18 results on '"Giona F"'
Search Results
2. Platelet activation and multidrug resistance protein-4 expression in children and adolescents with different subtypes of primary thrombocythemia.
- Author
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Giona F, Massimi I, Guarino ML, Santopietro M, Laurino M, Temperilli F, Palumbo G, Foà R, and Pulcinelli FM
- Subjects
- Adolescent, Blood Platelets, Child, Drug Resistance, Multiple, Humans, Platelet Activation, Platelet Aggregation Inhibitors, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential genetics, Thrombocytosis
- Published
- 2020
- Full Text
- View/download PDF
3. Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty.
- Author
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Giona F, Mariani S, Gnessi L, Moleti ML, Rea M, De Vellis A, Marzella D, Testi AM, and Foà R
- Subjects
- Adolescent, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Benzamides administration & dosage, Benzamides therapeutic use, Biomarkers metabolism, Child, Female, Hormones metabolism, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Piperazines administration & dosage, Piperazines therapeutic use, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Antineoplastic Agents adverse effects, Benzamides adverse effects, Bone and Bones drug effects, Bone and Bones metabolism, Growth Charts, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Piperazines adverse effects, Puberty drug effects, Pyrimidines adverse effects
- Published
- 2013
- Full Text
- View/download PDF
4. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis.
- Author
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Teofili L, Giona F, Torti L, Cenci T, Ricerca BM, Rumi C, Nunes V, Foà R, Leone G, Martini M, and Larocca LM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Asparagine genetics, Child, Child, Preschool, Disease Progression, Female, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Pedigree, Primary Myelofibrosis mortality, Risk Factors, Serine genetics, Splenomegaly mortality, Thrombocytosis complications, Thrombocytosis mortality, Thrombopoietin genetics, Thrombopoietin metabolism, Thrombosis mortality, Young Adult, Amino Acid Substitution genetics, Primary Myelofibrosis genetics, Receptors, Thrombopoietin genetics, Splenomegaly genetics, Thrombocytosis genetics, Thrombosis genetics
- Abstract
Unlabelled: Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL(Ser505Asn) mutation could be underestimated., Design and Methods: We extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL(Ser505Asn) mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis., Results: Fifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.
- Published
- 2010
- Full Text
- View/download PDF
5. Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia.
- Author
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Liu K, Martini M, Rocca B, Amos CI, Teofili L, Giona F, Ding J, Komatsu H, Larocca LM, and Skoda RC
- Subjects
- Adolescent, Adult, Asian People genetics, Child, Child, Preschool, Evidence-Based Medicine, Female, Haplotypes genetics, Humans, Infant, Italy, Male, Microsatellite Repeats genetics, Middle Aged, Pedigree, Young Adult, Founder Effect, Mutation genetics, Receptors, Thrombopoietin genetics, Thrombocytosis genetics, Thrombopoietin genetics, White People genetics
- Abstract
Background: Hereditary thrombocythemia is a rare disease characterized by increased megakaryopoiesis and overproduction of platelets. Germ line mutations have been identified in the genes for thrombopoietin (THPO) and its receptor, MPL. A clustering of familial cases with the MPL-G1073A mutation that results in a serine to asparagine substitution (S505N) has been recently reported in Italy. Here we performed haplotype analysis in nine families (eight Italian and one Japanese) with hereditary thrombocythemia carrying the MPL-S505N mutation in the MPL gene., Design and Methods: The MPL gene was examined by genomic DNA sequencing. Haplotype analysis was performed using microsatellites and single nucleotide polymorphisms., Results: Analysis of microsatellite markers and single nucleotide polymorphisms in the eight Italian families with hereditary thrombocythemia revealed the presence of a common haplotype compatible with a founder effect, which may have originated 23 generations ago. This haplotype was rarely observed in 132 unrelated individuals and was absent in a Japanese family with the MPL-S505N mutation., Conclusions: The recurrent MPL-S505N mutation found in the eight Italian families with hereditary thrombocythemia is likely due to a founder effect.
- Published
- 2009
- Full Text
- View/download PDF
6. A new severity score index for phenotypic classification and evaluation of responses to treatment in type I Gaucher disease.
- Author
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Di Rocco M, Giona F, Carubbi F, Linari S, Minichilli F, Brady RO, Mariani G, and Cappellini MD
- Subjects
- Bone Density, Bone Diseases, Metabolic etiology, Bone Marrow pathology, Enzyme Therapy, Gaucher Disease complications, Gaucher Disease pathology, Humans, Lung pathology, Phenotype, Viscera pathology, Gaucher Disease drug therapy, Gaucher Disease genetics, Severity of Illness Index
- Abstract
Background: Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment., Design and Methods: The new scoring system proposed here, the "Gaucher Disease Severity Score Index - Type I" (GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods on an equivalent basis., Results: The new scoring system, GauSSI-I, was developed. Six specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available., Conclusions: The GauSSI-I is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment.
- Published
- 2008
- Full Text
- View/download PDF
7. A novel heterozygous HIF2AM535I mutation reinforces the role of oxygen sensing pathway disturbances in the pathogenesis of familial erythrocytosis.
- Author
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Martini M, Teofili L, Cenci T, Giona F, Torti L, Rea M, Foà R, Leone G, and Larocca LM
- Subjects
- Adolescent, Adrenomedullin metabolism, Adult, Basic Helix-Loop-Helix Transcription Factors metabolism, Female, Humans, Hypoxia, Male, Polycythemia diagnosis, Receptors, Transferrin metabolism, Vascular Endothelial Growth Factor A metabolism, Basic Helix-Loop-Helix Transcription Factors genetics, Gene Expression Regulation, Heterozygote, Mutation, Oxygen metabolism, Polycythemia genetics, Polycythemia therapy
- Abstract
HIF2A transcription factor plays a central role in the regulation of the hypoxia responding pathway in mammalian cells, by modulating erythropoiesis and angiogenesis. Molecular alterations of oxygen sensing pathway constituents are implicated in hereditary erythrocytosis. Here we show that 2 members of a family with idiopathic erythrocytosis exhibited a new heterozygous G to A mutation at base 1605 of the exon 12 of hypoxia-inducible factor-2A (HIF2A) gene. This mutation determines the replacement of methionine by isoleucine at the position 535, very close to the position 531, where the hydroxyl acceptor prolyne is located. In addition, we found that mRNA expression of erythropoietin receptor, vascular endothelial growth factor, transferrin receptor, adrenomedullin and N-myc downstream regulated gene 1, up-regulated by HIF2A or hypoxia, were significantly higher in patients carrying the mutation than in normal controls. These results suggest that the HIF2A(M535I) gene mutation could induce hereditary erythrocytosis at a young age.
- Published
- 2008
- Full Text
- View/download PDF
8. Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients?
- Author
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Teofili L, Foà R, Giona F, and Larocca LM
- Subjects
- Adolescent, Adult, Age Factors, Algorithms, Amino Acid Substitution, Child, Child, Preschool, Diagnosis, Differential, Female, GPI-Linked Proteins, Humans, Isoantigens genetics, Janus Kinase 2 genetics, Male, Membrane Glycoproteins genetics, Mutation, Missense, Polycythemia Vera epidemiology, Polycythemia Vera pathology, Receptors, Cell Surface genetics, Receptors, Thrombopoietin genetics, Thrombocythemia, Essential epidemiology, Thrombocythemia, Essential pathology, Polycythemia Vera diagnosis, Polycythemia Vera genetics, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential genetics
- Published
- 2008
- Full Text
- View/download PDF
9. A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome.
- Author
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Testi AM, Moleti ML, Giona F, Annino L, Chiaretti S, Del Giudice I, Todisco E, D'Elia G, Ferrari A, Arcese W, and Mandelli F
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cytarabine administration & dosage, Dose-Response Relationship, Drug, Female, Hospitals, University, Humans, Idarubicin administration & dosage, Infant, Male, Rome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background and Objective: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance., Methods: In a clinical phase II study, the combination of a single high dose (HD) of idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L)., Results: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections., Interpretation and Conclusions: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD-ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
- Published
- 1997
10. A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome.
- Author
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Testi AM, Moleti ML, Giona F, Annino L, Chiaretti S, Del Giudice I, Todisco E, D'Elia G, Ferrari A, Arcese W, and Mandelli F
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Humans, Infant, Male, Rome, Universities, Antibiotics, Antineoplastic therapeutic use, Cytarabine therapeutic use, Idarubicin therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background and Objective: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance., Methods: In a clinical phase II study the combination of a single high dose (HD) idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L)., Results: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections., Interpretation and Conclusions: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD- ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
- Published
- 1997
11. Gonadal, adrenal, androgen and thyroid functions in adults treated for acute lymphoblastic leukemia.
- Author
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Giona F, Annino L, Donato P, and Ermini M
- Subjects
- Adolescent, Adult, Female, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Retrospective Studies, Endocrine System Diseases chemically induced, Methotrexate adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background and Methods: The limited and controversial data available regarding endocrine function in adults treated for acute lymphoblastic leukemia (ALL) prompted us to study the influence of chemotherapy on gonadal, adrenal androgen and thyroid function. Forty-eight ALL adults (30 men and 18 women) in first complete remission (CR) were investigated., Results: Severe reproductive function impairment was detected in 10/12 males receiving treatment, while endocrine function was affected in only 1 case. All but one off-therapy male showed normal reproductive function; moreover, endocrine function was impaired in only one male. Eight of 10 females receiving treatment showed hypergonadotropinemia and decreased estrogen levels. All off-therapy women reported regular menses, even though mild hypergonadotropinemia persisted in only 2 cases. Adrenal androgen function was depressed in 12/22 on-therapy patients in both sexes, and in 6/17 off-therapy males. All off-therapy females recovered completely. Dihydroepiandrosterone-sulfate (DHEA-S) serum levels were significantly correlated to the length of time-off therapy (p = 0.003), and inversely correlated to the age at diagnosis (p < 0.0001) in off-therapy males. All patients remained euthyroid, although 4 patients showed subclinical impairment of thyroid function., Conclusions: Our experience suggests that long-term prospective studies for ALL adults are necessary in order to better define the magnitude and duration of influence the chemotherapy has on endocrine function.
- Published
- 1994
12. Pregnancy in a young woman affected by essential thrombocythemia: a case report.
- Author
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Ferrari A, Mazzucconi MG, Martinelli E, Giona F, Paesano R, and Pachi A
- Subjects
- Abruptio Placentae, Adult, Female, Fetal Death, Humans, Pipobroman therapeutic use, Pregnancy, Smoking, Thrombocythemia, Essential drug therapy, Thrombophlebitis etiology, Pregnancy Complications, Hematologic, Thrombocythemia, Essential complications
- Published
- 1989
13. High-dose intravenous gammaglobulin (HDIVG): therapy of refractory ITP in adults and children.
- Author
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Mazzucconi MG, Ferrari A, Vignetti M, Giona F, Girolami D, Martinelli E, and Mandelli F
- Subjects
- Adolescent, Adult, Age Factors, Combined Modality Therapy, Drug Administration Schedule, Evaluation Studies as Topic, Female, Humans, Infusions, Intravenous, Injections, Intravenous, Male, Middle Aged, Purpura, Thrombocytopenic surgery, Immunization, Passive, Purpura, Thrombocytopenic therapy, gamma-Globulins administration & dosage
- Abstract
We performed 56 HDIVG administrations in adults (26) and children (30) affected by idiopathic thrombocytopenic purpura with two different schedules: a five-day course at 400 mg/kg/d and a "bolus" 1 gr/kg. Forty-five cases were treated in preparation for surgical operations and eleven for bleeding episodes. Response to the five-day course in adults was good in 3/24, fair in 13/24, poor in 8/24, while in children it was good in 14/26, fair in 9/26, poor in 3/26. The difference between adults and children is statistically significant. None of the responder patients submitted to surgical operation needed platelet infusions during surgery. Response to the "bolus" schedule (6 cases) in adults was poor in 1 case and good in the other one, and in children, fair in 3 cases and good in the other one. In responder patients treated for bleeding episodes we obtained clinical improvement with hemorrhage arrest. In adults the treatment was well-tolerated, while in children we observed 3/30 mild side effects and 1/30 important side effect.
- Published
- 1989
14. [Toxic effects of prophylaxis in meningeal leukemia: two cases of leukoencephalopathy (author's transl)].
- Author
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Mandelli F, Antonelli M, Giona F, Loasses A, Montuoro A, Prencipe M, and Sideri G
- Subjects
- Child, Humans, Infant, Leukemia, Lymphoid drug therapy, Leukemia, Lymphoid radiotherapy, Leukoencephalopathy, Progressive Multifocal chemically induced, Leukemia, Lymphoid complications, Leukoencephalopathy, Progressive Multifocal etiology, Methotrexate adverse effects
- Published
- 1982
15. Adult acute lymphoblastic leukemia: description and analysis of long-term survivors. A retrospective study.
- Author
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Giona F, Mazzucconi MG, Aloe Spiriti MA, Defazio D, De Luca AM, Ferrazza G, Martinelli E, and Mandelli F
- Subjects
- Adolescent, Adult, Female, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality
- Abstract
This retrospective study, including 118 patients with acute lymphoblastic leukemia (ALL) aged greater than 15 years, with a minimum follow-up of 6 years, was aimed at defining potentially "cured" adults with ALL. At present, 21 out of 92 patients who achieved complete remission (CR) are long survivors: 16 in first CR, off-therapy; 4 in 2nd CR (3 off-therapy); 1 in 3rd CR, on treatment. On the basis of available data, we tried to identify factors at diagnosis which might predict long-term survival: white blood cell (WBC) count on admission was the only significant prognostic factor for overall survival (p = 0.0002) and first CR duration (p = 0.0005). The survival hazard rate (risk of death from acute leukemia per day) reaches 0 between 8 and 9 years from diagnosis. From our data we can identify two groups of ALL long-term survivors: the first includes 16 patients in 1st continuous CR (CCR), 12 of whom in CCR for over 8 years may be considered "cured"; the second group comprises 5 patients, relapsing once or twice, alive in 2nd or 3rd CR.
- Published
- 1989
16. Evaluation of a polychemotherapeutic regimen including Idarubicin (4-demethoxydaunorubicin) in relapsed acute lymphocytic leukemia.
- Author
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Mandelli F, Testi AM, Aloe Spiriti MA, Giona F, Meloni G, Moleti ML, Amadori S, and Pacciarini MA
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols toxicity, Asparaginase therapeutic use, Child, Child, Preschool, Clinical Trials as Topic, Cytarabine therapeutic use, Daunorubicin administration & dosage, Daunorubicin therapeutic use, Female, Follow-Up Studies, Humans, Idarubicin, Male, Methotrexate therapeutic use, Vincristine therapeutic use, Antibiotics, Antineoplastic therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Daunorubicin analogs & derivatives, Leukemia, Lymphoid drug therapy
- Published
- 1986
17. Late intensification therapy for childhood acute lymphocytic leukemia.
- Author
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Meloni G, Mandelli F, Aloe Spiriti MA, Giona F, and Amadori S
- Subjects
- Child, Child, Preschool, Cytarabine administration & dosage, Humans, Long-Term Care, Recurrence, Thioguanine administration & dosage, Leukemia, Lymphoid drug therapy
- Published
- 1982
18. Results of two different conditioning regimens followed by ABMT in refractory acute lymphoblastic leukemia.
- Author
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Meloni G, De Fabritiis P, Pulsoni A, Sandrelli A, Giona F, Simone F, and Mandelli F
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Busulfan administration & dosage, Carmustine administration & dosage, Carmustine therapeutic use, Child, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cyclophosphamide analogs & derivatives, Cyclophosphamide pharmacology, Cytarabine administration & dosage, Cytarabine therapeutic use, Drug Resistance, Etoposide administration & dosage, Etoposide therapeutic use, Female, Humans, Male, Mitoxantrone administration & dosage, Mitoxantrone therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Transplantation, Autologous, Bone Marrow Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma surgery, Preoperative Care methods
- Abstract
Thirty-one patients affected by advanced ALL entered this study. Twenty (1 in I CR, 9 in II CR, 6 in III CR and 4 extramedullary relapses) were treated with the BMVC conditioning regimen. Eleven (9 in II CR, 2 in III CR) received the Busulfan plus Cytoxan conditioning regimen. Asta-Z 7654-purged marrow was reinfused at day 0. Both protocols were well tolerated. Two patients treated with the BMVC regimen died in aplasia from sepsis; 1 patient died in CR 5 months after transplantation, 13 relapsed after a median time of 4 months (range 1-31). Four patients are in CCR with a median follow-up of 16 months (range 11-24). In the BU + CY treated group no toxic deaths were observed. Four patients relapsed after a median of 3 months (range 2-7) and 7 are in CCR with a median follow-up of 5 months (range 2-28).
- Published
- 1989
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