The monumental cemetery of Parabita 1,was designed by G.R.A.U (Roman Architects and Urbanists Group) in 1967, is a project which deeply marked the Italian architectural panorama at the end of the ...1960s. The project was commissioned to the G.R.A.U 2 by the municipal administration as an extension of the existing nineteenth-century cemetery, to deal with the need to equip the cemetery area with new burial sites, ossuaries, mortuary and facilities. The area indicated in the land registry documents, attached to the design assignment, concerns development towards the north of the pre-existing cemetery enclosure and occupies a steep surface, almost square-shaped, located at the foot of a little hill that runs alongside the eighteenthcentury Alcantarini Convent and subsequently joins two roads (Fig. 1).
Hematopoietic stem cell transplantation (HSCT) recipients have been reported to have an increased risk of chronic graft versus host disease (cGVHD) and hematological and solid cancers. Oral ...manifestations are the first signs of cGVHD observed in the majority of patients, and oropharyngeal cancer is the most frequent secondary malignancy occurred after HSCT. In this study, we have evaluated the inflammatory infiltrate cell content and correlated with the vascular density in patients affected by primary oral squamous cell carcinoma (OSCC) from previous healthy controls and OSCC after cGVHD. Results have demonstrated that patients with OSCC after GVHD show a more consistent inflammatory infiltrate as compared with the OSCC ones. In detail, the inflammatory background composed of CD3-positive T cells, tryptase-positive mast cells, CD31-positive endothelial cells, and CD68-positive macrophages may be more pronounced in the setting of GVHD + OSCC than in the control group. By contrast, CD20-positive B cells and CD1a-positive dendritic cells were more abundant in the latter population. Finally, a positive correlation was found as between vascular density and inflammatory cell infiltration in both GVHD + OSCC and OSCC groups. Overall, these results confirm the role played by immune cells in enhancing tumor progression and angiogenesis and suggest a potential therapeutic strategy involving inhibition of recruitment of immune cells to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions.
Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, ...mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT
-RAs) and neurokinin 1 receptor antagonists (NK
-RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, open-label and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an every-other-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6), and 98.6% (delayed phase: days 7-8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.
Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness ...and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.
EMD of myeloma usually occurs several years after diagnosis and is associated with a very poor OS of <6 months due to the fact that there are no efficient treatment options. In rrMM with EMDs, the ...most effective treatment is a lymphoma-like polychemotherapy regimen such as PACE, Dexa-BEAM, and HyperCVAD followed by ASCT or allogeneic SCT. RT of soft-tissue plasmacytoma is the further treatment choice and results in a high rate of local control and a prolonged disease-free survival. We report the case of a 41-year-old man affected by ultra-high-risk symptomatic IgAλ MM with extramedullary intracranial soft-tissue relapsed after VTD-PACE followed by ASCT. The salvage program with KRd regimen determines a second biochemical and haematological remission and a gradual reduction in size of the extramedullary intracranial soft-tissue even in the absence of local aggressive radiotherapy, suggesting that carfilzomib and lenalidomide together could be effective also in this critical situation.
Purpose
Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell ...transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK
1
receptor antagonist (NK
1
RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT.
Methods
This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin’s lymphoma. Eighty-one patients participated.
Results
Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported.
Conclusion
NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT.
The aim of this study was to develop and validate a reliable clinical prediction rule that could be employed to identify patients at higher likelihood of mortality among those with hematological ...malignancies (HMs) and bacterial bloodstream infections (BBSIs).
We conducted a retrospective cohort study in nine Italian hematological units. The derivation cohort consisted of adult patients with BBSI and HMs admitted to the Catholic University Hospital (Rome) between January 2002 and December 2008. Survivors and nonsurvivors were compared to identify predictors of 30-day mortality. The validation cohort consisted of patients hospitalized with BBSI and HMs who were admitted in 8 other Italian hematological units between January 2009 and December 2010. The inclusion and exclusion criteria were identical for both cohorts, with type and stage of HMs used as matching criteria. In the derivation set (247 episodes), the multivariate analysis yielded the following significant mortality-related risk factors acute renal failure (Odds Ratio OR 6.44, Confidential Interval CI, 2.36-17.57, P<0.001); severe neutropenia (absolute neutrophil count <100/mm(3)) (OR 4.38, CI, 2.04-9.43, P<0.001); nosocomial infection (OR, 3.73, CI, 1.36-10.22, P = 0.01); age ≥65 years (OR, 3.42, CI, 1.49-7.80, P = 0.003); and Charlson Comorbidity Index ≥4 (OR, 3.01, CI 1.36-6.65, P = 0.006). The variables unable to be evaluated at that time (for example, prolonged neutropenia) were not included in the final logistic model. The equal-weight risk score model, which assigned 1 point to each risk factor, yielded good-excellent discrimination in both cohorts, with areas under the receiver operating curve of 0.83 versus 0.93 (derivation versus validation) and good calibration (Hosmer-Lemshow P = 0.16 versus 0.75).
The risk index accurately identifies patients with HMs and BBSIs at high risk for mortality; a better initial predictive approach may yield better therapeutic decisions for these patients, with an eventual reduction in mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
