Mobilization and transplantation of Philadelphia-negative peripheral- blood progenitor cells early in chronic myelogenous leukemia

Purpose: Mobilization of Philadelphia (Ph) chromosome-negative progenitors is now possible in many Ph¹-positive chronic myelogenous leukemia (CML) patients who had received interferon alfa (IFN-α) with no cytogenetic response. In this pilot study, we used this approach in patients without prior IFN-α therapy to determine if the number and quality of mobilized progenitors would be increased and to evaluate the potential effect of these cells as autografts. Patients and Methods: Twenty-two untreated patients were mobilized within 12 months of diagnosis. The treatment regimen consisted of the mini-ICE protocol. Beginning on day +8, granulocyte colony- stimulating factor (G-CSF) was used in all patients. Leukophoresis was performed as the patients were recovering from aplasia, when WBC count exceeded 0.8 x 10⁹/L. Results: In 14 patients, (63%) the leukophoresis product was entirely Ph¹-negative and in four patients the Ph¹-positive cell rate was ≤7%. Significant numbers of long-term culture-initiating cells (LTC-IC) and CD34⁺ Thy1⁺Lin^- cells were found in most of the Ph¹-negative collections that were tested. Twelve patients underwent autografting with their mobilized peripheral-blood progenitor cells (PBPC) (Ph¹-negative collections, 10 patients; major cytogenetic response, two patients). All patients engrafted and are olive; six have Ph¹-negative marrow 7 to 15 months after autografting. Posttransplant treatment was IFN-α combined with interleukin (IL)-2 because of the recent demonstration of synergistic activity in augmenting cytolytic activity. Conclusion: Intensive chemotherapy given in early chronic phase of CML is well tolerated and results in high numbers of circulating Ph¹-negative precursor cells.