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Abstract In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 106 PBSC/kg, 2.6% (n = 7) mobilized 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT’s impact on patient management. Sixty castration-sensitive high-risk (ISUP 4–5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22–17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Artificial intelligence is gaining interest among clinicians, but its results are difficult to be interpreted, especially when dealing with survival outcomes and censored observations. Explainable machine learning (XAI) has been recently extended to this context to improve explainability, interpretability and transparency for modeling results. A cohort of 231 patients undergoing an allogeneic bone marrow transplantation was analyzed by XAI for survival by two different uni- and multi-variate survival models, proportional hazard regression and random survival forest, having as the main outcome the overall survival (OS) and its main determinants, using the survex package for R. Both models’ performances were investigated using the integrated Brier score, the integrated Cumulative/Dynamic AUC and the concordance C-index. Global explanation for the whole cohort was performed using the time-dependent variable importance and the partial dependence survival plot. The local explanation for each single patient was obtained via the SurvSHAP(t) and SurvLIME plots and the ceteris paribus survival profile. The survex package common interface ensured a good feasibility of XAI for survival, and the advanced graphical options allowed us to easily explore, explain and compare OS results coming from the two survival models. Before the modeling results to be suitable for clinical use, understandability, clinical relevance and computational efficiency were the most important criteria ensured by this XAI for survival approach, in adherence to clinical XAI guidelines.

Maternal parasitemia and placental parasite load were examined in mother–newborn pairs to determine their effect on the congenital transmission of Trypanosoma cruzi. Parasitemia was qualitatively assessed in mothers and newborns by the microhematocrit test; parasite load was determined in the placental tissues of transmitting and non-transmitting mothers by the detection of T. cruzi DNA and by histology. Compared to transmitter mothers, the frequency and prevalence of parasitemia were found to be increased in non-transmitter mothers; however, the frequency and prevalence of parasite load were higher among the transmitter mothers than among their non-transmitter counterparts. Additionally, serum levels of interferon (IFN)-γ were measured by an enzyme-linked immunosorbent assay (ELISA) in peripheral, placental, and cord blood samples. Median values of IFN-γ were significantly increased in the cord blood of uninfected newborns. The median IFN-γ values of transmitter and non-transmitter mothers were not significantly different; however, non-transmitter mothers had the highest total IFN-γ production among the group of mothers. Collectively, the results of this study suggest that the anti-T. cruzi immune response occurring in the placenta and cord is under the influence of the cytokines from the mother’s blood and results in the control of parasitemia in uninfected newborns.

The aim of this study was to investigate whether the favorable characteristics of novel digital PET/CT (dPET) scanners compared to analog systems (aPET) could translate into an improved disease localization in prostate cancer (PCa) patients with early biochemical recurrence/persistence (BCR/BCP). A retrospective analysis was conducted on 440 consecutive analog (n = 311) or digital (n = 129) 68Ga-PSMA-11 PET/CT scans performed in hormone-sensitive ADT-free PCa patients with early-BCR/BCP (PSA at PET ≤ 2.0 ng/mL), previously treated with radical intent (radical-prostatectomy/radiotherapy). dPET showed a higher positivity rate compared to aPET (48.8% [63/129] vs. 37.3% [116/311], p = 0.03), despite the slightly lower median PSA value of the dPET cohort (0.33 [IQR: 0.26–0.61] vs. 0.55 [IQR: 0.40–0.85] ng/mL, p < 0.01). dPET detection rate was higher in both PSA ranges 0.2–0.5 ng/mL (39.0% [32/82] vs. 25.2% [34/135], p = 0.03) and 0.5–1.0 ng/mL (63.2% [24/38] vs. 40.8% [53/130], p = 0.02), but not for PSA ≥ 1.0 ng/mL. dPET detected a higher per patient median number of pathologic findings (PSMA-RADS ≥ 3) and multi-metastatic cases (>3 lesions) among N1/M1-positive scans (21.7% [10/46] vs. 8.6% [9/105], p = 0.03). Moreover, the proportion of uncertain findings among pathological lesions was significantly lower for dPET than aPET (24.4% [39/160] vs. 38.5% [60/156], p = 0.008). Overall, 68Ga-PSMA-11 dPET showed a better performance compared to aPET, resulting in a higher scan-positivity rate, a higher number of detected pathological lesions, and a lower rate of uncertain findings.

The study aimed to measure the frequency of occurrence of infections with helminths, protozoa, and risk factors of undernutrition and anemia among schoolchildren from the Bolivian highland (altiplano) and lowland (subtropical) rural regions, with a high frequency of gastrointestinal parasite infections. Cross-sectional data were collected from 790 children, 5–13 years old. Microscopic examination of stool using the Ritchie technique, hemoglobin testing using the HemoCue analyzer, and anthropometric measurements were performed. Over 60% and 20% of children were infected with protozoa and helminth parasites, respectively. Infections caused by pathogenic Hymenolepis nana (15.7–5.2%), Ascaris lumbricoides (41.9–28.5%), Giardia lamblia (30.1–11.2%), Entamoeba histolytica (5.7–0.7%), and nonpathogenic Entamoeba coli (48.9–16%), Blastocystis hominis (40.2–28.5%), Iodamoeba butschli (16.1–2.5%), Chilomastix mesnili (19.2–7.3%), and Entamoeba histolytica/dispar (7.4–5.5%) parasites, were more prevalent in the highlands than the lowlands. Single parasitic infections were more prevalent in the lowlands; polyparasitism of light or heavy intensity predominated in the highlands. A strongly increased risk of anemia and a low prevalence of wasting were determined in children in the highlands. A higher risk for stunting was associated with children of older age, and a low burden of intestinal helminths would prevent wasting in children of highlands. Infections with A. lumbricoides and G. lamblia pathogens in older children were not significant covariates for stunting. Environmental, nutritional, and parasitic factors may predispose to anemia in the highlands. A nutritional intervention and parasite control effort will substantially improve children´s health in the highlands.

High-resolution intraoperative PET/CT specimen imaging, coupled with prostate-specific membrane antigen (PSMA) molecular targeting, holds great potential for the rapid ex vivo identification of disease localizations in high-risk prostate cancer patients undergoing surgery. However, the accurate analysis of radiotracer uptake would require time-consuming manual volumetric segmentation of 3D images. The aim of this study was to test the feasibility of using machine learning to perform automatic nodal segmentation of intraoperative 68Ga-PSMA-11 PET/CT specimen images. Six (n = 6) lymph-nodal specimens were imaged in the operating room after an e.v. injection of 2.1 MBq/kg of 68Ga-PSMA-11. A machine learning-based approach for automatic lymph-nodal segmentation was developed using only open-source Python libraries (Scikit-learn, SciPy, Scikit-image). The implementation of a k-means clustering algorithm (n = 3 clusters) allowed to identify lymph-nodal structures by leveraging differences in tissue density. Refinement of the segmentation masks was performed using morphological operations and 2D/3D-features filtering. Compared to manual segmentation (ITK-SNAP v4.0.1), the automatic segmentation model showed promising results in terms of weighted average precision (97–99%), recall (68–81%), Dice coefficient (80–88%) and Jaccard index (67–79%). Finally, the ML-based segmentation masks allowed to automatically compute semi-quantitative PET metrics (i.e., SUVmax), thus holding promise for facilitating the semi-quantitative analysis of PET/CT images in the operating room.

Abstract Introduction This is a prospective, single-center trial in pediatric patients with sarcoma aiming to evaluate [18F]FDG PET/CT as a tool for early response assessment to neoadjuvant chemotherapy (neo-CTX). Methods Bone or soft tissue sarcoma patients with (1) baseline [18F]FDG PET/CT within 4 weeks prior to the start of neo-CTX (PET1), (2) early interim [18F]FDG PET/CT (6 weeks after the start of neo-CTX (PET2), (3) evaluation of neo-CTX response by histology or MRI, and (4) definitive therapy after neo-CTX (surgery or radiation) were included. Semiquantitative PET parameters (SUVmax, SUVmean, SUVpeak, MTV and TLG) and their changes from PET1 to PET2 (ΔPET) were obtained. The primary endpoint was to evaluate the predictive value of PET1, PET2 and ΔPET parameters for overall survival (OS) and time to progression (TTP). The secondary outcome was to evaluate if [18F]FDG PET/CT can predict the response to neo-CTX assessed by histopathology or MRI. Primary and secondary outcomes were also evaluated in a subpopulation of patients with bone involvement only. Results Thirty-four consecutive patients were enrolled (10 females; 24 males; median age 15.1 years). 17/34 patients (50%) had osteosarcoma, 13/34 (38%) Ewing's sarcoma, 2/34 (6%) synovial sarcoma and 2/34 (6%) embryonal liver sarcoma. Median follow-up was 39 months (range 16–84). Eight of 34 patients (24%) died, 9/34 (27%) were alive with disease, and 17/34 (50%) had no evidence of residual/recurrent disease. Fifteen of 34 (44%) and 19/34 (56%) were responders and non-responders, respectively. PET2-parameters were associated with longer TTP (p

Abstract Background Robust data reporting the survival of cancer patients on home parenteral nutrition (HPN) are lacking. The aim of this prospective, cohort study was to investigate clinical characteristics, predictive factors, and overall survival (OS) of adult‐malnourished cancer patients eligible for HPN according to the European guideline recommendations. Methods During the study period, 1658 cancer patients were consecutively evaluated in a tertiary university hospital. Of these, 761 who received HPN were grouped into four cohorts according to the provision of supplemental PN (SPN) or total (TPN) and whether they received chemotherapy (CT+ or CT‐): SPN/CT+ (n = 376), TPN/CT+ (n = 99), SPN/CT‐ (n = 191), and TPN/CT‐ (n = 95). Patient demographics, nutritional status, cancer‐related characteristics, and prognostic scores assessed at HPN start. The primary outcome was OS. Results Median OS was 8.9, 4.3, 5.7, and 2.2 months for the SPN/CT+, TPN/CT+, SPN/CT‐, and TPN/CT‐ cohorts, respectively. In multivariable analysis, predictors showing significant association with decreased survival were patient cohorts, modified Glasgow Prognostic Score (1 and 2 scores), weight loss (>15%) in the 3 months before HPN start, and TNM IV stage while protective factors of survival were Karnofsky Performance Status (>50), albumin level (>3.5 g/dL), oral protein intake, BMI (>20.5), and weight at HPN start. Conclusion For the first time, in four different cohorts of cancer patients on HPN, clinical characteristics and survival were compared. This large study showed that survival is significantly correlated with patient characteristics at HPN start and that the presence of favorable factors may determine even a fourfold increase in survival. These data are expected to assist physicians in the appropriate prescription of HPN.

BackgroundAllogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are exposed to an increased risk of invasive fungal infections (IFIs) due to neutropenia, immunosuppressive treatments, graft-versus-host disease (GvHD) and incomplete immune reconstitution. Although clinical benefit from antifungal prophylaxis has been demonstrated, IFIs remain a leading cause of morbidity and mortality in these patients. In the last decades, attention has also been focused on potential risk factors for IFI to tailor an antifungal prevention strategy based on risk stratification.Aim of the StudyThis retrospective single-center study aimed to assess the epidemiology and the prognostic factors of IFI in a large cohort of allo-HSCT patients.MethodsBetween January 2004 and December 2020, 563 patients with hematological malignancies received an allo-HSCT at the Stem Cell Transplant Unit in Turin: 191 patients (34%) received grafts from a matched sibling donor, 284 (50.5%) from a matched unrelated donor, and 87 (15.5%) from an haploidentical family member. The graft source was peripheral blood in 81.5% of the patients. Our policy for antifungal prophylaxis included fluconazole in matched related and unrelated donors, while micafungin was administered in patients receiving haploidentical transplant. According to this practice, fluconazole was administered in 441 patients (79.6%) and micafungin in 62 (11.2%), while only 9 patients received mold-active prophylaxis. Galactomannan testing was routinely performed twice a week; patients with persisting fever unresponsive to broad spectrum antibiotics were evaluated with lung high-resolution computed tomography (HRCT) scan. In case of imaging suggestive of IFI, bronchoalveolar lavage (BAL) was performed whenever feasible.Statistical AnalysisOnly probable/proven IFI (PP-IFI) occurring during the first 12 months after transplant have been evaluated. IFIs were classified as probable or proven according to the new revised European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) consensus criteria. Multivariate competing risk regression, binary logistic, and proportional hazard models were performed to identify risk factors for PP-IFI.ResultsA total of 58 PP-IFIs (n = 47 probable; n = 11 proven) occurred in our patients resulting in a cumulative incidence of 4.1%, 8.1%, and 9.6% at 30, 180, and 365 days, respectively. Molds were the predominant agents (n = 50 Aspergillus; n = 1 Mucor), followed by invasive candidemia (n = 5 non-albicans Candida; n = 1 Candida albicans; n = 1 Trichosporon). Lung was the most frequent site involved in patients with mold infections (47/51, 92.2%). Median time from HSCT to IFI was 98.44 days (0–365 days). Only 34.5% of patients with IFI were neutropenic at the time of infection. The presence of IFI had a significant impact on overall survival at 1 year (IFI, 32.8% vs. non-IFI, 54.6%; p < 0.001). IFI-related mortality rate was 20.7% in the overall population, 17% in patients with probable IFI, and 36% in patients with proven IFI. Multivariate competing risk regression revealed that donor type was the factor significantly associated to the risk of IFI [subdistribution hazard ratio (SDHR), 1.91, IC 1.13–3.20; p = 0.015]. BAL was informative in a consistent number of cases (36/57, 63.2%) leading to the identification of fungal (21), bacterial (4), viral (3), and polymicrobial (8) infections. Overall, 79 patients (14%) received a diagnostic-driven treatment, and 63 patients (11.2%) received a fever-driven treatment. Liposomal amphoteric B was the drug used in the majority of patients receiving diagnostic-driven therapy (30/79, 38%), while caspofungin was administered more frequently in patients who received a fever-driven strategy (27/63, 42.9%).ConclusionAccording to our experience, a non-mold active prophylaxis in patients undergoing allo-HSCT is feasible when combined with an intensive diagnostic work-up including CT scan and BAL. BAL performed at the onset of the disease may provide informative results in most patients. A diagnostic-driven treatment strategy may contribute to limit the use of costly antifungal therapies.

Background—Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are subject to major risks for bacterial bloodstream infections (BSIs), including emergent multidrug-resistant (MDR) organisms, which still represent the main cause of morbidity and mortality in transplanted patients. Methods: We performed an observational, retrospective, single-center study on patients undergoing allo-HSCT between 2004 and 2020 at the Stem Cell Transplant Unit in Turin to assess the incidence, etiology, and outcomes of BSIs and to explore any risk factors for bacteriaemia. Results: We observed a total of 178 bacterial BSIs in our cohort of 563 patients, resulting in a cumulative incidence of 19.4%, 23.8%, and 28.7% at 30, 100, and 365 days, respectively. Among isolated bacteria, 50.6% were Gram positive (GPB), 41.6% were Gram negative (GNB), and 7.9% were polymicrobial infections. Moreover, BSI occurrence significantly influenced 1-year overall survival. High and very high Disease Risk Index (DRI), an haploidentical donor, and antibacterial prophylaxis were found as results as independent risk factors for bacterial BSI occurrence in multivariate analysis. Conclusions: In our experience, GNB have overwhelmed GPB, and fluoroquinolone prophylaxis has contributed to the emergence of MDR pathogens. Local resistance patterns and patients’ characteristics should therefore be considered for better management of bacteremia in patients receiving an allogeneic HSCT.

Prostate-specific-membrane-antigen/positron-emission-tomography (PSMA-PET) can accurately detect disease localizations in prostate cancer (PCa) patients with early biochemical recurrence/persistence (BCR/BCP), allowing for more personalized image-guided treatments in oligometastatic patients with major impact in the case of bone metastases (BM). Therefore, this study aimed to identify predictors of BM at PSMA-PET in early-BCR/BCP hormone-sensitive PCa (HSPC) patients, previously treated with radical intent (radiotherapy or radical prostatectomy ± salvage-radiotherapy (SRT)). A retrospective analysis was performed on 443 68Ga-PSMA-11-PET/CT scans. The cohort median PSA at PET-scan was 0.60 (IQR: 0.38–1.04) ng/mL. PSMA-PET detection rate was 42.0% (186/443), and distant lesions (M1a/b/c) were found in 17.6% (78/443) of cases. BM (M1b) were present in 9.9% (44/443) of cases, with 70.5% (31/44) showing oligometastatic spread (≤3 PSMA-positive lesions). In the multivariate binary logistic regression model (accuracy: 71.2%, Nagelkerke-R2: 13%), T stage ≥ 3a (OR: 2.52; 95% CI: 1.13–5.60; p = 0.024), clinical setting (previous SRT vs. first-time BCR OR: 2.90; 95% CI: 1.32–6.35; p = 0.008), and PSAdt (OR: 0.93; 95% CI: 0.88–0.99; p = 0.026) were proven to be significant predictors of bone metastases, with a 7% risk increment for each single-unit decrement of PSAdt. These predictors could be used to further refine the indication for PSMA-PET in early BCR/BCP HSPC patients, leading to higher detection rates of bone disease and more personalized treatments.

A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged

We here describe a novel method for MYD88L265P mutation detection and minimal residual disease monitoring in Waldenström macroglobulinemia, by droplet digital polymerase chain reaction, in bone marrow and peripheral blood cells, as well as in circulating cell-free DNA. Our method shows a sensitivity of 5.00×10−5, which is far superior to the widely used allele-specific polymerase chain reaction (1.00×10−3). Overall, 291 unsorted samples from 148 patients (133 with Waldenström macroglobulinemia, 11 with IgG lymphoplasmacytic lymphoma and 4 with IgM monoclonal gammopathy of undetermined significance) were analyzed: 194 were baseline samples and 97 were followup samples. One hundred and twenty-two of 128 (95.3%) bone marrow and 47/66 (71.2%) baseline peripheral blood samples scored positive for MYD88L265P. To investigate whether MYD88L265P detection by droplet digital polymerase chain reaction could be used for minimal residual disease monitoring, mutation levels were compared with IGH-based minimal residual disease analysis in 10 patients, and was found to be as informative as the classical, standardized, but not yet validated in Waldenström macroglobulinemia, IGH-based minimal residual disease assay (r2=0.64). Finally, MYD88L265P detection by droplet digital polymerase chain reaction on plasma circulating tumor DNA from 60 patients showed a good correlation with bone marrow findings (bone marrow median mutational value 1.92×10−2, plasma circulating tumor DNA value: 1.4×10−2, peripheral blood value: 1.03×10−3). This study indicates that droplet digital polymerase chain reaction assay of MYD88L265P is a feasible and sensitive tool for mutation screening and minimal residual disease monitoring in Waldenström macroglobulinemia. Both unsorted bone marrow and peripheral blood samples can be reliably tested, as can circulating tumor DNA, which represents an attractive, less invasive alternative to bone marrow for MYD88L265P detection.

Introduction. Various pain management strategies for patients undergoing open excisional hemorrhoidectomy have been proposed, yet postoperative pain remains a frequent complaint. Objective. To determine whether mesoglycan (30 mg two vials i.m. once/day for the first 5 days postoperative, followed by 50 mg 1 oral tablet twice/day for 30 days) would reduce the edema of the mucocutaneous bridges and thus improve postoperative pain symptoms. Patients and Methods. For this prospective observational multicenter study, 101 patients undergoing excisional diathermy hemorrhoidectomy for III-IV degree hemorrhoidal disease were enrolled at 5 colorectal referral centers. Patients were assigned to receive either mesoglycan (study group SG) or a recommended oral dose of ketorolac tromethamine of 10 mg every 4–6 hours, not exceeding 40 mg per day and not exceeding 5 postoperative days according to the indications for short-term management of moderate/severe acute postoperative pain, plus stool softeners (control group CG). Results. Postoperative thrombosis (SG 1/48 versus CG 5/45) (p

Multiple myeloma is a plasma cell disorder characterized by malignant plasma cell infiltration in the bone marrow, serum and/or urine monoclonal protein and organ damage. The aim of this study was to investigate the impact of chromosome 1 abnormalities in a group of elderly patients (>65 years) with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-03-05 trial and treated with bortezomib, melphalan and prednisone or bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance. We also evaluated the link between chromosome 1 abnormalities and other clinical, genetic and immunophenotypic features by a multivariate logistic regression model. Interphase fluorescence in situ hybridization on immunomagnetically purified plasma cells and bone marrow multiparameter flow cytometry were employed. A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19+/CD117− immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma. Moreover, a detrimental effect of thalidomide, even when administered in association with bortezomib, was observed in patients with abnormal chromosome 1 as well as in those with 17p deletion, while the benefit of adding thalidomide to the bortezomib-melphalan-prednisone regimen was noted in patients carrying an aggressive CD19+/CD117− bone marrow plasma cell immunophenotype. This trial was registered at www.clinicaltri-als.gov as #NCT01063179.

BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p

The outcome of lymphoma has definitely improved over the last few decades which is mainly due to the introduction and development of novel and effective therapeutic approaches. Nevertheless, a small though notable group of patients may display a poor response to treatments, with a true refractoriness or a transient response followed by early relapse. The present review addresses the issue of refractory disease among patients with lymphoma, focusing on the overall incidence and the main clinical aspects associated with refractoriness.A evolução dos linfomas tem sido definitivamente melhorada ao longo das últimas décadas. Isto se deve principalmente devido à introdução e desenvolvimento de novas e efetivas abordagens terapêuticas. Apesar disto, uma pequena parcela deste notável grupo de pacientes pode apresentar uma pobre resposta aos tratamentos, com uma verdadeira refratariedade, ou com resposta transitória e precocemente uma recidiva. A presente revisão aborda este assunto da doença refratária nos pacientes com linfoma, enfocando sua incidência global e os principais aspectos clínicos associados à refratariedade.

Background Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive.Design and Methods To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters.Results Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets.Conclusions Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.

Abstract Methods: Enrolled in this study were 31 patients with different advanced carcinoma: 9 patients were given GEM (1 h i.v. infusion, 1000 mg/m2) followed after 5 min by VNR (10 min i.v. infusion, 25 mg/m2) (GEM-VNR sequence); 17 patients received VNR followed by GEM (VNR-GEM sequence), at the same doses and with the same infusion period; as a control group (GEM), 5 patients were given only single-agent gemcitabine (1 h i.v. infusion, 1000 mg/m2). [ABSTRACT FROM AUTHOR]