Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML

The current standard therapy in previously untreated adults with chronic phase (CP) of CML is imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML, accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in patients with these advanced CML is also disappointing because of low response rates as well as short response duration, and sudden transformation to BC is found even in initial CML CP patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib in terms of rapid response and higher molecular response in newly diagnosed CML patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active than imatinib even in patients with advanced CML. However, nilotinib in patients with imatinib-resistant or -intolerant CML BP showed low hematologic response and major cytogenetic response.(22, 23)

1. IMATINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE ACUTE LYMPHOBLASTIC LYMPHOMA (PH+ ALL) The trials combining imatinib with high-dose chemotherapy were successfully resulting in high response rate and longer survival and a role for bridging therapy to allogeneic hematopoietic stem cell transplantation (alloHSCT) by means of concurrent or alternating regimen in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL).(24-29) Current combination therapy of imatinib and chemotherapy became standard therapy of Ph+ ALL and new 2nd generation TKIs are investigating. These experiences may be translated into the treatment of CML BP. 2. HIGH-DOSE DAUNORUBICIN IN ACUTE MYELOID LEUKEMIA (AML) INDUCTION CHEMOTHERAPY Two recently published papers of randomized trials comparing standard dose daunorubicin (45 mg/m2 for 3 days) and high dose daunorubicin (90 mg/m2 for 3 days) demonstrated improved CR rate and survival with high dose daunorubicin in younger (60 years or younger) and older (over 60 years) patients, respectively.(30, 31) Therefore high-dose daunorubicin can be applied safely and effectively to the treatment of CML BP. 3. NILOTINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE CML MYELOID BLASTIC PHASE (MBP) OR PHYLADELPHIA POSITIVE AML We will try 2nd generation TKI, nilotinib and high-dose daunorubicin induction chemotherapy combination to find out the combination therapy can improve response rate and survival in patients with CML MBP.