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M Balzarotti

Publications and source records attributed to M Balzarotti.

17 recordsLinked to original sources
PubMed2002

Reduced intensity conditioning regimen followed by glycosylated G-CSF mobilized PBSCT in patients with solid tumors and malignant lymphomas.

The aim of this pilot study was to exploit the graft-versus-tumor potential of allogeneic transplants while improving safety of the procedure. Twelve patients with advanced hematological malignancies and solid tumors underwent a low intensity conditioning regimen (fludarabine and cyclophosphamide) followed by an allogeneic peripheral blood stem cell transplantation. The median time to achieve an absolute neutrophil count of more than 0.5 x 10(9)/l and an untransfused platelet count of more than 20 x 10(9)/l was 15 and 14 days, respectively. The main extra-hematological toxicities were mucositis and infections. Acute graft-versus-host (GVHD) disease was experienced by 62% of evaluable patients (grade II/B or III/C 80%) responsive to steroids. Extensive chronic GVHD was observed in 62% of patients. Non-relapse transplant-related mortality by day +30 was observed in three patients (25%). Eight out of 12 patients were full donor chimeric by day +100. One patient showed a mixed chimerism at day +37 when he died from progressive disease. One patient was in complete remission (CR) before allogeneic transplantation, and after transplantation four patients achieved CR and four experienced progressive disease. Our study confirms that a low intensity conditioning regimen for allogeneic stem cell transplantation is feasible and effective in heavily pretreated patients.

Adult↗
PubMed2002

Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose density of doxorubicin and cyclophosphamide.

BACKGROUND: Following our previous study of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) intensification in non-Hodgkin's lymphoma (NHL), in the present report we attempted to further increase dose intensity by shortening the between-course intervals with the support of growth factors. PATIENTS AND METHODS: A total of 67 patients were enrolled. With a fixed dose of doxorubicin 75 mg/m(2), cyclophosphamide (CTX) was started at a dose of 1750 mg/m(2) and increased by 250 mg/m(2) in consecutive cohorts of patients provided that no dose-limiting toxicity occurred. After the maximal tolerated dose (MTD) had been identified, this was used to treat more patients in order to confirm the feasibility of the regimen on a large scale, with the number of cycles being varied on the basis of disease extension. RESULTS: Twenty-three cases were enrolled in the CTX dose finding phase. Dose-limiting non-hematological toxicity occurred at 2250 mg/m(2). As the intermediate level of 2000 mg/m(2) had a borderline toxicity profile, a CTX dose of 1750 mg/m(2) was defined as the MTD. A total of 53 patients then received the MTD during the course of the study as a whole. At the MTD, toxicity was acceptable. Only 10 of 189 cycles (4%) required hospitalization due to infection or febrile neutropenia. Seventy-four percent of the patients achieved complete remission. Freedom from progression and overall survival at 12 months were 71% and 86% in the whole series, and 58% and 71% for high-risk cases, respectively. CONCLUSIONS: This intensified CHOP regimen is feasible on an outpatient basis. It can be safely considered a definitive treatment in patients at low and intermediate risk, and as induction before high-dose consolidation in high-risk cases.

Adult↗
PubMed2001

Mobilizing potential of ifosfamide/vinorelbine-based chemotherapy in pretreated malignant lymphoma.

The mobilizing potential and therapeutic activity of ifosfamide/vinorelbine-containing regimens with G-CSF support were explored in patients with pretreated malignant lymphomas. Ten patients with non-Hodgkin's lymphoma (NHL) received ifosfamide and vinorelbine, and 17 with Hodgkin's disease (HD) received ifosfamide, vinorelbine and gemcitabine (IGEV regimen), as induction chemotherapy before high-dose chemotherapy (HDT) with peripheral blood stem cell (PBSC) support. Most of the patients had been heavily pretreated with various chemotherapy regimens +/- radiotherapy. The target yield was > or =3 x 10(6) CD34+ cells/kg of body weight in order to support the subsequent myeloablative chemotherapy. The optimal PBSC harvest occurred on days 11 and 12, with no difference in CD34+ cell mobilization kinetics between the ifos- famide/vinorelbine and IGEV regimens. The median number of CD34+ cells/kg body weight collected was 10.9 x 10(6) (range 1.76-61.1 x 10(6)). The median total CD34+ cell/microl, CFU-GM and white blood cells (WBC) for all individual collections was 81.5/microl, 10 x 10(4)/kg, and 17 900/microl, respectively. The target yield of CD34+ cells was reached in 24 of 27 patients. Hematological side-effects were acceptable and no treatment-related hospitalizations or toxic deaths occurred. Fifteen patients have so far received high-dose therapy and PBSC reinfusion with rapid engraftment. These results confirm that ifosfamide and vinorelbine-based chemotherapy regimen with G-CSF support can be successfully and safely used to mobilize PBSCs.

Adult↗
PubMed2001

Lymphomas.

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Humans↗
PubMed2000

Fludarabine and cladribine in relapsed/refractory low-grade non-Hodgkin's lymphoma: a phase II randomized study.

BACKGROUND: It is unclear whether the purine analogs fludarabine (Flu) and cladribine (CdA) are non-resistant. PATIENTS AND METHODS: Sixty patients with relapsed or refractory low-grade NHL were randomly allocated to initial treatment with either Flu 25 mg/m2, or CdA 0.14 mg/kg, each for five consecutive days every four weeks. Upon treatment failure, eligible patients were crossed over to the other study drug. RESULTS: Overall response and CR were 68% and 48% with Flu, and 72% and 38% with CdA, respectively. For responders, actuarial three-year progression-free survival was 58% with Flu and 52% with CdA. Treatment with both drugs was well tolerated, with toxic effects primarily hematological. Two patients (8%) in the Flu group and 15 patients (47%, P = 0.001) in the CdA group were taken off study because of persistent hematological toxicity. After cross over, none of seven refractory patients responded, while eight of nine previously responsive patients achieved second responses. CONCLUSIONS: Our study confirms that Flu and CdA have similar response rates and durations. However, further studies are required to optimize the CdA schedule and dosage in order to ameliorate its toxic profile while maintaining antitumor activity. The two drugs appear to be cross-resistant.

Adult↗
PubMed1999

Dose-escalation of CHOP in non-Hodgkin's lymphoma.

BACKGROUND: CHOP is considered to be the gold standard for patients with histologically aggressive non-Hodgkin's lymphoma both in limited and advanced stages. In order to determine the maximum tolerable dose of an intensified CHOP regimen, a dose-escalation study of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with non-Hodgkin's lymphoma (NHL) was started. PATIENTS AND METHODS: With an increased fixed dose of doxorubicin at 75 mg/m2 instead of 50 mg/m2 on day 1 and standard doses of vincristine (1.4 mg/m2 on day 1) and prednisone (100 mg day 1 through 5), cyclophosphamide dose was escalated by increments of 250 mg/m2 in consecutive cohorts of at least three patients starting from 1000 mg/m2. Granulocyte-colony stimulating factor (G-CSF) support was added to the regimen starting from the dose-level inducing grade 4 neutropenia lasting more than five days in two patients. Dose limiting toxicity was defined as either the dose inducing grade 4 neutropenia lasting more than seven days despite the use of G-CSF, or grade 3-4 thrombocytopenia lasting more than seven days, or any grade 4 non-hematological toxicity other than alopecia. The dose-level below the one inducing dose-limiting toxicity was defined as maximum tolerable dose. All patients were treated on an outpatient basis. Dose-intensity parameters for single agent doxorubicin and cyclophosphamide as well as for the whole regimen were evaluated. RESULTS: Eighty-seven patients are evaluable over a four-year study period. At 1750 mg/m2 dose-level, G-CSF was added to the regimen according to described criteria. At the cyclophosphamide dose of 3000 mg/m2, dose-limiting hematological toxicity occurred in two patients, with one grade 4 thrombocytopenia and neutropenia and one grade 4 neutropenia lasting more than seven days. Thus, cyclophosphamide dose of 2750 mg/m2 was defined as maximum tolerable dose. CONCLUSIONS: CHOP intensification of approximately 1.8 times that of the standard regimen is feasible and safely administered on an outpatient basis with G-CSF support. Further investigation on the role of dose-intensity in the outcome of NHL should focus on the comparison of intensified CHOP regimen and standard CHOP or high-dose chemotherapy.

Adolescent↗
PubMed1999

PCR-based clonality analysis: a reliable method for the diagnosis and follow-up monitoring of conservatively treated gastric B-cell MALT lymphomas?

AIMS: We evaluated polymerase chain reaction (PCR) amplification of specific immunoglobulin heavy chain (IgH) gene rearrangements as a means of demonstrating monoclonality during follow-up of conservatively treated gastric MALT lymphoma, and compared the reproducibility of PCR on sequential frozen and paraffin-embedded endoscopic biopsies. We established an association between clonality detected by PCR and the histological observations. METHODS AND RESULTS: Sixty-nine pairs of sequential frozen and paraffin-embedded endoscopic biopsies from 21 conservatively treated patients were graded according to the Wotherspoon-Isaacson histological scoring system, which provides a measure of diagnostic confidence on a scale 0-5. PCR amplification of the IgH gene was performed using FR3/JH and FR2/JH primers. 68/69 paired samples (98.5%) showed identical mono- or polyclonal PCR amplification patterns. Forty-seven out of 48 pairs of samples sharing similar histological features produced identical amplification patterns in both fresh and paraffin-embedded tissues. In comparison with the histological grading, monoclonality was detected in 64.2% and 41.6% of samples scored 5 and 4, respectively. Conversely, among 64 samples scored 0-3, a monoclonal pattern was observed only in two samples, one of which was from a patient who relapsed 9 months later. CONCLUSIONS: PCR-based clonality analysis by demonstration of specific IgH gene rearrangement can be easily and reliably performed on both frozen and paraffin-embedded endoscopic biopsies. In conjunction with histological observation, this method can be used as a complementary tool to monitor MALT lymphoma regression during conservative treatment.

Clone Cells↗
PubMed1999

Ex vivo manipulation of hematopoietic stem cells for transplantation: the potential role of amifostine.

High-dose chemotherapy with autologous stem cell transplantation is an increasingly used procedure in oncohematologic diseases and represents a promising strategy in selected patients with solid tumors. In autologous stem cell transplantation, the risk of reinfusion of clonogenic tumor cells is a remarkable biologic obstacle that can be at least partly overcome by ex vivo graft purging to reduce residual tumor. Mafosfamide and 4-hydroxyperoxycyclophosphamide, active metabolites of cyclophosphamide, are the most widely used pharmacologic agents for ex vivo bone marrow purging. However, in addition to killing tumor cells, they are toxic to normal bone marrow as measured by reduced colony-forming unit granulocyte-macrophage (CFU-GM). Thus, the therapeutic index of these alkylating agents is narrow, and parameters for dose selection must include toxicity to normal bone marrow progenitor cells that can delay bone marrow engraftment and increase risk of infections, bleeding complications, hospitalization, and the need for a costly transplantation procedure. Amifostine (WR-2771, Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) selectively protects human CFU-GM progenitor cells from the cytotoxicities of active metabolites of cyclophosphamide without altering its cytotoxic effect on malignant cells. This has been demonstrated both in preclinical and clinical studies in patients with breast cancer, malignant lymphomas, and acute leukemia. Amifostine use during the ex vivo procedure significantly shortened the time to bone marrow engraftment with decreased incidence of infections and need for red blood cell transfusions.

Amifostine↗
PubMed1998

Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and clinical implications.

The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent.

Adolescent↗
PubMed1997

Initial chemotherapy for primary resectable large-cell lymphoma of the stomach.

BACKGROUND: We aimed to evaluate the safety and effectiveness of a conservative approach with short-term chemotherapy with or without consolidation radiotherapy in primary resectable large-cell gastric lymphoma in patients not requiring emergency surgery at presentation. PATIENTS AND METHODS: Seventeen consecutive patients presenting with resectable primary large-cell lymphoma of the stomach not requiring immediate surgery were initially treated with chemotherapy with or without consolidation radiotherapy. Subtotal or total resection of the stomach was planned only as salvage treatment for those patients who failed locally, or as emergency surgery in instances of acute iatrogenic complications of treatment. Chemotherapy included four to six cycles of an anthracycline-containing regimen, and consolidation radiotherapy was planned on the entire stomach and surrounding lymph node areas for complete responders readily capable of compliance with a daily treatment schedule at our Institution. RESULTS: None of the patients in the present series experienced acute iatrogenic morbidity or mortality from local complications. After a median follow-up of almost six years, two patients failing first-line chemotherapy have died of progressive lymphoma, while 15 patients are well and currently disease-free. CONCLUSIONS: Up-front chemotherapy as initial treatment for primary gastric large-cell lymphoma appears to be a safe and effective treatment by which most patients can probably be spared surgical gastrectomy. Consolidation radiation therapy on the stomach can probably improve on the effectiveness of chemotherapy alone. More experience is needed to elucidate the prognostic factors, treatment-related long-term toxic effects and the feasibility of such a treatment administered outside of highly specialized institutions.

Adult↗
PubMed1997

Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD.

PURPOSE: This study analyzed long-term results in patients with Hodgkin's disease who were resistant to or relapsed after first-line treatment with MOPP and ABVD. Response to salvage treatments and prognostic factors were also evaluated. PATIENTS AND METHODS: The study population included 115 refractory or relapsed patients among a total of 415 patients treated with alternating or hybrid MOPP-ABVD followed by radiotherapy (25 to 30 Gy) to initial bulky sites. The median follow-up duration of the present series was 91 months. Thirty-nine of 115 patients (34%) showed disease progression while on primary treatment (induction failures); 48 relapsed after complete remissions that lasted < or = 12 months and 28 after complete remission that lasted more than 12 months from the end of all treatments. RESULTS: At 8 years, the overall survival rate was 27%, being 54% and 28% in patients whose initial complete remission was longer or shorter than 12 months, respectively, and 8% in induction failures (P < .001). Response to first-line chemotherapy and disease extent at first progression significantly influenced long-term results, as well as the incidence and duration of complete remission. CONCLUSION: The present data confirm previous observations that showed the main prognostic factors to influence outcome after salvage treatment are response duration to first-line therapy and disease extent at relapse. The results indicate that patients who relapse after the alternating MOPP/ABVD regimen have a prognosis similar to that of patients who relapse after a four-drug regimen (MOPP or ABVD alone). Re-treatment with initial chemotherapy seems the treatment of choice for patients who relapse after an initial complete remission that lasts greater than 12 months, while the real impact of high-dose chemotherapy or new regimens should be assessed in resistant patients.

Adult↗
PubMed1996

Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma.

BACKGROUND: To assess the activity of single agent vinorelbine in pretreated non Hodgkin's lymphoma. PATIENTS AND METHODS: Twenty-three pretreated patients with non-Hodgkin's lymphoma (14 intermediate-high grade, nine low-grade) were treated with vinorelbine 30 mg/m2/week for six months or up to four doses after achieving CR. RESULTS: Among 13 evaluable patients with intermediate-high grade lymphoma, three obtained CR and three PR, for an overall response rate of 46% (95% CI: 19%-75%). Median duration of response was six months. Otherwise, vinorelbine did not show any significant activity inn chemotherapy-refractory low-grade non-Hodgkin's lymphoma. Toxicity was acceptable, and the drug was well-tolerated even in elderly patients. CONCLUSIONS: The good activity and tolerability of vinorelbine in relapsed intermediate-high grade lymphoma suggest its inclusion in first-line regimens, especially in elderly patients.

Adult↗
PubMed1993

Study of the HLA-DP beta 1 locus by the polymerase chain reaction technique in patients with Hodgkin's disease.

BACKGROUND: A number of reports have studied associations between Hodgkin's disease and HLA. Some of them established correlation between several antigens and Hodgkin's disease, and others found no correlations. METHODS: The HLA DP locus was determined by the polymerase chain reaction method in 31 Hodgkin's disease patients and 58 healthy controls. RESULTS: No significant difference between patients and controls was noted. CONCLUSIONS: Further investigations are needed to confirm the hypothesis of a possible role of the HLA complex as one of the factors involved in Hodgkin's disease.

Base Sequence↗
PubMed1993

Combined modality treatment for primary gastrointestinal non-Hodgkin's lymphoma: the Milan Cancer Institute experience.

BACKGROUND: The study analyzes clinical-pathologic features, treatment and outcome of all patients with primary lymphoma of the gastrointestinal tract (GI-NHL) seen during the past two decades at the Milan Cancer Institute. SUBJECTS AND METHODS: Clinical and histopathological data from 135 patients presenting with GI-NHL and disease localized within the abdomen were reviewed. Of these, 114 (84%) presented with limited disease (stage I and II), while 21 patients were found to have disease involvement of other abdominal organs (i.e., liver, pancreas, peritoneum) or more than one gastrointestinal site and were therefore classified as stage IV. Seventy-three percent presented with lymphoma in the stomach, 15% in the small intestine and 9% in the large bowel, while in 5 cases multiple localizations of the gastrointestinal tract were documented. Median age was 50 years, with one-fourth of patients older than 60 years. According to the revised Kiel classification for GI-NHL, 61% of patients presented with pure high-grade lymphoma, 9% high-grade NHL associated with residual low-grade lymphoma, and 30% had low-grade NHL. Nine percent presented with bulky disease, 5% with elevated LDH and 21% with a Karnofsky performance status (PS) < or = 80. RESULTS: Laparotomy with radical (108 patients) or palliative (15 patients) intent was performed in all patients who were not deemed at high risk of complication from major surgery. Complete removal of all measurable tumor was feasible in 101 patients, with no difference relative to primary site. Surgical morbidity and mortality were 11% and 2%, respectively. Overall, 83% of patients were treated with chemotherapy. Patients who did not receive systemic chemotherapy included 12 managed with surgery alone and 10 who received only postoperative irradiation mainly because of low-grade lymphoma with superficial disease. Of patients with limited disease, 99% achieved complete tumor remission. After a median follow-up of 73 months, 13 of 113 patients have relapsed, mostly (70%) outside the gastrointestinal tract. The actuarial 10-yr. freedom from progression (FFP) and overall survival (OS) were 84% and 86%, respectively. Aside from age, no other factor revealed a statistically significant impact on outcome. There was only a trend in favor of low-grade histology (FFP 97% vs. 79%), that failed to reach statistical significance. Of patients with advanced abdominal disease, 48% achieved complete remission with chemotherapy with or without prior surgical debulking. Actuarial 10-yr. FFP and OS were 44% and 42%, respectively. In this subset, tumor burden and LDH levels represented the most important prognostic factors affecting outcome. CONCLUSIONS: This retrospective study underscores the good results obtained in a wide and unselected population of patients with limited-stage primary GI-NHL following a combined-modality approach that included surgical debulking and systemic chemotherapy for most patients. Surgery alone can be considered adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the submucosa. Patients with advanced GI-NHL show a long-term outcome similar to that of patients with advanced NHL arising outside the gastrointestinal tract.

Aged↗