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1.
Blood ; 139(11): 1694-1706, 2022 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-34995355

RESUMEN

In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in first or second remission after myeloablative conditioning (MAC; n = 515) or non-MAC (n = 295) who underwent multiparameter flow cytometry-based MRD testing before as well as 20 to 40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85 of 104; 81.7%) than non-MAC (33 of 57; 57.9%) regimen (P = .002). Although non-MAC regimens were less likely to clear MRD, if they did, the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and "MRD conversion" for relapse (P = .020), RFS (P = .002), and OS (P = .001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared with the isolated use of pre-HCT MRD status or post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments in patients with AML.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Citometría de Flujo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/terapia , Neoplasia Residual/etiología , Estudios Retrospectivos , Acondicionamiento Pretrasplante
2.
Ann Hematol ; 102(2): 407-412, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36394580

RESUMEN

A retrospective analysis of 25 patients with a history of prostate cancer (PC) who subsequently underwent allogeneic hematopoietic cell transplantation (HCT) for treatment of a hematologic malignancy was performed. Median patient age was 66.7 years. Median duration from the diagnosis of PC to HCT was 4.2 years. Twenty-three patients had Gleason group 1 or 2 disease. Therapy included prostatectomy (n = 13) and external beam or brachytherapy (n = 9). Hematologic diagnoses included both myeloid (n = 15) and lymphoid neoplasms (n = 10). Twenty-four patients received either a nonmyeloablative or reduced intensity conditioning regimen. GVHD prophylaxis included a calcineurin inhibitor and mycophenolate mofetil ± sirolimus. Twenty patients had HLA-matched sibling or HLA-matched unrelated donors; five patients had HLA-mismatched donors. Eleven patients are alive, and 14 have died. Median survival was 2.5 years (range, .02-12.6 years). The major cause of death was hematologic relapse. Only one patient had evidence of recurrent PC, occurring 1.5 years posttransplant. In carefully selected patients with a prior history of PC, there was no evidence of rapid recurrence of the solid tumor (ST) after HCT. PC patients who are in remission from their ST or have control of their disease on therapy should be considered eligible for HCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/patología , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias Hematológicas/terapia , Neoplasias de la Próstata/terapia , Acondicionamiento Pretrasplante/efectos adversos
3.
Ann Hematol ; 102(6): 1375-1382, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37079069

RESUMEN

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65-84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response.


Asunto(s)
Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Anciano , Humanos , Mesilato de Imatinib/uso terapéutico , Antineoplásicos/efectos adversos , Pirimidinas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Resultado del Tratamiento , Inhibidores de Proteínas Quinasas/efectos adversos
4.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36834477

RESUMEN

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal post-remission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint.


Asunto(s)
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Inducción de Remisión , Biomarcadores , Neoplasia Residual/diagnóstico , Recurrencia
5.
Haematologica ; 107(12): 2823-2833, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-35295076

RESUMEN

Using a multiparametric flow cytometry assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients with acute myeloid leukemia. This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined measurable residual disease (MRD) threshold of 0.035% bone marrow residual leukemic cells (RLC) calculated on mononuclear cells, 154 (59%) of the 261 patients were negative (MRD <0.035%) and 107 (41%) were positive (MRD ≥0.035%). Using LOD and LOQ, we selected the following categories of patients: (i) LODneg if RLC were below the LOD (74; 28.4%); (ii) LODpos-LOQneg if RLC were between the LOD and LOQ (43; 16.5%); and (iii) LOQpos if RLC were above the LOQ (144; 54.4%). Two-year overall survival of these three categories of patients was 75.4%, 79.8% and 66.4%, respectively (P=0.1197). Given their superimposable outcomes, the LODneg and LODpos-LOQneg categories were combined. Two-year overall survival of LODneg/LODpos-LOQneg patients was 77.0% versus 66.4% of LOQpos individuals (P=0.043). This figure was challenged in univariate analysis (P=0.046, hazard ratio=1.6, 95% confidence interval: 1.01-2.54) which confirmed the independent role of the LOD-LOQ approach in determining overall survival. In the AML1310 protocol, using the threshold of 0.035%, 2-year overall survival of patients with MRD <0.035% and MRD ≥0.035% was 74.5% versus 66.4%, respectively (P=0.3521). In conclusion, the use of the LOD-LOQ method results in more sensitive detection of MRD that, in turn, translates into a more accurate recognition of patients with different outcomes.


Asunto(s)
Leucemia Mieloide Aguda , Adulto , Humanos , Citometría de Flujo/métodos , Leucemia Mieloide Aguda/diagnóstico , Límite de Detección , Neoplasia Residual/diagnóstico , Estudios Prospectivos
6.
Langenbecks Arch Surg ; 407(7): 3079-3088, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35697818

RESUMEN

PURPOSE: The aim of this study was to evaluate the safety and compliance with the enhanced recovery after surgery (ERAS) protocol in octogenarian patients undergoing colorectal surgery in 12 Italian high-volume centers. METHODS: A retrospective analysis was conducted in a consecutive series of patients who underwent elective colorectal surgery between 2016 and 2018. Patients were grouped by age (≥ 80 years vs < 80 years), propensity score matching (PSM) analysis was performed, and the groups were compared regarding clinical outcomes and the mean number of ERAS items applied. RESULTS: Out of 1646 patients identified, 310 were octogenarians. PSM identified 2 cohorts of 125 patients for the comparison of postoperative outcomes and ERAS compliance. The 2 groups were homogeneous regarding the clinical variables and mean number of ERAS items applied (11.3 vs 11.9, p-ns); however, the application of intraoperative items was greater in nonelderly patients (p 0.004). The functional recovery was similar between the two groups, as were the rates of postoperative severe complications and 30-day mortality rate. Elderly patients had more overall complications. Furthermore, the mean hospital stay was higher in the elderly group (p 0.027). Multivariable analyses documented that postoperative stay was inversely correlated with the number of ERAS items applied (p < 0.0001), whereas age ≥ 80 years significantly correlated with the overall complication rate (p 0.0419). CONCLUSION: The ERAS protocol is safe in octogenarian patients, with similar levels of compliance and surgical outcomes. However, octogenarian patients have a higher rate of overall complications and a longer hospital stay than do younger patients.


Asunto(s)
Cirugía Colorrectal , Recuperación Mejorada Después de la Cirugía , Anciano de 80 o más Años , Humanos , Anciano , Puntaje de Propensión , Estudios Retrospectivos , Octogenarios , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
7.
Mycoses ; 65(2): 233-238, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34883533

RESUMEN

BACKGROUND: Several studies in immunocompromised patients, such as those with HIV infection, undergoing cancer chemotherapy or organ transplant, have led to the development of guidelines on the use of prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP), in these specific conditions. Instead, since the association between PJP and acute myeloid leukaemia (AML) is not clearly defined, the role of prophylaxis in patients with AML is not yet established. METHODS: We retrospectively analysed 251 consecutive patients with newly diagnosed non-M3-AML, admitted at the Hematology Unit of University Tor Vergata in Rome, during the period 2010-2020. The aim of the study was to evaluate the incidence of PJP among AML patients during their first hospital admission, and to identify subjects at a high risk to develop PJP. RESULTS: Among 251 consecutive patients with non-M3-AML, 67 bronchoalveolar lavages (BAL) were performed. PJP was proven in 11/67 (16.7%) subjects undergoing BAL (11 males, median age 71 years), with an incidence of 4.3%. The most common reason for BAL execution were radiological findings such as ground-glass opacities (6/11, 55%) and atypical patterns like consolidations and nodules (5/11, 45%). One patient died because of PJP after 11 days of trimethoprim/sulfamethoxazole therapy. In multivariate analysis older age and smoking habit were independent factors significantly associated with PJP (p = .021 and 0.017 respectively). CONCLUSION: We conclude that PJP infection is not uncommon among patients with AML. If intensive chemotherapy is planned, physicians should be aware of this risk and prophylaxis should be considered, particularly in older patients.


Asunto(s)
Leucemia Mieloide Aguda , Neumonía por Pneumocystis , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/complicaciones , Masculino , Pneumocystis carinii , Neumonía por Pneumocystis/epidemiología , Estudios Retrospectivos
8.
Ann Hematol ; 100(7): 1743-1753, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33774681

RESUMEN

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.


Asunto(s)
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 Joven
9.
Int J Colorectal Dis ; 36(5): 929-939, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33118101

RESUMEN

PURPOSE: To analyze different types of management and one-year outcomes of anastomotic leakage (AL) after elective colorectal resection. METHODS: All patients with anastomotic leakage after elective colorectal surgery with anastomosis (76/1,546; 4.9%), with the exclusion of cases with proximal diverting stoma, were followed-up for at least one year. Primary endpoints were as follows: composite outcome of one-year mortality and/or unplanned intensive care unit (ICU) admission and additional morbidity rates. Secondary endpoints were as follows: length of stay (LOS), one-year persistent stoma rate, and rate of return to intended oncologic therapy (RIOT). RESULTS: One-year mortality rate was 10.5% and unplanned ICU admission rate was 30.3%. Risk factors of the composite outcome included age (aOR = 1.08 per 1-year increase, p = 0.002) and anastomotic breakdown with end stoma at reoperation (aOR = 2.77, p = 0.007). Additional morbidity rate was 52.6%: risk factors included open versus laparoscopic reoperation (aOR = 4.38, p = 0.03) and ICU admission (aOR = 3.63, p = 0.05). Median (IQR) overall LOS was 20 days (14-26), higher in the subgroup of patients reoperated without stoma. At 1 year, a stoma persisted in 32.0% of patients, higher in the open (41.2%) versus laparoscopic (12.5%) reoperation group (p = 0.04). Only 4 out of 18 patients (22.2%) were able to RIOT. CONCLUSION: Mortality and/or unplanned ICU admission rates after AL are influenced by increasing age and by anastomotic breakdown at reoperation; additional morbidity rates are influenced by unplanned ICU admission and by laparoscopic approach to reoperation, the latter also reducing permanent stoma and failure to RIOT rates. TRIAL REGISTRATION: ClinicalTrials.gov # NCT03560180.


Asunto(s)
Cirugía Colorrectal , Procedimientos Quirúrgicos del Sistema Digestivo , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Cirugía Colorrectal/efectos adversos , Humanos , Reoperación
10.
Int J Colorectal Dis ; 35(3): 445-453, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31897650

RESUMEN

BACKGROUND: ERAS implementation improved outcomes in patients undergoing colorectal surgery. The process of incorporating this pathway in clinical practice may be challenging. This observational study investigated the impact of systematic ERAS implementation on surgical outcomes in patients undergoing colorectal resections in a regional network of 10 institutions. METHODS: Implementation of ERAS pathway was designed using regular audits and a common protocol. All patients undergoing elective colorectal surgery between 2016 and 2017 were considered eligible. A collective database including 18 ERAS items, clinical and surgical data, and outcomes was designed. Univariate and multivariate analyses were performed for the following outcomes: morbidity, anastomotic leak, reinterventions, hospital stay, and readmissions. RESULTS: A total of 827 patients were included, and a mean of 11.3 ERAS items applied/patient was reported. Logistic regression indicated that an increased number of ERAS items applied reduced overall and severe morbidity (OR 0.86 and 0.87, respectively 95%CI 0.8197-0.9202 and 95%CI 0.7821-0.9603), hospitalization (OR 0.53 95%CI 0.4917-0.5845) and reinterventions (OR 0.84 95%CI 0.7536-0.9518) in the entire series. The same results were obtained for a prolonged hospitalization differentiating right-sided (OR 0.48 95%CI 0.4036-0.5801), left-sided (OR 0.48 95%CI 0.3984-0.5815), and rectal resections (OR 0.46 95%CI 0.3753-0.5851). An inverse correlation was found between the application of ERAS items and morbidity in right-sided and rectal procedures (OR 0.89 and 0.84, respectively 95%CI 0.7976-0.9773 and 95%CI 0.7418-0.9634). CONCLUSIONS: Systematic implementation of the ERAS pathway using multi-institutional audits can increase protocol adherence and improve surgical outcomes in patients undergoing colorectal surgery.


Asunto(s)
Enfermedades del Colon/cirugía , Vías Clínicas/organización & administración , Evaluación del Resultado de la Atención al Paciente , Atención Dirigida al Paciente/organización & administración , Enfermedades del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Italia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Evaluación de Programas y Proyectos de Salud , Reoperación , Adulto Joven
13.
Front Oncol ; 14: 1367393, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444680

RESUMEN

In patients with Acute Myeloid Leukemia (AML), the assessment of disease risk plays a central role in the era of personalized medicine. Indeed, integrating baseline clinical and biological features on a case-by-case basis is not only essential to select which treatment would likely result in a higher probability of achieving complete remission, but also to dynamically customize any subsequent therapeutic intervention. For young high-risk patients with low comorbidities burden and in good general conditions (also called "fit" patients), intensive chemotherapy followed by allogeneic stem cell transplantation still represents the backbone of any therapeutic program. However, with the approval of novel promising agents in both the induction/consolidation and the maintenance setting, the algorithms for the management of AML patients considered eligible for intensive chemotherapy are in constant evolution. In this view, we selected burning issues regarding the identification and management of high-risk AML, aiming to provide practical advice to facilitate their daily clinical management in patients considered eligible for intensive chemotherapy.

14.
Thromb Res ; 236: 30-36, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38387301

RESUMEN

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3-147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC.


Asunto(s)
Coagulación Intravascular Diseminada , Leucemia Mieloide Aguda , Humanos , Masculino , Anciano , Femenino , Coagulación Intravascular Diseminada/etiología , Estudios Retrospectivos , Leucemia Mieloide Aguda/complicaciones , Pronóstico , Coagulación Sanguínea
15.
Mediterr J Hematol Infect Dis ; 16(1): e2024054, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38984098

RESUMEN

Background: Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. Methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023. Results: We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation. Conclusions: Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy.

16.
Mediterr J Hematol Infect Dis ; 15(1): e2023013, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36660358

RESUMEN

Background: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined. Methods: We retrospectively analyzed 132 consecutive admissions of non-promyelocytic AML patients at the Hematology Unit of the University Tor Vergata in Rome between June 2019 and February 2022. MDRO swab-based screening was performed in all patients on the day of admission and once weekly after that. FUO was defined as fever with no evidence of infection. Results: Of 132 consecutive hospitalizations (69 AML patients), MDRO colonization was observed in 35 cases (26%) and resulted independently related to a previous MDRO colonization (p=0.001) and length of hospitalization (p=0.03). The colonization persistence rate in subsequent admissions was 64%. MDRO-related bloodstream infection was observed in 8 patients (23%) and correlated with grade III/IV mucositis (p=0.008) and length of hospitalization (p=0.02). FUO occurred in 68 cases (51%) and correlated with an absolute neutrophilic count <500µ/L at admission (0.04). Conclusion: In our experience, MDRO colonization is a frequent and difficult-to-eradicate condition that can arise at all stages of treatment. Prompt discharge of patients as soon as clinical conditions allow could limit the spread of MDRO. In addition, the appropriate use of antibiotics, especially in the case of FUO, and the contraction of hospitalization length, when feasible, are measures to tackle the further spread of MDRO.

17.
Mediterr J Hematol Infect Dis ; 15(1): e2023051, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37705524

RESUMEN

Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio.

19.
Sci Rep ; 12(1): 21231, 2022 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-36481766

RESUMEN

Bone marrow mesenchymal stem cells (BM-MSCs) exhibit multiple abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), including reduced proliferative and clonogenic capacity, altered morphology, impaired immunoregulatory properties and capacity to support hematopoiesis. Here, we investigated expression of the FOXM1 gene, a transcription factor driving G2/M gene expression, in BM-MSCs isolated from patients with MDS and AML, de novo and therapy-related, compared to BM-MSCs isolated from healthy donors (HD). We observed a statistically significant downregulation of FOXM1 expression in BM-MSCs isolated from MDS and AML patients, as compared to controls. In parallel, expression of FOXM1 mitotic targets (CCNB1, CDC20, PLK1 and NDC80) was suppressed in patients' BM-MSCs, as compared to HD. No differences in the expression of FOXM1 and its mitotic targets were observed in BM-mononuclear cells from the different sources. From a functional standpoint, silencing of FOXM1 mRNA in healthy MSC induced a significant decrease in the expression of its targets. In this line, healthy MSC silenced for FOXM1 showed an impaired ability to support hematopoiesis in vitro. These findings suggest that deregulation of FOXM1 may be involved in the senescent phenotype observed in MSC derived from myeloid neoplasms.


Asunto(s)
Proteína Forkhead Box M1 , Leucemia Mieloide Aguda , Células Madre Mesenquimatosas , Síndromes Mielodisplásicos , Humanos , Proteína Forkhead Box M1/genética , Síndromes Mielodisplásicos/genética , Leucemia Mieloide Aguda/genética
20.
Cancers (Basel) ; 15(1)2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36612132

RESUMEN

Informed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...].

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