The Efficacy of the Global Intensive Feeding Therapy on Feeding and Swallowing Abilities in Children with Autism Spectrum Disorder: A Pilot Study.

The present investigation aims to explore the efficacy of Global Intensive Feeding Therapy (GIFT) on feeding and swallowing abilities in children with autism spectrum disorder (ASD). GIFT was developed as an intensive rehabilitation approach, divided into 30 sessions for 2 weeks, three times a day. GIFT focused on (a) encouraging desensitization; (b) widening the food repertoire (in terms of both variety and quantity); (c) reducing inappropriate mealtime behaviors; and (d) encouraging the development of appropriate chewing and swallowing abilities. GIFT was preliminarily implemented among 11 children with a diagnosis of ASD. To measure the efficacy of GIFT, the Karaduman Chewing Performance Scale (KCPS), the Brief Autism Mealtime Behavior Inventory (BAMBI), and food repertoire were investigated using Wilcoxon signed-rank test in three different times: baseline (T1), after treatment (T2), and one month after treatment (T3). Using Bonferroni correction, statistically significant differences were found between T1 and T2 for behavioral issues, as measured with BAMBI (p = 0.007), as well as for chewing abilities as measured with KCPS (p = 0.005) and for food acceptance (p = 0.005). These improvements were maintained after a month of follow-up, thanks to the collaboration of families and/or primary caregivers. In conclusion, GIFT seems to be an effective approach to improving behavioral issues, food acceptance, and chewing abilities in children with ASD.

Development and Pilot Study of a Pediatric Screening for Feeding and Swallowing Disorders in Infants and Children: The Pediatric Screening-Priority Evaluation Dysphagia (PS-PED).

Feeding and swallowing disorders (FSD) are common during childhood, with a prevalence of 85% in children with neurodevelopmental disorders. A comprehensive screening is essential to identify FSD and improve health outcomes in a clinical setting. This study aims to develop a new Pediatric Screening tool capable of identifying FSD. This screening tool was developed in three steps: selecting variables based on clinical experience, searching the literature and finding agreement between experts with a two-round Delphi study. This process, which reached 97% of agreement between experts, led to the development of the Pediatric Screening-Priority Evaluation Dysphagia (PS-PED). PS-PED comprises 14 items divided into three main domains: clinical history, health status and feeding condition. We also carried out a pilot test for measuring internal consistency, as measured with Cronbach Coefficient alpha. Concurrent validity, as measured with Pearson correlation coefficient, was tested using a videofluoroscopy swallow study (VFSS) classified with the Penetration Aspiration Scale (PAS). The pilot test was conducted on 59 children with different health conditions. Our findings showed good internal consistency (alpha = 0.731), and a strong linear correlation with PAS (Pearson 0.824). Furthermore, comparing PS-PED and PAS scores, we find preliminary strong discriminant validity to identify children with FSD (p < 0.01). Our results provide evidence on using the 14-item PS-PED as a screening tool for FSD in a clinical sample of children with heterogeneous disease.

Clinical Management of Long-Term Survivors after Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma.

Compared to other patients suffering from hematological malignancies, classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients have a long life expectancy when in complete remission at the end of first, or sometimes second, line treatments [...].

Late Neurological and Cognitive Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: The continuously improving treatment outcome for classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) over the last 25 years has led to a high number of long-term survivors. The impact of treatment, however, can sometimes be dramatic and long-lasting. Focusing on peripheral neuropathy (PN), cognitive impairment, fatigue, anxiety, and depression, researchers of the Fondazione Italiana Linfomi conducted a systematic review of the literature to collect the available data on sequelae incidence as well as evidence of follow-up strategies for long-term cHL and DLBCL survivors. METHODS: The review was carried out under the methodological supervision of the Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. The literature search was conducted on three databases (MEDLINE, Embase, and the Cochrane Library) updated to November 2019. The selection process and data extraction were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 2236 abstracts were screened, 247 full texts were analyzed, and 35 papers were included in the final analysis. Fatigue was the most extensively studied among neuropsychological sequelae, with a mean prevalence among cHL survivors of 10-43%. Although many of the papers showed an increased incidence of PN, cognitive impairment, and anxiety and depression in long-term cHL and DLBCL survivors, no definite conclusions can be drawn because of the methodological limitations of the analyzed studies. No data on monitoring and follow-up strategies of PN and other neuropsychological sequelae were highlighted. CONCLUSIONS: Based on our findings, future studies in this setting should include well-defined study populations and have a longitudinal trial design to assess the outcomes of interest over time, thus as to structure follow-up programs that can be translated into daily practice.

Could art cycles have a detrimental effect on ovarian reserve? A retrospective case control study.

BACKGROUND: Even if it is supposed damage of repeated ART (assisted reproductive technology) cycles on oocyte pool, there is still no evidence in literature. Aim of the study is to investigate whether infertile women who undergo to several ART cycles can show a lower ovarian reserve measured by AMH (Anti-Mullerian hormone) levels. METHODS: The study includes 282 infertile women, between 18 and 42 years, and allocated into two groups: 159 women previously submitted to two or more ART cycles (group A) and 123 women never submitted naïve to-ART cycles (group B). We tested whether AMH, FSH, LH and E2 levels were significantly different between the two groups, stratifying according to age. RESULTS: Regardless to the age ranges bands, the AMH in group A was statistically significant lower than in group B with a statistical significance (P=0.047). In particular women aged over 35 previously submitted to one or more ART cycles showed lower AMH levels, than those paired with age, which had never been treated with ART. CONCLUSIONS: Despite the limitations of the study, our data demonstrate a reduced AMH levels in women aged over 35 previously submitted to two or more repeated ART-cycles compared to patients never treated before. The strength of this study is the actuality of the topic that has not been discussed before in detail.

Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: comparison between 2D and 3D-sonohysterosalpingography. A pilot study.

BACKGROUND: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D-3D-HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. METHODS: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. RESULTS: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81% of cases, with a sensitivity of 80% and a specificity of 92%. In group II, a correspondence was present in 88% of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (P<0.001). CONCLUSIONS: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.

Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers.

Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a "double hit score" upon positivity for BCL2 and MYC. PCDLBCL-NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B-cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a "non-germinal B-cell" profile, whereas "germinal center" cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC-LT, which often coexpressed MYC and BCL2. The impact of single factors on 5-year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group-PCDLBCL-NOS-exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.

Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: a systematic review.

This systematic review focuses on the literature evidence for residual ovarian function during treatment with hormonal contraceptives. We reviewed all papers which assessed residual ovarian activity during hormonal contraceptive use, using endocrine markers such as serum anti-Müllerian hormone (AMH) concentrations, FSH, LH, oestradiol, progesterone and sonographic markers such as antral follicle count (AFC), ovarian volume and vascular indices. We considered every type (oestroprogestin or only progestin) and dosage of hormonal contraceptive and every mode of administration (oral, vaginal ring, implant, transdermal patch). We performed an electronic database search for papers published from 1 January 1990 until 30 November 2015 using PubMed and MEDLINE. We pre-selected 113 studies and judged 48 studies suitable for the review. Most studies showed that follicular development continues during treatment with hormonal contraceptives, and that during treatment there is a reduction in serum concentrations of FSH, LH and oestradiol, and also a reduction in endometrial thickness, ovarian volume and the number and size of antral follicles. The ovarian reserve parameters, namely AFC and ovarian volume, are lower among users than among non-users of hormonal contraception; regarding the effect of hormonal contraception on AMH, there are still controversies in the literature.

Bendamustine and rituximab combination is safe and effective as salvage regimen in Waldenström macroglobulinemia.

According to the European Society for Medical Oncology and National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia, bendamustine (B) may be considered a suitable therapeutic option. To address the role of B in combination with rituximab (BR), we analyzed the outcome of 71 patients with relapsed/refractory disease, median age 72 years, treated with R 375 mg/m(2) day 1 and B days 1 and 2 (dosage ranging from 50 to 90 mg/m(2)). Patients had previously received a median number of 2 lines of treatment (range 1-5). Overall and major response rates were 80.2% and 74.6%. Major toxicity was grade 3/4 neutropenia occurring in 13% of courses. There was no significant association between baseline features or patients' characteristics and response achievement. Median progression-free survival was not reached after a median follow-up of 19 months (range 3-54). None of the patients developed aggressive lymphoma or secondary myelodysplastic syndrome/acute myeloid leukemia. BR was found to be an active and well-tolerated salvage regimen leading to rapid disease control.

Second surgery for recurrent endometriomas is more harmful to healthy ovarian tissue and ovarian reserve than first surgery.

OBJECTIVE: To evaluate the excised specimen with histologic analysis and to assess the antral follicle count (AFC) at follow-up. This is to determine whether excisional surgery for recurrent endometriomas is more harmful to ovarian tissue and to the ovarian reserve than first surgery. DESIGN: Prospective controlled study. SETTING: University hospital. PATIENT(S): Consecutive patients with pelvic pain and/or infertility undergoing laparoscopic excision of a monolateral ovarian endometrioma for the first time (17 patients) or for recurrence after previous surgery (11 patients). INTERVENTION(S): Laparoscopic excision of ovarian endometrioma and ultrasonographic evaluation 3 months after surgery. MAIN OUTCOME MEASURE(S): Cyst wall histologic evaluation (specimen thickness, presence and morphology of ovarian tissue) and evaluation of ovarian reserve with AFC and ovarian volumes of both the operated and contralateral, nonoperated ovary at follow-up. RESULT(S): The cyst wall specimen was significantly thicker in the recurrent endometrioma group than in the first surgery group (1.7 ± 0.3 mm vs. 1.1 ± 0.3 mm). Both main components of the cyst specimen (i.e., endometriosis tissue and ovarian tissue) were more represented in the recurrent endometrioma group than in the first surgery group. At sonographic follow-up, the operated ovary had a significantly lower AFC and volume than the contralateral nonoperated ovary in the recurrent endometrioma group, but not in the primary surgery group. CONCLUSION(S): Surgery for recurrent endometriomas is associated with evidence of a higher loss of ovarian tissue and is more harmful to the ovarian reserve evaluated by AFC and ovarian volume, if compared with endometriomas operated for the first time. Indications to surgery for recurrent endometriomas should be reconsidered with caution.

Emergency peripartum hysterectomy in a tertiary teaching hospital: a 14-year review.

PURPOSE: To determine incidence, risk factors, indications, outcomes, and complications of emergency peripartum hysterectomy (EPH) performed in a tertiary teaching hospital and to compare the results with literature data. METHODS: Retrospective study of 51 patients who underwent EPH at the Department of Gynecology, Obstetrics and Urology of the University of Rome Sapienza, from January 2000 to December 2013. Maternal characteristics of the index pregnancy and delivery, indications for EPH, operative and postoperative complications, maternal and neonatal outcome were acquired by the hospital records. Fisher's and Chi-square tests were performed for statistical analysis. RESULTS: There were 51 EPH out of 23,384 deliveries, for an incidence of 2.2 per 1,000 deliveries during the study period. Forty-nine EPHs were performed after caesarean delivery (CS) and two after vaginal delivery (p < 0.0001). The most common indications were abnormal placentation (49.0%), followed by uterine atony (41.2%), and uterine rupture (9.8%). Eighty percent of patients who underwent EPH with abnormal placentation had at least one previous CS (p < 0.01). Twenty-three patients (45.1%) underwent total hysterectomy, the most frequent indication being abnormal placentation (76%, p < 0.01). The remaining 28 patients underwent subtotal hysterectomy (54.9%), the most frequent indication being uterine atony (85.7%, p < 0.01). Maternal morbidity was 25.5% and mortality was 5.9%. Perinatal mortality was 3.9%. CONCLUSIONS: Abnormal placentation was the most common indication for EPH, requiring in most of the cases a total hysterectomy. Previous CS was a risk factor for abnormal placentation and in particular for pathological adherence of the placenta. EPH remains associated with a high incidence of morbidity and mortality.

Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial.

BACKGROUND: Up to 40% of elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) given a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP21) relapse or develop refractory disease. Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas. In phase 2 of the REAL07 trial, we aimed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated DLBCL. METHODS: REAL07 was an open-label, multicentre trial that was done in 13 centres in Italy and one in Germany. Eligible patients were aged 60-80 years; had newly diagnosed, untreated, CD20-positive, Ann Arbor stage II-IV DLBCL or grade 3b follicular lymphoma; had an Eastern Cooperative Oncology Group performance status of 0-2; had an International Prognostic Index (IPI) risk of low-intermediate, intermediate-high, or high; and were fit according to comprehensive geriatric assessment. Participants were to receive 15 mg oral lenalidomide on days 1-14 of six 21-day cycles, and standard doses of R-CHOP21 chemotherapy (375 mg/m(2) intravenous rituximab, 750 mg/m(2) intravenous cyclophosphamide, 50 mg/m(2) intravenous doxorubicin, and 1·4 mg/m(2) intravenous vincristine on day 1, and 40 mg/m(2) oral prednisone on days 1-5). The primary endpoint was frequency of overall response (complete response [CR] and partial response [PR]), which was assessed by (18)F-fluorodeoxyglucose ((18)F-FDG) PET at the end of the treatment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00907348. FINDINGS: 49 patients were included in phase 2: nine had been enrolled into phase 1 between Oct 23, 2008, and June 4, 2009, and had received the maximum tolerated dose of 15 mg lenalidomide; and 40 were enrolled into phase 2 between April 28, 2010, and June 3, 2011. 45 patients (92%, 95% CI 81-97) achieved a response (42 [86%] CR; three [6%] PR). Three patients (6%) did not respond and one (2%) died for reasons unrelated to treatment or disease. 277 (94%) of 294 planned cycles of lenalidomide and R-CHOP21 were completed. Grade 3-4 neutropenia was reported in 87 cycles (31%), grade 3-4 leukopenia in 77 (28%), and grade 3-4 thrombocytopenia in 35 (13%). No grade 4 non-haematological adverse events were reported. No patients died during the study as a result of toxic effects. INTERPRETATION: Lenalidomide with R-CHOP21 is effective and safe in elderly patients with untreated DLBCL. FUNDING: Fondazione Italiana Linfomi and Celgene.

Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group.

The International Extranodal Lymphoma Study Group coordinated a phase II trial to evaluate the activity and safety of everolimus in marginal zone lymphomas (MZLs). Thirty patients with relapsed/refractory MZLs received everolimus for six cycles or until dose-limiting toxicity or progression. Median age was 71 years (range, 51-88 years). Twenty patients had extranodal, six splenic, four nodal MZL. Twenty-four patients had stage III-IV. Median number of prior therapies was two (range 1-5). Seventeen patients had early treatment discontinuation, in most cases due to toxicity. Median number of cycles was 4.5 (range, 1-16). Among the 24 assessable patients, the overall response rate (ORR) was 25% (95% confidence interval: 10-47). Grade 3-4 adverse events were neutropenia and thrombocytopenia (17% of patients, each), infections (17%), mucositis and odontogenic infections (13%) and lung toxicity (3%). The median response duration was 6.8 months (range, 1.4-11.1+). After a median follow-up of 14.5 months, five deaths were reported: four deaths were due to lymphoma, one was due to toxicity. In an intent-to-treat analysis, the projected median progression-free survival was 14 months. The moderate antitumour activity of everolimus in relapsed/refractory MZLs and the observed toxicity limit its therapeutical applicability in these indolent entities. Lower doses of the drug and, perhaps, different strategies including combination with additional agents need to be explored.

Prognostic impact of monocyte count at presentation in mantle cell lymphoma.

An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

Risk factors of central nervous system relapse in mantle cell lymphoma.

Central nervous system (CNS) relapse has not been extensively studied in mantle cell lymphoma (MCL). We retrospectively analyzed the risk factors and pattern of CNS relapse in consecutive patients with MCL. We identified 142 cases of MCL treated from 1980 to 2011. Median age at diagnosis was 68 years; 82% of patients had advanced stage; extranodal disease was reported in 89% of cases and high serum lactate dehydrogenase (LDH) in 40%. Fourteen patients (10%) did not receive treatment at diagnosis. Chemotherapy was administered to 125 patients (88%), in 21 cases (15%) including drugs penetrating into the CNS or given intrathecally; 49 patients (35%) had rituximab. Ten patients had front-line autologous transplant. After a median follow-up of 7.9 years, CNS relapse occurred in 11 cases (7.8%) at a median of 13.8 months. Actuarial risk of CNS relapse was higher in patients with elevated LDH (p = 0.002), higher International Prognostic Index (IPI) score (p = 0.018) and blastoid histology (p < 0.0001). Blastoid histology retained significance at multivariate analysis. Median survival after CNS relapse was 6.3 months. No front-line treatment reduced the risk of CNS relapse. Our analysis confirms the poor outcome of MCL after CNS relapse and may allow the identification of patients needing prophylaxis of CNS relapse.

The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development.

Splenic marginal zone lymphoma (SMZL) is a B cell malignancy of unknown pathogenesis, and thus an orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis, we show that the SMZL exome carries at least 30 nonsilent gene alterations. Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting for ∼20% of cases. All NOTCH2 mutations are predicted to cause impaired degradation of the NOTCH2 protein by eliminating the C-terminal PEST domain, which is required for proteasomal recruitment. Among indolent B cell lymphoproliferative disorders, NOTCH2 mutations are restricted to SMZL, thus representing a potential diagnostic marker for this lymphoma type. In addition to NOTCH2, other modulators or members of the NOTCH pathway are recurrently targeted by genetic lesions in SMZL; these include NOTCH1, SPEN, and DTX1. We also noted mutations in other signaling pathways normally involved in MZ B cell development, suggesting that deregulation of MZ B cell development pathways plays a role in the pathogenesis of ∼60% SMZL. These findings have direct implications for the treatment of SMZL patients, given the availability of drugs that can target NOTCH, NF-κB, and other pathways deregulated in this disease.

Final results of a multicenter trial addressing role of CSF flow cytometric analysis in NHL patients at high risk for CNS dissemination.

This prospective study compared diagnostic and prognostic value of conventional cytologic (CC) examination and flow cytometry (FCM) of baseline samples of cerebrospinal fluid (CSF) in 174 patients with newly diagnosed aggressive non-Hodgkin lymphoma (NHL). FCM detected a neoplastic population in the CSF of 18 of 174 patients (10%), CC only in 7 (4%; P < .001); 11 patients (14%) were discordant (FCM(+)/CC(-)). At a median follow-up of 46 months, there were 64 systemic progressions and 10 CNS relapses, including 2 patients with both systemic and CNS relapses. Two-year progression-free and overall survival were significantly higher in patients with FCM(-) CSF (62% and 72%) compared with those FCM(+) CSF (39% and 50%, respectively), with a 2-year CNS relapse cumulative incidence of 3% (95% confidence interval [CI], 0-7) versus 17% (95% CI, 0-34; P = .004), respectively. The risk of CNS progression was significantly higher in FMC(+)/CC(-) versus FCM(-)/CC(-) patients (hazard ratio = 8.16, 95% CI, 1.45-46). In conclusion, FCM positivity in the CSF of patients with high-risk NHL is associated with a significantly higher CNS relapse risk and poorer outcome. The combination of IV drugs with a higher CNS bioavailability and intrathecal chemotherapy is advisable to prevent CNS relapses in FCM(+) patients.

Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP.

Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P = .0475); F-PET 83% versus 64% (P < .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio [HR] = 5.03, P = .015 vs 1.27, P = 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P = .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.

Integrated profiling of diffuse large B-cell lymphoma with 7q gain.

To characterize diffuse large B-cell lymphoma (DLBCL) with chromosome 7 gains, we combined clinical data with genomic, RNA and miRNA profiling. Gains were associated with age >60 years, female gender, a trend for higher complete response rate, lower death rate, and better overall survival in patients treated with R-CHOP. Lesions were inversely associated with bone marrow involvement and number of extra-nodal sites. Differentially expressed transcripts were enriched of genes belonging to specific pathways and miRNAs targets. MIR96, MIR182, MIR589, MIR25 were shown significantly up-regulated in 7q+ DLBCL by real-time PCR.

The host genetic background of DNA repair mechanisms is an independent predictor of survival in diffuse large B-cell lymphoma.

Several drugs used for diffuse large B-cell lymphoma (DLBCL) treatment rely on DNA damage for tumor cell killing. We verified the prognostic impact of the host DNA repair genotype in 2 independent cohorts of DLBCL treated with R-CHOP21 (training cohort, 163 cases; validation cohort, 145 cases). Among 35 single nucleotide polymorphisms analyzed in the training series, MLH1 rs1799977 was the sole predicting overall survival. DLBCL carrying the MLH1 AG/GG genotype displayed an increased death risk (hazard ratio [HR] = 3.23; P < .001; q =0 .009) compared with patients carrying the AA genotype. Multivariate analysis adjusted for International Prognostic Index identified MLH1 AG/GG as an independent OS predictor (P < .001). The poor prognosis of MLH1 AG/GG was the result of an increased risk of failing both R-CHOP21 (HR = 2.02; P = .007) and platinum-based second-line (HR = 2.26; P = .044) treatment. Survival analysis in the validation series confirmed all outcomes predicted by MLH1 rs1799977. The effect on OS of MLH1, a component of the DNA mismatch repair system, is consistent with its role in regulating the genotoxic effects of doxorubicin and platinum compounds, which are a mainstay of DLBCL first- and second-line treatment.