27 results on '"Morra, Enrica"'
Search Results
2. Management recommendations for chronic myelomonocytic leukemia: consensus statements from the SIE, SIES, GITMO groups.
- Author
-
Onida F, Barosi G, Leone G, Malcovati L, Morra E, Santini V, Specchia G, and Tura S
- Subjects
- Disease Management, Humans, Leukemia, Myelomonocytic, Chronic diagnosis, Consensus, Leukemia, Myelomonocytic, Chronic therapy, Practice Guidelines as Topic standards, Societies, Medical standards, World Health Organization
- Abstract
With the aim of reviewing critical concepts and producing recommendations for the management of chronic myelomonocytic leukemia, key questions were selected according to the criterion of clinical relevance. Recommendations were produced using a Delphi process and four consensus conferences involving a panel of experts appointed by the Italian Society of Hematology and affiliated societies. This report presents the final statements and recommendations, covering patient evaluation at diagnosis, diagnostic criteria, risk classification, first-line therapy, monitoring, second-line therapy and allogeneic stem cell transplantation. For the first-line therapy, the panel recommended that patients with myelodysplastic-type chronic myelomonocytic leukemia and less than 10% blasts in bone marrow should be managed with supportive therapy aimed at correcting cytopenias. In patients with myelodysplastic-type chronic myelomonocytic leukemia with a high number of blasts in bone marrow (≥ 10%), supportive therapy should be integrated with the use of 5-azacytidine. Patients with myeloproliferative-type chronic myelomonocytic leukemia with a low number of blasts (<10%) should be treated with cytoreductive therapy. Hydroxyurea is the drug of choice to control cell proliferation and to reduce organomegaly. Patients with myeloproliferative-type chronic myelomonocytic leukemia, and a high number of blasts should receive polychemotherapy. Both in myelodysplastic-type and myeloproliferative-type chronic myelomonocytic leukemia, allogeneic stem cell transplantation should be offered within clinical trials in selected patients.
- Published
- 2013
- Full Text
- View/download PDF
3. Splenectomy as a curative treatment for immune thrombocytopenia: a retrospective analysis of 233 patients with a minimum follow up of 10 years.
- Author
-
Vianelli N, Palandri F, Polverelli N, Stasi R, Joelsson J, Johansson E, Ruggeri M, Zaja F, Cantoni S, Catucci AE, Candoni A, Morra E, Björkholm M, Baccarani M, and Rodeghiero F
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Incidence, Infant, Male, Middle Aged, Postoperative Complications epidemiology, Prognosis, Purpura, Thrombocytopenic, Idiopathic drug therapy, Purpura, Thrombocytopenic, Idiopathic mortality, Retrospective Studies, Treatment Outcome, Young Adult, Purpura, Thrombocytopenic, Idiopathic surgery, Splenectomy
- Abstract
The treatment of choice in steroid-resistant immune thrombocytopenia is still controversial due to the recent advent of new drugs (anti-CD20 antibodies and thrombopoietin mimetics) that have encouraged a generalized tendency to delay splenectomy. Consequently, it is extremely importance to define the efficacy and safety of splenectomy in the long term. We retrospectively analyzed the data of 233 patients affected by immune thrombocytopenia who underwent splenectomy between 1959 and 2001 in 6 European hematologic institutions and who have now a minimum follow up of ten years from surgery. Of the 233 patients, 180 (77%) achieved a complete response and 26 (11%) a response. Sixty-eight of 206 (33%) responsive patients relapsed, mostly (75%) within four years from first response. In 92 patients (39.5%), further treatment was required after splenectomy that was effective in 76 cases (83%). In 138 patients (59%), response was maintained free of any treatment at last contact. No significant association between baseline characteristics and likelihood of stable response was found. Overall, 73 (31%) and 58 (25%) patients experienced at least one infectious or hemorrhagic complication, which was fatal in 2 and 3 patients, respectively. A stable response to splenectomy was associated with a lower rate of infections (P=0.004) and hemorrhages (P<0.0001). Thrombosis developed in 18 patients (8%) and was fatal in 4. Splenectomy achieved a long-term stable response in approximately 60% of cases. Complications mainly affected non-responding patients and were fatal in a minority.
- Published
- 2013
- Full Text
- View/download PDF
4. Relationship between pharmacokinetic profile of subcutaneously administered alemtuzumab and clinical response in patients with chronic lymphocytic leukemia.
- Author
-
Montagna M, Montillo M, Avanzini MA, Tinelli C, Tedeschi A, Visai L, Ricci F, Vismara E, Morra E, and Regazzi M
- Subjects
- Alemtuzumab, Antibodies, Monoclonal blood, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm blood, Antineoplastic Agents blood, Humans, Injections, Subcutaneous, Kinetics, Leukemia, Lymphocytic, Chronic, B-Cell blood, Lymphocyte Count, Middle Aged, Neoplasm, Residual, Treatment Outcome, Antibodies, Monoclonal pharmacokinetics, Antibodies, Monoclonal therapeutic use, Antibodies, Neoplasm therapeutic use, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
Alemtuzumab serum levels and clinical response after subcutaneous administration (10 mg 3 times/week for six weeks) have been explored in 29 chronic lymphocytic leukemia patients receiving the monoclonal antibody as consolidation. Serum concentrations after each administration gradually increased during the first week and more markedly during weeks 2 and 3, approaching the steady-state at week 6. Absorption continued slowly through the tissues for about 2-3 weeks after the last administration, starting to decrease thereafter. Difference between Responders and Non-responders was statistically significant: maximal concentration (Cmax) was 1.69 μg/mL vs. 0.44 μg/mL; concentration before subcutaneous administration (Cpre-dose) on day 15 was 0.7 vs. 0.21 μg/mL, area under curve (AUC0-12h) was 11.09 vs. 2.26 μgxh/mL for Responders and Non-responders, respectively. Higher systemic exposure to alemtuzumab correlated with a better clinical response and minimal residual disease. Results suggest that an adjusted schedule according to serum level could improve clinical outcome of patients receiving subcutaneous alemtuzumab.
- Published
- 2011
- Full Text
- View/download PDF
5. The incidence of pleural and pericardial effusion is not higher in patients receiving dasatinib at low doses. (Reply).
- Author
-
Visani G, Breccia M, Montefusco E, Morra E, Santini V, and Isidori A
- Subjects
- Dasatinib, Humans, Incidence, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Thiazoles adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Pericardial Effusion epidemiology, Pericardial Effusion etiology, Pleural Effusion epidemiology, Pleural Effusion etiology, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Thiazoles therapeutic use
- Published
- 2011
- Full Text
- View/download PDF
6. Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: Practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation.
- Author
-
Morra E, Barosi G, Bosi A, Ferrara F, Locatelli F, Marchetti M, Martinelli G, Mecucci C, Vignetti M, and Tura S
- Subjects
- Hematology, Humans, Italy epidemiology, Leukemia, Myeloid epidemiology, Leukemia, Myeloid genetics, Leukemia, Myeloid surgery, Societies, Medical, Bone Marrow Transplantation, Leukemia, Myeloid therapy, Practice Guidelines as Topic standards
- Abstract
As many options are now available to treat patients with de novo acute myeloid leukemia, the Italian Society of Hematology and two affiliated societies (SIES and GITMO) commissioned project to an Expert Panel aimed at developing clinical practice guidelines for acute myeloid leukemia treatment. After systematic comprehensive literature review, the Expert Panel formulated recommendations for the management of primary acute myeloid leukemia (with the exception of acute promyelocytic leukemia) and graded them according to the supporting evidence. When evidence was lacking, consensus-based statements have been added. First-line therapy for all newly diagnosed patients eligible for intensive treatment should include one cycle of induction with standard dose cytarabine and an anthracycline. After achieving complete remission, patients aged less than 60 years should receive consolidation therapy including high-dose cytarabine. Myeloablative allogeneic stem cell transplantation from an HLA-compatible sibling should be performed in first complete remission: 1) in children with intermediate-high risk cytogenetics or who achieved first complete remission after the second course of therapy; 2) in adults less than 40 years with an intermediate-risk; in those aged less than 55 years with either high-risk cytogenetics or who achieved first complete remission after the second course of therapy. Stem cell transplantation from an unrelated donor is recommended to be performed in first complete remission in adults 30 years old or younger, and in children with very high-risk disease lacking a sibling donor. Alternative donor stem cell transplantation is an option in high-risk patients without a matched donor who urgently need transplantation. Patients aged less than 60 years, who either are not candidate for allogeneic stem cell transplantation or lack a donor, are candidates for autologous stem cell transplantation. We describe the results of a systematic literature review and an explicit approach to consensus techniques, which resulted in recommendations for the management of primary non-APL acute myeloid leukemia.
- Published
- 2009
- Full Text
- View/download PDF
7. Consensus conference on the management of tumor lysis syndrome.
- Author
-
Tosi P, Barosi G, Lazzaro C, Liso V, Marchetti M, Morra E, Pession A, Rosti G, Santoro A, Zinzani PL, and Tura S
- Subjects
- Allopurinol therapeutic use, Disease Management, Hematologic Neoplasms complications, Humans, Italy, Urate Oxidase therapeutic use, Tumor Lysis Syndrome drug therapy
- Abstract
Tumor lysis syndrome is a potentially life threatening complication of massive cellular lysis in cancers. Identification of high-risk patients and early recognition of the syndrome is crucial in the institution of appropriate treatments. Drugs that act on the metabolic pathway of uric acid to allantoin, like allopurinol or rasburicase, are effective for prophylaxis and treatment of tumor lysis syndrome. Sound recommendations should regulate diagnosis and drug application in the clinical setting. The current article reports the recommendations on the management of tumor lysis syndrome that were issued during a Consensus Conference project, and which were endorsed by the Italian Society of Hematology (SIE), the Italian Association of Pediatric Oncologists (AIEOP) and the Italian Society of Medical Oncology (AIOM). Current concepts on the pathophysiology, clinical features, and therapy of tumor lysis syndrome were evaluated by a Panel of 8 experts. A consensus was then developed for statements regarding key questions on tumor lysis syndrome management selected according to the criterion of relevance by group discussion. Hydration and rasburicase should be administered to adult cancer patients who are candidates for tumor-specific therapy and who carry a high risk of tumor lysis syndrome. Cancer patients with a low-risk of tumor lysis syndrome should instead receive hydration along with oral allopurinol. Hydration and rasburicase should also be administered to patients with clinical tumor lysis syndrome and to adults and high-risk children who develop laboratory tumor lysis syndrome. In conclusion, the Panel recommended rasburicase for tumor lysis syndrome prophylaxis in selected patients based on the drug efficacy profile. Methodologically rigorous studies are needed to clarify its cost-effectiveness profile.
- Published
- 2008
- Full Text
- View/download PDF
8. Intense reversal of bone marrow angiogenesis after sequential fludarabine-induction and alemtuzumab-consolidation therapy in advanced chronic lymphocytic leukemia.
- Author
-
Molica S, Montillo M, Ribatti D, Mirabelli R, Tedeschi A, Ricci F, Veronese S, Vacca A, and Morra E
- Subjects
- Adult, Alemtuzumab, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow metabolism, Bone Marrow pathology, Female, Humans, Immunotherapy, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Neoplasm Staging, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Vidarabine therapeutic use, Antibodies, Monoclonal therapeutic use, Antibodies, Neoplasm therapeutic use, Bone Marrow blood supply, Bone Marrow drug effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Vidarabine analogs & derivatives
- Abstract
Background and Objectives: Increased bone marrow (BM) angiogenesis has been demonstrated in several hematologic malignancies. BM angiogenesis is significantly decreased in patients with chronic lymphocytic leukemia (CLL) treated with fludarabine. The anti-angiogenic potential of alemtuzumab in CLL has not yet been investigated. We, therefore, evaluated BM angiogenesis in CLL patients treated sequentially with fludarabine and low doses of alemtuzumab., Design and Methods: BM microvessel area was sequentially evaluated in 20 patients with advanced B-cell CLL who received, after a clinical response obtained with fludarabine-induction therapy, alemtuzumab, three times weekly for 6 weeks at a dose of 10 mg., Results: The complete response rate improved from 45% after fludarabine induction to 90% after alemtuzumab consolidation. The extent of BM angiogenesis decreased continuously after either fludarabine or alemtuzumab (p=0.0002; Kruskal-Wallis test). Thirteen out of 20 (65%) patients changed from having a monoclonal to a polyclonal pattern of IgH sequences after alemtuzumab consolidation. A separate evaluation carried out in patients who achieved molecularly undetectable disease, as defined by polymerase chain reaction negativity, and in patients who remained with minimal residual disease after therapy with alemtuzumab showed a significant reduction of BM microvessel area only in the former (p=0.0002). Finally, molecular responses and a significant reduction of BM angiogenesis were more common in patients who received the cumulative planned dose of alemtuzumab (i.e.,180 mg) than in patients who received reduced doses (p=0.007 and p=0.0001, respectively)., Interpretation and Conclusions: Overall, these data demonstrate a decrease in BM vascularity that characterized CLL patients who received low doses of subcutaneous alemtuzumab consolidation therapy after a clinical response to fludarabine induction therapy. Such a finding reflects, at least in part, the molecular response and cumulative dose of alemtuzumab.
- Published
- 2007
9. Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity.
- Author
-
Brusamolino E, Rusconi C, Montalbetti L, Gargantini L, Uziel L, Pinotti G, Fava S, Rigacci L, Pagnucco G, Pascutto C, Morra E, and Lazzarino M
- Subjects
- Adult, Aged, Antibodies, Monoclonal toxicity, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols toxicity, Cyclophosphamide administration & dosage, Cyclophosphamide toxicity, Doxorubicin administration & dosage, Doxorubicin toxicity, Filgrastim, Humans, Lymphoma, Large B-Cell, Diffuse complications, Lymphoma, Large B-Cell, Diffuse mortality, Middle Aged, Polyethylene Glycols, Prednisone administration & dosage, Prednisone toxicity, Recombinant Proteins, Rituximab, Treatment Outcome, Vincristine administration & dosage, Vincristine toxicity, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Granulocyte Colony-Stimulating Factor administration & dosage, Lymphoma, B-Cell drug therapy, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Background and Objectives: The aim of this study was to evaluate the feasibility and toxicity of CHOP-14, with rituximab (R-CHOP-14), supported by pegfilgrastim, in untreated diffuse large B-cell lymphoma (DLBCL)., Design and Methods: This study included 50 patients with DLBCL with a median age of 55 years (range: 22-70). Sixty-two percent had an International Prognostic Index score >1, 40% had bulky disease and 52% had stage IV disease. CHOP was administered every 14 days, preceded on day 1 by rituximab (375 mg/m2) and followed on day 3 by pegfilgrastim (6 mg per cycle). Toxicity was calculated over 277 cycles administered; feasibility was calculated over 227, since the first cycle in each patient was not susceptible to delay or dose-reduction., Results: Therapy was delivered on time in 92% of cycles, with the relative dose intensity being 95% for doxorubicin and cyclophosphamide. Grade 4 neutropenia developed in 19% of cycles and neutropenic fever in 4% of cycles (16% of patients), with a median duration of 3 days (range: 2-10). The program was completed in 40 of 50 patients (80%); reasons for withdrawal included progression in three patients, interstitial pneumonia in four, prolonged severe neutropenia in two and septic shock in one patient. Severe adverse events occurred on 12 occasions (4% of cycles), involving 11 patients (22% of total); the most frequent severe adverse event was interstitial pneumonia which occurred in seven patients (14% of total). In three cases, Pneumocystis carinii pneumonia was documented; no cotrimoxazole prophylaxis had been given and a correlation with hypogammaglobulinemia was observed. The complete remission rate was 74%; the 2-year event-free and overall survival rates were 72% and 68%, respectively., Interpretation and Conclusions: A single dose of pegfilgrastim per cycle of R-CHOP allowed on-time delivery of this chemotherapy in DLBCL, with a low incidence of febrile neutropenia; the risk of P. carinii pneumonia makes cotrimoxazole prophylaxis essential in this setting.
- Published
- 2006
10. Multiple lines of chemotherapy are the main risk factor for severe infections in patients with chronic lymphocytic leukemia with febrile episodes.
- Author
-
Molteni A, Nosari A, Montillo M, Cafro A, Klersy C, and Morra E
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Antineoplastic Agents adverse effects, Fever epidemiology, Infections epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
We report on febrile episodes occurring among 379 patients affected by chronic lymphocytic leukemia, observed from 1984 to 2002. One hundred and twenty eight patients (33.7%) developed 341 febrile episodes, of which 251 were documented infections (82 severe and 169 moderate). Among various risk factors, only previous treatment with multiple regimens of chemotherapy was associated with severity of infection (p=0.0005).
- Published
- 2005
11. Chronic lymphocytic leukemia: novel prognostic factors and their relevance for risk-adapted therapeutic strategies.
- Author
-
Montillo M, Hamblin T, Hallek M, Montserrat E, and Morra E
- Subjects
- Biomarkers, Cytogenetic Analysis, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Prognosis, Risk Assessment, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell therapy
- Abstract
Background and Objectives: Many years ago it was established that prompt treatment of early stage chronic lymphocytic leukemia (CLL), the stage at which almost two-thirds of CLL patients present, has no benefit over a management of watching and waiting, then treating progression. However, this fact was based on series treated ineffectually with chlorambucil, which were not stratified according to prognostic markers., Design and Methods: The prognosis and clinical course of CLL are heterogeneous. While some patients may have a normal life expectancy without requiring treatment, others die of drug-resistant disease as early as within two years of presentation. However, unlike the situation in non-Hodgkin's lymphoma, there is no standard Prognostic Index that can be used to group patients with CLL according to likely outcome or to guide treatment., Results: A number of clinical and biological factors of prognostic relevance, which may add to the classical assessment provided by the staging systems, have been identified. These include clinical characteristics, such as age, gender and performance status, and laboratory parameters reflecting the tumor burden or disease activity, such as lymphocyte count, lactate dehydrogenase (LDH) increase, bone marrow infiltration pattern or lymphocyte doubling time. Recently more informative prognostic parameters have been identified: serum markers such as soluble CD23, b2-microglobulin or thymidine kinase and genetic markers of tumor cells, such as genomic aberrations, gene abnormalities (p53, ATM), the mutation status of the variable segments of the immunoglobulin heavy chain genes (IGVH) or surrogate markers for these factors, such as CD38 and ZAP-70., Interpretation and Conclusions: From the clinician's perspective the importance of this new knowledge is how it affects treatment. It is now possible to produce molecular remissions even in advanced disease using combinations of purine analogs and monoclonal antibodies. Moreover, potentially curative therapeutic modalities such as autologous and allogeneic stem cell transplantation are becoming safer. Clinical trials of effective treatment stratified by more reliable prognostic markers are surely now warranted.
- Published
- 2005
12. Infectious toxicity using alemtuzumab.
- Author
-
Nosari A, Montillo M, and Morra E
- Subjects
- 2-Aminopurine analogs & derivatives, 2-Aminopurine therapeutic use, Alemtuzumab, Antibiotic Prophylaxis, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal, Murine-Derived, Antibodies, Neoplasm pharmacology, Antigens, CD immunology, Antigens, Neoplasm immunology, Antineoplastic Agents pharmacology, Bone Marrow Transplantation, CD52 Antigen, Clinical Trials as Topic, Cytomegalovirus Infections etiology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections prevention & control, Disease Susceptibility, Famciclovir, Ganciclovir therapeutic use, Glycoproteins antagonists & inhibitors, Glycoproteins immunology, Graft vs Host Disease prevention & control, Humans, Immunosuppressive Agents pharmacology, Incidence, Lymphoproliferative Disorders drug therapy, Opportunistic Infections etiology, Opportunistic Infections prevention & control, Pneumonia, Pneumocystis etiology, Pneumonia, Pneumocystis immunology, Pneumonia, Pneumocystis prevention & control, Rituximab, Transplantation Conditioning, Trimethoprim, Sulfamethoxazole Drug Combination therapeutic use, Viremia etiology, Viremia immunology, Viremia prevention & control, Virus Activation, Antibodies, Monoclonal adverse effects, Antibodies, Neoplasm adverse effects, Antineoplastic Agents adverse effects, Immunologic Deficiency Syndromes chemically induced, Immunosuppressive Agents adverse effects, Infections etiology
- Published
- 2004
13. The VAD-DCEP sequence is an effective pre-transplant therapy in untreated multiple myeloma.
- Author
-
Corso A, Barbarano L, Zappasodi P, Cairoli R, Alessandrino EP, Mangiacavalli S, Ferrari D, Fava S, Fiumanò M, Frigerio G, Isa L, Luraschi A, Klersy C, De Paoli A, Vergani C, Banfi L, Perego D, Ucci G, Pinotti G, Savarè M, Uziel L, Vismara A, Morra E, and Lazzarino M
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Cisplatin adverse effects, Cohort Studies, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Dexamethasone administration & dosage, Dexamethasone adverse effects, Doxorubicin administration & dosage, Doxorubicin adverse effects, Drug Administration Schedule, Etoposide administration & dosage, Etoposide adverse effects, Female, Hematopoietic Stem Cell Mobilization, Humans, Male, Melphalan therapeutic use, Middle Aged, Multiple Myeloma surgery, Neoadjuvant Therapy adverse effects, Neutropenia chemically induced, Thrombocytopenia chemically induced, Transplantation Conditioning adverse effects, Transplantation, Autologous, Treatment Outcome, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Background and Objectives: Standard treatment for patients with multiple myeloma is debulking chemotherapy with non-alkylating agents followed by a regimen to mobilize peripheral blood stem cells (PBSC) and the transplantation of the mobilized, autologous PBSC. The aim of this study was to evaluate the efficacy of a new regimen and compare it with that of a previous regimen., Design and Methods: In a large cohort of 106 patients (group I) we administered a new pre-transplant program which includes 2 courses of pulsed-VAD (vincristine, adriamycin, dexamethasone) followed by 2 courses of DCEP (dexamethasone, cyclophosphamide, etoposide and cis-platinum). We compared the efficacy of this new VAD-DCEP sequence, in terms of mobilizing capacity, toxicity and anti-myeloma activity in comparison with that of the previous VAD-high-dose cyclophosphamide program (group II, 40 patients)., Results: In group I 81/106 (76.4%) patients yielded >or= 4x10(6)/kg CD34+ cells, as did 30/40 (75%) in group II but with a significantly higher toxicity in this latter group. In detail, 9 patients in group I (8.5%) had WHO grade III neutropenia versus 35 in group II (87.5%), 5 patients of group I (4.7%) had grade III thrombocytopenia versus 12 patients in group II (30%), and 8 patients in group I (7.5%) experienced an infections fever versus 9 patients in group II (22.5%). Therefore, nearly all patients in group II had to be admitted to hospital (39/40, 97.5%). There was a higher percentage of responses (CR+VGPR+PR) in group I than in group II: 73% versus 50% (p=0.02)., Interpretation and Conclusions: the VAD-DCEP sequence has an adequate mobilizing capacity, without significant toxicity, and a good anti-myeloma activity, and therefore represents a safe and effective therapeutic approach for multiple myeloma patients at the onset of their disease.
- Published
- 2004
14. Aggressive systemic mastocytosis mimicking sclerosing cholangitis.
- Author
-
Marbello L, Anghilieri M, Nosari A, Minola E, Cairoli R, Ricci F, and Morra E
- Subjects
- Abdominal Pain etiology, Adrenal Cortex Hormones therapeutic use, Adult, Amino Acid Substitution, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biopsy, Needle, Bone Marrow pathology, Budd-Chiari Syndrome etiology, Cholangiopancreatography, Endoscopic Retrograde, Clone Cells pathology, Cytarabine administration & dosage, Diagnosis, Differential, Diarrhea etiology, Fatal Outcome, Female, Flushing etiology, Histamine H1 Antagonists administration & dosage, Histamine H1 Antagonists therapeutic use, Humans, Idarubicin administration & dosage, Liver pathology, Lymphoma diagnosis, Mast Cells pathology, Mastocytosis, Systemic complications, Mastocytosis, Systemic drug therapy, Mastocytosis, Systemic genetics, Mastocytosis, Systemic pathology, Mutation, Missense, Point Mutation, Prednisone administration & dosage, Proto-Oncogene Proteins c-kit genetics, Recurrence, Cholangitis, Sclerosing diagnosis, Mastocytosis, Systemic diagnosis
- Abstract
A 43 year-old woman presented with fever, abdominal pain, epato-splenomegaly, ascites, cholestasis, anemia, thrombocytopenia and previous diagnosis of sclerosing cholangitis based on liver biopsy and endoscopic retrograde cholangiopancreatography(ERCP). The bone marrow biopsy and the revision of liver biopsy using antitryptase stain diagnosed systemic mastocytosis. Because of the aggressive course of the disease the patient was treated with an acute myeloid leukaemia chemotherapy regimen without success.
- Published
- 2004
15. KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication.
- Author
-
Beghini A, Ripamonti CB, Cairoli R, Cazzaniga G, Colapietro P, Elice F, Nadali G, Grillo G, Haas OA, Biondi A, Morra E, and Larizza L
- Subjects
- Adult, Child, Core Binding Factors blood, Core Binding Factors genetics, DNA Mutational Analysis, Gene Expression Regulation, Neoplastic, Humans, Polymerase Chain Reaction, Gene Duplication, Leukemia, Myeloid, Acute genetics, Proto-Oncogene Proteins c-kit genetics
- Abstract
Background and Objectives: Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia., Design and Methods: In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations., Results: Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1%) adult CBFL cases and 6 of the 49 (12.2%) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele., Interpretation and Conclusions: These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.
- Published
- 2004
16. High incidence of neutropenia in patients treated with rituximab after autologous stem cell transplantation.
- Author
-
Cairoli R, Grillo G, Tedeschi A, D'Avanzo G, Marenco P, and Morra E
- Subjects
- Adult, Antibodies, Monoclonal, Murine-Derived, Bone Marrow Purging adverse effects, Female, Humans, Lymphoma, Follicular therapy, Lymphoma, Mantle-Cell therapy, Male, Middle Aged, Rituximab, Transplantation, Autologous, Antibodies, Monoclonal adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neutropenia etiology, Peripheral Blood Stem Cell Transplantation adverse effects
- Abstract
We report a high incidence of neutropenia in patients treated with rituximab prior to and following autologous stem cell transplantation (ASCT). Fourteen patients with follicular or mantle-cell lymphoma were treated with high dose (HD) therapy followed by an in vivo-purged autologous graft.
- Published
- 2004
17. Chronic lymphocytic leukemia 2003.
- Author
-
Morra E and Montillo M
- Subjects
- Humans, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Published
- 2004
18. Utility of percutaneous lung biopsy for diagnosing filamentous fungal infections in hematologic malignancies.
- Author
-
Nosari A, Anghilieri M, Carrafiello G, Guffanti C, Marbello L, Montillo M, Muti G, Ribera S, Vanzulli A, Nichelatti M, and Morra E
- Subjects
- Adenocarcinoma, Bronchiolo-Alveolar diagnosis, Adenocarcinoma, Bronchiolo-Alveolar pathology, Adult, Antifungal Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aspergillosis drug therapy, Aspergillosis etiology, Aspergillosis microbiology, Aspergillosis pathology, Aspergillus isolation & purification, Bronchoalveolar Lavage Fluid microbiology, Disease Susceptibility, Female, Hematologic Neoplasms drug therapy, Humans, Lung diagnostic imaging, Lung microbiology, Lung Diseases, Fungal drug therapy, Lung Diseases, Fungal etiology, Lung Diseases, Fungal microbiology, Lung Diseases, Fungal pathology, Lung Neoplasms diagnosis, Lung Neoplasms pathology, Male, Middle Aged, Mucorales isolation & purification, Mucormycosis drug therapy, Mucormycosis etiology, Mucormycosis microbiology, Mucormycosis pathology, Neoplasms, Multiple Primary diagnosis, Neoplasms, Multiple Primary pathology, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Tomography, X-Ray Computed, Aspergillosis diagnosis, Biopsy, Needle methods, Hematologic Neoplasms complications, Lung pathology, Lung Diseases, Fungal diagnosis, Mucormycosis diagnosis, Radiography, Interventional
- Abstract
Background and Objectives: The incidence of invasive filamentous fungal infections in hematologic patients is increasing as a consequence of high dose chemotherapy and bone marrow transplant procedures. Mortality is usually very high. The diagnosis is often difficult and yet a fast, accurate diagnosis is of fundamental importance for treating the infection and planning subsequent management of the hematologic disease. We evaluated the sensitivity of computed tomography (CT)-guided percutaneous biopsy in diagnosing pulmonary fungal infections., Design and Methods: Between 1997 and 2002 we performed 17 CT-guided percutaneous transthoracic lung biopsies in 17 hematologic patients with suspected filamentous fungi infection with negative BAL, to obtain a certain diagnosis and to know what species of fungi was responsible for infection. In all cases suspected mycosis began during the post-chemotherapy aplastic period. Patients were receiving antifungal therapy at the time of all biopsies. When the platelet count rose above 50 x 10(9)/L, CT-guided percutaneous lung biopsy with fine-needle aspiration for cytology was performed., Results: Twelve of 17 patients had histologic confirmation of the fungal infection (70.5%), 8 with Aspergillus spp. 4 with Mucorales spp. Biopsies provided non-specific results in 4 cases; in 2 of these cases, clinical course and response to therapy confirmed the diagnosis of mycosis; in the last case bronchoalveolar carcinoma was found as a new diagnosis. Cultures were positive in only 6 cases, all for Aspergillus spp. The sensitivity of CT-guided percutaneous lung biopsy was 70.6% and its positive predictive value (PPV) was 100%. This procedure provided an immediate diagnosis and only one side-effect (1 pneumothorax, without complications)., Interpretation and Conclusions: Histologic discrimination between aspergillosis and mucormycosis is very important for deciding secondary prophylaxis during transplant procedures, because Mucor is usually resistant to azoles.
- Published
- 2003
19. Clinical utility of the absolute number of circulating CD34-positive cells in patients with chronic myeloproliferative disorders.
- Author
-
Passamonti F, Vanelli L, Malabarba L, Rumi E, Pungolino E, Malcovati L, Pascutto C, Morra E, Lazzarino M, and Cazzola M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers blood, Cell Count, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Polycythemia Vera blood, Primary Myelofibrosis blood, Prospective Studies, Thrombocythemia, Essential blood, Antigens, CD34 blood, Antigens, CD34 metabolism, Hematopoietic Stem Cells metabolism, Myeloproliferative Disorders blood
- Abstract
Background and Objectives: Flow cytometry enumeration of peripheral blood CD34-positive cells provides reliable measurements of circulating hematopoietic progenitors in humans. Since the absolute number of circulating CD34-positive cells has been previously found to be elevated in myelofibrosis with myeloid metaplasia (MMM), we prospectively studied the clinical utility of this parameter in the work-up of patients with chronic myeloproliferative disorders., Design and Methods: Of the 248 consecutive patients enrolled in this study, 106 had polycythemia vera (PV), 90 essential thrombocythemia (ET), and 52 myelofibrosis with myeloid metaplasia (MMM). The study population included both newly diagnosed and established cases, and of these latter some patients were on cytoreductive treatment while others were chemotherapy naive. Both cross-sectional and longitudinal investigations were carried out. Flow cytometry enumeration of CD34-positive cells was performed using a single-platform assay., Results: Median numbers and ranges of circulating CD34-positive cells were 2.3x10(6)/L (0-5) in 20 control subjects, 2.2x10(6)/L (0-14) in those with PV, 2.4x10(6)/L (0-14) in those with ET, and 114x10(6)/L (6-2,520) in MMM patients. Analysis of variance demonstrated that values were markedly higher in MMM patients than in the remaining groups, and counts did not appear to fluctuate over short periods of follow-up. In both cross-sectional and longitudinal investigations on patients at clinical onset and/or out of cytoreductive treatment, a CD34-positive count of > or = 15x10(6)/L was always associated with MMM, clearly indicating a disease-related specificity., Interpretation and Conclusions: The absolute number of circulating CD34-positive cells is normal or anyhow lower than 15x10(6)/L in patients with uncomplicated PV or ET, whereas it is equal or above this cut-off in those with MMM, likely reflecting abnormal hematopoietic progenitor cell trafficking. Thus, enumeration of circulating CD34-positive cells may be useful in the work-up of patients with myeloproliferative disorders.
- Published
- 2003
20. Risk factors for the development of bacterial infections in multiple myeloma treated with two different vincristine-adriamycin-dexamethasone schedules.
- Author
-
Cesana C, Nosari AM, Klersy C, Miqueleiz S, Rossi V, Ferrando P, Valentini M, Barbarano L, and Morra E
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bacterial Infections mortality, Bacterial Infections pathology, Dexamethasone administration & dosage, Doxorubicin administration & dosage, Escherichia coli isolation & purification, Escherichia coli Infections epidemiology, Escherichia coli Infections mortality, Escherichia coli Infections pathology, Female, Humans, Klebsiella Infections epidemiology, Klebsiella Infections mortality, Klebsiella Infections pathology, Klebsiella pneumoniae isolation & purification, Male, Middle Aged, Multiple Myeloma epidemiology, Multiple Myeloma mortality, Pseudomonas Infections epidemiology, Pseudomonas Infections mortality, Pseudomonas Infections pathology, Pseudomonas aeruginosa isolation & purification, Retrospective Studies, Risk Factors, Severity of Illness Index, Staphylococcal Infections epidemiology, Staphylococcal Infections mortality, Staphylococcal Infections pathology, Staphylococcus aureus isolation & purification, Staphylococcus epidermidis isolation & purification, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bacterial Infections epidemiology, Multiple Myeloma drug therapy, Multiple Myeloma microbiology
- Abstract
Background and Objectives: We evaluated bacterial infections (BIs) in patients with multiple myeloma (MM) treated with two different schedules of vincristine-adriamycin-dexamethasone (VAD)., Design and Methods: Ninety-seven patients were studied during 340 VAD cycles. VAD was given by either continuous intravenous infusion (CII) to hospitalized patients or rapid intravenous infusion (RII) to outpatients. The characteristics of patients and VAD schedules were retrospectively analyzed to detect correlations with the incidence of BI., Results: By analyzing each VAD cycle, we found that profound hypogammaglobulinemia (p=0.06) and post-treatment neutropenia (p=0.08) were associated with a trend for a higher risk of infection, while renal function impairment was significantly correlated with BI risk at both univariate (p<0.02) and multivariate (p<0.002) analyses. Evaluating only the first 4 months of therapy, characterized by a significantly higher incidence of BI than the later period (p<0.0001), previously untreated disease was significantly correlated with BI risk (p<0.04), while male sex (p=0.06), CII schedule (p=0.07), and profound hypogammaglobulinemia (p=0.1) were associated with a tendency to a higher risk of infection; however, at multivariate analysis the latter two parameters independently predicted BI probability (p<0.015 and p<0.03, respectively) as did previously untreated disease (p<0.025). The high probability of CII-related infection was demonstrated to depend on the frequent development of nosocomial infections., Interpretation and Conclusions: Patients with profound hypogammaglobulinemia who receive VAD as first line treatment are at a major risk of BI up to the completion of the fourth month of therapy. In this setting hospitalization should be avoided and, if patients require admission, antibacterial prophylaxis with intravenous immunoglobulins could be appropriate and effective.
- Published
- 2003
21. Successful treatment with voriconazole of cerebral aspergillosis in an hematologic patient.
- Author
-
Marbello L, Nosari A, Carrafiello G, Anghilieri M, Cesana C, Cafro AM, D'Avanzo G, and Morra E
- Subjects
- Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Middle Aged, Opportunistic Infections drug therapy, Pyrimidines therapeutic use, Treatment Outcome, Triazoles therapeutic use, Voriconazole, Antifungal Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell complications, Neuroaspergillosis drug therapy
- Published
- 2003
22. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology.
- Author
-
Alessandrino EP, Amadori S, Barosi G, Cazzola M, Grossi A, Liberato LN, Locatelli F, Marchetti M, Morra E, Rebulla P, Visani G, and Tura S
- Subjects
- Consensus, Disease Management, Eligibility Determination, Evidence-Based Medicine, Humans, Italy, Societies, Medical, Myelodysplastic Syndromes therapy, Practice Guidelines as Topic standards
- Abstract
Background and Objectives: Novel therapeutic agents and strategies have been introduced into the management of myelodysplastic syndromes (MDS) in the last years. This has led to more treatment options and a better chance of long-term survival for MDS patients, but also to uncertainty regarding the optimal use and possible side effects of these treatments. The Italian Society of Hematology commissioned a project to develop guidelines for the therapy of MDS using evidence-based knowledge and consensus-formation techniques., Design and Methods: An Advisory Council (AC) shaped the project around a series of key clinical questions, performed a systematic search for evidence and graded the available evidence according to the Scottish Intercollegiate Guidelines Network (SIGN). A list of clinical questions was mailed to each of 10 senior hematologists composing the Expert Panel (EP): the panelists were asked to rank the most relevant questions, and to formulate answers to the questions according to the tables of evidence. A scenario phase followed, so as to reach a consensus on the three top ranked questions. The EP was asked to score patient profiles as appropriate or not appropriate for the therapeutic strategy under scrutiny, according to the RAND technique. Finally, from September 2001 to January 2002, four Consensus Conferences conducted according to the Nominal Group Technique were held in Milan, Italy. The overall goal of the conferences was to take a final decision upon the appropriateness of the uncertain scenarios and of the uncertain responses to the clinical questions., Results: Evidence was judged sufficient for providing recommendations on the use of allogeneic stem cell transplantation, leukemia-like chemotherapy, autologous stem cell transplantation, low-dose chemotherapy, danazol, immunosuppressive therapy, hypomethylating agents and hematopoietic growth factors. Specific recommendations for supportive therapy, including iron chelation, were issued. Allogeneic stem cell transplantation was unanimously considered as the only curative treatment for MDS patients, and recommendations on its use were agreed based on patient's age, risk, clinical features and donor availability. AML-like chemotherapy was also considered a valuable therapeutic option for subsets of MDS patients. Autologous stem cell transplantation was recommended for patients who lack an HLA identical donor and have achieved complete remission with AML-like chemotherapy. Decitabine, recombinant human erythropoietin and immunosuppressive therapy were judged valuable therapeutic options for subsets of MDS patients whereas low-dose cytarabine was not. Specific therapeutic strategies for those subjects younger than 18 years or older than 75 years and the strategy of watchful waiting were decided by patient-oriented questions., Interpretation and Conclusions: Using evidence and consensus, recommendations for the treatment of MDS were issued. Statements were graded according to the strength of the supporting evidence and uncertainty was explicitly declared.
- Published
- 2002
23. Hepatitis C virus infection in a hematology ward: evidence for nosocomial transmission and impact on hematologic disease outcome.
- Author
-
Silini E, Locasciulli A, Santoleri L, Gargantini L, Pinzello G, Montillo M, Foti L, Lisa A, Orfeo N, Magliano E, Nosari A, and Morra E
- Subjects
- Adolescent, Adult, Aged, Cross Infection virology, Female, Follow-Up Studies, Hematologic Neoplasms mortality, Hepacivirus genetics, Hepatitis C diagnosis, Hepatitis C epidemiology, Hospital Units, Humans, Male, Middle Aged, Cross Infection transmission, Hematologic Neoplasms complications, Hepatitis C etiology
- Abstract
Background and Objectives: Hepatitis C virus (HCV) infection is frequent among patients with hematologic malignancies and unapparent routes of infection may be important in this setting. Moreover, the impact of this infection on the outcome of the hematologic disease needs to be better defined., Design and Methods: To define sources and clinical courses of HCV infection, an epidemiologic study was performed on 13 patients newly admitted over one year who showed transaminase elevation and anti-HCV seroconversion. The investigation, started in August 1998, included laboratory tests and molecular analysis of virus isolates, and was extended to staff and blood donors. Clinical, hematologic and serologic surveillance of all infected patients were part of the subsequent follow-up study which started in September 1998 and was completed in December 2001., Results: Anti-HCV seroconversion was observed in 13 of 294 patients (4.4%), admitted to the unit from August 1997 and August 1998; 11 of the seroconverted cases had central catheters, 12 received transfusions. Transmission via blood derivatives and staff was ruled out. All patients were infected by genotype 1b and 11 harbored the same viral variant. HCV infection did not influence the course of the underlying disease or the use of specific therapies. Forty months after the outbreak, five patients are alive (one after autologous and one after allogeneic stem cell transplantation), while eight have died, seven of hematologic disease, and one of cardiac failure. None died of liver disease., Interpretation and Conclusions: The molecular data suggest a patient-to-patient nosocomial HCV transmission. After having analyzed all the possible routes of transmission, a series of preventive measures were adopted: search for HCV RNA in newly admitted patients, protection of mucosae and isolation of patients during neutropenic phases, and avoidance of multidose vials. As regards the impact of HCV infection on the outcome of the hematologic diseases, changes in the scheduled therapy, including stem cell transplantation, were not required.
- Published
- 2002
24. A combination of dexamethasone, cyclophosphamide, etoposide, and cisplatin is less toxic and more effective than high-dose cyclophosphamide for peripheral stem cell mobilization in multiple myeloma.
- Author
-
Corso A, Arcaini L, Caberlon S, Zappasodi P, Mangiacavalli S, Lorenzi A, Rusconi C, Troletti D, Maiocchi MA, Pascutto C, Morra E, and Lazzarino M
- Subjects
- Adult, Aged, Antigens, CD34 biosynthesis, Antineoplastic Combined Chemotherapy Protocols toxicity, Cisplatin toxicity, Cyclophosphamide toxicity, Dexamethasone toxicity, Etoposide toxicity, Female, Flow Cytometry, Humans, Leukocytes metabolism, Male, Middle Aged, Multiple Myeloma metabolism, Stem Cells cytology, Time Factors, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Cyclophosphamide therapeutic use, Dexamethasone administration & dosage, Etoposide administration & dosage, Stem Cells metabolism
- Abstract
Background and Objectives: The purpose of this study was to compare the efficacy and toxicity of two regimens for peripheral blood stem cell (PBSC) mobilization in multiple myeloma (MM) patients., Design and Methods: From 1995 to 2001, 116 patients were enrolled in two high-dose programs including autologous transplantation, adopting two mobilizing regimens: 61 patients were mobilized with high-dose cyclophosphamide (HD-Cy) at 4 g/m2 (group I), and 55 patients with DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) (group II), both followed by granulocyte colony-stimulating factor (G-CSF 5 mg/Kg/day) started 48 hours after chemotherapy., Results: The median number of CD34+ cells harvested was similar in the two groups (5.9 vs 5.82x106 cells/kg). The target of at least 4x106 cells/kg was reached in a higher percentage of patients in the DCEP group (75 vs 59%) (p=0.05). The proportion of poor mobilizers (<2x106 CD34+ cells/kg) was 21% with HD-Cy and 13% with DCEP (P=NS). In group I, 10 patients (16%) required packed red cell transfusions, 5 patients (8%) platelet support, and the majority of patients (87%) had a neutrophil count below 500/mL, whereas none did so in group II (p=0.0009, p=0.01, p=0.0009, respectively). Neutropenia-related fever occurred in 18% of patients in group I versus 0% in group II (p=0.0005). WHO grade >II extra-hematologic toxicities (microhematuria, cystitis, infections) were seen in 8 patients (13%) of group I vs 0 in group II (p=0.007)., Interpretation and Conclusions: DCEP is a better tolerated and more effective regimen than HD-Cy for peripheral stem cell mobilization in MM patients assigned to high-dose therapy programs.
- Published
- 2002
25. Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leukemia responding to fludarabine.
- Author
-
Montillo M, Cafro AM, Tedeschi A, Brando B, Oreste P, Veronese S, Rossi V, Cairoli R, Pungolino E, and Morra E
- Subjects
- Adult, Alemtuzumab, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal toxicity, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm administration & dosage, Antibodies, Neoplasm toxicity, Antineoplastic Combined Chemotherapy Protocols toxicity, Female, Humans, Injections, Subcutaneous, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Male, Middle Aged, Neoplasm, Residual drug therapy, Therapeutic Equivalency, Treatment Outcome, Vidarabine administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Vidarabine analogs & derivatives
- Abstract
Background and Objectives: Recent observations suggested that targeted monoclonal antibodies might be best employed in lymphoid malignancies under conditions of minimal residual disease. This prompted us to investigate the role of Campath-1H as treatment for patients with chronic lymphocytic leukemia (CLL) in whom fludarabine (FAMP) had produced a marked disease debulking with persistence of bone marrow (BM) infiltration or a complete remission (CR) without the disappearance of the molecular aberration (IgH monoclonal expression). As intravenous Campath-1H is almost invariably associated with reactions, sometimes of WHO grade 3-4, we adopted the subcutaneous route of administration, which proved to induce rare and mild adverse reactions but had comparable efficacy. DESIGN AND METHODS. Nine patients (7 males, 2 females) with a median age of 55 years (range 41-61) who responded to FAMP (1 had a CR, 5 a nodular partial remission [PRN], and 3 a partial remission [PR]), according to NCI Working Group Criteria, received subcutaneous Campath-1H, three times a week for 6 weeks in escalating doses up to 10 mg. Monoclonal rearrangement of IgH was present in all patients before immunotherapy. Patients received acyclovir and cotrimoxazole as infection prophylaxis. Granulocyte colony-stimulating factor (G-CSF), at the dosage of 5-10 microg/kg/die, or intermediate-dose Ara-C (800 mg/m(2)/q 12h x 6 doses), was administered to obtain peripheral blood stem cell (PBSC) mobilization., Results: All patients were evaluable for response. Five patients, 2 in PR and 3 in PRN after FAMP treatment, reached a CR. Three patients, one in PR, one in PRN and one in CR, converted to a molecular remission. In four out of seven patients PBSC harvesting was successful; more than 2.5 x 10(6) cells/kg were collected from all these patients. Collection was polyclonal for IgH gene rearrangement in three cases. One patient has been transplanted after cyclophosphamide and total body irradiation as conditioning regimen, without complications and with rapid hemopoietic engraftment. All patients were evaluable for toxicity. A WHO grade 1-2 skin reaction was observed in 5 patients at the site of injection. No infectious episodes were recorded. Two out of three patients presenting cytomegalovirus reactivation, without pneumonia, were successfully treated with oral gancyclovir., Interpretation and Conclusions: Subcutaneous Campath-1H administered to CLL patients with residual BM disease after FAMP proved to be safe and effective. Of nine patients, three obtained a molecular CR and five converted into a morphologic and immunophenotypic CR. In four of seven patients submitted to PBSC mobilization, this treatment also allowed a harvest uncontaminated by CD5/CD19 double-positive CLL cells, which was polyclonal for IgH gene rearrangement in three cases.
- Published
- 2002
26. Hepatosplenic gamma delta T-cell lymphoma with a novel cytogenetic alteration and cerebrospinal fluid infiltration: biological and clinical features.
- Author
-
Ferrari D, Girmenia G, Migliorini L, Nosari A, and Morra E
- Subjects
- Adult, Cerebrospinal Fluid cytology, Chromosomes, Human, Pair 4, Cytogenetic Analysis, Female, Gene Deletion, Humans, Liver Neoplasms genetics, Liver Neoplasms immunology, Lymphoma, T-Cell genetics, Lymphoma, T-Cell immunology, Neoplasm Invasiveness, Receptors, Antigen, T-Cell, gamma-delta genetics, Splenic Neoplasms genetics, Splenic Neoplasms immunology, Liver Neoplasms diagnosis, Lymphoma, T-Cell diagnosis, Splenic Neoplasms diagnosis
- Published
- 2002
27. Post-transplant lymphoproliferative disorders: improved outcome after clinico-pathologically tailored treatment.
- Author
-
Muti G, Cantoni S, Oreste P, Klersy C, Gini G, Rossi V, D'Avanzo G, Comoli P, Baldanti F, Montillo M, Nosari A, and Morra E
- Subjects
- Adult, Aged, Anti-Bacterial Agents therapeutic use, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antiviral Agents therapeutic use, Epstein-Barr Virus Infections drug therapy, Female, Heart Transplantation adverse effects, Helicobacter Infections complications, Helicobacter Infections drug therapy, Helicobacter pylori isolation & purification, Herpesvirus 4, Human isolation & purification, Humans, Immunocompromised Host, Interleukin-10 blood, Kidney Transplantation adverse effects, Life Tables, Liver Transplantation adverse effects, Lung Transplantation adverse effects, Lymphoproliferative Disorders epidemiology, Lymphoproliferative Disorders microbiology, Lymphoproliferative Disorders therapy, Lymphoproliferative Disorders virology, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications therapy, Postoperative Complications virology, Prognosis, Proportional Hazards Models, Remission Induction, Retrospective Studies, Risk Factors, Rituximab, Survival Analysis, Survival Rate, Time Factors, Treatment Outcome, Viral Load, Epstein-Barr Virus Infections complications, Immunosuppression Therapy adverse effects, Lymphoproliferative Disorders etiology, Postoperative Complications etiology, Transplantation adverse effects
- Abstract
Background and Objectives: Clinical and pathologic variability of post-transplant lymphoproliferative disorders (PTLDs), their aggressive behavior and the recognized therapy-related toxicity make management of patients with these disorders difficult. Assessment of first-line treatment and identification of prognostic factors need to be better defined., Design and Methods: Data on 40 PTLDs which developed in adult solid organ recipients were analyzed in order to evaluate clinical and pathologic features, response to treatment and prognostic factors. Data were collected retrospectively between 1989 and 1996; since 1997 a prospective study has been activated., Results: The median time from transplant to PTLD was 56 months. Regarding histologic features, plasmacytic hyperplasia was diagnosed in 5 patients (12.5%), polymorphic lymphoproliferative disorders in 3 (7.5%), malignant lymphoma in 32 (80%). The diagnosis was made at autopsy in eight patients (20%). Late-onset PTLDs (>12 months from transplant) occurred in 33 patients (83%), EBV-negative forms in 12 (31%). Relevant differences have been observed between EBV-positive and EBV-negative forms. Twenty-nine patients completed their scheduled treatment and are evaluable for outcome. The cumulative probability of survival at 1 year is 57% (CI 37.6-73.4) and the median survival time of the entire group has not been reached at 54 months. Clinical stage, performance status, lactate dehydrogenase and number of sites are predictive factors for survival. The International Prognostic Index and the PTLD index are able to identify different risk groups., Interpretation and Conclusions: Although rare, PTLDs are a significant cause of mortality in allograft recipients. Therapy tailored on histologic and clinical features of PTLD is feasible and is able to give long-lasting complete responses.
- Published
- 2002
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.