Imatinib Combined with Chemotherapy and Allogeneic Stem Cell Transplantation Results In Long Time Survival In Patients with De Novo Ph+ AML

Abstract 4368

De novo Philadelphia chromosome-positive acute myeloid leukemia is a rare condition with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) is always recommended to treat this disease although its results are not always satisfactory even in young patients. Imatinib is a protein tyrosine kinase inhibitor that has now been shown to be active in Ph+ chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia, however its role in Ph+ AML has not been extensively investigated. We present two patients with de novo Ph+ AML who received Imatinib combined with chemotherapy and allogeneic stem cell transplantation (allo-SCT), followed by Imatinib maintainance treatment after allo-SCT. These patients achieved long-term disease-free survival for 34 and 44 months respectively. Patient 1: A 19-year-old woman was admitted in October 2007 with fever and fatigue for one week. Physical examination showed pallor and severe sternal tenderness. Blood routine showed WBC 93.7×10⁹/L, Hb 80.7g/L, platelets 42×10⁹/L, 60% blast cells. Flow cytometry analysis of marrow mononuclear cells showed 84.41% blast cells positive for CD34, 80.49% for HLA-DR, 34.63% for CD13, and 5.71% for MPO. Karyotype at diagnosis was 46, XX, t (9; 22) (q34; 11) in 10 analyzed metaphases. Major BCR/ABL rearrangement (M-BCR-ABL, P210) was positive tested by real-time quantitative polymerase chain reaction(RQ-PCR). She was diagnosed with Ph+ AML (FAB M0). The patient was treated with 2 courses of DA chemotherapy then achieved bone marrow remission after the first course and achieved Complete Hemotology Response (CHR) after the second course. Then another 2 courses of high dose cytarabine were given. The status of minimal residual disease (MRD) was monitored by RQ-PCR for BCR-ABL/ABL ratio. After that BCR-ABL/ABL ratio was 68%, and then oral treatment with Imatinib 300mg/d×14d was started 4 months after diagnosis. Then 2 more cycles of Imatinib (300 mg/day for 14 days) following IA consolidation chemotherapy were taken and the patient maintained CHR and achieved statuses Complete Molecular Response (CMR) by her BCR-ABL/ABL ratio reducing to 0.4% 8 months after diagnosis. Then she took another course of Imatinib 400mg×4w therapy before allo-SCT. The patient underwent allo-SCT from a HLA-identical unrelated donor 9 months after diagnosis. STR analysis showed completely donor phenotype 1, 3 and 6 months after SCT. Imatinib (300 mg/day) was continued 74 days after SCT and the patient remains continuous CHR with Complete Cytogenetic Response (CCyR) and CMR till now. Patient 2: A 46-year-old man was admitted in Dec. 2004 with fever, cough and fatigue. Physical examination showed pallor and a small submaxillary lymphnode on the right. Blood Routine showed Hb 59g/L, platelets 115×10⁹/L, WBC 3.1×10⁹/L, and 24% blast cells. Bone barrow immunophenotype was CD34+, CD13+, CD117+, HLA-DR+ and MPO-. Karyotype analysis showed 46, XY, t (9; 22) (q34; 11) in 10 analyzed metaphases. Major BCR-ABL rearrangement was positive. He was diagnosed as Ph+ AML (FAB M0). The patient received induction chemotherapy as MA/VP plus Imatinib (400 mg/day×4w) and achieved CHR. Imatinib combined chemotherapy continued for another 7 more cycles. Imatinib was taken as 400 mg/day×2 w during the intermission period of chemotherapy. He had a bone marrow relapse with 18% blasts 48 days after the last chemotherapy, although CCyR and CMR were still maintained. Imatinib was added in a dose of 600mg/day and CHR achieved again 1 month later. The patient then took continuous Imatinib (400mg/day) until he received allo-SCT 26months after diagnosis. STR analysis showed completely donor phenotype 1, 3 and 6 months after SCT. Imatinib (400 mg/day) administration was continued and the patient maintained CHR and CMR in the following clinical course. However, he developed interstitial pneumonia 11 months after SCT and died from severe respiratory failure 30 months after SCT with CHR and CMR still maintained at that time. Our cases indicate that Imatinib combined with daunorubicin based chemotherapy followed by allo-SCT and Imatinib maintenance treatment appears to be the best way to treat Ph+ de novo AML, especially when Imatinib is used in an early phase of AML and when a complete molecular response is achieved before allo-SCT.