PubMed Health⌕ Search

Biomedical subjects

M Baccarani

Publications and source records attributed to M Baccarani.

At least 19 recordsLinked to original sources
PubMed1999

Autologous stem cell transplantation for T and null cell CD30-positive anaplastic large cell lymphoma: analysis of 64 adult and paediatric cases reported to the European Group for Blood and Marrow Transplantation (EBMT).

Anaplastic large cell lymphoma (ALCL) is a heterogeneous family of lymphoid tumours, among which the T and null cell types were recently listed in the REAL classification as a distinct entity. Reports on autologous stem cell transplantation (ASCT) in this group are only occasional. Sixty-four patients with T and null cell ALCL from 25 European centres had been registered with the European Group for Blood and Marrow Transplantation (EBMT) at the onset of this study. The median age was 25 years (range 3.2-53.0). Thirty of the 64 patients (47%) were in complete remission (CR), 18 (28%) in partial remission (PR), and the remaining 16 (25%) had a more advanced or chemotherapy-refractory disease at transplant. Eighty-one percent of the patients were conditioned with chemotherapy alone and 75% received marrow stem cells. All the patients transplanted in first CR (15), except one, maintained the CR over time; six of 15 transplanted in CR subsequent to first, six of 18 transplanted in PR and 14 of 16 transplanted in refractory or relapsed disease progressed. Actuarial overall survival (OS) at 10 years is 70%. Multivariate analysis showed that good status at transplant, younger age, absence of B symptoms and absence of extranodal disease indicated a better prognosis. These data suggest that ASCT should be considered as a possible treatment for chemosensitive patients in CR or PR. However, definitive conclusions cannot be drawn from this study and a prospective randomised trial between ASCT and conventional chemotherapy may be indicated.

Adolescent↗
PubMed1999

P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: biological and clinical implications.

P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance associated protein (MRP) expression and the blast cells' intracellular daunorubicin accumulation (IDA) were evaluated in 96 previously untreated cases of de novo acute non-lymphocytic leukaemia (ANLL). 47/96 patients (49%) were classified as PGP+ 44/ 96 (46%) as LRP+, and 8/96 (8%) as MRP+. The more frequent MDR clusters were PGP-/LRP-/MRP- (32/96 cases, 33%) and the PGP+/LRP+/MRP- (27/96 cases, 28%) followed by PGP+/LRP-/MRP- (15/96 cases, 16%) and PGP-/LRP+/MRP- (14/96 cases, 14%). A favourable karyotype was observed more frequently in PGP- and LRP-cases. A highly significant correlation was found between either PGP or LRP overexpression and leukaemic blast cell IDA. All the patients received standard induction and consolidation treatments containing MDR-related (idarubicin, mitoxantrone, etoposide) and other (arabinosyl cytosine) drugs. Multivariate analysis showed that PGP overexpression was significantly associated with a poor response to treatment, both in terms of primary resistance or shorter survival. Other independent prognostic factors were age and cytogenetics. LRP overexpression did not reach statistical significance, although for LRP+ cases the trend was unfavourable. Due to small numbers, no conclusion could be made regarding MRP overexpression, but 5/8 cases showed unfavourable karyotypic abnormalities, 8/8 had a defective IDA and 6/8 failed to achieve remission. This study showed that both PGP and LRP overexpression are common features in de novo ANLL at onset whereas MRP overexpression is more rare. It suggested that overexpression of one of the MDR related proteins was associated with a defective IDA, and confirmed that, in addition to age and cytogenetics, PGP retains an independent prognostic value. It also suggested that LRP did not affect clinical outcome when patients were treated with idarubicin or mitoxantrone and arabinosyl cytosine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Management of human cytomegalovirus infection and disease after allogeneic bone marrow transplantation.

BACKGROUND AND OBJECTIVE: Human cytomegalovirus (HCMV) infection and disease remain a major cause of morbidity and mortality after bone marrow transplantation. HCMV disease, especially pneumonitis, may be treated with ganciclovir and immunoglobulin but even so the outcome is poor with mortality rates of 30-70%. It is therefore imperative to treat HCMV infection before it develops into disease. The aim of this article is to describe the main strategies used to prevent HCMV infection and to improve the survival after CMV disease in bone marrow transplant recipients. INFORMATION SOURCES: In the present review, we examined personal papers in this field and articles published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Major advances have been made in preventing HCMV infection and disease through two different approaches, both of which reduce HCMV induced morbidity and mortality: In pre-emptive therapy, patients are given ganciclovir when HCMV infection is first identified and this is continued 3-4 months after transplantation; in prophylactic therapy ganciclovir is given to all patients at risk of HCMV disease from engraftment up to 3-4 months post transplantation. Each strategy has advantages and disadvantages and there is no evidence for the superiority of one over the other since the overall survival is the same and the incidence of death from HCMV disease is similar. PERSPECTIVES: The use of more sensitive tests such as HCMV PCR or antigenemia may improve the outcome but probably will not eradicate all HCMV disease. Future possible strategies could include adoptive transfer of CD8+ HCMV-specific cytotoxic T lymphocytes clones derived from the donor marrow or boosting donor or patient immunity using subunit anti-HCMV vaccines such as gB or pp65.

Acyclovir↗
PubMed1999

Splenectomy in hematology. Current practice and new perspectives.

BACKGROUND AND OBJECTIVE: Progress and changes in the management of blood diseases, in surgery and in video technology stimulate a critical reappraisal of splenectomy in hematology. DESIGN AND METHODS: We have collected information on the current practice of splenectomy in hematology in Italy and we have reviewed the results of a new technique of laparoscopic splenectomy (LS). RESULTS: Current splenectomy practice: the current practice in Italy is to offer splenectomy as front-line treatment for hereditary spherocytosis and as second-line for idiopathic thrombocytopenic purpura (ITP) and hemolytic anemia. Splenectomy is also offered in selected cases of leukemia and lymphoma but is going out of practice for hairy cell leukemia and Hodgkin's disease. The number of splenectomies that are performed every year is estimated to be higher than 10x10(6) persons (more than 500 cases per year). Laparoscopic splenectomy (LS): more than 700 cases of LS have been reported so far, for thrombocytopenia (470 cases) as well as for many other hematologic indications. The procedure carries a mortality of 0.8%, and a complication rate of 12%. Time spent in the operating theater ranges from 1.5 to 4 hours, blood transfusion requirement is minimal and the mean post-operative hospital stay is 3 days. INTERPRETATION AND CONCLUSIONS: Although a prospective comparison is not available, the results of LS compare favorably with the results of classic open splenectomy, so that LS is likely to become the technique of choice especially when the spleen is small, as in ITP. LS can also have some advantages in other cases of splenectomy, including splenomegaly for leukemia and lymphoma. These data and suggestions should stimulate and renew a discussion about splenectomy in hematology, with the purpose of establishing evidence-based guidelines.

Hematologic Diseases↗
PubMed1998

A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group.

BACKGROUND: Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa. METHODS: Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample. RESULTS: We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002). CONCLUSIONS: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.

Adult↗
PubMed1998

Impact of hepatitis C virus infection on clinical features, quality of life and survival of patients with lymphoplasmacytoid lymphoma/immunocytoma.

BACKGROUND: The non-Hodgkin's lymphoma (NHL) subgroup most frequently associated with hepatitis C virus (HCV) infection is the lymphoplasmacytoid lymphoma/immunocytoma (Lp-Ic). We have assessed the impact of the infection on the clinical features, quality of life and survival of HCV+ve Lp-Ic patients as compared to its impact in HCV-ve patients. PATIENTS AND METHODS: Seventy patients with Lp-Ic consecutively observed over a six-year period were studied. Clinical, virological and histopathological features were recorded at diagnosis. Quality of life was assessed using a scoring system including disease-related symptoms, performance status, working ability, hospital admissions and therapies required. RESULTS: Eighteen patients (26%) with HCV infection were identified. Significant differences between those patients and the HCV-ve group included number of symptomatic patients, Hb levels, serum protein levels, entity of the IgM monoclonal component, number of patients with cryoglobulins and with organ (liver, kidney) involvement, and entity and pattern of bone marrow infiltration. Survival rates were similar (P = 0.8383), but the quality-of-life score was significantly worse for the HCV+ve patients (P = 0.002). All anti-HCV Ab+ve patients tested positive for HCV RNA; genotype 2ac was detected in a significant proportion of cases. CONCLUSIONS: This study confirms that HCV infection is present in about one-third of patients with Lp-Ic. HCV infection does not seem to affect the overall survival of patients with Lp-Ic, but it affects the clinical expression of the disease, so that the overall quality of life of HCV+ve patients is significantly worse.

Adult↗
PubMed1998

Autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas in first complete or partial remission: a retrospective analysis of the outcome of 52 patients according to the age-adjusted International Prognostic Index.

The aim of the study was to retrospectively evaluate the outcome of patients with aggressive non-Hodgkin's lymphoma (NHL), undergoing autologous stem cell transplantation (ASCT) in first complete (CR) or partial (PR) remission, according to the age-adjusted International Prognostic Index (IPI). Fifty-two consecutive patients, aged less than 60 years, with intermediate- or high-grade NHL, and at least one of the following adverse risk factors: bulky disease, B symptoms or Ann Arbor stage III-IV, and at least a PR after CHT (and radiotherapy (RT) on residual mediastinal mass when required), underwent ASCT conditioned with BAVC. Sixty-five percent (33/52) of the patients achieved CR after CHT; 69% (36/52) after CHT + RT; 90% (47/52) after CHT +/- RT + ASCT. One death during conditioning and three major toxic events after ASCT were recorded. Overall survival (OS) is 98% at 37 months (16-88); disease-free survival (DFS) is 100% at 27 months (7-82). Comparing the observed results with those expected if patients were treated only with CHT, the sequential treatment including ASCT conferred an advantage in terms of CR rate of 14, 23 and 54%, respectively, in the low-intermediate (LI), high-intermediate (HI) and high (H)-risk groups, respectively. The 2-year OS advantage is 10, 21, 31 and 63%, respectively, and the 2-year DFS advantage is 12, 26, 38 and 39%, respectively. Even more striking is the 5-year projected advantage in the number of patients alive without disease, even when considering only the low (L) (P < 0.0001) and the LI (P < 0.0001) risk groups. For patients in the higher (HI + H) risk groups, ASCT should be included in the initial plan of treatment as consolidation of first CR or PR, but the differences seen in this study suggest a formal comparison in a randomized study also for patients in the LI risk group.

Adolescent↗
PubMed1998

Adjuvant treatment with cyclosporin A increases the toxicity of chemotherapy for remission induction in acute non-lymphocytic leukemia.

P-glycoprotein (Pgp)-related multidrug resistance (MDR) is frequently observed in acute non-lymphocytic leukemia (ANLL) and is associated with a poor response to standard chemotherapy. Cyclosporin A (CsA) is an effective downmodulator of Pgp-related MDR in vitro and has already been tested for that purpose in vivo also. Since Pgp is expressed in several normal cells and tissues, the modulation of Pgp can also modify total body exposure to antileukemic drugs and can alter and increase the toxicity of the antileukemic treatment. We report here the results of a study where 46 consecutive adult patients with ANLL were assigned to receive the same standard chemotherapy regimen of arabinosyl cytosine and idarubicin (IDA) for remission induction or consolidation, without or with CsA. Twenty-eight patients received 36 courses of chemotherapy without CsA and 18 patients received 32 courses of chemotherapy with CsA. CsA dose was 10-12.5 mg/kg/day and was given as a continuous i.v. infusion for 72 h. Whole blood CsA steady-state concentration ranged between 0.61 and 1.14 microM. The IDA area-under-the-curve was about twice as high in the cases that received CsA than in the other cases. CsA had no detectable effects on renal function and fluid balance, but significantly increased systemic blood diastolic pressure and conjugated bilirubine concentration. Furthermore, CsA-treated patients had greater, and more severe, oral and intestinal mucosal toxicity, with more severe adverse events, including more cases of gram-negative bacteremia, and with a delayed hemopoietic recovery. In conclusion, this study showed that an attempt at an effective downmodulation of Pgp-mediated MDR would substantially increase the hemopoietic and mucosal toxicity of antileukemic treatment and that the increase is accounted for, at least in part, by an increase of total body exposure to IDA.

Adult↗
PubMed1998

Multiple myeloma: presenting features and survival according to hospital referral. Eastern Cooperative Study Group on Monoclonal Gammopathies.

Two-hundred and 31 patients with a newly diagnosed multiple myeloma first seen and admitted to 17 hospitals located in the North-East of Italy between 1987 and 1992, were registered for a prospective study on the course of the disease. Median age was 68 years (range 41-90). Fifty-one per cent were in stage I, 9% in stage II and 40% in stage III. The presenting features and the survival of the 61 (26%) patients who were first admitted to a division of Hematology of a University Hospital (group HEM) were compared with those of the 170 (74%) patients who were referred to 16 divisions of Internal Medicine at General and County Hospitals (group INT). In the latter group, the patients were older (p = 0.002), had a poorer performance status ( p = 0.0001 ), a higher frequency of renal failure (p = 0.006) and anemia (p = 0.02) and higher beta2 microglobulin levels (p = 0.01). Median survival of group HEM patients did not differ significantly from group INT patients, if all stages were considered, but stage II and III patients of group INT had a significantly shorter median survival than advanced stage patients of group HEM (12 vs. 35 months, p = 0.01). If those older than 65 years or with unfavourable prognostic factors at presentation were excluded, prolonged survival of group INT patients was observed and the curves of the two groups did not differ significantly anymore. These results show that the patients recruited by a specialized centre may represent a selected population with better prognostic factors and younger age and this may affect analysis of clinical trials. Participation of minor centres in clinical trials may considerably contribute in improving interpretation of results of therapy in myeloma and be more representative of the entire population.

Adult↗
PubMed1998

BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine.

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.

2-Chloroadenosine↗
PubMed1998

P170 (Pgp) expression in leukemic cells after therapeutic exposure to arabinosyl cytosine.

The expression of the mdr-1 gene coding for a transmembrane 170 KD glycoprotein (P170 or PGP) is an important cause of multidrug resistance (MDR). In tumor cells the expression of the gene may vary and there is experimental evidence that it can be induced by exposure to MDR-unrelated agents. We investigated if the therapeutic exposure to Arabinosyl Cytosine (AC) could affect the level of P170 expression in the blast cells of acute non-lymphocytic leukemia (ANLL). The reactivity to the P170-directed MRK 16 monoclonal antibody of the marrow blast cells from 27 patients with ANLL prior and after treatment with standard dose AC was evaluated by flow cytometry. After treatment with AC the MRK 16 mean fluorescence index (MFI) was increased in 5/18 cases of primary and previously untreated ANLL and in 7/9 cases of relapsed or secondary leukemia. Overall, the mean value of the MFI was 6.8+/-3.6 before and 9.0+/-3.8 after AC (P=0.001, Wilkoxon matched pairs test). Therapeutic exposure to AC in vivo may increase P170 expression in leukemic cells. This may influence the definition and the quantitation of resistance and may have therapeutic implications, concerning the association with other cytotoxics and the use of MDR modifiers.

Journal Article↗
PubMed1998

Autologous stem cell transplantation for multiple myeloma: a single centre experience.

Thirty-two patients with multiple myeloma (MM) were autografted in our Centre over a 3-year period. Twenty-three patients had a newly diagnosed MM submitted to one induction regimen and 9 had a refractory or relapsing disease treated with at least two different chemotherapy lines: 15 out of 32 patients were sensitive to conventional treatment. In 2 patients BM was harvested while in the majority PBSC were collected after administration of 7 g/m2 Cyclophosphamide plus G-CSF (in 25 patients) or G-CSF alone at the dose of 16 microg/Kg/daily for 5-7 days (in 5 patients). Conditioning regimen was busulfan 16 mg/Kg plus melphalan 120 mg/m2. One patient died of cerebral hemorrhage after reinfusion of PBSC. Out of 31 evaluable patients, 24 (77%) had a response which was complete in 6 patients (19%) and partial in 18 patients (58%), 5 cases (17%) had no response, and 2 (6%) showed myeloma progression. There was a statistical difference in the outcome between newly diagnosed and pretreated patients (p = 0.003). At a median follow-up of 9 months (range 5-37), two patients had died for progression and 3 out of the 29 alive, relapsed after 17, 18 and 36 months respectively. Although median overall survival was not reached, there was a significant survival benefit for autografted patients in comparison with a matched control group conventionally treated in our Centre before 1994 (p = 0.02).

Journal Article↗
PubMed1998

P-glycoprotein (PGP), and not lung resistance-related protein (LRP), is a negative prognostic factor in secondary leukemias.

BACKGROUND AND OBJECTIVE: In cell lines, there is an ongoing debate about the role of the lung resistance-related protein (LRP) whereas the role played by P-glycoprotein (PGP) in determining a multidrug resistance is well known. The aim of this study was to evaluate the frequency and the role of a PGP and an LRP overexpression in affecting the intracellular daunorubicin accumulation (IDA) and in predicting the therapy outcome on a subset of overt secondary acute non lymphocytic leukemias (ANLL). An adjunctive point was to evaluate the efficacy of the reversal agent SDZ PSC 833 (PSC) in counteracting impaired IDA. DESIGN AND METHODS: By flow cytometry, PGP and LRP expression and the IDA were evaluated on 54 overt secondary ANLL PGP and LRP overexpressions were respectively defined by an MRK-16 mean fluorescence index (MFI) > or = 6 (PGP+) and by an LRP-56 MFI > or = 5 i.e. by MRK-16 and LRP-56 MFIs higher than the one observed in normal leukocytes. The blasts' IDA was studied after a two-hour incubation in 1000 ng/mL daunorubicin in the presence or in the absence of the MDR reversal agent SDZ PSC 833 (PSC) 1.6 mumol. RESULTS: A PGP overexpression was detected in 40/54 (74%) cases while an LRP overexpression was observed on 33/54 (61%) cases. No differences were found in terms of PGP and LRP expressions between ANLL developing after chemo/radiotherapy (therapy-related ANLL) or evolving from a myelodysplastic syndrome (MDS-related ANLL). Compared to the PGP-, the PGP+ cases showed a significantly lower mean IDA (DNR NMFI 196 +/- 46 vs. 267 +/- 53, p < 0.001). The co-incubation of DNR with the PSC significantly increased only the mean IDA of the PGP+ cases, that grew from a DNR NMFI of 196 +/- 46 to a DNR NMFI of 284 +/- 67 (p < 0.0001). With respect to normal leukocytes, even the PGP- cases had an impaired IDA suggesting that other mechanisms, including an LRP overexpression, could affect the IDA. A strongly negative correlation was observed between PGP overexpression and therapy outcome, in fact, 8/10 (80%) PGP- but only 2/27 (7%) PGP+ patients obtained complete remission (p = 0.0002). Moreover, 7/33 (21%) cases showing an impaired IDA (NMFI < 280) but 4/4 (100%) with NMFI > 280 had complete remission (p = 0.006). No correlation was found between therapy response and LRP or CD34 expression. INTERPRETATION AND CONCLUSIONS: This data suggests that an important role in determining therapy outcome is played by PGP in secondary leukemias. Even if the LRP is frequently overexpressed in secondary leukemias and is likely to contribute to the reduction of the intracellular drug accumulation, the role played by LRP in determining the therapy-outcome has still to be cleared.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Autologous stem cell transplantation in multiple myeloma: a single center experience.

This study shows the feasibility and safety of autologous stem cell transplantation in 32 of 98 multiple myeloma patients referred to our institution over a 3-year period. Complete response rate was 19% and partial response rate 58%. A significantly better outcome was shown among newly diagnosed patients in comparison with pretreated patients.

Adult↗