 2/patient): 23 (49%), 20 (42%), and 4/47 (9%) patients received pure monotherapy, mixed monotherapy/combination, and pure combination treatment, respectively. Combination treatment was started at a median of 8 (IQR: 2, 19) days post-IMI diagnosis. Antifungal management was complex, with 163 treatment courses prescribed overall, 48/163 (29.4%) concerning antifungals in combination. The clinical reasons motivating the selection of initial combination antifungal therapy included severe IMI (18, 38%), lack of antifungal susceptibility data (14, 30%), lack of pathogen identification (5, 11%), and combination treatment until reaching a therapeutic azole serum level (6, 13%). The most common combination treatments were azole/liposomal amphotericin-B (28%) and liposomal amphotericin-B/echinocandin (21%). Combination treatment was administered cumulatively for a median duration of 28 days (IQR: 7, 47): 14 (IQR: 6, 50) days for IA and 28 (IQR: 21, 34) days for non-IA IMI (p = 0.18). Overall, 12-week mortality was 30%. Mortality was significantly higher among patients receiving ≥50% of treatment as combination (logrank = 0.04), especially those with non-IA IMI (logrank = 0.03). CONCLUSIONS: Combination antifungal treatment is frequently administered in allogeneic HCT recipients with IMI to improve clinical efficacy, albeit in an inconsistent and variable manner, suggesting a lack of relevant data and guidance, and an urgent need for new studies to improve therapeutic options.

19.
Transplant Cell Ther ; 27(1): 67.e1-67.e7, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32980547

RESUMEN

Outcomes of hematopoietic stem cell transplantation (HSCT) are influenced by comorbidities, disease type, and status at transplantation. Several prognostic scores can be used, such as the disease risk index (DRI) or the hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Recently, a new prognostic tool, the disease risk comorbidity index (DRCI), combining the DRI and the HCT-CI, was published. The DRCI determines 6 patient groups (very low risk [VLR], low risk [LR], intermediate risk 1 [IR-1], intermediate risk 2 [IR-2], high risk [HiR], and very high risk [VHR]) with a significant predictive value for overall survival (OS), disease-free survival (DFS), relapse incidence (RI), and graft-versus-host disease-free/relapse-free survival (GRFS). However, the DRCI has not been evaluated for patients allografted with partially in vitro T cell depleted (pTDEP) grafts. In our center, we offer pTDEP to reduce graft-versus-host disease for patients in complete remission at transplant time. In this retrospective study, we investigated the DRCI in 404 adult patients (including 37.6% pTDEP) undergoing a first HSCT for hematological malignancies from 2008 to 2018. Because of the small number of patients in LR, VLR and LR were combined for analysis. In the entire cohort, 2-year OS was 84.4% (95% CI, 71.6% to 97.2%) for LR, 61.6% (54.8% to 68.4%) for IR-1, 45.7% (33.3% to 58.1%) for IR-2, 31% (19.4% to 42.6%) for HiR, and 30.9% (14.5% to 47.3%) for VHR (P < .001). In addition, the DRCI was predictive of DFS, RI, and GRFS but not of nonrelapsed mortality and graft-versus-host disease. Our study confirms similar results with the original publication but gives less accurate prognosis information than the DRI and HCT-CI when used separately. In conclusion, the DRCI does not seem to offer more relevant information than the DRI and HCT-CI to help physicians and patients for the HSCT decision.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfocitos T , Adulto , Comorbilidad , Humanos , Recurrencia Local de Neoplasia , Estudios Retrospectivos
20.
J Interv Card Electrophysiol ; 61(3): 469-477, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32749567

RESUMEN

PURPOSE: Generator impedance (Im) mapping with constant contact force (CF) by tip catheter at PV isolation (PVI) was assessed for a proposal of tissue characterization at PV-LA junction (PV-LAJ). METHODS: In this observational, prospective, single-center study, Im mapping at constant CF = 10 g (± 2 g) was performed before PVI at PV-LAJ. PV in-vein, PV ostium (PVos), and antrum (PVan) contours were manually traced based on the 3D electroanatomic map (3DEAM) integrating intracardiac echocardiography and computerized tomography. PVan contour-methods based on Im mapping was defined on 3DEAM as the atrial-like Im contour closest to PVos, and its distance from anatomical PVan contour > 5 mm was assumed as the non-concordance marker between contour and methods. RESULTS: Sixty-two patients (62 ± 9 years; 43 males) were enrolled, and 244 PV-LAJ were assessed. From in-vein PV to LA and, less prominently, from PVos to PVan and LA, Im showed a unidirectional decrease with highly variable individual-specific distribution and values. PVan non-concordance was found in 59/665 segments (8.8%), 18% of PV-LAJs, and 53% of pts; it prevailed in superior PV-LAJ and measured on average 7.2 ± 1.1 mm. Im decrease patterns and non-concordance were not associated with any clinical or anatomical feature, including PV dimensions and shape. CONCLUSIONS: Im mapping of LA-PVJ at constant CF added to 3DEAM may consistently track the tissue transition from PV to LA. PVan identified by Im was often located more toward LA than the 3D anatomical PVan, particularly in LSPV, suggesting the potential advantage of avoiding ablation of venous-like tissue. Im mapping can deserve further investigation for target characterization at LA-PVJ.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Anciano , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Impedancia Eléctrica , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Resultado del Tratamiento
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