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F Lauria

Publications and source records attributed to F Lauria.

At least 55 records · Page 3Linked to original sources
PubMed1995

The presence of lymphoid-associated antigens in adult acute myeloid leukemia is devoid of prognostic relevance.

The immunophenotype of 110 adult patients with diagnosis of acute myeloblastic leukemia (AML) was analyzed using a wide panel of monoclonal antibodies (mAbs). Leukemic blasts were tested by applying direct immunofluorescence analysis and dual-fluorescence staining, and two groups of patients were identified: 56/110 (51%) expressing only myeloid antigens (My/AML) and 54/110 (49%) expressing both myeloid and lymphoid antigens (Ly/AML). CD13 and CD33 were expressed in almost all FAB subtypes, whereas CD14, frequently expressed in M4 and M5 subtypes (70%), was rarely expressed in M0 + M1 cases (9%). On the contrary, CD34, expressed in 77% of M0 + M1 cases, was practically absent in M3 and M5 subtypes (6% and 7%, respectively). CD2 and CD7 antigens were found in 34% and 42% of patients respectively, whereas B cell-associated antigens, such as CD10 and CD19, were found in 31% and 18% of patients. Cytogenetic abnormalities characteristically present in AML patients were also analyzed and, except for t(8;21) which was found in both groups of patients, the other abnormalities were frequently found in cases coexpressing lymphoid-associated antigens. Finally, the complete remission (CR) rate, survival and event-free survival were analyzed according to the presence of lymphoid markers and also of some specific antigens such as CD7 and CD34. The only prognostic difference was represented by CD34+ patients who showed a reduction in the CR rate compared with CD34- patients (65% versus 82%) (p = 0.05) which became more evident when the mean intensity of fluorescence was considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Low doses of rIL2 after autologous bone marrow transplantation induce a "prolonged" immunostimulation of NK compartment in high-grade non-Hodgkin's lymphomas.

Ten patients with high-grade non-Hodgkin's lymphoma (HG-NHL) entered a subcutaneous (s.c.) recombinant interleukin 2 (rIL2) trial within 2 months of undergoing autologous bone marrow transplantation (ABMT). Immunological studies, consisting in T- and natural killer (NK)-cell subset assessment, together with functional assays, such as NK activity and CD16-mediated redirected killing assay, were performed before therapy, after 2 weeks, and then monthly. Phenotypic analysis showed a significant increase (p = 0.01) of CD16 and CD56 NK cells, from 12% to 28% and from 17% to 37%, respectively. In particular, the CD56bright NK cell population showed a tenfold increase, while CD56dim NK cells remained unmodified compared with pretreatment values. The expression of IL2 receptors was also studied and a significant increase (p = 0.01) of CD122 (p75)-positive cells from 8% to 30% was found, while no significant increase was observed in CD25 (p55)-positive cells. Furthermore, rIL2 administration led to an increase of NK activity even at the lowest effectors:target ratio and to an increase of CD16-mediated redirected killing assay. These phenotypic and functional modifications lasted throughout the duration of rIL2 therapy and remained after completion of therapy. In addition, none of the ten patients relapsed, and two of them who started IL2 treatment while still showing residual disease experienced a complete disappearance of the disease after 10 and 7 months of therapy, respectively. Our data suggest that infusion of rIL2 s.c. after ABMT is safe, can selectively increase NK cell number and function, and may have a beneficial effect on the minimal residual disease.

Adult↗
PubMed1995

Cytofluorimetric and functional analysis of c-kit receptor in acute leukemia.

The SR-1 monoclonal antibody (MoAb) recognizes an epitope of the c-kit receptor (KR), present on normal hemopoietic CD34+ stem cells as well as on blasts from patients with acute leukemia. Cytometric analysis by indirect immunofluorescence with the SR-1 MoAb was performed in 98 patients with acute myeloblastic leukemia (AML) and in 37 patients with acute lymphoblastic leukemia (ALL) in order to detect the presence of the KR and to examine its prognostic significance. Sixty-nine of 98 (70%) AML patients were SR-1 positive independently of the FAB subtype, although a higher incidence of SR-1 positive cases was observed in M4 and M5 AML and in those cases that also coexpressed lymphoid antigens. Fourteen AML samples were studied by Northern blot analysis and the KR mRNA was detected in the majority of SR-1 positive cases and also in 2 of 3 SR-1 negative samples. Furthermore, "in vitro" cultures from 15 cases showed that recombinant human Stem cell factor (rhSCF) induced an increased proliferative activity in most tested cases (11/15); this was further enhanced when rhSCF was combined with rhIL-3 + rhGM-CSF (p = 0.007) and with the GM-CSF/IL-3 fusion protein PIXY321 (p = 0.003). Thirty-seven ALL cases were also studied and all but one were SR-1 negative. Interestingly, the only SR-1 positive case also coexpressed myeloid antigens and showed an "in vitro" response when stimulated with rhSCF. Finally, the complete remission (CR) rate, survival and event-free survival were evaluated in 75 AML patients who received standard and identical chemotherapy; unlike previous studies which utilized a different anti-KR MoAb (YB5.B8) and which showed a poor prognosis for KR positive patients, we were unable to document any significant difference in CR rate, survival and event-free survival.

Adolescent↗
PubMed1994

Phenotypic, functional and molecular analysis of CD3- LGL expansions indicates a relationship to two different CD3- normal counterparts.

In this study we have analysed the CD3 and TCR transcript expression in three CD3- large granular lymphocyte (LGL) expansions. These LGL populations show a heterogenous attern of expression for CD2, CD8, CD16, CD56 and CD57 antigens. LGL1 is CD2+CD8-CD16+CD56+CD57+, while LGL2 is CD2-CD8+CD16-CD56-CD57-; LGL3 is similar to LGL1, except for CD8 antigen expression. Functional analysis has revealed a different behaviour of these LGL expansions in a cytotoxicity assay against the NK-sensitive K562 cell line. LGL1 and 3 display a significant NK-like activity, while LGL2 is inefficient against K562 target cells. TCR and CD3 transcript characterization of LGL expansions 1 and 3 showed that they expressed multiple TCR delta transcripts, a non-functional TCR beta transcript, CD3-zeta and -epsilon mRNA, but they lacked CD3 delta transcript and they lacked or expressed at very low levels of CD3 gamma transcript. On the other hand, LGL2 expressed TCR delta, CD3-gamma, -epsilon and -zeta transcripts, while it lacked CD3 delta mRNA. On the basis of these data, LGL1 and 3 seem to be closely related to peripheral blood mature natural killer (NK) cells, whereas LGL2 displays a pattern of TCR and CD3 expression similar to that found in CD1-2-3-4-8-16-thymocytes.

Adult↗
PubMed1994

Increased expression of myeloid antigen markers in adult acute lymphoblastic leukaemia patients: diagnostic and prognostic implications.

By applying direct immunofluorescence with a dual-staining technique we were able to demonstrate that 20/37 (54%) patients with acute lymphoblastic leukemia (ALL) expressed both lymphoid and myeloid antigens on the same leukaemic cells. CD13 and CD33 myeloid antigens were detected in 18/20 and in 15/20 cases respectively, and both in 13. Molecular studies confirmed that the four patients with T-cell phenotype had molecular rearrangement of T-cell receptor (TcR) beta chain, and 26 ALL patients with 'B-cell' phenotype showed JH rearrangement. Two ALL patients without (ALL/My-) and three with myeloid antigens (ALL/My+) also demonstrated bcr/abl rearrangement. Both groups of patients had similar presenting features such as age, sex, Hb level, white blood cells, platelet counts and cytogenetic features. Complete response was achieved in 16/17 (94%) ALL/My- patients and in 15/18 (83%) ALL/My+ patients (two deaths occurred during induction) with a mean duration of 17 and 16 months respectively and with similar survival and event-free survival curves. Myeloid antigen expression in adult ALL patients may occur more frequently than previously reported. The presence of myeloid antigen does not identify, in our series, a higher-risk subgroup of patients, although lack of any statistical evidence of prognostic significance needs to be confirmed in a larger case study.

Adolescent↗
PubMed1994

Rapid restoration of natural killer activity following treatment with 2-chlorodeoxyadenosine in 22 patients with hairy-cell leukemia.

We report on the T-cell profile and natural killer (NK) function in 22 hairy cell leukemia patients before and 2 and 6 months after a single 7-day course of 2-CdA therapy at a dose of 0.1 mg/kg daily continuous infusion. Before treatment, two groups of patients were identified in respect to NK activity: the first (12/22) had a normal number of T and NK cells and a normal NK activity, the second (10/22) showed a severe reduction of CD3+, CD4+, CD16+, and CD56+ cells, together with impaired NK activity. All patients had increased serum levels of the soluble interleukin 2 receptor (sIL-2R). Along with a high complete remission rate (77%), treatment with 2-CdA produced a significant reduction (p = 0.001) of total lymphocytes (from 1.59 x 10(9)/l to 0.72 x 10(9)/l), and particularly of CD4+ cells (from 0.68 x 10(9)/l to 0.23 x 10(9)/l), while CD8+, CD16+ and CD56+ cells were less affected. Despite the dramatic reduction of lymphocytes which lasted for more than 6 months, 7/10 patients with impaired NK function before starting 2-CdA therapy normalized the cytotoxic function within 2 months. In conclusion, 2-CdA produces a severe reduction of lymphocytes in general, and of CD4 lymphocytes in particular, whilst it may produce a significant increase in the proportion of NK cells leading, together with a normalization of the sIL-2R serum levels, to a rapid restoration of the NK cytotoxic function in the majority of patients.

Adult↗
PubMed1994

[Infectious endocarditis following artificial insemination. A clinical case report and review of the literature].

We describe a case of infective endocarditis in a 33 year old patient, with mitral valve prolapse (MVP), who underwent nine attempts of artificial insemination with semen by donor. Several blood cultures demonstrated the presence of Enterococcus faecalis; the same agent was identified in some vaginal cultures. Despite antibiotic therapy, infective endocarditis was complicated by severe mitral regurgitation, followed by the rupture of a chorda tendinea. The patient underwent cardiac surgery: valvuloplasty of posterior mitral cusp, chordae tendineae in Goretex and anulus reinforcement with autologous pericardium. MVP is the most common heart disease associated with infective endocarditis in non-drug addict patients (32-54%). The review of the literature did not show any other case of infective endocarditis after artificial insemination procedures. Because of the large spread of these procedures, we think antibiotic prophylaxis of infective endocarditis should be considered in patients with MVP.

Adult↗
PubMed1994

Molecular evaluation of clonal remission in hairy cell leukemia patients treated with 2-chlorodeoxyadenosine.

Several reports have documented complete and long-lasting remissions in hairy cell leukemia (HCL) patients after a single one-week course of 0.1 mg/kg/d of 2-Chlorodeoxyadenosine (2-CdA) administered by intravenous infusion. In these studies the evaluation of the clinical response was based on physical examination, blood cell counts, as well as cytochemical and immunological detection of residual leukemic cells. Since HCL is a chronic lymphoproliferative disorder characterized by the expansion of monoclonal B cells, analysis of the configuration of the immunoglobulin gene regions represents a valuable tool towards a more accurate monitoring of treatment response. We hereby describe the molecular assessment of the neoplastic clone in six HCL patients treated with 2-CdA; in five of them a disappearance of the rearranged bands could be documented in bone marrow cells aspirated between 2 and 21 months after a single course of continuous infusion 2-CdA. The last HCL case analyzed, revealed molecular persistence of the neoplastic clone. In all cases but one, the molecular evaluation was in agreement with the definition of clinical response based on conventional analysis. This study demonstrates that HCL patients treated with 2-CdA show a high incidence of molecularly-defined complete remissions, the likelihood of which is much greater than for patients treated with Interferon alpha.

Bone Marrow↗
PubMed1994

Retreatment with 2-CdA of progressed HCL patients.

Thirty seven hairy cell leukemia (HCL) patients, 35 males and 2 females with a median age of 53 years, were treated with a single course of 2-Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days by continuous infusion. Twenty nine (78%) achieved a complete remission (CR) and 8 (22%) a partial remission (PR); four of the latter progressed after 6, 12, 18 and 24 months. All have been retreated with 2-CdA and 2 achieved a CR, 1 a PR and the last one is not yet evaluable. The overall median duration of response was 18 months, ranging from 4 to 30 months from the end of therapy. Circulating hairy cells and spleen enlargement, when present, disappeared within 2 weeks after completing treatment. A significant neutropenia was observed in almost all patients mainly in those who had less than 1,000/microliters neutrophils when treatment was started, together with a significant lymphocytopenia which lasted for more than 12 months. The hemoglobin and platelet levels were marginally affected. Fever was observed in 14 patients; in 8 of them it was short-lived (< or = 48 hours) and apparently not infection-related, while in the remaining 6 it was attributed to infection. Clinical tolerance was very good and none of the patients complained of nausea, vomiting or hair loss. In conclusion, our study confirms the efficacy of 2-CdA in HCL, including patients who progressed after treatment with 2-CdA.

Adult↗
PubMed1994

Expression of the IL2 receptor alpha, beta and gamma chains in hairy cell leukemia.

The expression of the interleukin 2 (IL2) receptor chains was investigated by immunofluorescence and mRNA analysis in typical and variant hairy cell leukemia (HCL) cases. While typical hairy cells express both the alpha and the beta chains, variant HCL express the IL2 receptor beta chain on the surface membrane but not the alpha chain. Both typical and variant HCL have mRNA transcript of the p64 molecule (gamma chain). In B-cell chronic lymphocytic leukemia (B-CLL), EBV-transformed lymphoblastoid cell lines and normal B lymphocytes the expression of the IL2 receptor alpha and beta chains is very weak or negative. Furthermore, in B-CLL the IL2 receptor gamma chain shows a weaker expression compared to HCL. Both classic and variant HCL cases appear capable of proliferating in the presence of exogenous IL2, though the proliferative response of variant HCL appears lower than that of typical cases. Since in variant HCL the IL2 receptor alpha chain could not be induced by different stimuli, it appears that the CD25 antigen may not be essential in the process of IL2-promoted growth, while p75 and p64 play a primary role in IL2 activation. Taken together, it is suggested that the expression of IL2 receptors is up- or down-regulated during the process of B-cell lineage activation and differentiation.

Leukemia, Hairy Cell↗
PubMed1994

In vitro susceptibility of acute leukemia cells to the cytotoxic activity of allogeneic and autologous lymphokine activated killer (LAK) effectors: correlation with the rate and duration of complete remission and with survival.

Acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) blasts were studied for their sensitivity to the lytic activity of normal allogeneic interleukin 2 (IL-2) activated killer (LAK) cells, and of autologous LAK effectors generated at the time of complete remission (CR). In 12 of 23 ALL cases (52%), the blasts were susceptible to normal LAK cells (> 15% lysis) and ten of them achieved a CR. Of the remaining 11 LAK-resistant cases, seven obtained a CR. No correlation was found between susceptibility to LAK activity, cytomorphology, immunophenotype, CR duration and survival. Eighteen of the 26 AMLs tested (70%) were susceptible to normal LAK cells, and nine of the 13 cases studied (70%) were also lysed by autologous LAK effectors generated at CR. No clearcut correlation was observed between blast sensitivity to normal LAK cells and morphologic cytotype, though a higher incidence of resistant cases was observed in the M4 subgroup. All AMLs susceptible to normal LAK cells but one achieved a CR, while this occurred only in three of the eight resistant cases (p = 0.004). The median survival and event-free survival duration in the resistant patients were significantly shorter (p = 0.03 and p = 0.02, respectively) compared to those of the susceptible patients. In ten ALL and in six AML, which at presentation displayed less than 10% circulating blasts, the susceptibility of the leukemic population to normal and autologous LAK effectors could be tested, both at diagnosis and at remission. All cases but one were resistant to autologous LAK cells generated at diagnosis, while at CR, seven cases (four ALL and three AML) became susceptible to autologous LAK cells (p = 0.01). The remaining nine were resistant to both allogeneic and autologous LAK effectors. Taken together, these findings suggest that in AML, but not in ALL, the LAK cell compartment may play a role in the clinical course and overall outcome of the disease.

Adolescent↗
PubMed1993

Phenotypic analysis of hairy cell leukemia: "variant" cases express the interleukin-2 receptor beta chain, but not the alpha chain (CD25).

Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder in which the pathologic cells show a strong expression of CD25 (interleukin-2 [IL-2] receptor alpha chain or p55). "Variant" cases of HCL, characterized by hyperleukocytosis, neoplastic elements with a prominent nucleolus and a higher nucleo/cytoplasmic ratio, and an easily obtained bone marrow aspirate, lack surface CD25 determinants. Limited information is available on the expression of the IL-2 receptor beta chain (p75) on normal and neoplastic B cells. In this study, we have assessed by immunofluorescence and mRNA analysis the presence of the IL-2 receptor alpha and beta chains on 12 cases of classic HCL, as well as on 3 variant cases. The results obtained show that, while the alpha chain of the IL-2 receptor is present only on classic HCL, the IL-2 receptor beta chain (p75) is expressed on both the classic and variant form. Unlike hairy cells, only 8 of the 15 B-cell chronic lymphocytic leukemia cases tested showed a weak expression of the p75 antigen on a small proportion of cells. Purified B lymphocytes from normal healthy controls, as well as Epstein-Barr virus-transformed lymphoblastoid cell lines, showed a weak staining for the p75 determinant, while being CD25-. The results of this study suggest that the expression of the alpha and beta chains of the IL-2 receptor appears to be upregulated or downregulated during the process of B-cell-lineage activation and differentiation.

Adult↗
PubMed1993

Pentostatin in prolymphocytic leukemia: phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group.

BACKGROUND: B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias are aggressive variants of chronic lymphoid leukemias. The small studies conducted to date have shown median survival durations of approximately 3 years for patients who have B-cell prolymphocytic leukemia and 7.5 months for those who have T-cell prolymphocytic leukemia, compared with about 8 years for patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, chemotherapy consisting of alkylating agents such as cyclophosphamide and chlorambucil combined with prednisone has achieved overall response rates of 50% to 70%, but this regimen has resulted in response rates of less than 25% in prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies. PURPOSE: This prospective phase II trial by the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer was performed to assess the activity and toxicity of DCF in prolymphocytic leukemia. METHODS: Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then every other week for three doses. Patients who had at least partial response received maintenance therapy once a month for a maximum of 6 months. Fourteen patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic leukemia, as evidenced by morphologic and immunologic criteria; three were previously untreated, eight had been given one or two chemotherapeutic regimens, and nine had been given more than two. RESULTS: One patient died of an unknown cause during the first 6 weeks of treatment, and one died of disseminated toxoplasmosis during the period of maintenance therapy, 5 months after achieving partial remission. Nine (45% response rate) of the 20 patients achieved partial remission, including seven (50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell prolymphocytic leukemia. The median duration of response was 9 months (range, 2-30 months); for patients with B-cell prolymphocytic leukemia, the median remission duration was 12 months. No complete remission was observed. Toxic effects included nausea and vomiting (30%), infections (30%), and transient increase in liver enzymes (35%) and in creatinine (20%) levels. Eight patients experienced thrombocytopenia, the major hematologic toxic effect; four had grade 3 or 4 toxic effects. CONCLUSION: DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens. IMPLICATIONS: Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia.

Adult↗
PubMed1993

Expression of adhesion molecules on acute leukemic blast cells and sensitivity to normal LAK activity.

Antigenic expression of CD54 and CD58 adhesion molecules was investigated on leukemic blast samples from ten patients with acute lymphoblastic (ALL) and 14 with acute myeloblastic (AML) leukemia. The mean intensity of fluorescence (MIF) was calculated and correlated with sensitivity of blast cells to the lytic activity of allogeneic lymphokine-activated killer (LAK) cells. CD54 antigen was expressed in all AML cases with an MIF of 11.2 while in ALL, though present in the majority of cases, it was absent in one case and expressed in less than 30% of blasts in two others, with an overall MIF of 3.0. CD58 expression was similar in both groups of patients, with an MIF of 7.6 in ALL and 7.0 in AML. In addition, in six of the ten ALL cases and in two of the 14 AML cases, leukemic blasts proved to be "resistant" to the cytotoxic activity of normal allogeneic LAK effectors. In these "LAK-resistant" patients, the CD54 antigenic expression was lower (p = 0.03) than in "LAK-sensitive" patients with an MIF of 1.7 vs 4.9 in ALL and 1.35 vs 12.9 in AML cases. Finally, blocking of CD54 and/or CD58 receptors on leukemic blasts resulted in a slight reduction of 51Cr release. Findings suggest that CD54 is differently expressed on myeloid and lymphoid blasts and that there is a correlation between CD54 MIF and susceptibility of blasts to the LAK activity.

Antigens, CD↗