Biomedical subjects

Franco Mandelli

Publications and source records attributed to Franco Mandelli.

70 records · Page 4Linked to original sources

PubMed2002

Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study.

Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs.

Adult↗

PubMed2002

Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.

BACKGROUND: Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, the product of the Philadelphia chromosome. Imatinib mesylate, formerly STI571, is a selective inhibitor of this kinase. METHODS: A total of 532 patients with late--chronic-phase CML in whom previous therapy with interferon alfa had failed were treated with 400 mg of oral imatinib daily. Patients were evaluated for cytogenetic and hematologic responses. Time to progression, survival, and toxic effects were also evaluated. RESULTS: Imatinib induced major cytogenetic responses in 60 percent of the 454 patients with confirmed chronic-phase CML and complete hematologic responses in 95 percent. After a median follow-up of 18 months, CML had not progressed to the accelerated or blast phases in an estimated 89 percent of patients, and 95 percent of the patients were alive. Grade 3 or 4 nonhematologic toxic effects were infrequent, and hematologic toxic effects were manageable. Only 2 percent of patients discontinued treatment because of drug-related adverse events, and no treatment-related deaths occurred. CONCLUSIONS: Imatinib induced high rates of cytogenetic and hematologic responses in patients with chronic-phase CML in whom previous interferon therapy had failed.

Administration, Oral↗

PubMed2002

Therapy-related myelodysplastic syndrome-acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem.

The use of all-trans retinoic acid (ATRA) in combination with chemotherapy has markedly improved the prognosis for patients with acute promyelocytic leukemia (APL); the higher complete remission (CR) and survival rates now reported in this disease almost approach those obtained for other highly curable hematologic malignancies. Of 77 patients with APL who were consecutively treated at a single institution and who achieved CR after induction and consolidation therapy, 5 (6.5%) acquired therapy-related myelodysplasia (tMDS), acute myelogenous leukemia (AML), or both (tMDS-AML). Of these, 3 of 46 (6.5%) patients received front-line chemotherapy with or without ATRA and acquired tMDS-AML while in first remission of APL. Two underwent repeated chemotherapy cycles with ATRA because of APL relapse and acquired tMDS-AML while in the second or third remission of APL. In 2 patients, clinical and biologic characteristics of tMDS-AML were as expected for postalkylating forms (long latency, MDS phase preceding AML, karyotypic aberrations involving chromosomes 5 or 7), even though one of them had not previously received alkylating drugs. Three of the 5 patients died shortly after tMDS-AML diagnosis, one is alive with tMDS, and one is alive and in CR after allogeneic bone marrow transplantation. The occurrence of tMDS-AML after successful therapy for APL is an emerging problem. The availability of prognostic score systems at initial diagnosis and monitoring of residual disease by polymerase chain reaction might allow better tailoring of treatment intensity in APL to spare unnecessary toxicity and to minimize the risk for tMDS-AML in patients who are presumably cured.

Adolescent↗

PubMed2002

Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma.

Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m(2) intravenously, weekly for 4 weeks). After CHOP, 57% achieved a complete response (CR), 37% a partial response (PR), and 6% were nonresponders (NR). At this stage, patients proving PCR-negative (n = 41) or failing to achieve a clinical response (n = 8) were excluded from rituximab treatment. Seventy-seven patients received rituximab and entered a scheduled MRD follow-up program. At the first molecular follow-up (+12 weeks), 59% had converted to PCR negativity in the BM and PB, with a further increase documented at the second control (+28 weeks) with 74% PCR negative. At the last molecular follow-up (+44 weeks), 63% of the patients remained PCR negative. At 3 years, the estimated overall survival of all patients is 95% (95% confidence interval [CI], 86-98). For patients achieving PCR-negative status following CHOP and therefore excluded from rituximab treatment, freedom from recurrence (FFR) was 52% (95% CI, 28-71). For patients treated with rituximab, a durable PCR-negative status was associated with a better clinical outcome since FFR was 57% (95% CI, 23-81) compared with 20% (95% CI, 4-46) in patients who never achieved or lost the molecular negativity (P <.001).

Adult↗

PubMed2002

Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study.

The GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN) pretreatment on complete remission (CR) achievement and length, the influence of the addition of cyclophosphamide (random I) to a conventional 4-drug induction on CR rate and duration, and whether an early post-CR intensification (random II) by an 8-drug consolidation could improve CR duration. Median follow-up of this study was 7.3 years. From January 1988 to April 1994, among 794 adult (> 12 but < 60 years) patients registered, 778 were eligible. Their median age was 27.5 years; 73% had B-lineage acute lymphoblastic leukemia (ALL) and 22% had T-lineage disease; 18% showed associated myeloid markers; 47 of 216 analyzed patients (22%) had Philadelphia chromosome-positive ALL. Response to PDN pretreatment was observed in 65% of cases. CR was achieved in 627 patients (82%). Resistant patients and induction death rates were 11% and 7%, respectively. Random II was applied to 388 patients with CR; 201 had maintenance alone and 187 had consolidation followed by maintenance. The relapse rate was 60%; isolated central nervous system relapses were 8% of all CRs and 13% of all relapses. Median survival (overall survival [OS]), continuous complete remission (CCR), and disease-free survival (DFS) were 2.2, 2.4, and 2 years, respectively. PDN pretreatment response resulted the main independent factor influencing CR achievement, OS, CCR, and DFS; the addition of cyclophosphamide in induction significantly influenced CR achievement in a multivariate analysis. Neither induction intensification nor early consolidation appeared to influence CCR and DFS duration. For the first time PDN pretreatment response proved to be a powerful factor predicting disease outcome in adult ALL patients.

Adolescent↗

PubMed2002

Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): report of a case and literature review.

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder of unknown etiology, usually associated with lymph node enlargement in various superficial or deep sites. It usually shows a prolonged clinical course with occasional exacerbation and remission phases. We describe the long-term follow-up of a case of SHML that showed typical clinical features and in which various therapeutic strategies were attempted. Chemotherapy and alpha-interferon (IFN) were ineffective; surgery was ultimately required with satisfactory results. From an extensive literature review we found different treatment strategies in SHML in the 80 cases published between 1969 and 2000. Spontaneous resolution of adenopathies is frequently observed: 32 out of 40 cases which did not receive chemotherapy, radiotherapy, or surgery were healthy at the time of publication. Radiotherapy alone showed conflicting results: 3 complete remissions (CR) were obtained in the 9 patients treated. Surgical debulking when required was effective--8/9 CR--while chemotherapy showed generally negative results. IFN has been previously employed in only one case. In conclusion, clinical observation without treatment is advisable when possible. In the presence of vital organ compression and/or extranodal localization with important clinical signs, surgical debulking may be necessary. Radiotherapy has shown limited efficacy, while chemotherapy is in general ineffective. More experience is needed to evaluate the role of IFN.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Conservative treatment for patients over 80 years with acute myelogenous leukemia.

In order to evaluate the best treatment of very elderly patients with AML, we have retrospectively analyzed 60 cases of patients aged more than 80 years, with a diagnosis of AML and observed from January 1988 to December 1998. Six of these patients were subsequently referred to other centers; of the remaining 54 patients, 20 (37%) received only supportive care, whereas 34 (63%) required palliative chemotherapy to control leukocytosis, after a median time from diagnosis of 9 days (range 0-253). Median overall survival was 13 weeks (range 1-105): 21 (39%) and 6 (11%) patients survived more than 6 and 12 months, respectively. Twenty-eight patients (51.8%) died from progressive disease, 19 (35.1%) died from AML-related or unrelated causes in the phase of stable disease, while in 7 patients the cause of death was unknown. In univariate analysis, PS > 2 and WBC > 50 x 10(9)/L had an adverse prognostic significance on survival. Our results, as compared with those reported in the literature for patients over 80 years treated with intensive chemotherapy, support the idea that intensive chemotherapy is usually not indicated in very elderly patients with AML, and that conservative treatment and the primary strategy of "watch-and-wait" presently seems to be the best choice.

Aged↗

PubMed2002

Management of disease-related anemia in patients with multiple myeloma or chronic lymphocytic leukemia: epoetin treatment recommendations.

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients often develop anemia due to the disease process and effects from disease therapy. Blood transfusion, the established treatment, has an immediate effect in improving patients' hemoglobin levels. However, this effect is transient and transfusion is associated with several risks, including infections and mild to life-threatening immunologic reactions. A newer option is recombinant human erythropoietin (epoetin); a biological treatment that leads to increased hemoglobin levels over an extended time without the risks of blood transfusion. Extensive evidence has shown that epoetin is effective in the treatment of cancer-associated anemia. An international expert panel met to develop treatment recommendations for the use of epoetin in MM and CLL patients. Based on the available data, it is recommended that treatment be initiated only after other possible causes of anemia are eliminated. Epoetin should be administered to any patient with hemoglobin < or=10 g/dl. Patients with hemoglobin 10-12 g/dl should receive epoetin if they suffer from significant symptoms of anemia and/or have progressively decreasing hemoglobin values. Dosage should be initiated at 10 000 IU three times/week or 40 000 IU once/week and be titrated to maintain hemoglobin at 12 g/dl. Nonresponsive patients (<1 g/dl increase over four weeks) may have their dose increased to 20 000 IU three times/week or 60 000 IU once/week, respectively. Epoetin treatment should be discontinued if there is no response to the increased dosage, or hemoglobin >14 g/dl. Treatment should resume for patients who exceed 14 g/dl, at a reduced dosage, if their hemoglobin falls below 12 g/dl.

Anemia↗

PubMed2002

A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

Adolescent↗

PubMed2002

Advances in the understanding and management of acute promyelocytic leukemia.

Considerable progress has been made over the past decade in the understanding and management of acute promyelocytic leukemia (APL). At the laboratory level, molecular mechanisms underlying the arrest of differentiation that typically features in this malignancy, have been clarified and currently provide important models for addressing future investigation aimed at releasing the maturation block in other malignancies. In the clinic, advances in the management of APL have converted this rapidly fatal disease into the most frequently curable leukemia in adults. Use of retinoids in combinatorial protocols with anthracycline-based chemotherapy for front line treatment currently results in long-term survival and potential cure in at least 60% of newly diagnosed patients. Even after relapse, the disease is still curable in a high percentage of cases by various approaches including combinations of chemotherapy, retinoids, arsenic trioxide, stem cell transplantation and antibody-targeted chemotherapy. Genetic testing for identification of the disease-specific gene rearrangement and monitoring of residual disease have proved critical in establishing correct diagnosis and better evaluate the response to therapy at the molecular level. Current 'hot' issues for clinical investigation include: (i) better understanding and management of the severe coagulopathy present at diagnosis in most patients; (ii) the definition of risk categories to improve identification of patients at highest risk of relapse and (iii) the translation of successful differentiation therapy to other leukemia subsets.

Cytogenetic Analysis↗

PubMed2002

The effects of anemia in hematologic malignancies: more than a symptom.

Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.

Anemia↗

PubMed2002

Continuous low dose of melphalan and prednisone in patients with multiple myeloma of very old age or severe associated disease.

INTRODUCTION AND OBJECTIVE: The management of elderly patients with multiple myeloma is a relevant problem because it concerns a great number of patients. Patients with multiple myeloma who are very old or who have severe associated diseases have a dismal outcome. For these patients we retrospectively evaluated the effect of a mild approach with continuous low-dose melphalan and prednisone (cMP). DESIGN AND METHODS: 109 patients with multiple myeloma, observed between 1985 and 2000, were treated with cMP; 67 were treated at time of diagnosis (group A; median age 78 years) and 42 as a second or subsequent line of therapy (group B; median age 72 years). The toxicity of the treatment was compared with a control group of 29 patients aged over 70 years, treated in the same institution with the conventional cyclical melphalan/prednisone regimen. RESULTS: Major or minor responses were obtained in 32% of patients in group A and 13% of patients in group B. Disease was stabilised in 45% of group A and 47% of group B and progressed in 5 and 18%, respectively. Median survival was, respectively, 19 and 24 months in group A and B. Among the 42 patients who received cMP as a second-line therapy (group B), 36 (86%) had previously been treated according to the standard cyclical melphalan/prednisone schedule; of these 12 (33%) obtained a better M protein reduction after cMP compared with the previous response to first-line cyclical melphalan/prednisone. The cMP schedule was generally well tolerated, and the rate of haematological toxicity was lower than for a historical control group receiving cyclical melphalan/prednisone. CONCLUSION: The cMP treatment schedule is well tolerated and results in a high proportion of patients with stable disease, with acceptable survival even in patients with advanced disease.

Aged↗

PubMed2002

AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at 21 weeks of gestation.

Explore the source record for details and available documents.

Adult↗

PubMed2002

Dose intensification with autologous stem cell transplantation in relapsed and resistant Hodgkin's disease.

BACKGROUND AND OBJECTIVES: Patients affected by Hodgkin's disease (HD) resistant to induction therapy or who have a brief duration of first remission have a poor outcome. DESIGN AND METHODS: We retrospectively reviewed the clinical data of 28 patients affected by Hodgkin's disease who relapsed 6 to 24 months from completion of treatment (14 patients) or who were refractory to first-line therapy or relapsed very early (14 patients). All the 28 patients were treated with salvage chemotherapy plus a conditioning regimen followed by peripheral blood stem cell transplant (PBCST) or autologous bone marrow transplant (ABMT). RESULTS: At a median follow-up of 35.5 months (range 14-119), of the 14 patients responding to first-line therapy but who relapsed > 6 months off therapy, 10 (72%) are alive, well and in complete remission (CR), 2 (14%) are alive with disease at 39 and 83 months from transplant, and 2 (14%) died 26 and 63 months after their transplant from acute myeloid leukemia and HD, respectively. At a median follow-up of 39 months, the overall survival (OS) is 68% and the event-free survival (EFS) is 56%. At a median follow-up of 30 months (1-98), of the 14 patients refractory to first-line therapy or who relapsed very early, 9 (64%) are alive in CR, 1 (7%) is alive with disease and 4 (29%) have died of their disease (3 patients) or myelodysplastic syndrome (1 patient). The OS is 58% and the EFS is 52%. There are no statistically significant differences in terms of OS and EFS between the two groups of patients. INTERPRETATION AND CONCLUSIONS: Our study shows that salvage chemotherapy followed by a conditioning regimen and autotransplant is an effective, feasible and well-tolerated scheme of therapy not only for patients with HD who relapse after first-line treatment, but also for those resistant to first-line treatment.

Adult↗

PubMed2002

Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients.

BACKGROUND AND OBJECTIVES: The objective of improving the quality of responses of chronic lymphocytic leukemia (CLL) patients has led to the design of protocols that combine fludarabine (FDR) with synergistic drugs. We evaluated the efficacy and toxicity of a schedule that includes fludarabine, ara-C, novantrone and dexamethasone (FAND) for the management of previously treated CLL patients under 60 years old. DESIGN AND METHODS: Thirty-one patients underwent FAND treatment. Twenty-three patients had active disease (relapsed patients: 9; unresponsive to prior therapy: 14). Eight patients had a partial response (PR) to prior therapy and were treated with the aim of further reducing residual disease. The FAND schedule included fludarabine (25 mg/m(2) i.v. days 1-3), ara-C (1 g/m(2) i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m(2) i.v. day 1) and dexamethasone (20 mg i.v. days 1-3). Infection prophylaxis consisted of fluconazole, acyclovir, trimethoprim/sulfamethoxasole and granulocyte colony-stimulating factor (G-CSF) in the presence of severe neutropenia. RESULTS: A response was observed in 7/14 refractory patients (complete response-CR: 29%), in all 9 relapsed patients (CR: 78%) and in 7/8 patients (CR: 87.5%) treated in PR. Taken together, 18 CRs were obtained and in 14 (78%) this was associated with a flow cytometric remission (CD5+/CD20(weak+) PB lymphocytes: <10%). Severe granulocytopenia occurred after 86 of the 124 administered courses (69%), but only after 10/86 courses (12%) were major infections recorded. In 10/15 mobilized patients (cyclophosphamide + G-CSF: 6 patients; FAND + G-CSF: 9 patients) after FAND > or = 2 x 10(6)/kg CD34+ cells were collected. Nine patients were autografted in CR and showed a longer response duration than the 9 patients in CR who did not receive further therapy after FAND (53 vs 30% at 41 months; p = 0.05). INTERPRETATION AND CONCLUSIONS: FAND associated with extensive infection prophylaxis and G-CSF support is a highly cytoreductive and well-tolerated treatment for CLL patients and in most cases does not hamper subsequent stem cell mobilization.

Adult↗

PubMedDate not supplied

Feasibility and results of a multimodality approach in elderly patients with localized intermediate to high-grade non-Hodgkin's lymphomas.

AIMS AND BACKGROUND: A prospective clinical study to determine efficacy and feasibility of a brief course or standard course of anthracycline-based chemotherapy and consolidation radiation therapy in non-Hodgkin's lymphoma patients over 60 years of age. METHODS: Twenty-five consecutive patients with stage I-IE intermediate to high-grade non-Hodgkin's lymphoma aged 60 and older were treated in an outpatient setting in the Radiotherapy Oncology and Hematology units. All patients had a performance status of 0-1 according to WHO criteria. The survival end points, ie, overall survival, disease-free survival and event-free survival, were considered. Lactate dehydrogenase value, nodal versus extranodal localization and dose intensity were assessed as risk factors for disease-free and overall survival. A comparison using logrank analysis with a well-matched group of stage I-IE non-Hodgkin's lymphoma patients aged less than 60 years was performed. RESULTS: The 5-year overall and disease-free survival rates were 90% and 86%, respectively. There was no statistical difference with respect to the younger population regarding these survival end points. Finally, the 5-year event-free survival was 85% and 86% for elderly and younger patients, respectively, without statistical difference (P = 0.41). Neither acute nor late toxicity (G3-G4) was observed during chemotherapy and radiotherapy treatment and the follow-up in the elderly group. CONCLUSIONS: We confirm the efficacy and feasibility of a full-dose combined chemoradiotherapy in elderly patients with a good performance status with localized I-IE intermediate to high-grade non-Hodgkin's lymphoma.

Aged↗