Figure 4.
Peripheral blood blast counts before and during imatinib therapy in 3 representative patients achieving CHR, NLE, and more than 50% reduction in blast count. (A) This 73-year-old man (PN 7) was diagnosed with AML M1. Because of age and concomitant disease he received modified induction chemotherapy (5 + 2) consisting of cytosine arabinoside 200 mg/m2 for 5 days and idarubicin 12 mg/m2 for 2 days. On day 18 after start of chemotherapy, the white blood count was 0.9 × 109/L with 20% blasts. As blasts persisted, BM cytology (2% blasts) and biopsy (5% blasts) was performed and raised the question of persistence of a small population of leukemic blasts. Because FACS analysis of BM MNCs revealed persistence of a cell population (15%) featuring the initial AML immunophenotype, the patient was considered refractory, and imatinib 600 mg/d was commenced on day 24 after start of chemotherapy. Intermittent presence of blasts in peripheral blood was documented until day 24 of imatinib therapy. On day 35 of imatinib therapy the patient had a white blood count of 8.0 × 109/L with 3.9 × 109/L neutrophils and 0% blasts. The platelet count was 139 × 109/L, and a bone marrow aspirate showed remission with 0.5% blasts. Temporally, the recovery of hematopoiesis is consistent with the time course anticipated if chemotherapy had been successful. However, in patients who achieve remission with chemotherapy persisting blasts in PB and detected by BM FACS analysis are not expected. The IRS for c-kit was 12, and 71% of blasts in BM were c-kit–positive by FACS analysis (Table 4). (B) This is a 52-year-old woman (PN 9) who was diagnosed with secondary AML M2 deriving from MDS/RAEB (myelodysplasia/refractory anemia with excess blasts). Because of numerous serious complications during the first cycle of induction chemotherapy, she then underwent matched unrelated donor stem cell transplantation. Her posttransplantation course was complicated by acute graft-versus-host disease (GVHD) grade 3 and chronic extensive GVHD. Thirteen months after stem cell transplantation she experienced a cytogenetic relapse, and the immunosuppressive regimen was discontinued. However, 19 months later there was hematologic relapse. Therefore, she was started on imatinib 600 mg/d. Four days prior to start of imatinib her white blood count was 7.6 × 109/L with 15% blasts. Platelet count was 149 × 109/L. A bone marrow aspirate showed 5% blasts, and cytogenetics revealed multiple aberrations involving chromosomes 1, 3, 7, 9, 10, and 19. No metaphases deriving from the sex-mismatched donor could be identified. On treatment with imatinib, a steady decrease of PB blasts was observed. BM aspiration obtained on day 38 already showed 0% blasts, and cytogenetics revealed partial reappearance (3 of 32) of donor type metaphases. Treatment with imatinib was continued, and on day 140 the patient cleared PB blasts. The IRS for c-kit was 12, and 90% of blasts in BM were c-kit–positive by FACS analysis (Table 4). (C) This is a 80-year-old woman (PN 14) diagnosed with AML M5a deriving from MDS. The patient presented with a WBC of 14.0 × 109/L with 30% blasts; platelet count was 8 × 109/L with a hemoglobin of 10.2 g%. A bone marrow aspirate showed 40% blasts. Because of her age and concomitant disease this patient was treated with imatinib as upfront therapy. Significant reduction of PB blasts was rapidly achieved on imatinib treatment. However, after 31 days the patient decided to stop experimental therapy and asked for hospice care. The IRS for c-kit was 4, and 59% of blasts in BM were c-kit–positive by FACS analysis (Table 4).