Autologous PBSC transplant for late onset AML after mafosfamide-purged and TBI-containing autologous BMT.
Renato BassanSergio CortelazzoAlessandro RambaldiP. E. CornelliGianmaria BorleriPiermario BellavitaAndrea BiondiTiziano Barbui
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Mitoxantrone
Salvage therapy
Idarubicin
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Abstract: Patients with non‐Hodgkin's lymphoma (NHL) who fail to respond to first‐line treatment or relapse after having shown complete or partial remission have a poor prognosis, especially in high‐grade NHL. Several salvage regimens show considerable toxicity and a poor long‐term outcome. In this retrospective study we analyzed data of 55 patients (34 men and 21 women) with a median age of 66 years (range: 18–89). The combination chemotherapy (VIM) consisted of VP‐16 (etoposide) 65 mg/m 2 , ifosfamide 650 mg/m 2 and mitoxantrone 3 mg/m 2 and was administered on 3 consecutive days along with mesna as uroprotection. Patients were treated for refractory disease or relapse and did not qualify for high‐dose chemotherapy and ABMT. Stages according to the An Arbor classification were: stage I/16, II/4, III/8 and IV/37 patients. Thirty‐three patients suffered from high‐grade and 22 from low‐grade NHL. Toxicity (WHO recommendations) was very mild. High‐grade NHL showed a better response rate (18/33, 46%) than low‐grade NHL (7/22, 36%). Overall response was 41% (12 CR and 11 PR) with a median duration of 36 months (range: 6–57 months). The combination therapy investigated exhibits mild toxicity even in extensively pretreated or elderly patients. The overall response rate of 41% might be improved by increased dosage and growth factor support.
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Abstract Although combination chemotherapy induces complete remission in 60–90% of adults with acute lymphoblastic leukemia, only 20–45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m 2 IV qd × 5), ifosfamide (1.5 g/m 2 /d × 5), and mitoxantrone (8 mg/m 2 /d IV × 3) in 11 adult patients with relapsed or refractory ALL. The median follow‐up of all patients completing therapy is 208 days (30–484+ days). Eight of 11 (73%; 95% confidence interval 45–92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50–151 days). Median time to granulocyte > .5 × 10 9 /L was 28 days (21–46 days) and the median time to platelet recovery > 20 × 10 9 /L was 24 days (21–39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patients with resistant ALL.
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Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.
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Idarubicin
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Refractory (planetary science)
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