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BACKGROUND: Managing SARS-CoV-2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab-cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real-life data in a heterogeneous cohort are few. METHODS: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab-cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch-and-wait strategy, followed in our center, during a median follow-up of 249 (45-325) days. RESULTS: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment-related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab-cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti-CD20 monoclonal antibodies and B-non-Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred. CONCLUSION: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity.
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COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Hematológicas , Humanos , Anciano , Infección Irruptiva , SARS-CoV-2 , Anticuerpos Monoclonales , Enfermedades Hematológicas/complicacionesRESUMEN
Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment.
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PURPOSE: To evaluate the role of stereotactic body radiation therapy (SBRT) delivered after external-beam fractionated irradiation in non-small-cell lung cancer (NSCLC) patients with clinical stage III A, B. MATERIALS AND METHODS: All patients received three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) (60-66 Gy/30-33 fractions of 2 Gy/5 days a week) with or without concomitant chemotherapy. Within 60 days from the end of irradiation, a SBRT boost (12-22 Gy in 1-3 fractions) was delivered on the residual disease. RESULTS: Here we report the mature results of 23 patients homogeneously treated and followed up for a median time of 5.35 years (range 4.16-10.16). The rate of overall clinical response after external beam and stereotactic boost was 100%. No treatment-related mortality was recorded. Radiation-related acute toxicities with a grade ≥ 2 were observed in 6/23 patients (26.1%): 4/23 (17.4%) had esophagitis with mild esophageal pain (G2); in 2/23 (8.7%) clinical radiation pneumonitis G2 was observed. Lung fibrosis (20/23 patients, 86.95%) represented a typical late tissue damage, which was symptomatic in one patient. Median disease-free survival (DFS) and overall survival (OS) were 27.8 (95% CI, 4.2-51.3) and 56.7 months (95% CI, 34.9-78.5), respectively. Median local progression-free survival (PFS) was 17 months (range 11.6-22.4), with a median distant PFS of 18 months (range 9.6-26.4). The 5-year actuarial DFS and OS rates were 28.7% and 35.2%, respectively. CONCLUSIONS: We confirm that a stereotactic boost after radical irradiation is feasible in stage III NSCLC patients. All fit patients who have no indication to adjuvant immunotherapy and presenting residual disease after curative irradiation could benefit from stereotactic boost because outcomes seem to be better than might be historically assumed.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Traumatismos por Radiación , Radiocirugia , Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Radiocirugia/efectos adversos , Radiocirugia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Radioterapia de Intensidad Modulada/métodos , Etopósido/uso terapéuticoRESUMEN
The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph'+ ALL) patients post-allogeneic transplantation is limited. We retrospectively collected data on 25 Ph'+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of BCR/ABL1, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph'+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered.
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Imidazoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Piridazinas/uso terapéutico , Enfermedad Aguda , Adulto , Quimioprevención/métodos , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Proteínas de Fusión bcr-abl/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Estudios Retrospectivos , Terapia Recuperativa/métodos , Prevención Secundaria/métodos , Análisis de Supervivencia , Trasplante Homólogo , Adulto JovenRESUMEN
We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; Pâ¯=â¯.015; 50% PFS not reached versus 26 months, Pâ¯=â¯.003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; Pâ¯=â¯.001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval [CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%).
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Trasplante de Células Madre Hematopoyéticas , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sistema de Registros , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sociedades Médicas , Tasa de SupervivenciaRESUMEN
Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.
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Inhibidores de la Angiogénesis/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/análogos & derivados , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mieloma Múltiple/terapia , Recurrencia , Inducción de Remisión , Talidomida/uso terapéutico , Trasplante HomólogoRESUMEN
Ph'+ acute lymphoblastic leukemia (Ph'+-ALL) is an oncohematologic disorder for which allogeneic bone marrow transplantation still offers the only chance of cure. However, relapse is the main reason for treatment failure, also after hematopoietic stem cell transplantation (HSCT). New drugs, such as third generation tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have expanded the therapeutic landscape, especially in patients who relapsed before HSCT. Very few reports, up to now, have described the use of both classes of these new agents in combination with donor lymphocyte infusions (DLI) in the setting of patients who relapsed after HSCT. We report on a young patient affected by Ph'+-ALL, who relapsed after the second HSCT and who reached molecular remission and long-term disease control by treatment with the anti-CD22 monoclonal antibody inotuzumab ozogamicin, DLI, and the 3rd generation TKI ponatinib.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Imidazoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Piridazinas/uso terapéutico , Femenino , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Inotuzumab Ozogamicina , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Inducción de Remisión , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND: Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes. OBJECTIVE: The purpose of this study was to describe the pattern of mesocolic lymph node metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection. DATA SOURCES: EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip node; lymph node resection colon; and complete or total and mesocolic excision. STUDY SELECTION: Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were excluded. MAIN OUTCOME MEASURES: The risk of metastases in the central mesocolic lymph nodes was measured. RESULTS: A total of 2052 articles were screened, of which 277 underwent full-text review. The 47 studies fulfilling the inclusion criteria were very heterogeneous, and meta-analyses were not considered appropriate. The risk of central mesocolic lymph node metastases for right-sided cancers varies between 1% and 22%. In sigmoid cancer, the risk is reported in ≤12% of the patients and is associated with advanced T stage. LIMITATIONS: The retrospective design and heterogeneity, in terms of definitions of lymph node location, tumor sites, stage, morphology, pathology assessment, and inclusion criteria (selection bias), of the included studies were limitations. Also, anatomic definitions were not uniform. CONCLUSIONS: The present literature cannot give a theoretical explanation of a better oncological outcome after extended lymph node dissection. Consensus for a standardization of anatomical definitions and surgical and pathological assessments is warranted for future mapping studies.
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Colectomía/métodos , Neoplasias del Colon , Errores Diagnósticos/prevención & control , Ganglios Linfáticos , Metástasis Linfática/diagnóstico , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Humanos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Mesocolon , Medición de RiesgoRESUMEN
BACKGROUND: In computed tomography (CT), the image contrast is given by the difference in X-ray attenuation in the various tissues of the patient and contrast media are used to enhance image contrast in anatomic regions characterized by similar attenuation coefficients. OBJECTIVE: Aim of the present work is to enlarge the range of applicability of the method previously introduced for organ dosimetry in contrast-enhanced CT, by studying the effects of X-ray beam quality on the parameters of the model. Furthermore, an experimental method for the evaluation of the attenuation properties of iodinated solutions is proposed. METHODS: Monte Carlo simulations of anthropomorphic phantoms were carried out to determine a bi-parametrical (a and b) analytical relationship between iodine concentration and dose increase in organs of interest as a function of the tube kilo-voltage peak potential (kVp) and filtration. Experimental measurements of increments in Hounsfield Units (HU) were conducted in several CT scanners, at all the kVp available, in order to determine the parameter γ which relates the HU increment with the iodine mass fraction. A cylindrical phantom that can be filled with iodine solutions provided with an axial housing for a pencil ionization chamber was designed and assembled in order to measure the attenuation properties of iodine solutions under irradiation of a CT scanner and to obtain a further validation of Monte Carlo simulations. RESULTS: The simulation-derived parameters of the model, a and b, are only slightly dependent upon the tube kilo-voltage peak potential and filtration, while such scanner-dependent features influence mainly the experimentally-derived γ parameter. Relative dose variations registered by the ionization chamber inside the iodine-filled cylindrical phantom decrease when the X-ray mean energy increases, and reaches about 50% for 10âmg/ml of iodine. CONCLUSIONS: The dosimetric method for contrast-enhanced CT can be applied to all CT scanners by adopting average simulative parameters and by carrying out a simple measurement with a series of iodine contrast solutions. The novel experimental methodology introduced can provide a direct measurement of iodine attenuation properties.
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Medios de Contraste/química , Yodo/química , Dosis de Radiación , Tomografía Computarizada por Rayos X/instrumentación , Tomografía Computarizada por Rayos X/métodos , Simulación por Computador , Humanos , Método de Montecarlo , Fantasmas de ImagenAsunto(s)
Ácidos y Sales Biliares/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Liraglutida/uso terapéutico , Síndromes de Malabsorción/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Receptor del Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Humanos , Liraglutida/farmacología , Síndromes de Malabsorción/etiología , Masculino , Persona de Mediana Edad , Sobrepeso/complicaciones , Inducción de Remisión/métodos , Resultado del TratamientoRESUMEN
To date, no prospective study on Plerixafor 'on-demand' in combination with chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on-demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34(+) cells in peripheral blood was reduced by 'on-demand' strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34(+) cells 2 × 10(6) /kg decreased from 20·9 to 4·0% (P = 0·0001). The on-demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a 'bias-adjusted set of controls'. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G-CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/administración & dosificación , Linfoma/terapia , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Anciano , Bencilaminas , Eliminación de Componentes Sanguíneos/economía , Eliminación de Componentes Sanguíneos/métodos , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/economía , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Humanos , Linfoma/tratamiento farmacológico , Linfoma/cirugía , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Trasplante de Células Madre de Sangre Periférica/economía , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
We conducted a prospective study aimed at investigating the prognostic value of the dynamic of a-GVHD progression from cutaneous to visceral involvement. In 108 consecutive patients who underwent allogeneic HSCT, we classified a-GVHD according to a "GHVD skin dynamic": 18/82 patients started Corticosteroid (CS) within 48 h (Group 1); 13/82 started CS within days 3-7 (Group 2); Group 3A (n 31) was defined when Skin GVHD Overall Grade 1, left untreated for 1 week, showed an increase in involved body surface area <5 %; Group 3B (n 20), was defined when Skin GVHD Overall Grade 1, left untreated at 1 week, had an increase in involved body surface area >5%. These four groups had distinctive 2-y OS. Patients could be then grouped into "poor risk" (Group 1 and Group 3B) and "good risk" (Group 2 and Group 3A). "Poor risk" had inferior OS in univariate and multivariate analysis, (HR 2.222; 95% CL: 1.017-4.855; p 0.04). Among the patients with skin-only Grade 1 GVHD, subgroup 3A had an OS of 75.1% versus 39.8% found in subgroup 3B (p = 0.03). The dynamic of skin GVHD may be used to classify a-GVHD and guide treatment in Overall Grade 1 skin-only GVHD.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Prospectivos , Trasplante Homólogo , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Pronóstico , Corticoesteroides/uso terapéutico , Estudios RetrospectivosRESUMEN
After European Medicines Agency (EMA) approval, national pricing and reimbursement procedures are necessary to guarantee access to drugs, based on the willingness to pay and the recognition of therapeutic value. These can result in delays in drug availability for patients, even for those with important unfmet needs for whom it may be necessary and ethical to ensure access. The objective of this study was to evaluate the use of ruxolitinib for patients with graft-versus-host disease (GvHD) after EMA approval at the University Hospital of Catania. We analysed data about the use of ruxolitinib in patients with GvHD, describing their basic characteristics, their outcomes and the cost of the treatment. In the reference period, 24 ruxolitinib treatments were started according to the Summary of Product Characteristic. The average treatment duration was 10 months. Twenty patients showed a response, maintained over time, with no adverse reactions. The total expenditure amounts to EUR 963,424. The use of ruxolitinib in a real population confirms its role in an important therapeutic need. The quantification of costs requires a reflection on the sustainability of early access to medicines authorised by the EMA for serious diseases and in the absence of therapeutic alternatives.
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Data on the efficacy of high-dose chemotherapy and autologous stem cell transplantation (ASCT) for classical Hodgkin lymphoma (cHL) patients who failed a PET-driven first-line therapy are limited.We retrospectively evaluated 220 adult cHL patients who underwent ASCT from 2009 to 2021 at 11 centers in Italy. Overall, 49.5% had refractory disease, 23.2% relapsed < 12 and 27.3% ≥12 months from the end of first-line chemotherapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 73.8% and 89.4%. In univariable analysis for PFS events PET-2+ (HR 2.69, p = .001), anemia (HR 2.22, p = .019), refractory disease (HR 1.76, p = .045), less than CR before ASCT (HR 3.24, p < .001) and >2 lines of salvage therapy (HR 2.52; p = .004) were associated with a higher risk of failure after ASCT. In multivariable analysis, >2 lines of salvage therapy (HR 3.28, p = .004) and RT before ASCT (HR 3.00, p = 0.041) retained significance.ASCT is an effective salvage approach for cHL patients treated in the era of PET-adapted therapies.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Adulto , Humanos , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia Recuperativa , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Trasplante Autólogo , Trasplante de Células Madre , Tomografía de Emisión de PositronesRESUMEN
Gold nanoparticles (GNPs) are a promising radiosensitizer agent in radiotherapy. Through a simulation performed with the Geant4 Monte Carlo code, we evaluated the dose enhancement effect of GNPs during therapies with an x-ray tube operating at 150 kV (E = 55 keV and E(max) = 150 keV) and we studied the impact of GNP diffusion out of the tumour vessels, in terms of antiangiogenic and cytotoxic effects. Firstly, a single x-ray beam was assumed to irradiate a parallelepiped volume of soft tissue, in which a GNP-doped "target" volume was placed at different depths. Average dose enhancement factors (DEF) in presence of GNPs were obtained as a function of the target depth and GNP concentration, uniformly distributed; values ranging between 1.6 for 10 mg Au/g at 0 cm and 7.2 for 200 mg Au/g at 5 cm were determined. Furtherly, a second geometry was adopted, in which a blood capillary vessel (10 µm thick and 10 µm of inner radius) was placed at the centre of a cubic volume of soft tissue; doses and DEFs to the capillary endothelium as well as to the surrounding viable tumour were evaluated, for different models of GNP diffusion. Our results indicate that the radial DEF profiles around the vessel are in close relationship with the radial profiles of GNP concentration assumed, except for at sharp gradients of concentration. DEFs at the endothelium ranged from 1.6 to 6.5, for GNP concentrations in the blood of 10 and 200 mg/ml, respectively. These data can be helpful for the development of new and more specific GNP-based radiosensitizers of potential interest in radiotherapy, exploiting the combined benefit of anti-angiogenic and cytotoxic dose enhancement effects.
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Inhibidores de la Angiogénesis/administración & dosificación , Oro/farmacología , Nanopartículas del Metal/administración & dosificación , Modelos Biológicos , Neoplasias Experimentales/irrigación sanguínea , Neoplasias Experimentales/terapia , Inhibidores de la Angiogénesis/química , Animales , Simulación por Computador , Difusión , Células Endoteliales/efectos de los fármacos , Células Endoteliales/efectos de la radiación , Oro/química , Nanopartículas del Metal/química , Ratones , Método de Montecarlo , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/radioterapia , Fantasmas de Imagen , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/química , Dosificación RadioterapéuticaRESUMEN
Abdominal ultrasound exams play a major role in the diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). The development of portable hand-held ultrasound devices (HHUS) has been shown to facilitate the diagnosis of many diseases, but little data on the value of HHUS in the diagnosis of SOS/VOD are available. We performed a study aimed at validating portable ultrasound (US) devices in the setting of hematopoietic stem cell transplant (HCT). Sixteen evaluable patients undergoing allogeneic HCT were studied using conventional US and HHUS during the first 3 weeks after transplant. The results obtained demonstrate that there is a close correlation between conventional and handheld ultrasound examination in the measurement of the right hepatic lobe (r = 0.912, p < 0.0001), the left hepatic lobe (r = 0.843, p < 0.0001), the portal vein (PV) (r = 0.724, p < 0.0001), and the spleen (r = 0.983, p < 0.0001) based on Pearson's correlation. The same data, analyzed through Lin's concordance correlation coefficient, evidenced a substantial level of agreement in the comparison of the spleen and right hepatic lobe, while a lower grade of agreement in the measurement of the portal vein and left hepatic lobe. Moreover, there was good agreement between results obtained by the two types of ultrasound devices in assessing ascites (p < 0.0001), gallbladder thickening (p < 0.0001), and the direction of PV flow (p < 0.0001). HHUS device allows the study of HokUs-10 parameters with an excellent agreement with conventional US, and may contribute to SOS/VOD diagnosis.
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Monoclonal T-cell lymphocytosis has been reported in patients with concomitant autoimmune diseases, viral infections, or immunodeficiencies. Referred to as T-cell large granular lymphocytic leukemia (T-LGLL), most cases cannot identify the triggering cause. Only small case series have been reported in the literature, and no treatment consensus exists. T-cell lymphocytosis may also appear after the transplant of hematopoietic stem cells or solid organs. Rare cases have been reported in patients undergoing autologous stem cell transplant (ASCT) for hematological diseases (including multiple myeloma or non-Hodgkin's lymphoma). Here, we describe the singular case of a patient who underwent ASCT for Hodgkin's lymphoma and displayed the onset of T-LGLL with an uncommonly high number of lymphocytes in peripheral blood and their subsequent spontaneous remission.
RESUMEN
Among the myeloproliferative diseases, myelofibrosis is a widely heterogeneous entity characterized by a highly variable prognosis. In this context, several prognostic models have been proposed to categorize these patients appropriately. Identifying who deserves more invasive treatments, such as bone marrow transplantation, is a critical clinical need. Age, complete blood count (above all, hemoglobin value), constitutional symptoms, driver mutations, and blast cells have always represented the milestones of the leading models still used worldwide (IPSS, DIPSS, MYSEC-PM). Recently, the advent of new diagnostic techniques (among all, next-generation sequencing) and the extensive use of JAK inhibitor drugs have allowed the development and validation of new models (MIPSS-70 and version 2.0, GIPSS, RR6), which are continuously updated. Finally, the new frontier of artificial intelligence promises to build models capable of drawing an overall survival perspective for each patient. This review aims to collect and summarize the existing standard prognostic models in myelofibrosis and examine the setting where each of these finds its best application.
RESUMEN
Ruxolitinib is a JAK1/2 inhibitor that has revolutionized the approach to myelofibrosis. On the one side, this drug can rapidly improve the symptoms related to the hematological disease; on the other side, the inhibition of JAK1/2 can lead to immunosuppression which may increase the risk of infections, due to a change in the cytokine balance in favor of anti-inflammatory cytokines, to direct inhibition of immune cells, and to the suppression in the production of specific antibodies. In this patient setting, much is known about possible viral and bacterial infections, while little is reported in the literature concerning parasitic infections, specifically leishmaniasis. Leishmania is a parasitic infection that can cause serious problems in immunosuppressed patients. The parasite can invade the bloodstream and cause a wide range of symptoms, including fever, weight loss, and anemia. In severe cases, it can lead to multi-organ failure and, rapidly, death. Early diagnosis and prompt treatment are essential especially for these patients, unable to respond adequately. In this case and the following review of the existing literature, the cytokine kinetics and the production of specific anti-Leishmania antibodies represent characteristic aspects capable of providing a more in-depth understanding of the mechanisms underlying these complex clinical cases in an immunocompromised patient.