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BACKGROUND: Continuous fluid infusions delivered between therapies by piggy-back systems avoid disconnection and reconnection of central venous catheters (CVCs), thereby reducing opportunities for line contamination. However, the impact of continuous versus intermittent infusions on central line-associated bloodstream infections (CLABSIs) is unknown. AIM: To investigate the effect of temporary infusion interruption and line disconnection, with or without use of a 70% isopropyl alcohol cap (IPA-C) on CLABSI rates in haematology patients. METHODS: Quasi-experimental study in two haemato-oncology units. At baseline (P1, September 2020 to August 2021), continuous intravenous piggy-back infusions were mandatory. In a first intervention phase (P2, September 2021 to August 2022), infusion disconnections were implemented with use of a 70% isopropyl alcohol cap (IPA-C) for passive decontamination. In a second intervention phase (P3, September 2022 to August 2023), infusion disconnections continued without the use of IPA-C. Rates of CLABSI were compared across the three intervention periods using segmented Poisson regression. FINDINGS: A total of 11,039 catheter-days across 764 CVCs and 16,226 patient-days were included. Twenty-one CLABSIs were recorded across all intervention periods. Compared with P1, incidence rate ratios (IRRs) for CLABSI did not significantly change in P2 (IRR 0.76 (95% CI 0.27-2.15)) and P3 (IRR 0.79 (95% CI 0.28-2.22)). No CVCs were removed due to occlusion during the study period. Five of 21 CLABSIs were polymicrobial, and coagulase-negative staphylococci were isolated in 19/21 cases (90%). CONCLUSION: Interruption of continuous infusions in haemato-oncology patients with a CVC was not associated with a substantial change in CLABSI rates, whether or not an IPA-C was used.
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Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Transporte Activo de Núcleo Celular , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Humanos , Hidrazinas , TriazolesRESUMEN
Since July 2007 prospective life-long follow-up (FU) for unrelated (URD) and related donors (RD) is mandatory in Switzerland and data on every allogeneic haematopoietic progenitor cell (HPC) donation are collected prospectively. We report the real-world experience of HPC donation during a 10-year study period (01.07.2007-30.06.2017) with basic characteristics and FU data. 1105 donors underwent 1155 HPC donation procedures. Eighty percent of first donations performed by 802 (73%) RDs and 303 (27%) URDs were peripheral blood stem cells (PBSC), 20% bone marrow (BM). Male donors were over-represented as URD (60% male vs 40% female). Main differences between RDs and URDs concerned age and pre-existing health disorders. RDs were significantly older at first donation (median age 48 years) compared to URD (34 years, p < 0.0001) and had more pre-existing health problems: 25% vs 9% in URD (p < 0.0001). No fatal complications occurred, collection related severe adverse events (SAE) after first donation were not significantly different between groups (RD 1.2%, URD 0.99%), incidence rates for neoplastic and autoimmune diseases did not exceed the rates of the general population. RDs are a more heterogeneous and potentially more vulnerable group, but if donor evaluation is performed appropriately, HPC donation is still safe.
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Donantes de Tejidos , Donante no Emparentado , Femenino , Estudios de Seguimiento , Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Suiza/epidemiologíaRESUMEN
Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p ≤ 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2-4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.
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Reparación del ADN/genética , Variación Genética , Enfermedad Injerto contra Huésped/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Antineoplásicos Alquilantes/farmacocinética , Busulfano/farmacocinética , Niño , Preescolar , Estudios de Cohortes , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Pruebas Genéticas , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Heterocigoto , Humanos , Incidencia , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated pipeline and de novo analysis on pooled routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal, and unexpected viruses. RESULTS: Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nucleotide sequences in 24/25 patients. Sequences of ≥ 3 distinct viruses were detected in 16/25 patients; Anelloviridae (24/25) and human pegivirus-1 (9/25) were the most prevalent. In 7 patients with fatal outcomes, viral sequences not assessed by routine investigations were identified with mNGS and confirmed by RT-PCR. These cases included Usutu virus (1), rubella virus (1 vaccine strain and 1 wild-type), novel human astrovirus (HAstV) MLB2 (1), classic HAstV (1), human polyomavirus 6 and 7 (2), cutavirus (1), and bufavirus (1). CONCLUSIONS: Clinically unrecognized viral infections were identified in 28% of highly immunocompromised allo-HSCT recipients with steroid-refractory/dependent GvHD in consecutive samples. These identified viruses have all been previously described in humans, but have poorly understood clinical significance. Rubella virus identification raises the possibility of re-emergence from past infections or vaccinations, or re-infection. Video abstract.
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Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Esteroides , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Esteroides/efectos adversos , Esteroides/uso terapéutico , Adulto JovenRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
More effective treatment modalities are urgently needed in patients with acute myeloid leukemia (AML) of older age. We hypothesized that adding lenalidomide to intensive standard chemotherapy might improve their outcome. After establishing a safe lenalidomide, dose elderly patients with AML were randomly assigned in this randomized Phase 2 study (n = 222) to receive standard chemotherapy ("3 + 7") with or without lenalidomide at a dose of 20 mg/day 1-21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without lenalidomide (20 mg/day 1-21). The CR/CRi rates in the two arms were not different (69 vs. 66%). Event-free survival (EFS) at 36 months was 19% for the standard arm versus 21% for the lenalidomide arm and overall survival (OS) 35% vs. 30%, respectively. The frequencies and grade of adverse events were not significantly different between the treatment arms. Cardiovascular toxicities were rare and equally distributed between the arms. The results of the present study show that the addition of lenalidomide to standard remission induction chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR2294 in The NederlandsTrial Register (www.trialregister.nl).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción/mortalidad , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Citarabina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida/administración & dosificación , Leucemia Mieloide Aguda/patología , Masculino , Síndromes Mielodisplásicos/patología , Pronóstico , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Because commensal viruses are defined by the immunologic tolerance afforded to them, any immunomodulation, such as is received during haematopoietic stem-cell transplantation, may shift the demarcation between innocuous viral resident and disease-causing pathogen. METHODS: We analysed by deep-sequencing the plasma virome of 40 allogeneic haematopoietic stem-cell transplantation patients 1 month after transplantation. Because human pegivirus (HPgV) was highly prevalent, we performed a 1-year screening of 122 plasma samples by specific real-time reverse transcription PCR assay. We used the log-rank test and the Gray test to assess association with outcomes, and the Mann-Whitney test and multivariable linear regression model to assess association with T-cell reconstitution. RESULTS: Polyomaviruses (PyV) (20/40 patients), anelloviruses (16/40), pegiviruses (14/40) and herpesviruses (14/40) were most frequently identified, including ten cytomegalovirus; three Epstein-Barr virus; two herpes simplex virus type 1; one human herpesvirus 6b and one human herpesvirus 7; 18 Merkel cell-PyV; two BK-PyV; three PyV-6; and one JC-PyV. Papillomavirus and adenovirus were identified in 11 and two patients, respectively. The HPgV specific real-time reverse transcription PCR screening identified 51 of 122 positive samples, high virus loads and persistent infections up to 1 year after transplantation. Comparison between patients with or without HPgV infection at time of transplantation did not reveal a significant difference in infections, engraftment, survival, graft vs. host disease, relapse or immune reconstitution. CONCLUSIONS: The blood virome after allogeneic haematopoietic stem-cell transplantation includes several DNA viruses, notably herpesviruses and PyV. Among RNA viruses, HPgV is highly prevalent and persists for several months, and it thus may deserve special attention in further research on immune reconstitution.
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Virus ADN/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas , Virus ARN/aislamiento & purificación , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Instituciones Oncológicas , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Suiza/epidemiologíaRESUMEN
Comparisons of hematopoietic stem cell transplantation (HSCT) methods in retrospective studies are often hampered by the heterogeneity of comparison groups. The refined disease risk index (DRI) is a potentially interesting tool to compare HSCT protocols as it is based on the disease type and burden at transplant and stratifies patients into four prognostic groups for overall survival (OS). We included 265 patients with partial T-cell-depleted graft (TDEP) and 163 non-TDEP patients in a retrospective study and compared outcomes following stratification using the refined DRI. The 2-year OS rate for TDEP patients was 81.6, 60.9 and 43.3% for the low-, intermediate- and high-risk groups, respectively (P<0.001). For non-TDEP patients, the 2-year OS rate was 62.9, 48.8, 44.2 and 7.6% for the low-, intermediate-, high- and very-high-risk groups, respectively (P<0.001). There was no significant difference when comparing OS between TDEP and non-TDEP for the low-, intermediate- and high-risk groups, but TDEP patients had less acute GvHD grades II-IV. In conclusion, we confirm that the refined DRI is a valuable tool to compare the outcomes of different HSCT protocols. We demonstrate also that TDEP did not impact on the outcome of HSCT, but it did reduce the incidence of acute GvHD.
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Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Células Madre Hematopoyéticas/métodos , Depleción Linfocítica/métodos , Adolescente , Adulto , Anciano , Femenino , Neoplasias Hematológicas/terapia , Humanos , Depleción Linfocítica/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Linfocitos T , Trasplantes/normas , Trasplantes/trasplante , Resultado del Tratamiento , Adulto JovenAsunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Linfocitos T/citología , Quimera por Trasplante , Adolescente , Adulto , Antígenos CD34/metabolismo , Femenino , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Infecciones por Virus ADN , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Torque teno virus , Adolescente , Adulto , Anciano , Aloinjertos , Infecciones por Virus ADN/sangre , Infecciones por Virus ADN/epidemiología , Infecciones por Virus ADN/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We have conducted a retrospective study on 251 patients from three centers in France and Switzerland between 2004 and 2010 with the goal to evaluate the impact of HLA-DRB3/B4/B5 allele mismatching after HLA-10/10-matched unrelated allogeneic hematopoietic stem cell transplantation (HSCT). Fourteen (5.5%) patients receiving HSCT from an HLA-10/10-matched unrelated donor had a mismatched DRB4 donor, 23 (9.5%) patients had a mismatched DRB3 donor and 214 (85%) had a fully matched unrelated donor (HLA-10/10) without DRB3- or DRB4-mismatched donor. We compared the outcomes of 37 patients with a DRB3 or DRB4 mismatch with the rest of the population. The median survival for a patient without DRB3/4 mismatch was 18 months (95% confidence interval (CI), 13-29), for DRB3-mismatched patients 32 months (95% CI, 13-NR) and for DRB4-mismatched patients 7 months (95% CI, 3-NR). The multivariate analysis showed a significant impact of DRB4 mismatching on survival (Hazards ratio (HR)=2.1 (95% CI, 1.01-4.67), P=0.045), acute GvHD (HR=2.66 (95% CI, 0.99-7.09) P=0.05) and on transplant-related mortality (HR=2.8; (95% CI, 1.7-4.4) P=0.024). In the view of an impact of DRB4 locus mismatch on clinical outcome, it would be important to confirm this observation in a prospective study as it may be worth considering DRB4 in the unrelated donor selection.
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Cadenas HLA-DRB4/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Histocompatibilidad/inmunología , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Femenino , Francia , Prueba de Histocompatibilidad , Humanos , Masculino , Estudios Retrospectivos , Análisis de Supervivencia , Suiza , Resultado del Tratamiento , Donante no EmparentadoRESUMEN
Unrelated donor searches in Switzerland require high-resolution HLA typing for HLA-A/B/C/DRB1/DRB3,4/DQB1 loci. We evaluated this strategy accepting donors with ⩾9/10 match. Of 802 unrelated donor transplants in 2000-2013, 570 were 10/10 matched, 31 were DRB3/4 mismatched, 261 were single-allele mismatched and 13 had 2 allele mismatches. Of the 261 single-allele disparities, 60 concerned HLA-A/-B, 55 HLA-C and 73 HLA-DRB1/-DQB1 loci. Transplants were reduced intensity conditioning (289, 36%), marrow (187, 23%), EBMT risk score was low in 39, intermediate I in 331, intermediate II in 333 and high in 99 patients. Five-year survival was 48±4%. HLA affected survival in the multivariate model adjusted for risk score. HLA-A/-B and HLA-C mismatches had twice the mortality risks, whereas HLA-DRB1/-DQB1 mismatches were similar to matched transplants. HLA-DRB3/4 mismatches were associated with a nonsignificant increased mortality risk. HLA-DRB3/4 mismatches had higher graft-versus-host disease and transplant-related mortality risks and lower relapse rates compared with matched transplants. We show significant effects of HLA class I, but not HLA class II, mismatches. The lack of impact of DRB1 disparities may be related to the lower immunogenicity of the DRB1*11:01/11:04 and DRB1*14:01/14:54 mismatches, representing 46% of DRB1 incompatibilities. These results support a matching algorithm that prioritizes mismatches considered as more permissive.
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Cadenas beta de HLA-DQ/inmunología , Cadenas HLA-DRB1/inmunología , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Antígenos de Histocompatibilidad Clase I/inmunología , Prueba de Histocompatibilidad , Donante no Emparentado , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Selección de Donante , Femenino , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , SuizaRESUMEN
The aim of this registry-based retrospective study was to analyze the outcome of second allogeneic hematopoietic SCT (alloHSCT_2) performed in patients with lymphoma who had relapsed after a first allogeneic transplant (alloHSCT_1). Patients ⩾18 years who had received an alloHSCT_2 for lymphoma relapse between 2000 and 2011 were eligible. One hundred and forty patients were identified. The diagnosis was Hodgkin lymphoma (HL) in 31%, diffuse large B-cell lymphoma in 14%, T-cell lymphoma in 12%, indolent lymphoma in 19%, mantle cell lymphoma in 16% and other lymphomas in 8% of the patients. The median interval from alloHSCT_1 to alloHSCT_2 was 19 (range 4-116) months. Disease status at alloHSCT_2 was chemosensitive in 46%, refractory in 43% and unknown in 11% of the patients. Three-year PFS, OS, relapse incidence and nonrelapse mortality were 19%, 29%, 58% and 23%, respectively. PFS and OS were significantly affected by refractory disease at alloHSCT_2 and a short interval between alloHSCT_1 and alloHSCT_2. Long-term PFS was observed across all lymphoma subsets except for aggressive B-cell lymphoma. In conclusion, alloHSCT_2 is feasible and can result in long-term disease control in patients with lymphoma recurrence after alloHSCT_1, in particular if relapse occurs late and is chemosensitive.
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Linfoma/mortalidad , Linfoma/terapia , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: This study assessed whether a cycle of "routine" therapeutic drug monitoring (TDM) for imatinib dosage individualization, targeting an imatinib trough plasma concentration (C min) of 1,000 ng/ml (tolerance: 750-1,500 ng/ml), could improve clinical outcomes in chronic myelogenous leukemia (CML) patients, compared with TDM use only in case of problems ("rescue" TDM). METHODS: Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5 years. Patients were allocated 1:1 to "routine TDM" or "rescue TDM." The primary endpoint was a combined outcome (failure- and toxicity-free survival with continuation on imatinib) over 1-year follow-up, analyzed in intention-to-treat (ISRCTN31181395). RESULTS: Among 56 patients (55 evaluable), 14/27 (52 %) receiving "routine TDM" remained event-free versus 16/28 (57 %) "rescue TDM" controls (P = 0.69). In the "routine TDM" arm, dosage recommendations were correctly adopted in 14 patients (median C min: 895 ng/ml), who had fewer unfavorable events (28 %) than the 13 not receiving the advised dosage (77 %; P = 0.03; median C min: 648 ng/ml). CONCLUSIONS: This first target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" because of small patient number and surprisingly limited prescriber's adherence to dosage recommendations. Favorable outcomes were, however, found in patients actually elected for target dosing. This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions. The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents.
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Antineoplásicos/administración & dosificación , Benzamidas/administración & dosificación , Monitoreo de Drogas/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Adulto , Anciano , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Benzamidas/farmacocinética , Benzamidas/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Piperazinas/farmacocinética , Piperazinas/uso terapéutico , Medicina de Precisión/métodos , Estudios Prospectivos , Pirimidinas/farmacocinética , Pirimidinas/uso terapéutico , Resultado del TratamientoRESUMEN
Several T-cell depletion (TCD) techniques are used for haploidentical hematopoietic SCT (HSCT), but direct comparisons are rare. We therefore studied the effect of in vitro TCD with graft engineering (CD34 selection or CD3/CD19 depletion, 74%) or in vivo TCD using alemtuzumab (26%) on outcome, immune reconstitution and infections after haploidentical HSCT. We performed a retrospective multicenter analysis of 72 haploidentical HSCT in Switzerland. Sixty-seven patients (93%) had neutrophil engraftment. The 1-year OS, TRM and relapse incidence were 48 (36-60)%, 20 (11-33)% and 42 (31-57)%, respectively, without differences among the TCD groups. In vivo TCD caused more profound lymphocyte suppression early after HSCT, whereas immune recovery beyond the second month was comparable between the two groups. Despite anti-infective prophylaxis, most patients experienced post-transplant infectious complications (94%). Patients with in vivo TCD had a higher incidence of CMV reactivations (54% vs 28%, P=0.015), but this did not result in a higher TRM. In conclusion, TCD by graft engineering or alemtuzumab are equally effective for haploidentical HSCT.
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Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Depleción Linfocítica/métodos , Linfocitos T/inmunología , Adolescente , Adsorción , Adulto , Alemtuzumab , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígenos CD19/metabolismo , Antígenos CD34/metabolismo , Antineoplásicos/uso terapéutico , Complejo CD3/metabolismo , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped , Movilización de Célula Madre Hematopoyética , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Recurrencia , Estudios Retrospectivos , Suiza , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Adulto JovenRESUMEN
Despite the introduction of novel drugs, cure of multiple myeloma remains rare. Allo-SCT can induce long-term remission, but randomized studies in advanced disease are lacking and the influence of novel drugs remains unclear. In our retrospective analysis of all patients with myeloma allografted in Switzerland, 95 patients were transplanted between 1988 and 2011. Most patients were heavily pre-treated, and 53% received novel drugs before transplant. In all, 51% were allografted after relapse or progression. Transplant trends changed over time with an increase in reduced intensity conditioning and unrelated donors. At the time of analysis 47 patients remained alive, with a median follow-up of survivors of 53 months. Acute GVHD II-IV and chronic GVHD (cGVHD) occurred in 49% and 53%, respectively; TRM at 5 years was 18%. Five-year OS and PFS were 51% and 29%, respectively. Patients who received transplant upfront vs after relapse had a significantly better outcome, as well as those who had a related donor and achieved CR post transplant. We found no impact of pre-treatment with novel drugs or cGVHD. Although long-term remission following allo-SCT can be achieved, GVHD and TRM remain major limitations. Our series suggests that benefit is highest when allo-SCT is used early in the disease.
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Mieloma Múltiple/cirugía , Trasplante de Células Madre/métodos , Adulto , Anciano , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
The impact of the 2009 H1N1-Influenza A (H1N1) pandemic in allogeneic hematopoietic SCT recipients (allo-HSCT) is not yet well defined. Between May 2009 and May 2010, all allo-HSCTs who presented with respiratory symptoms were screened for the presence of the H1N1 virus. Oseltamivir resistance was assessed and chart reviews were performed for all cases. In all, 51 of 248 (20%) allo-HSCT recipients followed at our outpatient clinic were screened. We identified 10 patients with H1N1 infection. Close contact with children was the most commonly suspected mode of transmission. Upper and lower respiratory tract infections were present in eight and five patients, respectively. Lymphopenia (<1 G/L) was the most frequent biological abnormality. High immunosuppression was responsible for severe infection requiring mechanical ventilation associated with prolonged viral shedding in three patients who had significant comorbidities and GvHD. Two of them developed an oseltamivir-resistant strain and both patients died subsequently despite intensive therapy, resulting in a case fatality rate of 20%. In conclusion, although most allo-HSCTs had mild symptoms from H1N1 infection, severe immunosuppression and emergence of oseltamivir resistance were likely responsible for a substantial morbidity, further supporting the need for vaccination and monitoring of close contacts, especially children.