Interferon-α protects Philadelphia-negative progenitors from exhaustion in chronic myeloid leukemia patients with cytogenetic response

Introduction: Normal immature hematopoietic progenitors are relatively well preserved in most patients newly diagnosed with chronic myeloid leukemia, but tend to decline rapidly with time. Such exhaustion could reflect a suppressive effect of the Philadelphia positive clone expansion and/or be induced by Interferon-α treatment. Patients and methods: A total of 51 CML patients were classified into three groups. Newly diagnosed untreated patients were group A (n=30). Of the 21 treated individuals with Interferon-α, for at least 12 months, 15 showed no cytogenetic response (group B) while six showed persisting major/complete response (group C). Patients belonging to groups A and B were mobilized with chemotherapy plus G-CSF while patients of group C received a short course of G-CSF only. Results: Patients responding to IFN-α (group C) showed comparable numbers of bone marrow Ph ^- long-term culture initiating cells to those of newly diagnosed individuals (group A): 8.5 (6 MNC vs 10.5 (- LTC-IC collected was significantly lower in patients of group B 1.8 (0-325) × 10 ²/kg than in patients of either group A 31.3 (0-952) × 10 ²/kg (P2/kg (P+ metaphases, but Ph ^- progenitors in their bone marrow, mobilized normal amounts of Ph ^- progenitors. Conclusion: These findings suggest that the decline of normal hematopoietic progenitors, currently observed in the majority of CML patients, is not induced by IFN-α treatment, but it is likely due to the expanding leukemic clone. They also indicate that normal hematopoietic reservoir is consistently preserved in patients given IFN-α early after diagnosis and achieving a stable cytogenetic response.