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9. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, Mario, De Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, M. T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, S. F., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, A. M., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, E. M., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, M. C., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, A. M., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, Renato, Pizzolo, G., Meneghini, V., and Rodighiero, F.

Published
2015

10. Standard- versus high-dose lenograstim in adults with hematologic malignancies for peripheral blood progenitor cell mobilization

Author

Romeo, A., Chierichini, A., Spagnoli, Alessandra, Vittori, M., Vacca, M., Gozzer, M., Spadea, A., Anaclerico, B., Dessanti, M. l., D'Andrea, M., Toglia, G., Annino, L., Petti, M. c., Mengarelli, A., and Arcese, W.

Subjects
Adult, Male, Adolescent, Dose-Response Relationship, Drug, Hematopoietic Stem Cell Transplantation, Antigens, CD34, Middle Aged, Hematopoietic Stem Cells, Transplantation, Autologous, Hematopoietic Stem Cell Mobilization, Lenograstim, Recombinant Proteins, Young Adult, Treatment Outcome, Adjuvants, Immunologic, Predictive Value of Tests, Hematologic Neoplasms, Granulocyte Colony-Stimulating Factor, Humans, Female, Hospital Costs, Settore MED/15 - Malattie del Sangue, Aged, Retrospective Studies
Abstract

The aim of this retrospective, multicenter study was to compare high- versus standard-dose lenograstim after chemotherapy in collecting target dose of CD34+ peripheral blood progenitor cells (PBPCs) in adult candidates for autologous transplant.A total of 166 consecutive patients (28 acute leukemias [ALs], 77 lymphomas, 61 multiple myeloma [MM]) underwent 182 mobilization procedures. Only the first were analyzed. The CD34+ cell target was at least 2×10(6) , 4×10(6) , and 8×10(6) /kg and lenograstim started on days +19, +1, and +5 from the end of chemotherapy for AL, lymphomas, and MM, respectively. Eighty-seven and 79 patients, respectively, received 5 and 10µg/kg/day lenograstim subcutaneously (sc). An analysis to evaluate factors predicting satisfactory procedures and outcome of transplants performed with first-mobilization-procedure PBPCs was conducted. Most patients received 6mg of pegfilgrastim or 5µg/kg/day lenograstim sc after transplant.In multivariate analysis, high-dose lenograstim (p=0.053) in MM and male sex (p=0.028) were positive predictive factors for reaching cell target. Fludarabine negatively influenced stimulation length (p=0.002). Apheresis, CD34+ cells mobilized and collected, blood volume processed, side effects, transplants performed, and engraftment time were similar between lenograstim cohorts. Pegfilgrastim versus lenograstim delayed platelet (PLT) recovery times (13 days vs. 11 days, p=0.036).High-dose lenograstim more efficiently mobilized MM patients requiring the highest PBPC target but did not influence transplants performed and engraftment time. Male patients mobilized more efficiently. Fludarabine negatively influenced stimulation length. Finally, pegfilgrastim seems to delay PLT recovery.

Published
2010

12. Arsenic trioxide in the treatment of advanced acute promyelocytic leukemia

Author

Carmosino, I., Latagliata, R., Giuseppe Avvisati, Breccia, M., Finolezzi, E., Lo Caco, F., and Petti, M. C.

Subjects
Adult, Male, Remission Induction, Antineoplastic Agents, Oxides, Middle Aged, Combined Modality Therapy, Arsenicals, Arsenic Trioxide, Leukemia, Promyelocytic, Acute, Recurrence, Child, Preschool, Humans, Female, Settore MED/15 - Malattie del Sangue, Bone Marrow Transplantation
Abstract

Eleven patients with advanced APL were treated with ATO (0.15 mg/Kg daily). Eight (73%) achieved molecular CR, but 5 relapsed, 1 died in molecular CR, 1 was lost to follow-up and 1 is still alive in CR after allogeneic transplantation. We suggest that ATO may be effective also in advanced APL, but given the short CR, it seems indicated only in patients eligible for transplant procedures.

Published
2004

13. The Italian Way of Treating Acute Promyelocytic Leukemia (APL), Final Act

Author

Avvisati, G., Petti, M. C., LO COCO, F., Testi, A. M., Fazi, P., Specchia, G., Malagola, M., DI BONA, E., Recchia, A., Marmont, F., Buelli, M., Lazzarino, M., DI RAIMONDO, Francesco, Leoni, F., Kropp, M. G., Veneri, D., Micolis, I., Rossi, G., Venditti, A., and Mandelli, F.

Published
2003

14. Melphalan treatment in patients with myelofibrosis with myeloid metaplasia

Author

Petti, M. C., Latagliata, R., Spadea, T., Spadea, A., Montefusco, E., ALOE SPIRITI, Maria Antonietta, Avvisati, G., Pescarmona Beccia, M., and Breccia, Massimo

Subjects
blastic phase, melphalan, metaplasia, myelofibrosis with myeloid, myelofibrosis with myeloid metaplasia
Published
2002

17. A phase II study of VP-16, intermediate-dose Ara-C and carboplatin (VAC) in advanced acute myelogenous leukemia and blastic chronic myelogenous leukemia

Author

Amadori, S., ALESSANDRA PICARDI, Fazi, P., Testi, A. M., Petti, M. C., Montefusco, E., and Mandelli, F.

Subjects
Adult, Male, myelogenous leukemia, Adolescent, Remission Induction, Cytarabine, Middle Aged, chemotherapy, Survival Analysis, Disease-Free Survival, Treatment Outcome, Leukemia, Myeloid, Child, Preschool, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, carboplatin, Humans, Female, Blast Crisis, Child, Settore MED/15 - Malattie del Sangue, Bone Marrow Transplantation, Etoposide
Abstract

Thirty-one patients with either advanced AML (18) or blastic CML (13) were treated with an intensive timed sequential combination of VP-16 (100 mg/m2/day i.v., days 1-3 and 8-10), intermediate-dose Ara-C (500 mg/m2 i.v. over 1 h q 12 h, days 1-3 and 8-10) and carboplatin (150 mg/m2/day i.v. continuous infusion, days 1-3 and 8-10). CR rates were 9/18 (50%) for patients with AML and 9/13 (69%) for those with blastic CML, for an overall CR rate of 58%. Among patients with AML, CR rates for specific subgroups were: primary resistant disease 2/6; resistant relapse 1/5; second relapse 6/7. Ten patients were refractory to VAC and three (10%) died of complications during marrow hypoplasia. Median overall survival was 7 months, and median DFS of the 18 responders 4 months. The major toxicity was myelosuppression and infection. The VAC regimen has significant activity and acceptable toxicity in myelogenous leukemias. The very high response rate observed in blastic CML warrants further testing of carboplatin-based regimens in this poor-risk form of leukemia.

Published
1996

26. Clinical and biological features of acute promyelocytic leukemia patients developing retinoic acid syndrome during induction treatment with all-trans retinoic acid and idarubicin

Author

Breccia, M., primary, Latagliata, R., additional, Carmosino, I., additional, Cannella, L., additional, Diverio, D., additional, Guarini, A., additional, De Propris, M. S., additional, Petti, M. C., additional, Avvisati, G., additional, Cimino, G., additional, Mandelli, F., additional, and Lo-Coco, F., additional

Published
2008
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33. Treatment of elderly patients (=60 years) with newly diagnosed acute promyelocytic leukemia. Results of the Italian multicenter group GIMEMA with ATRA and idarubicin (AIDA) protocols.

Author

Mandelli, F, Latagliata, R, Avvisati, G, Fazi, P, Rodeghiero, F, Leoni, F, Gobbi, M, Nobile, F, Gallo, E, Fanin, R, Amadori, S, Vignetti, M, Fioritoni, G, Ferrara, F, Peta, A, Giustolisi, R, Broccia, G, Petti, M C, and Lo-Coco, F

Subjects
LEUKEMIA, OLDER people
Abstract

In all, 134 elderly patients (median age 66 years, range 60-75 years) with newly diagnosed acute promyelocytic leukemia (APL) were enrolled in two successive protocols of the Italian multicenter group GIMEMA. All patients received an identical induction with all-trans retinoic acid and idarubicin; 116 (86%) entered complete remission (CR), two (2%) were resistant and 16 (12%) died during induction. After CR, 106 patients received further therapy whereas 10 did not, because of refusal (n = 5) or toxicity (n = 5). Consolidation consisted of three chemotherapy courses in the AIDA protocol (AIDA, 67 patients) or, since 1997, of an amended protocol including only the first cycle (amended AIDA, aAIDA, 39 patients). In the AIDA group, 43 patients (64%) completed consolidation, while seven (11%) and 17 (25%) patients were withdrawn after first and second courses, respectively; nine patients (13%) died in CR and 12 (18%) relapsed. In the aAIDA group, all patients received the assigned treatment; two patients (5%) died in CR and six (15%) relapsed. In the AIDA and aAIDA series, the 3-year overall and discase-free survival rates were 81 and 83% (P = NS), 73 and 72% (P = NS), respectively. We highlight here the frequency and severity of complications linked to intensive chemotherapy in this clinical setting and suggest that, in APL of the elderly, less intensive postremission therapy allows significant reduction of severe treatment-related toxicity and may be equally effective. [ABSTRACT FROM AUTHOR]

Published
2003

34. Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991).

Author

Petti, M C, Spadea, A, Avvisati, G, Spadea, T, Latagliata, R, Montefusco, E, Cosenza, M, and Malagnino, F

Subjects
*POLYCYTHEMIA vera, *LEUKEMIA, *LEUKEMIA epidemiology, *HETEROCYCLIC compounds, *ANTINEOPLASTIC agents, *DISEASE incidence, *RETROSPECTIVE studies, *SECONDARY primary cancer, *BONE marrow diseases, *LONGITUDINAL method
Abstract

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV. [ABSTRACT FROM AUTHOR]

Published
1998
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35. Intraventricular thrombosis during all-trans retinoic acid treatment in acute promyelocytic leukemia.

Author

Torromeo, C, Latagliata, R, Avvisati, G, Petti, M C, and Mandelli, F

Subjects
THROMBOSIS, TRETINOIN, MYELOID leukemia, PATIENTS
Abstract

Focuses on two patients with acute promyelocytic leukemia who developed intraventricular thrombosis during induction treatment with all-trans retinoic acid (ATRA). Presence of normal coagulative profile in the patients; Features of intraventricular thrombi observed; Evidence of thrombi during or after resolution of ATRA syndrome.

Published
2001
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36. Clinical and biological aspects of acute monocytic leukemia (a retrospective study of 29 patients)

Author

Petti, M. C., Sergio Amadori, Annino, L., Arcese, W., Avvisati, G., Di Lorenzo, A., Gastaldi, R., and Mandelli, F.

Subjects
Adult, Male, Neoplastic, Leukemia, Monocytic, Adolescent, Daunorubicin, Acute, Middle Aged, Cell Transformation, Cell Transformation, Neoplastic, Bone Marrow, Leukemia, Monocytic, Acute, Humans, Female, Retrospective Studies, Aged, Child, Settore MED/15 - Malattie del Sangue
Published
1982

38. Autologous bone marrow transplantation in patients with AML in second complete remission (CR)

Author

Meloni, G., Fabritiis, P., Sergio Amadori, Petti, M. C., Pulsoni, A., Sandrelli, A., and Mandelli, F.

Subjects
Amsacrine, Male, Adolescent, Remission Induction, Cytarabine, Infant, Carmustine, Combined Modality Therapy, Transplantation, Autologous, Leukemia, Myeloid, Acute, Evaluation Studies as Topic, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Child, Bone Marrow Transplantation, Etoposide
Published
1989

40. Long-term survival in adult acute leukemia. A multicenter study of 56 patients

Author

Tura, S., Gobbi, M., Cavo, M., Bachetti, G., Mandelli, F., Sergio Amadori, Petti, M. C., Quattrin, N., Rosa, L., Storti, E., Rizzo, S. C., Bernasconi, C., Salvaneschi, L., Paolino, W., Infelise, V., Dini, E., Barbui, T., Bruzzese, L., Abbadessa, A., Martelli, M. F., and Rambotti, P.

Subjects
Adult, Male, Leukemia, Adolescent, Age Factors, Middle Aged, Prognosis, Leukemia, Lymphoid, Leukemia, Myeloid, Acute, Humans, Drug Therapy, Combination, Female, Child, Aged
Published
1982

41. Treatment of recurrent promyelocytic leukemia with a combination regimen utilizing amsacrine, cytosine arabinoside and 6-thioguanine (AAT)

Author

Avvisati, G., Petti, M. C., Petrucci, M. T., Falconi, E., MARIA CRISTINA TIRINDELLI, and Mandelli, F.

Subjects
Adult, Amsacrine, Male, Leukemia, Promyelocytic, Acute, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Cytarabine, Humans, Female, Middle Aged, Thioguanine
Abstract

Nine patients with recurrent acute promyelocytic leukemia have been treated between July, 1984 and November, 1987 with a combination therapeutic regimen consisting of amsacrine, cytosine arabinoside and thioguanine (AAT). Complete remission was achieved in 5/9 patients, one person died in aplasia of hepatic failure, and the remaining 3 died from heart failure with resistant disease. The 5 patients who achieved CR were successively treated with allogeneic (n = 2) or autologous bone marrow transplantation (n = 3). As of December, 1988 there were only 2 patients still alive and in CR, both underwent autologous bone marrow transplantation. The duration of the second complete remission in these two patients is 48+ and 29+ months, respectively. Moreover the overall survival duration for these two patients is 88+ and 41+ months, respectively. These data confirm that the AAT regimen is useful in treating recurrent acute promyelocytic leukemia, a disease otherwise characterized by a catastrophic clinical course during the recurrent phase.

Published
1989

42. Serum interleukin-2 (IL-2), soluble IL-2 receptors and tumor necrosis factor-alfa levels are significantly increased in acute myeloid leukemia patients

Author

Cimino, G., Amadori, S., Cava, M. C., Sanctis, V., Petti, M. C., Di Gregorio, A. O., Cecilia Sgadari, Vegna, L., and Mandelli, F.

Subjects
Myeloid, Adult, Male, Adolescent, Adult, Aged, Female, Humans, Interleukin-2, blood, Leukemia, Acute, blood/mortality, Male, Middle Aged, Prognosis, Receptors, Interleukin-2, analysis/blood, Survival Rate, Tumor Necrosis Factor-alpha, analysis, Leukemia, Adolescent, Tumor Necrosis Factor-alpha, Receptors, Interleukin-2, analysis/blood, Middle Aged, Prognosis, blood/mortality, Survival Rate, Leukemia, Myeloid, Acute, blood, Receptors, Humans, Female, Aged
Abstract

Serum interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R) and tumor necrosis factor-alfa (TNF-alpha) levels were determined in 66 previously untreated consecutive patients with acute myeloid leukemia (AML) and in 22 normal volunteers. The following mean (+/- SE) values were observed in patients and controls, respectively: 35 +/- 14.7 (range 0.5-500) and 0.7 +/- 0.02 (0.5-0.8 U/ml for IL-2 (p = 0.001); 1622 +/- 289 (110-10,600) and 422 +/- 30 (207-666) U/ml for sIL-2R (p = 0.0001); 1247 +/- 196 (218-4672) and 152 +/- 11 (75-308) pg/ml for TNF-alpha (p = 0.0001). With respect to the FAB classification system, we found a significantly different distribution of serum IL-2 mean values in distinct subcategories, i.e. 3.4 +/- 1.9 U/ml in M1-M2-M3 and 42.4 +/- 20.4 U/ml in M4-M5 subgroups, respectively (p = 0.01), whereas sIL-2R and TNF-alpha levels were 1144 +/- 322 U/ml and 1120 +/- 317 pg/ml in M1-M2-M3 patients and 1945 +/- 317 U/ml and 1270 +/- 259 pg/ml in the M4-M5 group. A significantly positive correlation between TNF-alpha and sIL-2R (r = 0.53; p = 0.002) was also detected in the M4-M5 group. Sixty-three out of 66 patients received an intensive chemotherapy program. Univariate analysis showed that age and sIL-2R greater than 2000 U/ml significantly affected both complete remission rate and overall survival, whereas by multivariate analysis, age was the only independent variable significantly influencing survival. These data confirm recent in vitro evidence suggesting the role of IL-2, sIL-2R, and TNF-alpha in the control of normal hematopoiesis and leukemogenesis. Since the availability of recombinant cytokines for clinical use in AML, it is crucial to understand their spectrum of interaction in order to select the appropriate combination for in vivo administration.

43. Kidney carcinoma revealed by autoimmune hemolytic anemia

Author

Gabriella GIRELLI, Adorno, G., Perrone, M. P., Arista, M. C., Cardillo, A., Vegna, M. L., Petti, M. C., and Mandelli, F.

Subjects
Adult, Male, Humans, Anemia, Hemolytic, Autoimmune, Adenocarcinoma, Kidney Neoplasms

44. Survival of elderly patients with acute myeloid leukemia

Author

Pulsoni, A., Pagano, L., Latagliata, R., Casini, M., Cerri, R., Crugnola, M., Paoli, L., Di Bona, E., Invernizzi, R., Marmont, F., Petti, M. C., Rigolin, G., Ronco, F., Spadano, A., Maria Elena Tosti, Visani, G., Mele, A., and Mandelli, F.

Subjects
acute myeloid leukemia treatment, elderly, survival

45. In vitro purging with BCR-ABL antisense oligodeoxynucleotides does not prevent haematologic reconstitution after autologous bone marrow transplantation

Author

Fabritiis, P., Sergio Amadori, Petti, M. C., Mancini, M., Montefusco, E., Picardi, A., Geiser, T., Campbell, K., Calabretta, B., and Mandelli, F.

Subjects
Antigens, CD, Bone Marrow Purging/methods, Bone Marrow Transplantation/methods, Hematopoiesis, Leukemia BCR-ABL Positive/therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Bone Marrow Purging, Humans, Antigens, CD34, Oligonucleotides, Antisense, Transplantation, Autologous, Bone Marrow Transplantation
Abstract

We treated a patient with chronic myeloid leukaemia in accelerated phase with autologous bone marrow transplantation. Before reinfusion, cells were purged in vitro with a 26-mer phosphorothioate antisense oligodeoxynucleotide specific for the B2A2 junction. Incubation with antisense oligodeoxynucleotides produced a 24 and 41% reduction of CFU-GM and CD34+ cells, respectively. However, an in vitro test previously performed as a screening for patient inclusion in this procedure, revealed a 38 and 75% reduction of colony formation after 24-h and 168-h incubation, respectively. The patient showed bone marrow engraftment 15 days after reinfusion and haematological reconstitution after 17 and 25 days for platelets and neutrophils, respectively. Using fluorescence in situ hybridization in interphase nuclei, we demonstrated the presence of a proportion of Ph-negative cells in repeated controls after the autograft. The patient is now in unmaintained complete haematological remission 9 months after the autograft.

46. Acute non lymphoid leukemia treatment: An update

Author

Mandelli, F., Petti, M. C., and maria antonietta aloe spiriti

Subjects
Leukemia, Acute Disease, Antineoplastic Combined Chemotherapy Protocols, Humans, Bone Marrow Transplantation

47. Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia

Author

Sergio Amadori, Meloni, G., Petti, M. C., Papa, G., Miniero, R., and Mandelli, F.

Subjects
Male, Leukemia, Myeloid, Acute, Dose-Response Relationship, Drug, Cytarabine, Drug Evaluation, Humans, Female, Mitoxantrone, Drug Administration Schedule
Abstract

Forty-seven patients with primary refractory, relapsed, and previously untreated, poor risk AML were entered into a phase II study of intermediate dose ARA-C (IDAC) (1 g/m2 i.v. over 6 hr, daily for 6 days) with sequential mitoxantrone (MITOX) (6 mg/m2 i.v. bolus 3 hr after the end of each ARA-C infusion). Overall, complete remission was induced in 31 patients (66%), and 1 additional patient entered a partial remission. Seven patients (15%) died of infection during marrow hypoplasia. Response to IDAC + MITOX was influenced by sensitivity to previous therapy: patients with primary refractory and early relapse AML responded less well to the regimen (CR rate 28% and 33%, respectively), as compared to those with previously untreated (CR rate 64%) or late relapse disease (CR rate 85%). Sixteen patients continue in CR at 1-12+ months. Except for the expected severe myelosuppression, the regimen was well tolerated with minimal extramedullary toxicity. The data indicate that the sequential combination of IDAC and MITOX is an effective and tolerable regimen for AML. Consideration should be given to applying this program at earlier stages of AML therapy.

48. BAVC regimen in CR AML patients

Author

Meloni, G., Vignetti, M., Paolo de Fabritiis, Petti, M. C., Pinto, M. R., Testi, A. M., Vegna, M. L., and Mandelli, F.

Subjects
Adult, Amsacrine, Adolescent, Graft Survival, Remission Induction, Cytarabine, Infant, Middle Aged, Carmustine, Transplantation, Autologous, Survival Rate, Leukemia, Myeloid, Acute, Italy, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Humans, Neoplasm Recurrence, Local, Child, Bone Marrow Transplantation, Etoposide, Follow-Up Studies

49. Coronaric thrombotic events in acute promyelocytic leukemia during all-trans retinoic acid treatment: a role for adhesion molecules overexpression?

Author

Torromeo, C, Latagliata, R, Avvisati, G, Petti, M C, and Mandelli, F

Subjects
LEUKEMIA, RETINOIDS, THROMBOSIS, CELL adhesion molecules, CLINICAL trials, COMPARATIVE studies, CORONARY disease, RESEARCH methodology, MEDICAL cooperation, RESEARCH, TRETINOIN, EVALUATION research, ACUTE promyelocytic leukemia, DISEASE complications
Abstract

Presents an observation on coronaric thrombotic events in acute promyelocytic leukemia patients (APL) during all-trans retinoic treatment. Characteristics of APL; Major risk factor for arterial thrombosis.

Published
1999
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50. Differences among young adults, adults and elderly chronic myeloid leukemia patients

Author

D. Ielo, Mario Cazzola, A. De Vivo, Mario Petrini, G. Fioritoni, Simona Sica, Fausto Castagnetti, B. Falini, Miriam Fogli, Agostino Cortelezzi, C. Viganò, Giuliana Alimena, Maurizio Musso, G. Spinosa, Flavia Salvi, Giancarlo Latte, Michele Pizzuti, Nicola Cantore, D. Luzzi, B. Ronci, Francesco Merli, Mario Boccadoro, Diamante Turri, Monica Bocchia, Patrizia Tosi, A. M. Carella, Simona Luatti, G. Semenzato, Mariella Grasso, Nicoletta Testoni, Giovanni Martinelli, Ester Pungolino, Giuseppe Tagariello, A. Russo Rossi, Simona Soverini, Francesca Ronco, Franco Iuliano, Giovanni Rosti, Alberto Bosi, Tamara Intermesoli, Dario Ferrero, Sara Galimberti, Giovanna Rege-Cambrin, Ferdinando Porretto, Sabina Russo, Roberto Latagliata, Pellegrino Musto, E. Morra, Agostino Tafuri, Franca Falzetti, Francesco Cavazzini, P. Galieni, Marzia Salvucci, F. Rodighiero, Stefana Impera, Fausto Dore, P. De Fabritiis, V. Meneghini, Elisabetta Calistri, Paolo Vigneri, Ivana Pierri, Michele Cavo, Massimo Pini, Fabrizio Ciccone, Domenico Russo, E Trabacchi, Franco Gherlinzoni, Michele Baccarani, Ilaria Iacobucci, Roberto Sartori, Paolo Avanzini, D. Noli, Roberto Marasca, Simonetta Pardini, A. Malpignano, Maria Concetta Petti, Bruno Martino, M. Bergamaschi, Giovanni Pizzolo, Valeria Santini, E Orlandi, Catia Bigazzi, Serena Rupoli, Giuseppe Saglio, I. Cervello, Clementina Caracciolo, Anna Merli, R. Di Lorenzo, Enrico Pogliani, Francesco Lanza, Mariella Girasoli, M. Apolinari, Caterina Musolino, Francesco Fabbiano, D. Vallisa, Mario Annunziata, Gabriele Gugliotta, V. De Stefano, Ignazio Majolino, Sergio Storti, P. Leoni, Adele Capucci, Massimo Breccia, Alessandro Isidori, Carmen Fava, Gianni Binotto, Carlo Gambacorti-Passerini, L. Pacilli, Mario Tiribelli, Luciano Levato, Felicetto Ferrara, N. Di Renzo, Anna D'Emilio, Francesco Pisani, Fabio Stagno, Monica Crugnola, M. Trawiska, Patrizia Pregno, Marzia Defina, Stefano Molica, Mario Luppi, Michele Malagola, Davide Rapezzi, A. M. Liberati, E. De Biasi, A. Iurlo, Umberto Vitolo, Silvana Capalbo, Maria Teresa Bochicchio, F. Di Raimondo, Franco Aversa, Giuseppe Visani, Fausto Palmieri, Alessandro Rambaldi, Sergio Siragusa, Massimiliano Bonifacio, Luigiana Luciano, Giorgina Specchia, Elisabetta Abruzzese, A. De Blasio, Francesco Albano, Antonio Cuneo, Emilio Usala, Alfonso Zaccaria, R Fanin, Francesca Palandri, Fabrizio Pane, Enrico Montefusco, A. Gozzini, Giulio Rossi, Emanuele Angelucci, A. Bacigalupo, Marco Gobbi, Michele Cedrone, Castagnetti, F., Gugliotta, G., Baccarani, M., Breccia, M., Specchia, G., Levato, L., Abruzzese, E., Rossi, G., Iurlo, A., Martino, B., Pregno, P., Stagno, F., Cuneo, A., Bonifacio, M., Gobbi, M., Russo, D., Gozzini, A., Tiribelli, M., de Vivo, A., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., on behalf of the, GIMEMA CML Working Party [.., Palandri, F., Testoni, N., Luatti, S., Soverini, S., Iacobucci, I., Bochicchio, M.T., Apolinari, M., Fogli, M., Cervello, I., ]., Castagnetti, Fausto, De Vivo, A., Pane, Fabrizio, Salvi, F., Pini, M., Leoni, P., Rupoli, S., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Albano, F., Russo Rossi, A., Rambaldi, A., Intermesoli, T., Bochicchio, M. T., Capucci, A., Malagola, M., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., Storti, S., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Impera, S., Molica, S., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cavazzini, F., Bosi, A., Santini, V., Capalbo, S. F., Spinosa, G., Pierri, I., Bergamaschi, M., Carella, A. M., Bacigalupo, A., De Blasio, A., Ciccone, F., Di Renzo, N., Musolino, C., Russo, S., Cortelezzi, A., Morra, E., Pungolino, E. M., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti Passerini, C., Luciano, L., Ferrara, F., Annunziata, M., Latte, G., Noli, D., Rege Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Aversa, F., Crugnola, M., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidori, A., Fioritoni, G., Di Lorenzo, R., Vallisa, D., Trabacchi, E., Petrini, M., Galimberti, S., Pizzuti, M., Zaccaria, A., Salvucci, M., Ronco, F., Ielo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Musto, P., De Stefano, V., Sica, S., Latagliata, R., De Fabritiis, P., Trawiska, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Petti, M. C., Pisani, F., Tafuri, A., Montefusco, E., Iuliano, F., Dore, F., Pardini, S., Bocchia, M., Defina, M., Liberati, A. M., Luzzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Gherlinzoni, F., Calistri, E., Fanin, R., Pizzolo, G., Meneghini, V., Rodighiero, F., D'Emilio, A., Castagnetti, F, Gugliotta, G, Baccarani, M, Breccia, M, Specchia, G, Levato, L, Abruzzese, E, Rossi, G, Iurlo, A, Martino, B, Pregno, P, Stagno, F, Cuneo, A, Bonifacio, M, Gobbi, M, Russo, D, Gozzini, A, Tiribelli, M, De Vivo, A, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Salvi, F, Pini, M, Leoni, P, Rupoli, S, Galieni, P, Bigazzi, C, Cantore, N, Palmieri, F, Albano, F, Russo Rossi, A, Rambaldi, A, Intermesoli, T, Palandri, F, Testoni, N, Luatti, S, Soverini, S, Iacobucci, I, Bochicchio, M, Apolinari, M, Fogli, M, Cervello, I, Capucci, A, Malagola, M, Malpignano, A, Girasoli, M, Angelucci, E, Usala, E, Storti, S, De Biasi, E, Tagariello, G, Sartori, R, Di Raimondo, F, Vigneri, P, Impera, S, Molica, S, Lanza, F, Viganò, C, Grasso, M, Rapezzi, D, Cavazzini, F, Bosi, A, Santini, V, Capalbo, S, Spinosa, G, Pierri, I, Bergamaschi, M, Carella, A, Bacigalupo, A, De Blasio, A, Ciccone, F, Di Renzo, N, Musolino, C, Russo, S, Cortelezzi, A, Morra, E, Pungolino, E, Luppi, M, Marasca, R, Pogliani, E, GAMBACORTI PASSERINI, C, Luciano, L, Ferrara, F, Annunziata, M, Latte, G, Noli, D, Rege Cambrin, G, Fava, C, Semenzato, G, Binotto, G, Fabbiano, F, Turri, D, Siragusa, S, Caracciolo, C, Musso, M, Porretto, F, Aversa, F, Crugnola, M, Cazzola, M, Orlandi, E, Falini, B, Falzetti, F, Visani, G, Isidori, A, Fioritoni, G, Di Lorenzo, R, Vallisa, D, Trabacchi, E, Petrini, M, Galimberti, S, Pizzuti, M, Zaccaria, A, Salvucci, M, Ronco, F, Ielo, D, Merli, F, Avanzini, P, Tosi, P, Merli, A, Musto, P, De Stefano, V, Sica, S, Latagliata, R, De Fabritiis, P, Trawiska, M, Majolino, I, Pacilli, L, Ronci, B, Cedrone, M, Petti, M, Pisani, F, Tafuri, A, Montefusco, E, Iuliano, F, Dore, F, Pardini, S, Bocchia, M, Defina, M, Liberati, A, Luzzi, D, Boccadoro, M, Ferrero, D, Vitolo, U, Gherlinzoni, F, Calistri, E, Fanin, R, Pizzolo, G, Meneghini, V, Rodighiero, F, and D'Emilio, A

Subjects
Male, Pediatrics, Host response, BCR-ABL, Chronic myeloid leukemia, Prognosis, Tyrosine kinase inhibitors, Young adults, Adult, Age Factors, Aged, Aged, 80 and over, Antineoplastic Agents, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Middle Aged, Prospective Studies, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Spleen, Splenomegaly, Young Adult, Oncology, Hematology, Tyrosine kinase inhibitor, Disease, Antineoplastic Agent, Tyrosin kinase inhibitor, Protein-Tyrosine Kinase, hemic and lymphatic diseases, 80 and over, Age Factor, Young adult, Chronic, Leukemia, Incidence (epidemiology), Myeloid leukemia, bcr-abl1, chronic myeloid leukemia, prognosis, tyrosine kinase inhibitors, young adults, Human, medicine.medical_specialty, Prognosi, Protein Kinase Inhibitor, NO, medicine, Adult patients, business.industry, medicine.disease, Clinical trial, Prospective Studie, Medicine (all), Immunology, BCR-ABL Positive, BCR-ABL, chronic myeloid leukemia, prognosis, tyrosine kinase inhibitors, young adults, business, Myelogenous
Abstract

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Published
2015

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