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Lymphoma

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

Leukemia volume 15, pages 256–263 (2001)Cite this article

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/μl 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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Acknowledgements

We thank the laboratory staff and nurses of the Divisione Universitaria di Ematologia and Centro Dipartimentale Trapianto Midollo – S Giovanni Hospital, Torino for help and patient care. This work was supported in part by Consiglio Nazionale delle Ricerche, Rome, Italy (special project ACRO, grant No. 96.00742.PF39 to TC and No. 96.00615.PF39 to AP) and by Associazione Italiana Ricerca sul Cancro, Milan, Italy.

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  1. P Corradini

    Present address: Unità Trapianto, Ist Sc. S. Raffaele, Milano, Italy

Authors and Affiliations

  1. Dipartimento di Medicina e Oncologia Sperimentale, Divisione Universitaria di Ematologia, Italy

    C Tarella, F Zallio, D Caracciolo, A Cuttica, P Corradini, P Gavarotti, M Ladetto & A Pileri

  2. Serv. Univ., Torino, Italy

    V Podio

  3. Serv. Osped di Medicina Nucleare, Torino, Italy

    A Sargiotto

  4. Divisione Universitaria di Radioterapia-Azienda Ospedaliera S Giovanni Battista di Torino, Torino, Italy

    G Rossi

  5. Unità Trapianto Midollo, Ist Naz. Tumori, Milano, Italy

    AM Gianni

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Tarella, C., Zallio, F., Caracciolo, D. et al. 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. Leukemia 15, 256–263 (2001). https://doi.org/10.1038/sj.leu.2402011

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