title: Autologous peripheral stem cell transplantation of the blastic phase of chronic myeloid leukemia following sequential high-dose cytosine arabinoside and melphalan.
abstract: Blast-phase chronic myelogenous leukemia (CML) is the terminal phase in CML and is uniformly fatal. We treated 12 patients with blast-phase CML with a program of high-dose cytarabine 3.0 g/m2 and melphalan 140 mg/m2, followed by reinfusion of stem cells obtained from peripheral blood during the chronic phase. Seven patients achieved either a partial or complete hematologic remission, while five patients showed no response to therapy. One patient returned to chronic phase features with loss of a chromosomal abnormality acquired at blast phase, restoration of hematopoiesis, and a decrease in the amount of bone marrow blasts to less than 10%. Six patients cleared their peripheral blasts and showed recovery of their myeloid and platelet lineages, but all six required treatment for acceleration within 3 months. Of the five nonresponding patients, three died with aplastic bone marrow, one patient never cleared peripheral blasts after chemotherapy, and one patient had evidence of peripheral blasts 3 weeks after the autologous stem cell reinfusion. None of the patients returned to a normal karyotype. The ablative regimen was effective in eradicating bone marrow blasts to < 10% in 8 of 10 patients in whom interpretable bone marrow samples were performed following chemotherapy. Overall, the median survival for all patients from the time of stem cell reinfusion was 5.5 months. We conclude that autotransplants with peripheral blood can successfully be used to support hematopoiesis during high-dose therapy for CML blast crisis, however, has no role by itself in the curative therapy of blast crisis 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 therapy for patients without a histocompatible marrow donor. However, the autotransplant may be more effective when used during the chronic phase of CML, with the use of hematopoietic growth factors, and with reinfusion of stem cells depleted of the malignant Philadelphia chromosome-positive clone.
authors.affiliation: Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
authors.forename: U A
authors.initials: UA
authors.lastname: Matulonis
authors.forename: J D
authors.initials: JD
authors.lastname: Griffin
authors.forename: G P
authors.initials: GP
authors.lastname: Canellos
mesh_terms: D000328:Adult; D001804:Blood Transfusion, Autologous; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006410:Hematopoiesis / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D008875:Middle Aged; D014182:Transplantation, Autologous
chemical_list: D003561:Cytarabine; D008558:Melphalan