Chemotherapy, Filgrastim and Peripheral Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia

OBJECTIVES:

• Assess clinical outcomes, survival, and morbidity of transplantation therapy in patients with chronic myelogenous leukemia when treated with high dose chemotherapy and filgrastim (G-CSF) followed by autologous retrovirally transduced peripheral blood stem cell (PBSC) transplantation.
• Determine whether this priming treatment can increase the fraction of benign Philadelphia chromosome (Ph) negative hematopoietic progenitors in PBSC and reduce the incidence of persistent or recurrent leukemia after autologous transplantation with mobilized PBSC in these patients.
• Assess whether retroviral transduction of mobilized PBSC progenitors determines the contribution of malignant Ph positive progenitors contaminating the graft to relapse after transplantation in these patients.
• Determine whether this priming treatment can expand the benign progenitor population in the PBSC collections from these patients.

OUTLINE: In the priming phase, patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SQ) daily beginning on day 4 and continuing until the completion of leukapheresis. Peripheral blood stem cells (PBSC) are harvested 4-7 times between days 10 and 21 beginning when blood counts recover (CD34+ cells are selected from 2 of these PBSC collections and transduced with the LN NEO virus prior to cryopreservation).

In the transplant phase, patients who have not received prior radiotherapy receive cyclophosphamide IV over 2 hours daily on days -7 and -6 and total body irradiation on days -4 through -1. Autologous PBSC and LN NEO transduced CD34+ cells are reinfused on day 0. Patients also receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

Patients who have received prior radiotherapy receive oral busulfan every 6 hours on days -10 through -7 and cyclophosphamide IV daily on days -6 through -3. Autologous PBSC and LN NEO transduced CD34+ cells are reinfused on day 0. Patients also receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

All patients then receive interferon alfa SQ daily until disease progression or unacceptable toxicity.

Patients are followed at 3 weeks; at 3, 6, 9, 12, 18, and 24 months; and then annually thereafter.

PROJECTED ACCRUAL: A total of 4-26 patients will be accrued for this study.