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G Perla

Publications and source records attributed to G Perla.

18 recordsLinked to original sources
PubMed2001

Treatment of "poor risk" acute myeloid leukemia with fludarabine, cytarabine and G-CSF (flag regimen): a single center study.

We describe a single center experience of 41 consecutive patients with poor prognosis acute myeloid leukemia (AML) who received a single course of FLAG regimen consisting of Fludarabine 30 mg/m2/day plus Cytarabine 2 gr/m2/day (days 1-5) and G-CSF 5 mg/Kg/day (from day 0 to polymorphonuclear recovery) as salvage therapy. Eleven patients were primarily refractory to previous chemotherapy, 10 patients were in first relapse, 2 patients in second relapse and 7 patients in relapse after transplants. Eleven cases were defined as secondary AML (diagnosis of AML made after a preexisting diagnosis of myelodysplastic syndrome). The median age was 52.6 years (range 16-72); 29 patients were males and 12 females. Overall, 23 (56%) patients reached complete remission (CR), 3 patients died of infection (2) or hemorrhage (1) during induction, and 15 (36%) patients had resistant disease. The highest CR rates (80%) were obtained in relapsed cases; de novo and secondary AML registered 60% and 45% of CR rates, respectively. Patients achieving CR received a second FLAG course as consolidation and were submitted to an individualized program post-remission therapy, depending on the age and performance status. Hematological and non hematological toxicities were acceptable. In conclusion, our data confirm that FLAG is a an high effective treatment for poor prognosis AML and in young patients allows intensive post remissional therapy including allogeneic BMT.

Acute Disease↗
PubMed2001

CD38 expression correlates with adverse biological features and predicts poor clinical outcome in B-cell chronic lymphocytic leukemia.

CD38 identifies a surface molecule with multi-functional activity. Its prognostic importance in B-cell chronic lymphocytic leukemia (B-CLL) is currently under investigation in view of the fact that two different groups have recently indicated that CD38 expression could be an independent prognostic marker in B-CLL. We analyzed the clinico-biological features of 61 immunologically typical (CD5+CD23+) B-CLL patients stratified according to the CD38 expression. Twenty-two (36%) patients expressed CD38 in more than 30% of CD19-positive cells and were considered as CD38-positive B-CLL. Atypical morphology (p 0.02), peripheral blood lymphocytosis (p 0.01) and diffuse histopathologic bone marrow pattern (p 0.003) were findings found to be closely associated with CD38 expression. On the other hand, A and B Binet stages (p 0.02) and interstitial bone marrow involvement (p 0.005) were more represented in the CD38-negative B-CLL group. Trisomy 12 was detected more frequently in the CD38-positive B-CLL group, while 13q14 deletions mainly occurred in CD38-negative group (p 0.005). Finally, median survival of CD38-positive B-CLL patients was 90 months, while it was not reached at 180 months in CD38-negative patients. Taken together, our data strongly suggest that the evaluation of CD38 expression may identify two groups patients with B-CLL greatly differing in their clinico-biological features.

ADP-ribosyl Cyclase↗
PubMed2001

Morphologically typical and atypical B-cell chronic lymphocytic leukemias display a different pattern of surface antigenic density.

Recent evidences suggest that B-cell chronic lymphocytic leukemia (B-CLL) may have heterogeneous biological and clinical features. Immunological phenotype may be useful for distinguishing these different forms of disease. We used a quantitative flow cytometric approach to analyze the expression of several membrane molecules (CD19, CD20, CD22, CD23, CD11c, CD5, CD79b) commonly used to diagnose and characterize B-CLL in a choort of 84 consecutive B-CLL patients diagnosed according to morphological and immunological findings. We found that morphologically so-called "atypical" B-CLL displayed a significantly higher number of CD20 and CD22 molecules than typical forms. On the other hand, CD19 was found to be more expressed in typical B-CLL, although without reaching statistical significance. Finally, no difference was detected with respect to CD23, CD79b, CD11c and CD5 number of molecules/per cell between typical and atypical B-CLL. Other clinico-biological features, such as surface membrane immunoglobulin density, percentage of CD79b and FMC7 expression, peripheral blood lymphocytosis, trisomy 12 and advanced clinical stages were also found to be more frequent in atypical B-CLL. In conclusion, our data confirm the hypothesis that atypical B-CLL is a disease sustained by more mature B-cells, closely related but, at the same time, clearly distincted from neoplastic cells of typical B-CLL.

Adult↗
PubMed2001

Adding growth factors or interleukin-3 to erythropoietin has limited effects on anemia of transfusion-dependent patients with myelodysplastic syndromes unresponsive to erythropoietin alone.

BACKGROUND AND OBJECTIVES: Recombinant erythropoietin (r-EPO) induces erythroid responses in patients affected by myelodysplastic syndromes (MDS). However, the response rate declines to 10-15% in MDS with substantial transfusion needs. Both in vitro and in vivo studies have suggested that the addition of growth factors (G-CSF, GM-CSF) or interleukin-3 (IL-3) may potentiate the effect of r-EPO on dysplastic erythropoiesis. The aim of this study was to evaluate the effects of the combination of r-EPO with G-CSF, GM-CSF or IL-3 on the anemia of heavily transfusion-dependent MDS patients, previously unresponsive to r-EPO alone. PATIENTS AND METHODS: Sixty patients with transfusion-dependent MDS, already treated without significant erythroid response with r-EPO alone, were scheduled to receive, for at least 8 weeks, r-EPO subcutaneously at the dose of 300 U/kg t.i.w. in combination with G-CSF (300 microcg s.c. t.i.w., 27 patients), or GM-CSF (300 microcg s.c. t.i.w., 23 patients), or IL-3 (5 microcg/kg s.c. t.i.w., 10 patients), after a two-week pre-phase during which G-CSF, GM-CSF and IL-3 were administered daily at the same dose, as single drugs. RESULTS: Ten patients were not evaluable for erythroid response because of relevant side effects related to GM-CSF or IL-3 administration. Overall, among 50 patients who completed the study, there were 3 erythroid responses (as determined by complete abolition of red-cell transfusions): 1 (4%) in the G-CSF + r-EPO and 2 (10.5%) in the GM-CSF + r-EPO treated groups. No patient responded to the combination of r-EPO + IL-3. All responders had inappropriate serum levels of endogenous EPO and a relatively short disease duration. Both responders to GM-CSF + r-EPO developed acute myeloid leukemia 2-9 months after the start of the combined therapy. A third elderly patient, treated with the same association, developed marrow hypoplasia. A significant increase in leukocyte count occurred in 96% of patients who received r-EPO + G-CSF, 78.9% of those treated with r-EPO + GM-CSF and 66% of subjects receiving r-EPO + IL-3. A significant increase in platelet count was observed in a single patient receiving r-EPO and GM-CSF, while a slight decrease in platelet count with respect to baseline levels occurred in about 20% of patients. INTERPRETATION AND CONCLUSIONS: Our results suggest that the combination of r-EPO with G-CSF, GM-CSF or IL-3, at least at the doses and schedules employed in the present study, has limited efficacy on the anemia of heavily transfusion-dependent MDS patients previously unresponsive to r-EPO alone. However, in this setting of patients, the combination of G-CSF or GM-CSF + r-EPO may occasionally be effective in subjects with low circulating levels of serum EPO and short disease duration.

Adult↗
PubMed2000

Minimally differentiated acute myeloid leukemia (AML M0): clinico-biological findings of 29 cases.

Twenty-nine cases of minimally differentiated acute myeloid leukemia or AML M0 identified among 441 AML diagnosed in the last 12 years are reported. In all cases, flow cytometric analysis using a large panel of monoclonal antibodies and cytogenetic and molecular studies (IgH, TcRbeta, BCR/ABL, AML1/ETO and CBFB-MYH11 rearrangements) were performed. Of the 29 patients, 27 were treated with intensive chemotherapy based on GIMEMA protocols. We noted a greater incidence of older (over 60 years) and male patients (52% and 65%, respectively). CD33, CD13, CD7 and TdT were expressed in 79.3%, 82.7%, 58.6% and 42.8% of cases, respectively. Antigenic MPO was present in 17 of 22 cases (77.3%). Most cases expressed CD34 (93.1%), HLA-DR (93.1%), CD117 (80%) and CD45RA (87%). CD45RO and CD90 were consistently negative. In all cases, we observed an up-expression of bcl-2 and a down-expression of CD95 with an inverse trend between the two markers (r -5253; p 0.03). Karyotypic abnormalities were demonstrated in 53.6% of cases. Of these, 6 involved chromosomes 5, 7 and 8, t(9;22), confirmed by the BCR/ABL transcript, was detected in one case. Rearrangements of the TcRbeta and IgH chains were observed in 3 and 2 cases, respectively. No AML1/ETO and CBFB-MYH11 transcripts were found. Twelve out of 27 patients (44%) achieved a complete remission (CR) (in 2 cases after rescue therapy). Seven early (range 1-9 months) and one late (32 months) relapses were observed. Five patients are alive, but only the 4 who underwent bone marrow transplantation are in persistent first CR. In conclusion, AML M0 is a subtype of AML antigenically well detectable, endowed with many adverse parameters (older age, TdT and CD34 expression, resistance to apoptosis, unfavorable cytogenetic abnormalities) and poor prognosis. A very aggressive consolidation treatment can be useful to improve the outcome.

Acute Disease↗
PubMed1999

Establishment and growth regulation of a novel ovarian cancer cell line from a poorly-differentiated adenocarcinoma: proposal for a new treatment.

A continuously growing cultured cell line has been obtained in vitro, starting from a specimen of ascites fluid obtained from a patient with ovarian cancer, in whom a poorly-differentiated adenocarcinoma was diagnosed. This cell line, named OC-A1, is routinely grown in standard, serum-supplemented culture medium and has been fully stabilized to long-term growth and characterized for both cultural and genetic parameters. OC-A1 cells express a set of characteristics, as determined in vitro which, when compared with the in vivo primary tumor, confirm the high malignity of this cancer. In addition, karyotype analysis showed a translocation of chromosome 8 which is correlated with the amplification of c-myc oncogene. However, the expression of this oncogene was found to be significantly inhibited by a new regulatory activity, recently found to be present in a liposarcoma cell line. Conditioned medium from these cells was indeed able to inhibit the growth of OC-A1 cells, arresting their cell cycle in the G1 phase and inducing them to apoptosis. Finally, the cell programmed death appeared to be related to the expression of antioncogene p53.

Adenocarcinoma↗
PubMed1997

Identification of chromosome changes in acute myeloid leukemia (AML-M2) by molecular cytogenetics.

Karyotyping with fluorescence in situ hybridization (FISH) is reported in two rare cases of AML-M2 FAB. In the first case FISH analysis confirmed the presence of a t(7;11)(p15:p15) translocation in a complex karyotype that also showed an unbalanced translocation involving the other chromosome 7, a rare rearrangement between chromosomes 9 and 20, and four or five copies of a small marker derived from chromosome 9. In the second case whole chromosome painting with probes for chromosomes 8, 14, and 21 revealed the presence of a masked t(8;21) translocation in which one chromosome 14 was involved in a newly discovered rearrangement, i.e., t(8;14;21)(q22-q24;q11;q22). Moreover , double color FISH using ETO-CDR P1 probe and a cosmid for the 5' part of AML-1 on chromosome 21 showed a two color signal on the 8q-, suggesting a recombination between ETO and AML 1. Molecular cytogenetics overcomes limitation of chromosome banding in the interpretation of complex rearrangements.

Adult↗
PubMed1996

Are "early" and "late" T-acute lymphoblastic leukemias different diseases? A single center study of 34 patients.

Clinical and biological parameters were retrospectively reviewed in 34 cases of T-lineage acute lymphoblastic leukemia (T-ALL), classified as "early" (20 cases) or "late" (14 cases) subgroups, according to the degree of blast cell differentiation, assessed by immunophenotyping. In "early" T-ALL, age, co-expression of "immature" (CD34 and HLA-Dr) or myeloid (My+) antigens, proliferative activity (as evaluated by Ki67 monoclonal antibody), and expression of the "multidrug-resistance" (MDR) phenotype (as determined by C-219 monoclonal antibody) were significantly higher, while WBC count and expression of CDl0 were significantly lower, than in "late" T-ALL. Furthermore, although no statistically significant difference was found between the two groups, "late" T-ALL more frequently displayed a greater extramedullary tumor mass ("lymphoma-like" syndrome), LI FAB morphology and a normal karyotype. A single patient, with "late" T-ALL, also showed positivity for TCR gamma/delta chains, specific monoclonal antibodies. On the whole, 30 patients (88.2%) achieved complete remission: 16(80%) were "early" and 14(100%) "late" T-ALL. No statistical difference was found between the two groups with respect to disease free survival (42% vs 54% at six years), whereas median overall survival was significantly shorter in "early" T-ALL (23 months vs median not yet reached at six years for "late" T-ALL, p < 0.05). We conclude that "early" and "late" T-ALL show clinical and biological differences, that could perhaps justify differential therapeutic approaches.

Adolescent↗
PubMed1995

Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia.

The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/microliter) measured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 19.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values < 5 U/microliter). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK > 38 U/microliters, a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK < 38 U/microliter (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK > 38 U/microliters and 9/69 (13%) of those with lower levels at diagnosis (P < 0.0001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.

Acute Disease↗
PubMed1988

Tetraploidy (92,XXYY) in an acute nonlymphocytic leukemia (M1) patient following autologous bone marrow transplantation.

Tetraploidy (4n = 92) without structural chromosome aberrations was found in bone marrow cells of a patient with acute nonlymphocytic leukemia, FAB classification M1, following autologous bone marrow transplantation. This finding, which remained undetected during the remission phases and appeared at relapses, progressed to a hypotetraploid modal number (74 chromosomes) at the terminal phase of the disease. Together with two previous observations in patients with acute lymphoblastic leukemia with L2 morphology and a null cell immunotype, this observation supports the hypothesis that tetraploid karyotypes may represent unusual and aspecific patterns of clonal evolution.

Adult↗
PubMed1986

Ring chromosome 21 in healthy persons: different consequences in females and in males.

A stable ring chromosome 21 was found in an azoospermic man with an otherwise normal phenotype. Meiotic studies in another known azoospermic male with r(21) had indicated that breakdown of spermatogenesis resulted from pairing failure of chromosome 21, followed by degenerative changes in the chromosomes, before the cells had completed the first meiotic division. While primary sterility was a constant feature in the three adult males, eight healthy females with r(21) were fertile. However, they were at risk for Down syndrome and spontaneous abortions.

Adult↗
PubMedDate not supplied

Prenatal diagnosis of recurrence of cystic hygroma with normal chromosomes.

Cyst-like masses in the neck and back region, simulating an encephalocele, were detected by midtrimester ultrasound examinations in two sib fetuses. After termination, the fetuses were found to have large cystic hygromas. The present observation strongly suggests the existence of an autosomal recessive type of cystic hygroma.

Adult↗
PubMedDate not supplied

A complex mosaicism 45,X/46,X,del(Xq)/46,X,idic(Xq) in a patient with secondary amenorrhea.

A complex mosaicism involving the X chromosome was found in a 35-year-old female affected by secondary amenorrhea and short stature. Her karyotype was: 45,X[20]/46,X,del(X)(pter-->q26::qter)[15]/46,X,idic(X)(pter-->q26::q26-->pter)[9]. No cell contained both abnormal X chromosomes. This observation would suggest a possible mechanism underlying the formation of isodicentric chromosomes.

Adolescent↗
PubMedDate not supplied

Modifications of erythropoiesis in myelodysplastic syndromes treated with recombinant erythropoietin as evaluated by soluble transferrin receptor, high fluorescence reticulocytes and hypochromic erythrocytes.

BACKGROUND: The aim of this study was to evaluate changes in erythropoiesis induced in vivo by recombinant erythropoietin (r-EPO) treatment in myelodysplastic syndromes (MDS), by means of some new, non invasive laboratory parameters. PATIENTS AND METHODS: Serum levels of soluble transferrin receptor (STR), a marker of total marrow erythroid activity, and automated detection of high fluorescence reticulocytes (HFR) and hypochromic erythrocytes (HE) (respectively, indexes of effective erythropoiesis and functional iron deficiency) were longitudinally measured in 25 MDS patients treated with r-EPO, and then correlated with conventional clinical and laboratory features. RESULTS: Stimulation of erythropoiesis was documented in 8 patients, whose serum STR levels showed a significant, early (within 16 days) increase during treatment with r-EPO. However, only 3 of these patients demonstrated a concomitant rise in HFR, and these were the only subjects who experienced a significant clinical response. Two of these patients also developed a functional iron deficiency while on treatment, as documented by an increase in HE, despite normal serum iron, transferrin saturation and even very high levels of ferritin. They needed iron supplementation to maintain the response to r-EPO. No variation in STR, HFR or HE occurred in the remaining 17 unresponsive patients during at least two months of treatment. Serum levels of thymidine kinase, as aspecific marker of cellular proliferative activity, paralleled those of STR. No correlation was found between STR, HFR or HE and serum levels of endogenous EPO, hemoglobin or transfusion requirements in MDS patients. CONCLUSIONS: These findings suggest that there is a heterogeneous and complex pattern of erythroid response in MDS patients treated with r-EPO. In addition, our results indicate that STR, HFR and HE may provide useful information for the clinical management of these patients.

Adolescent↗