15-year follow-up of myeloma patients receiving 140 MG/M2 melphalan without hematopoietic stem cell or growth factor support as initial therapy

R. Powles*, B. Sirohi, J. Treleaven, S. Singhal, D. Cunningham, M. Gore, S. Kulkarni, C. Horton, R. Saso, J. Mehta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Between November 1981 and April 1986, 63 previously untreated myeloma patients (30-67 y, median 48; 51% stage III; 41 IgG, 12 IgA, 6 light chain, 3 non-secretory, 1 IgD) received 140mg/m2 melphalan (140Mel) with (n=22) or without (n=41) methylprednisolone (1.5 g x 5) as initial therapy. All patients received a priming dose of cyclophosphamide (400 mg/m2) on day -7 to limit gut damage. Neither hematopoietic growth factors nor stem cells were used. 10 patients died of toxicity at 2-40 days (median 20); 8 due to neutropenic sepsis. 21 patients (33%) attained CR, 31 (49%) attained PR, and 2 did not respond. 2 patients are alive in continuous CR 15 and 16 y after 140Mel without any additional therapy. 51 patients experienced disease progression 2-128 months (median 19) after 140Mel, and received low-dose cyclophosphamide (n=l), 140Mel (n=2), no therapy (n=8), infusional chemotherapy (n=16), or infusional chemotherapy followed by 200 mg/m2 melphalan and autotransplantation (n=24). 11 patients eventually received further high-dose therapy on disease progression. All but 1 of the 51 patients experiencing disease progression after 140Mel eventually died of disease or consequences of further therapy at 1-176 months (median 32). One patient developed myelodysplastic syndrome 13 y after 140Mel; having received 3 more courses of high-dose melphalan (200 mg/m2 x 2, and 140 mg/m2 x 1 ) in the interim. As of July 2000, 3 patients are still alive: 2 in continuous CR (15 and 16 y after 140Mel)and 1 in stable PR (progression after initial CR attained with 140Mel). The median overall survival (OS) of the whole group is 4 y (range, 2 d to 16 y), and the median eventfree survival 16 mo (range, 2 d to 16 y). The actuarial 5-y and 10-y OS is 46% (95% CI, 3458) and 19% (95% CI, 11-30) respectively. These data provides the longest available followup on patients treated with high-dose melphalan. While it is clear that the majority of the patients relapse following therapy, the 2 long-term survivors raise the intriguing possibility that a small minority may not relapse. The leukemogenic potential of 140Mel appears to be very limited. The availability of growth factors and effective maintenance therapy may make this approach worth exploring again.

Original languageEnglish (US)
Pages (from-to)292b
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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