George Paterakis

AbstractThe work describes an experimental investigation of propane flames established through fuel injection and gradual premixing with preheated and vitiated oxidizing air, within a double-cavity arrangement, formed along a cylinder and two concentric disks. Ignition of the inlet stratified and vitiated mixture and flame stabilization is established at the recirculation region of the afterbody disk. Measurements of mean velocities, temperatures, OH* and CH* chemiluminescence and gas analysis provided information for the interpretation of the relative variations in flame structure and burner performance. The study illustrates some aspects regarding the influence of the preheated/vitiated conditions on the combustion of the inlet stratified fuel-air mixture profile, with respect to flame front stabilization, disposition, and burner emissions. Some important differences in the vitiated flame structure and topology are discussed in comparison to the unvitiated case characteristics, in an initial effort to e...

The work presents comparisons of the flame stabilization characteristics of axisymmetric disk and 2D slender bluff-body burner configurations, operating with inlet mixture stratification, under ultralean conditions. A double cavity propane air premixer formed along three concentric disks, supplied with a radial equivalence ratio gradient the afterbody disk recirculation, where the first flame configuration is stabilized. Planar fuel injection along the center plane of theleading faceof a slender square cylinder against the approach cross-flow results in a stratified flame configuration stabilized alongside the wake formation region in the second setup. Measurements of velocities, temperatures,OH∗andCH∗chemiluminescence, local extinction criteria, and large-eddy simulations are employed to examine a range of ultralean and close to extinction flame conditions. The variations of the reacting front disposition within these diverse reacting wake topologies, the effect of the successive s...

The value and exact type of intensive chemotherapy of unselected elderly AML patients in terms of overall survival (OS) and quality of life remains controversial. Despite recent improvements in supportive measures during cytotoxic therapy, elderly AML patients continue to exhibit lower remission rates, higher toxicity, more relapses and eventually a worse survival. The present analysis evaluates in a retrospective manner the outcome of 57 homogeneously treated AML patients >60yrs during a period of 70 months (Nov 2001 to Aug 2007). The protocol schedule included an initial course of mitoxantrone+ cytarabine 3+5 (12mg/m2/d and 100mg/m2 q12h respectively) followed by a second abbreviated course of mitoxantrone+ cytarabine 2+5, followed by a final course of idarubicin+cytarabine+ thioguanine 2+7+7 (10mg/m2/d, 100mg/m2 q12h and 100mg/m2/d respectively). G-CSF at 5μg/Kg was added to all courses to accelerate hematopoietic recovery. Our patient population consisted of 30 cases of de no...

Immunoglobulin kappa (IGK) locus rearrangements were analyzed in 164 κ-light chain (LC) expressing chronic lymphocytic leukemia (CLL) cases and 95 λ-LC expressing CLL cases. In κ-CLL, 151 IGKV-J transcripts were successfully amplified by RT-PCR; 147/151 were in frame; four out-of-frame IGKV-J transcripts were heavily mutated and contained one or more stop codons, presumably introduced by somatic hypermutation; in all four cases the corresponding expressed transcript was also mutated. DNA-PCR identified 24/164 κ-CLL cases (15%) with double IGKV-J rearrangements; 9/24 non-expressed IGKV-J rearrangements were in-frame; 3/9 were mutated. The most frequently used IGKV genes in expressed IGKV-J rearrangements were: 3–20, 1-39/1D-39, 1–5 and 4-1; the IGKV4-1 gene was by far the most frequent in non-expressed IGKV-J rearrangements (9/24 cases, 33%). In λ-CLL, a total of 65 IGKV-J rearrangements were amplified in 59/95 cases (62.0%); six cases had two different rearrangements. IGVK4-1 was the most frequently used gene (14/65 sequences, 21.5%), followed by IGKV1-16 (8 cases,12.3%), 1-33/1D-33 and 2-30 (7 cases each, 10.8%). IGKV-J transcripts were detected by RT-PCR in 10/59 λ-CLL cases with IGKV-J rearrangements, of which four were in-frame and six out-of-frame. Seven IGKV-J rearrangements in λ-CLL had less than 100% homology to germline; 3/7 were in-frame; 6/7 patients had mutated IGHV and 5/7 had mutated IGLV genes. In κ-CLL, biased usage of the IGKJ1/IGKJ2 genes was observed both in expressed (69%) and non-expressed rearrangements (78%); in contrast, in λ-CLL, downstream IGKJ (IGKJ3-5) usage was observed in 32/59 sequences (53%). Nonproductive rearrangements involving the kappa deleting element (KDE) that render the IGK locus inactive were also analyzed. In κ-CLL, 22/147 cases (15%) carried IGKV to KDE rearrangements, while 24/147 cases (16.5%) carried IGKJ-C- INTRON (JKI) to KDE rearrangements. In λ-CLL, IGKV-KDE rearrangements were amplified in 55/94 cases (59%); JKI-KDE rearrangements were amplified in 52/94 cases (56%). IGKV1D-43 was the most frequent gene in IGKV-KDE joints in κ-CLL (4/22 cases); in contrast, the most frequent genes in IGKV-KDE joints in λ-CLL were IGKV3-20 and IGKV2-30 (9/55 and 7/55 cases, respectively). In conclusion, the present study confirms IGK locus rearrangements in the vast majority of λ-LC expressing CLL cases. Differential usage of IGKJ genes along with significant IGKV repertoire differences in both IGKV-J and IGKV-KDE rearrangements between κ- and λ-CLL allude to prolonged IGK locus recombination before CLL clonogenic cells became λ-producers. The inactivation of productive and potentially functional IGKV-J joints by secondary rearrangements indicates a role for receptor editing in shaping the expressed IG repertoire in CLL. Finally, the identification of mutated, non-expressed IGKV-J rearrangements both in κ- and λ-CLL might be considered as evidence for secondary rearrangements occurring after the onset of somatic hypermutation, at least in a proportion of cases.

ETV6/RUNX1 rearrangement, being the most common genetic abnormality in childhood ALL, is combined with controversial prognostic behavior and frequent late relapses, indicating the need for identification of additional prognostic markers. In our study, we examined the relation between ETV6/RUNX1 and presenting clinical/biological features, co-existing subclones/secondary aberrations, early response to treatment (MRD) and their impact on outcome in a pediatric cohort of 133 ALL pts , treated in one Center over a 12-year period. Data from 133 newly diagnosed ALL pts(83 males) with a median age of 5.1 yrs(range 1.2-16.7), have been retrospectively recorded and analyzed. Pts were consecutively diagnosed and homogeneously treated on BFM based protocols during the years 2000-2011. FISH evaluation using commercial probe sets was performed for the detection of ETV6-RUNX1, E2A-PBX1, BCR-ABL fusion genes, MLL gene rearrangements as well as ETV6, RUNX1, CDKN2A/2B and other gene duplications, de...

Hydroxyurea (HU) is a widely used cytotoxic agent that is known to induce fetal hemoglobin (HbF) production. HU-induced HbF production is beneficial for some patients with β-thalassemia and also ameliorates the severity of pain episodes in sickle cell anemia. Various cell culture systems have been used to elucidate the implicated mechanisms. We have previously demonstrated in both K562 human erythroleukemic cells and human erythroid cells (hAEC) that HU increases the transcription of low-expressed globin genes as well as the splicing efficiency of primary globin transcripts; however, other post-transcriptional effects could not be excluded. In this study, we extended our analysis in order to further understand the effect of HU on erythropoiesis and the molecular mechanisms involved in globin gene elevation. Peripheral blood hAEC from normal individuals were cultured in a two-phase liquid culture. Erythropoietin was added only to phase II. Erythroid cells in phase II were exposed to ...

This study was designed to maximize the recovery of the desirable cell populations contained in the cord blood (CB) freezing bag, in order to optimize donor selection for adolescents and adults. To evaluate this hypothesis, high volume CB units (CBUs) were categorized into three volume collection groups (120-139, 140-159 and >or=160 ml) and were randomly split before volume reduction into two half low volume CBUs; (a) and (b). Using the SEPAX Cell Processing System, all CBUs were standardized to 26 ml. In 128 high volume split CBUs, the WBC, mononuclear cell and CD34+ cell recoveries were significantly higher (P <or= 0.05; 80%, 79.89% and 87.41% respectively) than those of the 106 high volume nonsplit CBUs (59.7%, 62.82% and 68.62% respectively), resulting in significantly higher (P <or= 0.05) mean weights of the potential recipients. The strategy of splitting high volume CBUs into two half low volume CBUs improves the recovery of the cells and is an attractive option for ex vivo expansion, in order to facilitate the CB transplantation in adults who are not eligible for single CB transplantation because of limitations of cell dose.

T-ALL has increasing incidence during adolescence and it is rarely associated with Philadelphia chromosome positivity. Moreover, extremely rare is the event of Philadelphia chromosome negativity at diagnosis and leukemia clone evolution with t(9;22) at relapse. Such a patient is being described and relevant issues are being raised. A 14 year old boy was diagnosed with leukemia due to malaise and ecchymoses. CBC revealed: WBC 170 k/uL (80% blasts), Hb 13.1 gr/dL, Ht 37.7% and PLT of 26 k/uL. Bone marrow confirmed the diagnosis of ALL (L2 morphology). Bone marrow flow cytometry depicted a T II ALL by EGIL classification (Tdt 54%, cCD3 99%, CD7 96%, CD2 96%, CD4 0%, CD8 2%, CD5 75%, TCRαβ 0%, CD1α 0%, sCD3 31%). Karyotype with G-banding, technically failed. By PCR, blasts were negative for TEL-AML1, E2A-PBXand MLL-AF4 while RNA coding for proteins p190 and p210 was also negative. Additionally, the 9 chromosome was evaluated by FISH technique (centromere and 9p21 areas/genes p16/p14 and...

Shape changes of abnormally deformed red cells in aperture impedance haematology analysers are known to affect MCV, MCHC and haematocrit estimation. However, different counters vary in the manifestation of this effect. We performed a comparative study among five analysers. Three of them are based on impedance without hydrodynamic focusing (Coulter STKR, Cell-Dyn3000 Abbott and K-1000 Sysmex). The other two use hydrodynamic focusing, either with impedance (NE-8000 Sysmex) or two angle laser scatter (H*1 Bayer). A novel method of analysis was applied. Two hundred and three specimens with abnormal red cells and 50 normal specimens (according to ICSH criteria) were assayed. In all samples the PCV was estimated by the reference method without correction for trapped plasma. A true MCHC value was estimated from the mean haemoglobin value and the PCV. The shape effect was assessed by three linear regressions: 1) haematocrit deviations from PCV (corrected for any calibration bias) versus true MCHC; 2) analyser MCHC vs. true MCHC; 3) MCV vs. MCH. The regressions for the analysers with hydrodynamic focusing indicated no significant shape effect. Aperture impedance analysers without focusing varied in their behaviour. The Coulter STKR and the Cell-Dyn3000 both showed strong correlation of haematocrit deviations with true MCHC, poor MCHC correlations and linear MCV-MCH regressions. The K-1000 showed minor indications of such an effect. We conclude that comparative studies are needed to quantitate red cell shape effect errors among various impedance analysers.

MLL rearrangements in childhood ALL and specifically that of the t(4;11)(q21;q23) translocation, have been associated with unfavorable prognosis; however, MLL rearrangements in children represent an extremely heterogeneous group, whose prognostic diversity needs further refinement. Aim of this study is to present the epidemiological, clinical, immunophenotypic and genetic features as well as the outcome of our cohort patients with ALL and MLLrearrangements. 167 ALL pts with a median age of 5.1 yrs (range 0.5-17.5), have been retrospectively recorded and analysed. Pts were consecutively diagnosed and treated on BFM based protocols in a single Center during the years 2000-2013. Evaluation upon diagnosis included conventional cytogenetics, i-FISH and RT-PCR for the detection of MLLrearrangements in 11q23 chromosomal region and FCM for the detection of MRD. Αdditionally, this study was designed to assess the predictive value of an MTT (3-[4,5-dimethylthiazol-2,5-diphenyl] tetrazolium bromide) in vitro assay for the evaluation of leukemic cell resistance/sensitivity to cytotoxic drugs and to compare these results with clinical and laboratory parameters in cases of MLL-positive childhood ALL. Thus, the chemoresistance of leukemic cells was ascertained by means of an MTT assay in all 11 pts positive for MLL rearrangements and in vitro drug resistance to prednisolone (PDN), asparaginase (ASP), vincristine (VCR), daunorubicin (DNR), etoposide (VP-16) and cytosine arabinoside (ARA-C) was evaluated. Eleven (6/11 boys) out of the 167 pts (6.6%) were positive for 11q23 rearrangements, with a median age of 2.3 yrs (0.49-14.72). 2/11 (18.2%) presented with mediastinal, 4/11(36.4%) with CNS and 1/11(9.1%) with testicular infiltration. The median WBC was 109210/μl (4300-700000/μl), while 8/11 pts presented with WBC> 50000/μl. Immunophenotype revealed 5/11 pts with pre pre B-ALL (including 2 infant-ALL), 2/11 pre B-ALL, 2/11 B-common-ALL and 2/11 pts with T-III cortical ALL while 1/11 patient presented with mature type ALL of B-cell origin. The median DNA index was 1.0 (0.96-1.26). Cytogenetics revealed complex karyotype and t(2;9)(p13;p13-q21) in 1/11 patient, t(4;11)(q21;q23) in 2/11, atypic t(11;19)(q23;p13.3) in 2/11 and t(10;11)(p12;q23) in 1/11 patient, while no cytogenetic abnormalities were detected in 4/11 children (failure in 1/11). I-FISH analysis demostrated MLL rearrangement in all pts, with additional concomitant aberrations del9p21(1/11), 3x9q34, 3x11q23 and del 3΄MLL (1/11), 5-10x21q22(+AML1) and del5'MLL (1/11). 8/11 pts were treated according to ALL BFM protocols (BFM 95/2000/ALLIC-2009), 2/11 according to Interfant protocols (Pilot 98/06) and 1/11 according to the NHL-BFM 2004 (R4 therapy group). 10/11 pts were stratified and treated according to the High Risk Arm. The results of the MTT assay revealed that all patients bearing MLL rearrangements were resistant to asparaginase, while 6/11 pts were also resistant to PDN. Infant ALLs and t(4;11)(q21;q23) cases that were associated with the most unfavourable prognosis, were all bearing extremely chemoresistant leukemic cells to all the cytotoxic drugs administered and evaluated by the MTT assay. Among the pts treated with ALL protocols, 4/10 were poor prednisone responders on day 8 of remission-induction therapy,…

AimsThe causes and diagnosis of ‘double-negative’ (CD3+CD4−CD8−) T-cell lymphocytosis are not well studied. We aimed to define the causes of double-negative T-cell lymphocytosis in children and adults, and to identify simple clinical and laboratory features that would help to differentiate between the underlying conditions.MethodsWe collected clinical and laboratory data on 10 children and 30 adults with significantly increased peripheral-blood double-negative T-cells (>10% of total lymphocytes). We identified conditions associated with double-negative T-lymphocytosis with flow cytometry, peripheral-blood morphology and T-cell receptor-gene rearrangement studies. Patients were assigned to diagnostic categories on the basis of these test results.Results and conclusionsThe causes of double-negative T-cell lymphocytosis in children were autoimmune lymphoproliferative syndrome (ALPS) and reactive γ/δ Τ-lymphocytosis. T-cell large granular lymphocyte (T-LGL) leukaemia, reactive γ/δ T-...

The theory of universal emotions suggests that certain emotions such as fear, anger, disgust, sadness, surprise and happiness can be encountered cross-culturally. These emotions are expressed using specific facial movements that enable human communication. More recently, theoretical and empirical models have been used to propose that universal emotions could be expressed via discretely different facial movements in different cultures due to the non-convergent social evolution that takes place in different geographical areas. This has prompted the consideration that own-culture emotional faces have distinct evolutionary important sociobiological value and can be processed automatically, and without conscious awareness. In this paper, we tested this hypothesis using backward masking. We showed, in two different experiments per country of origin, to participants in Britain, Chile, New Zealand and Singapore, backward masked own and other-culture emotional faces. We assessed detection an...

The extensive use of etoposide has been implicated in the development of secondary acute myelogenous leukemia (AML) with unfavorable prognostic characteristics and most often involvement of the 11q23 locus. The case herein being presented exhibits favorable characteristics and poses the question whether it represents a secondary malignancy or a second primary event. A five year old boy was diagnosed with a mass of the posterior fossa representing anaplastic ependymoma of the brain stem (medulla oblongata) without CNS nor distant metastases. After partial resection of the tumor, the patient received 53 Gy to the tumor bed and 30 Gy to the neuroaxis followed by temozolamide p.o. for 4 cycles. Following this treatment, symptoms improved, he was ambulatory and back to school. Two years later he relapsed with unresectable tumor and received etoposide (VP-16) at 100 mg/m2/day for 21 days of 28 cycles, with a palliative intent. The treatment proved efficacious to him and he continued to re...

The authors describe a 7-year-old boy with TEL/AML1-positive pre-B acute lymphoblastic leukemia, with hemizygous 9p21 deletion at presentation and no p16(INK4A) protein expression. Despite an initial response to a standard chemotherapy regimen, the patient suffered two hematologic relapses and died 34 months after diagnosis. The authors discuss the possibility that complete p16(INK4A) gene inactivation may adversely modify the prognostic significance of TEL/AML1 fusion in childhood acute lymphoblastic leukemia, and present evidence from clinical and in vitro observations in favor of this assumption.

Early lymphoid differentiation is characterized by antigen receptor gene rearrangements; the rearrangement process is governed by two lymphoid-specific genes, RAG (recombinase activating gene)-1 and -2. The available data on the incidence and prognostic significance of clonal immunoglobulin heavy chain (IgH) gene rearrangements in acute myeloid leukemia (AML) are rather contradictory. The aim of this study was to evaluate the incidence and prognostic significance of RAG-1 and -2 mRNA transcripts and clonal IgH gene rearrangements in a cohort of uniformly treated AML patients; the available literature is also reviewed. The study was performed on 76 AML patients, newly diagnosed between August 1996 and November 1999. RAG-1/-2 gene expression was analyzed by a reverse transcriptase polymerase chain reaction technique and IgH gene rearrangements were detected with variable region (VH) family-specific and consensus framework region (FWR)-2 and/or-3 primers. Statistical associations were ...

In B‐acute lymphoblastic leukemia (B‐ALL), the identification of cytogenetic prognostic factors is important for stratifying patients into risk groups and tailoring treatment accordingly. The purpose of this study was to propose flow cytometric (FCM) scoring systems (SSs) for predicting t(12;21)(p13;q22), t(9;22)(q34;q11), t(11q23), and t(1;19)(q23;p13.3) translocations.

The rate of success in the treatment of pediatric acute lymphoblastic leukemia (ALL) has been increased steadily during the last decades. The five years’ event free survival rate is nearly 80% for children with ALL. Attempts to boost cure rates further with the use of hematopoietic stem cell transplantation have improved for some but not all, subtypes of ALL. The best hope for continued progress lies in a better understanding of the pathogenesis, the basis of resistance to chemotherapy, and finally better organized clinical trials. The present study has been based on organizing and exploring new clinical correlations among clinical data obtained from molecular genetic profile, in vitro chemosensitivity and genetic polymorphisms of detoxifying enzymes. During the last 3 years 43 newly diagnosed ALL patients, 27 boys and 16 girls, aged 23 months to 14 years old were included in this study. Bone marrow and/or peripheral blood samples were studied for karyotyping aberrations. The presen...

Immunoglobulin kappa (IGK) locus rearrangements were analyzed in 164 κ-light chain (LC) expressing chronic lymphocytic leukemia (CLL) cases and 95 λ-LC expressing CLL cases. In κ-CLL, 151 IGKV-J transcripts were successfully amplified by RT-PCR; 147/151 were in frame; four out-of-frame IGKV-J transcripts were heavily mutated and contained one or more stop codons, presumably introduced by somatic hypermutation; in all four cases the corresponding expressed transcript was also mutated. DNA-PCR identified 24/164 κ-CLL cases (15%) with double IGKV-J rearrangements; 9/24 non-expressed IGKV-J rearrangements were in-frame; 3/9 were mutated. The most frequently used IGKV genes in expressed IGKV-J rearrangements were: 3–20, 1-39/1D-39, 1–5 and 4-1; the IGKV4-1 gene was by far the most frequent in non-expressed IGKV-J rearrangements (9/24 cases, 33%). In λ-CLL, a total of 65 IGKV-J rearrangements were amplified in 59/95 cases (62.0%); six cases had two different rearrangements. IGVK4-1 was the most frequently used gene (14/65 sequences, 21.5%), followed by IGKV1-16 (8 cases,12.3%), 1-33/1D-33 and 2-30 (7 cases each, 10.8%). IGKV-J transcripts were detected by RT-PCR in 10/59 λ-CLL cases with IGKV-J rearrangements, of which four were in-frame and six out-of-frame. Seven IGKV-J rearrangements in λ-CLL had less than 100% homology to germline; 3/7 were in-frame; 6/7 patients had mutated IGHV and 5/7 had mutated IGLV genes. In κ-CLL, biased usage of the IGKJ1/IGKJ2 genes was observed both in expressed (69%) and non-expressed rearrangements (78%); in contrast, in λ-CLL, downstream IGKJ (IGKJ3-5) usage was observed in 32/59 sequences (53%). Nonproductive rearrangements involving the kappa deleting element (KDE) that render the IGK locus inactive were also analyzed. In κ-CLL, 22/147 cases (15%) carried IGKV to KDE rearrangements, while 24/147 cases (16.5%) carried IGKJ-C- INTRON (JKI) to KDE rearrangements. In λ-CLL, IGKV-KDE rearrangements were amplified in 55/94 cases (59%); JKI-KDE rearrangements were amplified in 52/94 cases (56%). IGKV1D-43 was the most frequent gene in IGKV-KDE joints in κ-CLL (4/22 cases); in contrast, the most frequent genes in IGKV-KDE joints in λ-CLL were IGKV3-20 and IGKV2-30 (9/55 and 7/55 cases, respectively). In conclusion, the present study confirms IGK locus rearrangements in the vast majority of λ-LC expressing CLL cases. Differential usage of IGKJ genes along with significant IGKV repertoire differences in both IGKV-J and IGKV-KDE rearrangements between κ- and λ-CLL allude to prolonged IGK locus recombination before CLL clonogenic cells became λ-producers. The inactivation of productive and potentially functional IGKV-J joints by secondary rearrangements indicates a role for receptor editing in shaping the expressed IG repertoire in CLL. Finally, the identification of mutated, non-expressed IGKV-J rearrangements both in κ- and λ-CLL might be considered as evidence for secondary rearrangements occurring after the onset of somatic hypermutation, at least in a proportion of cases.

BACKGROUND: Apart from t(11;14)(q13;q32), MCL is also characterized by other nonrandom cytogenetic findings. These additional aberrations are well studied at diagnosis and believed to represent clonal evolution during lymphomagenesis, but little is known about karyotypic changes during the course of the disease. METHODS: The study included 33 patients with MCL. In all cases, an interphase FISH assay was performed at diagnosis on lymphoma cells from peripheral blood, bone marrow or touch imprints of involved sites. Commercial probes were employed for the detection of t(11;14), +12, 13q−, and abnormalities of ATM, p53, p16, TEL, c-MYC and BCL6 genes. In 14 cases, the same FISH screening was repeated at least once (up to four times) during the course of the disease, at relapse or in the context of partial or no response. RESULTS: The most frequent additional findings at diagnosis were ATM deletion in 15 cases (45.5%) and 13q− in 12 cases (36.4%), followed by p16 deletion (3 cases; 1 ho...

Late-onset neutropenia (LON) is a complication of Rituximab of yet unknown pathophysiology. We investigated potential underlying mechanisms in 12 patients with various non-Hodgkin lymphoma (NHL) subtypes who developed LON without identifiable causes at a median of 95 (range 67–420) days after completion of the intended treatment with Rituximab ± chemotherapy. The study also included two control groups: healthy donors (n=25) for comparative analysis of bone marrow (BM) functional parameters; NHL patients treated with similar Rituximab ± chemotherapy regimens without LON for comparative evaluation of peripheral blood and BM lymphocyte subpopulations (n=38) and BM pathology findings (n=27). Ten of 12 patients with LON and 33/38 NHL controls developed profound B-cell depletion. Inverted CD4/CD8 cell ratios were observed in 10/12 LON cases vs. 13/38 NHL controls (p<0.01). A rise in CD8 cell count >1.0x109/L was identified in 8/12 LON cases vs. 8/38 NHL controls (p<0.01). T-large...

Hyper-CVAD represents an intensified program for the treatment of acute and chronic lymphoid malignancies. This protocol has been proposed as a highly efficient treatment for adult ALL with acceptable toxicity profile. Purpose: In our Institution, Hyper-CVAD was initiated in September 1999 and used as the primary treatment of adult ALL. We analyse and report here our results focusing on the efficacy and the toxicity of the program. Patients and methods: Patient population consisted of 24 de novo ALL (7 T-cell, 17 B-cell). M/F ratio was 11/13, median age 39 yrs,mean age 42,1 yrs (range 18–68 yrs). 7/24(29,1%) patients were older than 50yrs. Hyperleukocytosis of more than 100x109/L was present in 6/24(25%) cases (3 T-cell,3 B-cell), while splenomegaly, hepatomegaly and bulky disease were documented in 19/24, 17/24 and 1/24 cases respectively. Cytogenetic analysis was performed in 23/24 patients: in 11/23 it was normal, in 1/23 showed del(12), in 1/23 revealed just polyploidy and faile...

Treatment-response assessment via quantification of MRD has become a corner-stone for risk stratification in childhood ALL. Although MRD has been shown to retain independent prognostic significance, the relationship with other prognostic variables has been incompletely explored. Moreover, determination of the most reliable treatment time-point for FCM-MRD evaluation that would serve as the best surrogate marker in predicting relapse, is still an issue of debate. To determine the utility of sequential measurements of FCM-MRD, with specific emphasis on day 33 and its correlation with known prognostic factors and outcome, we retrospectively analyzed the results of FCM-MRD study/data of 825 bone marrow samples of 133 children with ALL, at different treatment time-points, during induction and early consolidation (days 15, 33, 78, week 22-24, at start and at the end of maintenance therapy). All patients were homogeneously treated on BFM-based protocols and prognostic groups were defined b...

Dysfunction of cell membrane is a recognized consequence of the pathogenetic process underlying the ß-thalassemia syndromes and it is reasonable to hypothesize that surface structures crucial for the development of erythroid lineage may also be affected. The study included six adult splenectomized patients with ß-thalassemia intermedia. Expression of a4ß1 integrin (CD49d/CD29), a5ß1 integrin (CD49e/CD29) and transferrin receptor (CD71) on peripheral