2.0 Rationale for Current Protocol and Study Outline: 
Patients with CML who lack a suitable related or 
unrelated marrow donor eventually succumb to their disease. 
Recently, a number of approaches have shown the capacity to 
induce populations of Ph- cells. In vivo treatments such as 
interferon, intensive cytoreductive chemotherapy without 
transplant and the autotransplant process itself have been 
shown to generate Ph- cells. 4 In some patients, complete 
remissions have been sustained for over 5 years. 4 We 
propose to treat patients with combined sequential 
approaches where each therapy is designed to induce a 
maximum number of Ph- cells prior to collection of 
autologous peripheral blood stem cells and marrow. 
Treatment approaches will differ depending on whether 
the patient has early or advanced stage disease (see 
schema) . Based on the success of interferon alpha in early 
CML, patients with first chronic phase CML, designated Group 
1, will receive treatment with interferon alpha continued to 
a point of maximum cytogenetic response. Then, interferon 
treated patients in the chronic phase (excluding those who 
achieve a complete hematologic and cytogenetic remission) 
will receive cytoreductive therapy with high dose cytarabine 
and daunorubicin followed by G-CSF to generate additional 
Ph- cells. During recovery from this therapy peripheral 
blood stem cells will be harvested and stored. 
At least two weeks later patients will be treated with 
5-f luorouracil (5-FU) and marrow will be harvested and 
stored 10 days later. 5-FU has been found to enrich marrow 
for cycling progenitor cells such as HPP-CFC and CFU-C. 5 
Also, 5-FU has been used in murine systems and non-human 
primate models to enhance retroviral transduction of 
progenitor cells. 6 
As soon as possible (at least within 12 months of 
harvesting) , or, if CML progresses to advanced stage 
disease, patients in Group 1 will undergo high dose 
cyclophosphamide/TBI and infusion of peripheral blood stem 
cells/autologous bone marrow. Post-transplant G-CSF will be 
given to all patients to enhance marrow recovery. 
In contrast, patients with advanced CML, Group 2 
(accelerated phase, interferon resistance, blast phase, > 
1st chronic phase) , will not receive interferon initially 
since it is rarely effective in patients with advanced 
disease. Instead patients will be treated with high dose 
cytarabine, daunorubicin followed by G-CSF to re-establish 
chronic phase disease and potentially generate Ph- cells. 
(for patients with suspected lymphoblastic crisis, a 
vincristine/prednisone regimen will be employed prior to 
cytoreductive therapy) . Like patients in Group 1, patients 
in Group 2 will undergo peripheral blood collection during 
the recovery phase from cytoreductive chemotherapy and 
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