patients with early chronic phase CML, therapy with 
interferon alpha resulted in a 73% complete clinical and 
hematologic remission. 1 The overall median duration of 
hematologic remission and survival was 41 and 62 months 
respectively. Twenty-seven percent of patients achieved a 
major cytogenetic response with 19% attaining a complete 
cytogenetic response (CCR) determined on at least one 
cytogenetic analysis. Median time to CCR in those treated 
with interferon alpha 2a was 12 months. Eleven patients 
continued in CCR for 6-45 months (median 30) . Patients who 
failed to obtain a major cytogenetic response had 
significantly shorter durations of hematologic relapse-free 
survival (p=0.002). 
Unfortunately, most interferon responsive patients 
eventually relapse or progress by manifesting increased 
numbers of Ph+ cells. Cytogenetic responses to interferon- 
alpha therapy are infrequent and brief in late chronic phase 
and in the accelerated and blastic phases. 15 
Induction Chemotherapy to Suppress Ph+ Cells in CML : 
Kantarjian and co-workers have used high dose 
cytarabine and daunorubicin to induce major cytogenetic 
responses in interferon-resistant patients or patients who 
have evolved to the accelerated or blast phases of 
disease. 2,3 Although 30-50% of patients achieve major 
cytogenetic remissions, responses are usually brief but are 
sufficient to collect peripheral blood or marrow stem cells 
for autologous stem cell transplantation. GM-CSF is added to 
augment myeloid recovery from this regimen and to enhance 
the collection of progenitor cells. 3 
Autologous Marrow Transplantation and 5-FU Modulation of 
Human Bone Marrow ; 
Following chemotherapy or total body irradiation, the 
capacity for stem cell renewal is dependent on the dose or 
amount of marrow ablative therapy used. As a consequence, 
survival of humans exposed to increasing doses of 
chemotherapy and total body irradiation declines 
progressively due to pancytopenia and failure of marrow 
recovery. Autotransplantation of human marrow to recipients 
with recurrent neoplastic diseases prepared with otherwise 
lethal conditioning | regimens usually leads to complete 
marrow recovery. 15 ' 16 
Theoretically, shortening the time required for marrow 
recovery would improve survival and lessen morbidity. 
Techniques to shorten recovery in humans have included the 
use of recombinant human hemopoietic growth factors 
following transplantation of stem cells 16-21 or the use of 
chemotherapy mobilization of peripheral blood stem cells 
with or without growth factors. 22-27 In one report the use 
Recombinant DNA Research, Volume 16 
[149] 
