The relationship between facial skeletal class and expert-rated interpersonal skill: an epidemiological survey on young Italian adults

BACKGROUND: The facial region plays a major role in determining physical attractiveness, so we assessed the hypothesis that the capability of successfully managing interpersonal relationships in young adults might be related to the facial skeletal class. METHODS: 1,014 young subjects applying to the Military Academy of Pozzuoli, Italy, were enrolled and the cephalometric evaluation was performed by calculating the angular relationships between skeletal points localized by the lateral cephalogram of the face, sorting the subjects in three groups corresponding to each major facial skeletal class. Concurrently, the subjects were evaluated by a team of psychiatrists administering the MMPI-2 test followed by a brief colloquium with each candidate, in order to identify those subjects characterized by low skills for managing interpersonal relationships. RESULTS: According to the psychiatric evaluation about 20% of the subjects were considered potentially unable to manage successfully interpersonal relationships (NS). Males displayed an about two-fold increased risk of being NS. No differences were shown in the distribution of the NS male subjects among the three different facial skeletal classes. On the other hand, NS females displayed a different distribution among the three facial skeletal classes, with a trend of about two-fold and four-fold, respectively, for those subjects belonging to classes II and III, respect to those belonging to class I. CONCLUSION: Females may be more sensitive to physical factors determining beauty, such as the facial morphology certainly is. This finding appears to be interesting especially when thinking about possible orthodontic interventions, although further study is certainly needed to confirm these results

DETECTION OF RARE COPIES OF BCR-ABL1 TRANSCRIPT IN PATIENTS WITH PHILADELPHIA POSITIVE (PH ) ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) WITH A HIGH SENSITIVE NANOFLUIDIC ARRAY

BACKGROUND: Ph+ ALL is observed in about 20-30% of adult ALL and is associated with a very poor prognosis and early relapse. Tyrosine kinase inhibitors have improved overall treatment results, with a rapid response and a complete remission (CR) rate ranging 90%. Nevertheless most patients experienced hematological relapse in a short time, also after hematopoietic stem cell transplantation. Molecular analysis based on quantitative assays (i.e. quantitative polymerase chain reaction, qPCR) provides detection of residual leukemic cells measuring BCR-ABL1 transcript level and becomes necessary in the monitoring of minimal residual disease to confirm molecular CR and to detect early relapse. AIM: To investigate the efficacy of a high sensitive method based on nanofluidic platform (Fluidigm Corporation, South San Francisco, CA) to detect and quantify residual and rare BCR-ABL1 copies in Ph+ ALL patients who obtained molecular remission as assessed by conventional qPCR. METHODS AND PATIENTS: The 12.765 Digital array (Fluidigm) is a nanofluidic biochip that consists in twelve panels, each containing 765 individual reaction chambers of 6 nL volume. Samples are portioned prior to qPCR into the single chambers of the panel; as fluorescent signal is produced only in chambers containing copies of the target sequence, digital array provides an absolute quantification by counting the number of positive reactions. Following amplification, digital raw data are processed by the BioMark Digital PCR Analysis software (Fluidigm), that estimates the true number of molecules per chamber using the Poisson probabilistic distribution. At the time of writing, we analyzed 22 Ph+ ALL samples (11 positive for the P190 BCR-ABL1 isoform and 11 for the P210 ) who were in complete (87%) or major (13%) molecular response (BCR-ABL1/ABL ratio ≤ 0.001 or < 0.1, respectively) as assessed by conventional qPCR; RNA integrity was evaluated using the control gene ABL. RESULTS: First, we assessed the sensitivity and reproducibility of the assay using six serial dilutions of plasmids (Ipsogen) expressing known copy number of BCR-ABL1 P190 transcript (10000; 1000; 100; 50; 10; 1 copies). A 2 µl volume of input cDNA was loaded and two panel for each dilution were used. Analysis parameter chosen for digital raw data processing were automated set threshold of 0.65 and target Ct range 20-40. Results showed a detection rate until a copy of target sequence and a pairing significantly effective between replicates (p= 0.0014, Paired t TEST analysis). We then analyzed duplicates of Ph+ ALL samples with a positive control for each chip: digital array resulted positive in 58% of complete molecular response samples, with 5.5 as median number of copies detected (range 0.5-11). CONCLUSIONS: The Fluidigm nanofluidic platform provides a high sensitive assay, able to detect until a single copy of BCR-ABL1 transcript with greater accuracy than conventional qPCR, as demonstrated for samples in molecular remission, and could provide an accurate monitoring method for Ph+ ALL CR patients. Further studies to confirm these results are actually ongoing. Supported by European LeukemiaNet, AIL, AIRC, FIRB 2006, Ateneo RFO grants, Project of integreted program (PIO), Programma di Ricerca Regione – Università 2007 – 2009

AZACITIDINE IN MYELODYSPLASTIC SYNDROMES: RETROSPECTIVE EVALUATION OF LONG-RESPONDER PATIENTS

Introduction. Azacitidine (AZA) has proven effective in myelodysplastic syndromes (MDS). The duration of haematological response is limited (median 13.6 months) (Fenaux, 2009), although some patients (pts) show a prolonged response. These data prompted us to retrospectively analyse our MDS pts treated with AZA, in order to enucleate longresponder pts (duration of response 6520 months). METHODS. From September 2004, in our Institution, 52 MDS pts (40 males), median age: 70 (37-85) yrs, were treated with AZA, following 4 different treatment regimens: 9 pts received the AZA 7 regimen (AZA 7: 75 mg/sqm/die SC for 7 days/28 days); 6 pts received the combination of AZA 7 with valproic acid and all-trans-retinoic acid ; while 25 and 12 pts respectively received the alternative regimens AZA 5-2-5 and AZA 5 (Lyons, JCO 2009). 37 pts (71%) showed a IPSS high-risk MDS, while 15 pts (29%) with IPSS low-risk MDS received AZA because of refractoriness or ineligibility to erythropoietin, or secondary MDS. Moreover, as our group (Follo, 2009) demonstrated that phosphoinositide-phospholipase C (PIPLC) beta1 may represent a target for AZA, we quantified the degree of PI-PLCbeta1 methylation and gene expression before and during AZA administration. RESULTS. 9 pts (17.3%) showed a prolonged hematologic response ( 65 20 months). Pre-treatment clinical and haematologic features of long-responders: sex (M/F): 4/5; median age: 69 (52- 84); WHO: RCMD-RS: 1 pt; RAEB-1: 1 pt; RAEB-2: 7 pts; IPSS risk: low: 1 pt; int-1: 2 pts; int-2: 5 pts; high: 1 pt; IPSS cytogenetic risk: low: 7 pts; interm: 1 pt; high: 1 pt; ECOG: 0-1: 8 pts, 65 2: 1 pt; transfusion need (N\ub0 U)/8 weeks: < 4 : 4 pts; 65 4 : 5 pts; time from diagnosis (months): < 6 : 6 pts; 65 6 : 3 pts. Therapeutic regimen: AZA 7: 3 pts; AZA 5: 3 pts; AZA 5-2-5: 3 pts. Therapeutic response: median number of cycles: 19 (8-59); median time to 1st response: 3 (2-6) months; type of response: Complete Remission (CR): 3 pts; Hematologic Improvement (HI): 6 pts; cytogenetic remission: 1 pt; median duration of response: 30 (24-66) months; doubling of platelet count after 1st cycle: 4 pts; toxicity (grade > 2): 3 pts; 4 pts are still maintaining hematologic response, 3 pts are still alive but discontinued treatment because of disease progression, and 2 pts died (1 for AML and 1 for cachexy). Median survival (from the start of AZA): 38 (25-103) months. All the pts showed an increase in PI-PLCbeta1 expression, that was maintained along with the hematologic response. 15 pts (28.8%) showed a short-lived reponse (< 20 months), 5 pts (9.6%) show a shorter response but are still on treatment, 2 pts underwent allogeneic transplantation after 5 and 10 months. 7 pts (13.4%) are not evaluable for response (< 6 cycles), and 14 pts (26.9%) did not respond to AZA. Conclusions. Our data show that a limited but significant fraction of MDS pts show a long-lasting hematologic and molecular response to AZA

CLINICAL OUTCOME OF T- ACUTE LYMPHOBLASTIC LEUKEMIA/ LYMPHOMA (T-ALL/T-LBL): THE BOLOGNA EXPERIENCE

Background: Precursor T cell ALL/LBL occurs most frequently in late childhood, adolescence, and young adulthood, with a 2:1 male predominance; it comprises 15 and 25 percent of childhood and adult ALL, respectively, and 2 percent of adult non-Hodgkin lymphoma. In adult patients prognosis is poor, due to the high incidence of relapse even after allogenic stem cell transplantation. Aims: To identify new targets, to optimize therapy, to reduce toxicity and to improve clinical outcome. Methods: We retrospectively analysed and currently report clinical outcome results about 52 newly diagnosed and younger than 60 years T-ALL patients (median age 30 years, range 14-73 years) treated, from 2006 to 2012 according to standard chemotherapy regimen, including adapted pediatric-like schedule, BFM protocol, and adult schedules. After induction, all the patients underwent consolidation for at least one course. All the patients shared the same strategy for intensification, that consisted, when available, in allogenic or autologous stem cell transplantation. Detailed data about cytogenetics and molecular biology will be provided on site. Durations of complete remission (CR) and overall survival (OS) were estimated according to the Kaplan-Meier method. The CR duration was calculated from start of CR to first evidence of disease recurrence. Results: Informed consent was obtained; after a single induction course 41/52 patients obtained a CR (78.8%) and 2 patients a partial remission (PR) (3.8%) for an overall response rate (ORR) of 82.6%. Seven patients (13.4%) had resistant disease, and 2 (3.8%) died during induction. After a median follow-up of 22.7 months, 19 patients (36.5%) are still in CR. The median CR duration and OS were 12.3 and 23.15 months, respectively. The most common grade 3 adverse events included gastro-intestinal toxicities (i.e. nausea, vomiting, mucositis and diarrhoea) and liver dysfunction. Summary and Conclusions:Our analysis confirms, in line with literature data, that, despite intensive chemotherapeutic treatments and stem cell transplantation, T-ALL and T-LBL adult patients still show a bad prognosis. The relatively satisfying induction remission rate is followed, in most cases, by a high relapse rate. Therefore, a molecular stratification approach, based on gene-expression profile analysis (Ferrando et al., Cancer Cell 2002) should be routinely performed, in order to identify new targets, to optimize therapy, to reduce toxicity and to improve clinical outcome

CLINICAL OUTCOME OF T-ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA (T-ALL/TLBL): THE BOLOGNA EXPERIENCE

Background. Precursor T cell ALL/LBL occurs most frequently in late childhood, adolescence, and young adulthood, with a 2:1 male predominance; it comprises 15 and 25 percent of childhood and adult ALL, respectively, and 2 percent of adult non-Hodgkin lymphoma. In adult patients prognosis is poor, due to the high incidence of relapse even after allogenic stem cell transplantation. Design and Methods. We retrospectively analysed and currently report clinical outcome results about 52 newly diagnosed and younger than 60 years T-ALL patients (median age 30 years, range 14-73 years; 37/15 M/F; 41/52 T-ALL e 11/52 T-LBL) treated, from 1991 to 2011 according to standard chemotherapy regimen, including adapted pediatric-like schedule (10 pts), BFM protocol (3 pts) and adult schedules (39 pts). After induction, all the patients underwent consolidation for at least one course. All the patients shared the same strategy for intensification, that consisted, when available, in allogenic or autologous stem cell transplantation. Detailed data about cytogenetics and molecular biology will be provided on site. Durations of complete remission (CR) and overall survival (OS) were estimated according to the Kaplan-Meier method. The CR duration was calculated from start of CR to first evidence of disease recurrence. Results. Informed consent was obtained; after a single induction course 41/52 patients obtained a CR (78.8%) and 2 patients a partial remission (PR) (3.8%) for an overall response rate (ORR) of 82.6%. Seven patients (13.4%) had resistant disease, and 2 (3.8%) died during induction. After a median follow-up of 22.7 months, 19 patients (36.5%) are still in CR. The median CR duration and OS were 12.3 and 23.15 months, respectively. The most common grade 3 adverse events included gastro-intestinal toxicities (i.e. nausea, vomiting, mucositis and diarrhoea) and liver dysfunction. Conclusions. Our analysis confirms, in line with literature data, that, despite intensive chemotherapeutic treatments and stem cell transplantation, TALL and T-LBL adult patients still show a bad prognosis. The relatively satisfying induction remission rate is followed, in most cases, by a high relapse rate. Therefore, a molecular stratification approach, based on gene-expression profile analysis (Ferrando et al, Cancer Cell 2002) should be routinely performed, in order to identify new targets, to optimize therapy, to reduce toxicity and to improve clinical outcome. Supported by: European LeukemiaNet, AIRC, AIL, PRIN 2010-2011, Fondazione del Monte di Bologna e Ravenna

Nelarabine front-line therapy for adult T-Lymphoblastic leukaemia/Lymphoma (T-LBL/ALL): preliminary results of a single centre experience

Background: Precursor T cell LBL/ALL occurs most frequently in late childhood, adolescence, and young adulthood, with a 2:1 male predominance; it comprises 15 and 25 percent of childhood and adult ALL, respectively, and 2 percent of adult non-Hodgkin lymphoma. Nelarabine is an anticancer prodrug of arabinofuranosylguanine (ara-G); it inhibits DNA synthesis and leads to high molecular weight DNA fragmentation and cell death. Aims: Nelarabine has showed relevant efficacy in phase II clinical trials, both in pediatric and in adult LBL/ALLpopulations. Methods:We report clinical outcome results of 9 newly diagnosed and younger than 60 yearsT-ALL patients (median age 29 years, range 22-45 years, 3/6 M/F, 8 T-ALL, 1 T-LBL) treated according to pediatric-like adapted schedule. Cytogentics data and molecular biologic features will be provided on site. Induction cycle included Vincristine, daunoblastine, L-asparaginase and Prednisone. After induction, all the patients received consolidation therapy with cyclophosphamyde, L-asparaginase, Cytarabine and 6-Mercaptopurine. Subsequently all the patients receveid Nelarabine 1500 mg/sqm (days 1-3-5 every 21) for two cycles. All the patients shared the same strategy for intensification, which consisted in allogenic stem cell transplantation, if available, or additional courses of consolidation chemotherapy. Durations of complete remission (CR) and overall survival (OS) were estimated according to the Kaplan-Meier method. The CR duration was dated from start of CR to first evidence of disease recurrence. Results: After a single induction course, 9/9 patients obtained a CR (100%). Eight patients underwent an allogenic bone marrow transplantation. Aftera median follow-up of 24 months, 7/9 patients (78%) are alive in CR. The median CR duration and OS were 13.4 and 24.4 months, respectively. Neurological toxicity of grade 3has not been reported. We did not observe grade 3-4 haematological toxicity. Summary / Conclusion: Nelarabine is a promising drug, which induces a remarkable complete remission rate at the expense of a very low and manageable toxicity