Bone marrow transplantation for advanced acute leukemia: A pilot study of high-energy total body irradiation, cyclophosphamide and continuous infusion etoposide

B. Bostrom, D. J. Weisdorf, T. Kim, J. H. Kersey, N. K.C. Ramsay

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33 Scopus citations

Abstract

Leukemic relapse following bone marrow transplantation (BMT) for acute leukemia is the most common cause of treatment failure. Because a more intensive pre-transplant preparative regimen may prevent disease recurrence we have designed a novel intensive conditioning regimen for BMT using high-energy total body irradiation (total dose 850 cGy; energy 24 MV; midplane received dose rate 26 cGy/min; day -6) followed by cyclophosphamide (dose 50 mg/kg/day; schedule 2-h infusion; days -5, -4, -3) and continuous infusion high-dose etoposide (dose 500 mg/m2/day; schedule: 22-h infusion; days -5, -4, -3). Between February 1987 and December 1988, 45 patients with advanced acute leukemia received transplants using this regimen. Twenty-five purged auto-transplants were done for B-lineage (n=18), T-lineage (n=6) or biphenotypic (n=1) acute lymphoblastic leukemia, with 12 in remission and 13 in relapse at the time of transplantation. Of these, nine had non-relapse deaths and 16 have relapsed between 1 and 19 months (median 3 months) following transplantation. Of note all the T-lineage patients relapsed including two transplanted in remission and five transplanted in relapse. Nineteen patients received histocompatible allogeneic transplants and one underwent syngeneic transplantation. Of seven patients with acute lymphoblastic leukemia transplanted in refractory relapse, three have had an overt relapse, three died of interstitial pneumonitis and only one survives disease free 15 months after transplantation. Of 13 patients with acute non-lymphocytic leukemia and variants (11 who were transplanted in relapse) three died without relapse, three have relapsed and seven survive disease free from 9 to 27 months (median 20 months) after transplantation. Significant toxic events encountered with this preparative regimen included: universal, but reversible oral mucositis requiring continuous infusion narcotic analgesia; seven cases of lethal interstitial pneumonitis; two cases of fatal unexplained encephalopathy; four episodes of transient hemorrhagic cystitis; and five episodes of cutaneous desquamation of the palms, soles and intertriginous skin folds. The outcome in patients allografted for acute non-lymphoblastic leukemia and variants suggests further experience with this conditioning regimen is warranted in this disease. New approaches to BMT for acute lymphoblastic leukemia are necessary as it does not appear that manipulation of preparative regimens will improve the outcome in any appreciable way.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalBone marrow transplantation
Volume5
Issue number2
StatePublished - 1990

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