High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: High tolerability with reversible cardiotoxicity

C. Tarella, F. Zallio, D. Caracciolo, A. Cuttica, P. Corradini, P. Gavarotti, M. Ladetto, V. Podio, A. Sargiotto, G. Rossi, A. M. Gianni, A. Pileri

Research output: Contribution to journalArticle

Abstract

Hematological and extrahematological toxicity of high-dose (hd) mitoxantrone (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at disease onset). Autograft was the final part of a hd-sequential (HDS) chemotherapy program, including a debulkying phase (1-2 APO ±2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara-C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd-MITO, given at 60 mg/m2 on day -5; (2) hd-L-PAM, given at 180 mg/m2 on day -2; (3) PBPC autograft, with a median of 11 × 106 CD34+/kg, or 70 × 104 CFU-GM/kg, on day 0. A rapid hematological recovery was observed in most patients, with ANC >500/μL and Plt >20 000/μI values reached at a median of 11 and 10 days since autograft, respectively. The good hemopoietic reconstitution allowed the delivery of consolidation radiotherapy (RT) to bulky sites in 53 out of 57 candidate patients, within 1 to 3 months following autograft; five of these patients required back-up PBPC re-infusion due to severe post-RT pancytopenia. Few severe infectious complications were recorded. There was one single fatal event due to severe pancytopenia following whole abdomen RT. Cardiac toxicity was evaluated as left ventricular ejection fraction (LVEF), monitored by cardiac radionuclide scan. LVEF prior to and after autograft was significantly reduced (median values: 55% vs 46%) in 58 evaluated patients; however, a significant increase to a median value of 50% was observed in 45 patients evaluated at 1 to 3 years since autograft. At a median follow-up of 3.6 years, 92 patients are alive, with a 7-year overall survival projection and 6.7-year failure-free survival projection of 77% and 69%, respectively. We conclude that a conditioning regimen with hd-MITO/L-PAM fits well within the HDS program. It implies good tolerability and reversible cardiotoxicity and it may have contributed to the good long-term outcome observed in this series of patients.

Original languageEnglish
Pages (from-to)256-263
Number of pages8
JournalLeukemia
Volume15
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Mitoxantrone
Melphalan
Autografts
Lymphoma
Blood Cells
Stem Cells
Pancytopenia
Radiotherapy
Stroke Volume
Granulocyte-Macrophage Progenitor Cells
Survival
Cardiotoxicity
Cytarabine
Etoposide
Methotrexate
Radioisotopes
Abdomen
Cyclophosphamide
Drug Therapy

Keywords

  • Autograft
  • Cardiotoxicity
  • Conditioning regimen
  • HDS
  • Lymphoma
  • Mitoxantrone

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients : High tolerability with reversible cardiotoxicity. / Tarella, C.; Zallio, F.; Caracciolo, D.; Cuttica, A.; Corradini, P.; Gavarotti, P.; Ladetto, M.; Podio, V.; Sargiotto, A.; Rossi, G.; Gianni, A. M.; Pileri, A.

In: Leukemia, Vol. 15, No. 2, 2001, p. 256-263.

Research output: Contribution to journalArticle

Tarella, C. ; Zallio, F. ; Caracciolo, D. ; Cuttica, A. ; Corradini, P. ; Gavarotti, P. ; Ladetto, M. ; Podio, V. ; Sargiotto, A. ; Rossi, G. ; Gianni, A. M. ; Pileri, A. / High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients : High tolerability with reversible cardiotoxicity. In: Leukemia. 2001 ; Vol. 15, No. 2. pp. 256-263.
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abstract = "Hematological and extrahematological toxicity of high-dose (hd) mitoxantrone (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at disease onset). Autograft was the final part of a hd-sequential (HDS) chemotherapy program, including a debulkying phase (1-2 APO ±2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara-C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd-MITO, given at 60 mg/m2 on day -5; (2) hd-L-PAM, given at 180 mg/m2 on day -2; (3) PBPC autograft, with a median of 11 × 106 CD34+/kg, or 70 × 104 CFU-GM/kg, on day 0. A rapid hematological recovery was observed in most patients, with ANC >500/μL and Plt >20 000/μI values reached at a median of 11 and 10 days since autograft, respectively. The good hemopoietic reconstitution allowed the delivery of consolidation radiotherapy (RT) to bulky sites in 53 out of 57 candidate patients, within 1 to 3 months following autograft; five of these patients required back-up PBPC re-infusion due to severe post-RT pancytopenia. Few severe infectious complications were recorded. There was one single fatal event due to severe pancytopenia following whole abdomen RT. Cardiac toxicity was evaluated as left ventricular ejection fraction (LVEF), monitored by cardiac radionuclide scan. LVEF prior to and after autograft was significantly reduced (median values: 55{\%} vs 46{\%}) in 58 evaluated patients; however, a significant increase to a median value of 50{\%} was observed in 45 patients evaluated at 1 to 3 years since autograft. At a median follow-up of 3.6 years, 92 patients are alive, with a 7-year overall survival projection and 6.7-year failure-free survival projection of 77{\%} and 69{\%}, respectively. We conclude that a conditioning regimen with hd-MITO/L-PAM fits well within the HDS program. It implies good tolerability and reversible cardiotoxicity and it may have contributed to the good long-term outcome observed in this series of patients.",
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AU - Zallio, F.

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AU - Cuttica, A.

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AU - Gavarotti, P.

AU - Ladetto, M.

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AU - Gianni, A. M.

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N2 - Hematological and extrahematological toxicity of high-dose (hd) mitoxantrone (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at disease onset). Autograft was the final part of a hd-sequential (HDS) chemotherapy program, including a debulkying phase (1-2 APO ±2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara-C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd-MITO, given at 60 mg/m2 on day -5; (2) hd-L-PAM, given at 180 mg/m2 on day -2; (3) PBPC autograft, with a median of 11 × 106 CD34+/kg, or 70 × 104 CFU-GM/kg, on day 0. A rapid hematological recovery was observed in most patients, with ANC >500/μL and Plt >20 000/μI values reached at a median of 11 and 10 days since autograft, respectively. The good hemopoietic reconstitution allowed the delivery of consolidation radiotherapy (RT) to bulky sites in 53 out of 57 candidate patients, within 1 to 3 months following autograft; five of these patients required back-up PBPC re-infusion due to severe post-RT pancytopenia. Few severe infectious complications were recorded. There was one single fatal event due to severe pancytopenia following whole abdomen RT. Cardiac toxicity was evaluated as left ventricular ejection fraction (LVEF), monitored by cardiac radionuclide scan. LVEF prior to and after autograft was significantly reduced (median values: 55% vs 46%) in 58 evaluated patients; however, a significant increase to a median value of 50% was observed in 45 patients evaluated at 1 to 3 years since autograft. At a median follow-up of 3.6 years, 92 patients are alive, with a 7-year overall survival projection and 6.7-year failure-free survival projection of 77% and 69%, respectively. We conclude that a conditioning regimen with hd-MITO/L-PAM fits well within the HDS program. It implies good tolerability and reversible cardiotoxicity and it may have contributed to the good long-term outcome observed in this series of patients.

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