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M Bocchia

Publications and source records attributed to M Bocchia.

At least 19 recordsLinked to original sources
PubMed2000

Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses.

Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor-specific antigen that is also the oncogenic protein required for neoplasia. CML is characterized by the t(9;22) that results in the bcr-abl fusion oncogene and in the expression of a chimeric protein product p210. Previously we have shown that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and class II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine. We evaluated the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each received either 50 microg, 150 microg, 500 microg, or 1500 microg total peptide mixed with 100 microg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation ((3)H-thymidine incorporation) and cytotoxicity (chromium-51 release) responses were measured. All 68 vaccinations were well tolerated without significant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3) and/or DTH responses (n = 2) were generated that lasted up to 5 months after vaccination. Cytotoxic T lymphocytes have not been identified. In conclusion, a tumor-specific, bcr-abl derived peptide vaccine can be safely administered to patients with chronic-phase CML and can elicit a bcr-abl peptide-specific immune response despite the presence of active disease in these patients and approximately 10(12) leukemia cells. (Blood. 2000;95:1781-1787)

Adjuvants, Immunologic↗
PubMed2000

Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients.

Fludarabine (FLUDA) based chemotherapy has shown promise in both initial and salvage treatment of low-grade non Hodgkin's lymphomas (LG-NHL). Recently, more aggressive therapies followed by autologous hemopoietic progenitor cell rescue, have also been successfully employed in these patients. However, this procedure, due to several factors including previous therapeutic regimens, is often limited by an inadequate collection of peripheral blood stem cell (PBSC). At present, very little data is available on the effect of FLUDA containing regimens in PBSC collection. We report our preliminary experience showing a possible correlation between FLUDA based chemotherapy regimens employed before mobilization and inability to collect an adequate number of blood derived hematopoietic progenitors for autologous PBSC transplantation in LG-NHL patients.

Adult↗
PubMed1999

Elderly aggressive-histology non-Hodgkin's lymphoma: first-line VNCOP-B regimen experience on 350 patients.

Age is a risk factor and a prognostic parameter in elderly aggressive-histology non-Hodgkin's lymphoma (NHL) patients. Several adapted chemotherapeutic regimens have recently been designed and tested on elderly patients. Several of these trials have shown that older aggressive-histology NHL patients can benefit from specific and adequate treatment capable of curing a percentage of these patients. Between January 1992 and September 1997, 350 previously untreated aggressive-histology NHL patients greater than 60 years of age were treated with a combination therapy including cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (VNCOP-B). Complete remission (CR) was achieved by 202 (58%) patients and partial remission (PR) by 87 (25%), whereas the remaining 61 (17%) patients were nonresponders. The overall response rate (CR + PR) was 83%. Clinical and hematologic toxicities were modest, because 71% of the patients received granulocyte colony-stimulating factor (G-CSF). The CR rates for the three age groups (60 to 69, 70 to 79, and >/=80 years) were similar: 61%, 59%, and 56%, respectively. At 5 years, the relapse-free survival rate was 65%, the overall survival rate was 49%, and the failure-free survival rate was 33%. In the multivariate analysis, prognostic factors associated with longer survival or longer relapse-free survival turned out to be localized disease stage (P =.001) and good performance status (P =.0002). Application of the International Prognostic Factor Index was significantly associated with outcome (P =.001). These data confirm on a large cohort of patients that the VNCOP-B regimen is effective in inducing good CR and relapse-free survival rates with only moderate toxic effects in elderly aggressive-histology NHL.

Aged↗
PubMed1999

Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications.

BACKGROUND AND OBJECTIVE: It has been widely demonstrated that one single 7-day course continuous infusion (c.i.) 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily is dramatically effective in inducing high and prolonged complete remission (CR) rates in patients with hairy-cell leukemia (HCL). However, 2-CdA administration often results in severe neutropenia and lymphocytopenia both responsible for the infectious complications observed in these patients. We previously reported preliminary data regarding the effectiveness and toxicity of a modified protocol of 2-CdA administration (0.15 mg/kg 2 hours infusion once a week for 6 courses) in 25 HCL patients. This treatment schedule produced a similar overall response rate compared to standard 2-CdA regimen and appeared to be followed by a lower incidence of infectious episodes. In the present study we report response rate and toxicity of weekly 2CdA administration in a larger cohort of patients and with a longer follow-up. DESIGN AND METHODS: In a group of HCL patients with a pronounced decrease in neutrophils count (< 1 x 10(9)/L), we modified the standard protocol (0.1 mg/kg daily x 7 days c.i.) by administering 2-CdA at a dose of 0.15 mg/kg 2 hours infusion once a week for 6 courses. Thirty HCL patients, 24 males and 6 females with a median age of 56 years (range 37-76), entered into this protocol. Seventeen out of 30 patients were at diagnosis while the remaining 13 had been previously treated with alpha-interferon (alpha-IFN) (7), or 2-CdA (4) or deoxycoformycin (DCF) (2). RESULTS: Overall, 22/30 (73%) patients achieved CR and 8 (27%) partial remission (PR) with a median duration of response at the time of writing of 35 months, ranging from 6 to 58 months. Five patients (1 CR and 4 PR) have so far progressed. The treatment was very well tolerated. Five out of 30 patients (16%) developed severe neutropenia (neutrophils < 0.5 x 10(9)/L) and only in two of them we did register an infectious complication which required treatment with systemic antibiotics and granulocyte colony-stimulating factor (G-CSF). INTERPRETATION AND CONCLUSIONS: In conclusion, we confirm that weekly administration of 2-CdA at a dose of 0.15 mg/kg for 6 courses appears to be very effective in HCL inducing a high CR rate, similar to that observed with daily c.i. administration. CR durability and relapse/progression rates are also comparable to standard 2-CdA schedule. Moreover this new regimen seems to be safer in pancytopenic patients, markedly reducing life-threatening infectious complications.

Adult↗
PubMed1999

Favorable impact of low-dose fludarabine plus epirubicin and cyclophosphamide regimen (FLEC) as treatment for low-grade non-Hodgkin's lymphomas.

BACKGROUND AND OBJECTIVE: In recent years, conventional dose of fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of low-grade non-Hodgkin's lymphomas (LG-NHL). In particular, FLU and cyclophosphamide (CY) or FLU and mitoxantrone or idarubicin combined regimens have shown considerable therapeutic activity both as first line and salvage therapies, producing overall response rates ranging from 40-50% in previously treated patients and up to 70-90% in untreated ones. However severe neutropenia and infective complications have been reported in a significant number of patients. Based on these premises we evaluated the efficacy and toxicity of a new regimen combining low-doses of FLU with epirubicin (EPI) and CY (FLEC) in a group of advanced treatment-requiring LG-NHL patients. The aim of this study was to evaluate a strategy aimed at lowering therapy-related toxic effects without affecting the reported good response rate. DESIGN AND METHODS: Thirty patients with de novo, relapsed or refractory LG-NHL entered the study. FLEC regimen was as follows: EPI 60 mg/m(2) i.v. on day one, plus FLU 15 mg/m(2)/day i.v. (max 25 mg) and CY 250 mg/m(2)/day i.v. for four days. RESULTS: All 30 patients were evaluable for response, 13 (43%) fulfilled the criteria for CR and 11 (36%) for PR with an overall response rate of 79%. None of the 13 patients who achieved CR had relapsed after a follow-up of 2 to 23 months (median duration 13 months). With regard to age, 13/14 older patients (>/= 70 years) responded to the treatment and 9 of them maintained their response after a median of 13 months (range 2-22); six of the 14 (43%) obtained a CR. Therapy-related toxicity was mild regardless of age, neutropenia (43%) and fever of undetermined origin (26%) being the major side effects. Remarkably, a documented infection was recorded only in 2/30 (6%) patients. INTERPRETATION AND CONCLUSIONS: A low-dose FLU-based FLEC regimen appeared to be effective for advanced treatment-requiring LG-NHL, reproducing a similar overall response rate (79%) reported to have been achieved with other FLU based combination therapies. Toxic side effects were negligible and in particular documented infections were remarkably uncommon even in the group of elderly patients.

Adult↗
PubMed1999

CD30 positive (non-anaplastic) peripheral T-cell lymphoma of the thyroid gland.

Primary non-Hodgkin's lymphoma of the thyroid gland are infrequent tumors. They almost exclusively derive from B cells of mucosa-associated lymphatic tissue and only a very small minority of them is represented by T cell lymphomas. CD30 molecule, other than in Hodgkin's and Redd-Sternberg' cells, is strictly associated with anaplastic large cell lymphoma and ALK lymphomas, the latter being identified by the monoclonal antibody ALK1. We report a case of CD30-positive non-anaplastic (ALK1-negative) peripheral T cell lymphoma of the thyroid gland and speculate on aspects concerning diagnosis and the morphologic and immunohistochemical findings.

Adult↗
PubMed1999

How do patients with aggressive non-Hodgkin's lymphoma treated with third-generation regimens (MACOP-B and F-MACHOP) fare in the long-term?

BACKGROUND AND OBJECTIVE: To examine the long-term clinical course and prognostic factors of patients with advanced aggressive non-Hodgkin's lymphoma (NHL) treated with third-generation regimens as front-line chemotherapy. DESIGN AND METHODS: A total of 348 patients aged <60 years received MACOP-B or F-MACHOP regimen between September 1988 and August 1993 for advanced stage aggressive NHL. RESULTS: Of these, 249 (71.5%) obtained a complete response (CR); 65/249 (26%) subsequently relapsed. The CR rates for MACOP-B and F-MACHOP were 70.5% and 72%, respectively, while the relapse-free survival rates (RFS) at 9 years were 66% and 74%, respectively. The overall survival rate at 9 years was 61% for MACOP-B and 67% for F-MACHOP patients. Of the relapses, 78.5% were early (<24 months) and 21.5% late. Eleven out of 65 (17%) patients are in continuous second CR with a median follow-up of 45 months; most of them have been salvaged with high-dose therapies. The validity of the International Prognostic Index was confirmed in long-term analysis. INTERPRETATION AND CONCLUSIONS: With a 9-year RFS, it is possible to consider cured 50% of the patient with aggressive NHL treated with a third-generation regimen. About a quarter of the CRs relapse and late relapse occurs in roughly 20% of all relapsed patients. In these patients high-dose chemotherapy followed by autologous bone marrow or hematopoietic stem cell transplantation seems to be a very reliable approach in terms of long-term second CR. Finally, the IPI score maintains its pivotal role in terms of stratifying patients according to different risk subsets also in long-term analysis.

Adolescent↗
PubMed1999

Fludarabine-based chemotherapy in untreated mantle cell lymphomas: an encouraging experience in 29 patients.

BACKGROUND AND OBJECTIVE: A prospective study to evaluate the role of fludarabine alone or in combination with idarubicin in untreated patients with mantle cell lymphoma (MCL). DESIGN AND METHODS: Twenty-nine untreated patients with mantle cell lymphoma were stochastically treated with intravenous fludarabine at a dose of 25 mg/m(2)/day for 5 days (11 patients) or with a combination of fludarabine and idarubicin (FLU-ID) (fludarabine 25 mg/m(2) i.v. on days 1 to 3 and idarubicin 12 mg/m(2) i.v. on day 1 (18 patients). For both regimens, cycles were given at three-week intervals for a total of six courses. According to the International Prognostic Index, the most part of high-intermediate and high risk factor patients were in the FLU-ID subset: 7 (39%) patients vs. 2 (18%) in the fludarabine alone subset. RESULTS: Of the 29 patients, 8 (28%) obtained a complete response and 10 (35%) a partial response, with an overall response rate of 63%. The remaining 11 (37%) patients did not respond to the therapy. The overall response rates were 64% (7 patients) in the fludarabine group and 61% (11 patients) in the FLU-ID group. The complete response rate was 27% (3 patients) for fludarabine and 28% (5 patients) for FLU-ID. The toxicity was mild in terms of neutropenia and infections, and no fatalities occurred due to drug-induced side effects. INTERPRETATION AND CONCLUSIONS: These results suggest the efficacy of fludarabine alone or in combination with idarubicin in MCL patients. It will be important to increase this experience and to assess other fludarabine-containing regimens, in particular with cyclophosphamide plus idarubicin and with mitoxantrone and or cyclophosphamide, to test the true role of this approach in MCL.

Adult↗
PubMed1998

Anaplastic large cell lymphoma Hodgkin's-like: a randomized trial of ABVD versus MACOP-B with and without radiation therapy.

During the last few years, morphological, immunohistochemical, and genetic findings have placed anaplastic large cell lymphoma (ALCL) as a distinct clinicopathologic entity, and several reports have focused on the existence of different subtypes of the tumor. Particular attention has been paid to the ALCL-Hodgkin's-like (HL) subtype, which seems to be on the border between Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL). From September 1994 to July 1997, during the course of an Italian multicentric trial, 40 ALCL-HLs were randomized to receive as front-line chemotherapy MACOP-B (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin-a third-generation HG-NHL regimen) or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine-a scheme specific for HD). All patients with bulky disease in the mediastinum at diagnosis underwent local radiotherapy after the chemotherapeutic program. Complete response (CR) was achieved in 17 of the 19 (90%) patients who were treated with MACOP-B, and in 19 of the 21 (91%) patients who were administered ABVD. The probability of relapse-free survival, projected at 32 months, was 94% for the MACOP-B subset and 91% for the ABVD subset. The majority of patients with mediastinal bulky disease obtained CR (evaluated with 67Ga single photon emission computed tomography [SPECT]) after their radiotherapy. The present study suggests that ALCL-HL, in line with its borderline status, responds in an equivalent way to third-generation chemotherapy for HG-NHL and to conventional HD treatment in terms of both CR and relapse-free survival rates. However, as to the latter, a longer follow-up period may be needed before stating the absolute equivalence of the two regimens used.

Adolescent↗
PubMed1998

CD4+/CD45RA+ 'naive' T cells and immunological response to influenza virus vaccine in B-cell chronic lymphocytic leukaemia patients.

B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by a high frequency of infections, including those of viral aetiology. Previous reports have demonstrated a specific immunologic response to influenza virus vaccine in B-CLL patients with normal IgG levels. In this study, we have evaluated different immunophenotypically defined B and T cell subsets in 18 B-CLL patients before immunization with killed-influenza-virus vaccine. A correlation between immunological response to vaccination and both absolute numbers of CD4+/CD45RA+ naive T cells and CD5- B cells was found. These data may suggest a supporting role of the CD4+/CD45RA+ T cell subset in the specific antibody response to vaccination with influenza virus vaccine in B-CLL patients.

Adult↗
PubMed1998

[Hematological changes in hyperthyroidism. A case report].

A case of microcytic anemia, leukopenia (with lymphocytic reduction prevalence) and light thrombocytopenia is reported. The case occurred to a 63-year old diabetic woman suffering from Basedow's disease. The thyropathy was diagnosed first and the patient did not undergo to any previous treatment with antithyroid agents. The bone marrow aspiration only showed slight dyserythropoietic notes, with slight reduction of myeloid-erythroid ratio. The blood cell indexes rapidly normalized as soon as euthyroidism was achieved by radioiodine therapy (I131, 4mCi), and this led to think there was a relationship between thyropathy and blood modifications. The patient was subsequently treated with levothyroxine because of the occurrence of a iatrogenic hypothyroidism. Two years later, during a follow-up, all the hematologic parameters were normal, as well as the serum concentration of thyroid hormones and TSH (during opotherapy). We report the hematologic alterations most frequently observed in hyperthyroidism and underline the peculiarity of this case as it shows the simultaneous alterations of different cellular lines in the same patient.

Anemia↗
PubMed1998

Long-term follow-up of non-Hodgkin's lymphoma patients treated with ProMACE-CytaBOM: an effective regimen for the intermediate grade subtype.

Long-lasting results achieved in 54 patients with aggressive non-Hodgkin lymphoma treated with Pro-MACE-CytaBOM regimen were evaluated. Twenty-four out of 54 (45%) patients achieved a complete remission and 13 of them are still in continuous remission with a median survival of 53.5 months. Interestingly, in 16 patients with intermediate grade histology we obtained an overall response rate of 100%.

Adult↗
PubMed1997

Modulation of p53, WAF1/p21 and BCL-2 expression during retinoic acid-induced differentiation of NB4 promyelocytic cells.

The NB4 cell line, established from a patient with APL, carries the t(15; 17) and undergoes differentiation along the granulocytic pathway when exposed to retinoic acid (RA). The NB4 cell line was used as a model for exploring the expression of genes and proteins implicated in growth regulation, differentiation and apoptosis during treatment with RA. NB4 cells undergo a series of cytological and molecular alterations during RA treatment--Day 1: cell differentiation marked by an increase in CD11b is evident. Day 2: WAF1/p21 mRNA and then protein rise, though they drop 2 days later. Day 3: the percentage of cells in S phase begins to decrease and G1 arrest begins. Day 4: p53 mRNA level and then protein levels fall. Day 5: CD11b/BCL-2 double staining cells are markedly reduced. No signs of apoptosis were observed after up to 8 days of treatment with RA. These results demonstrate that NB4 cells treated with RA rapidly differentiate and arrest at G1 phase concurrent with p53-independent WAF1/p21 induction; in addition, phenotypic differentiation appears to commence before changes in cell cycle progression. An explanation for the decrease in p53 as well as the lack of apoptosis immediately after BCL-2 downregulation will require further study.

Antigens, CD↗
PubMed1997

Long-lasting complete remission in patients with hairy cell leukemia treated with 2-CdA: a 5-year survey.

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received alpha-interferon. Thirty out of 40 patients (75%) achieved complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up duration for patients in CR has been 48 months (range 30-66). Five of the complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after treatment as documented by the increase of hairy cells (Hc) in the bone marrow and two of them, who were retreated with 2-CdA after showing an initial impairment of peripheral blood values, obtained a second CR. The remaining three relapsed patients were never retreated and still show normal peripheral counts after 30, 38 and 40 months. Twelve of the continuous complete responder patients are still in CR after more than 5 years. In contrast, 8 out of 10 partial responders progressed after 8-36 months and all of them were retreated with 2-CdA at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR, three a better PR and one patient died 6 months after the second 2-CdA course because of infectious complications. Two additional patients, both in CR, died after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted of febrile episodes recorded in 16 patients: in seven of them, fever lasted only 24-48 h after the end of treatment and was apparently not infection-related. In the remaining nine patients, showing in addition severe neutropenia (neutrophils less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2-CdA induces a very high proportion of complete and long-lasting remissions in patients with HCL. In a number of cases relapse at bone marrow level may not affect peripheral blood values for prolonged time. However, in those patients with initial pancytopenia a retreatment with 2-CdA is still effective in inducing a durable second CR.

2-Chloroadenosine↗
PubMed1996

Specific human cellular immunity to bcr-abl oncogene-derived peptides.

Chronic myelogenous leukemia (CML) cells are characterized by a t(9;22) translocation, which can encode one of two chimeric P210 bcr-abl fusion proteins, comprising products of either the b2a2 or the b3a2 exon junction. The junctional sequences represent potentially immunogenic tumor-specific antigens. Despite their intracellular location, the fusion proteins might be recognized immunologically by T lymphocytes if peptides, derived from these unique sequences, are capable of presentation by the major histocompatibility complex molecules. We previously found that four peptides, 9 to 11 amino acids long, spanning the b3a2 CML breakpoint bind with high or intermediate affinity to purified HLA class I molecules A3, A11, B8, or both A3 and A11. We tested the ability of these peptides to elicit specific class I restricted cytotoxic T lymphocytes (CTLs) in vitro in HLA-matched healthy donors. In addition, a longer b3a2 CML-breakpoint-derived peptide, 25 aminoacids in length (b3a2-25), was studied for its ability to induce peptide-specific, class II-mediated, T-cell proliferation. In four of four HLA-A3 donors tested, CML-A3/A11-peptide specific CTLs were induced that killed an allogeneic HLA-A3-matched peptide pulsed leukemia cell line. In two of three HLA-A3 donors, the CML-A3/A11 peptide was able to induce killing of autologous and allogeneic HLA-matched peptide-pulsed peripheral blood mononuclear cells (PBMC). CML-A3 peptide induced peptide specific CTLs in one of the four HLA A3 donors tested. No killing was observed in two HLA-B8 and two HLA-A11 donors. PBMC from seven donors were also tested for anti b3a2-25 peptide proliferation in a thymidine incorporation assay. Specific proliferation was detected in three donors, all of the HLA-DR11 haplotype. These data represent the first evidence of a cytolytic human immune response against CML bcr-abl oncogene-derived peptides and provide a rationale for developing peptide-based vaccines for this disease.

Amino Acid Sequence↗
PubMed1996

[Temporal arteritis associated with hyperthyroidism and complicated by angina pectoris. A case report].

A case of temporal arteritis is described in a woman of 67, affected by non insulin dependent diabetes mellitus, associated with polymyalgia rheumatica and complicated by angina pectoris. Angina, which appeared a few days after diagnosis, was coupled with electrocardiographic alterations, which did not seem sensitive to nitrates but went back when steroid at full dose was added. The patient was also affected by Basedow disease, which was present during the whole course of the vasculitis. Furthermore islet-cell antibodies (ICA) were present. HLA typing showed the presence of the B8, DR3 haplotype. The patient died after 22 months from the diagnosis of digestive hemorrhage, probably favoured by extended cortisone therapy, while signs of arteritis were still evident.

Aged↗