AUTOLOGOUS PERIPHERAL STEM-CELL TRANSPLANTATION OF THE BLASTIC PHASE OF CHRONIC MYELOID-LEUKEMIA FOLLOWING SEQUENTIAL HIGH-DOSE CYTOSINE-ARABINOSIDE AND MELPHALAN

Blast-phase chronic myelogenous leukemia (CML) is the terminal phase i n CML and is uniformly fatal. We treated 12 patients with blast-phase CML with a program of high-dose cytarabine 3.0 g/m(2) and melphalan 14 0 mg/m(2), followed by reinfusion of stem cells obtained from peripher al blood during the chronic phase. Seven patients achieved either a pa rtial or complete hematologic remission, while five patients showed no response to therapy. One patient returned to chronic phase features w ith loss of a chromosomal abnormality acquired at blast phase, restora tion of hematopoiesis, and a decrease in the amount of bone marrow bla sts to less than 10%. Six patients cleared their peripheral blasts and showed recovery of their myeloid and platelet lineages, but all six r equired treatment for acceleration within 3 months. Of the five nonres ponding patients, three died with aplastic bone marrow, one patient ne ver cleared peripheral blasts after chemotherapy, and one patient had evidence of peripheral blasts 3 weeks after the autologous stem cell r einfusion. None of the patients returned to a normal karyotype. The ab lative regimen was effective in eradicating bone marrow blasts to <10% in 8 of 10 patients in whom interpretable bone marrow samples were pe rformed following chemotherapy. Overall, the median survival for all p atients from the time of stem cell reinfusion was 5.5 months. We concl ude that autotransplants with peripheral blood can successfully be use d to support hematopoiesis during high-dose therapy for CML blast cris is, however, has no role by itself in the curative therapy of blast cr isis CML. A small number of patients can be restored to chronic phase features, and this may provide an opportunity to administer subsequent alternative treatments designed to eradicate the malignant stem cell population. Autotransplants with stem cells may also be used as therap y for patients without a histocompatible marrow donor. However, the au totransplant may be more effective when used during the chronic phase of CML, with the use of hematopoietic growth factors, and with reinfus ion of stem cells depleted of the malignant Philadelphia chromosome-po sitive clone. (C) 1994 Wiley-Liss, Inc.