Outcome of FLAG and FLANG Regimens in the Treatment of Acute Leukemias Patients

Abstract

Introduction: Despite all improvement in the treatment of acute myeloid leukemia (AML) patients, the management in relapsed or refractory disease is still controversial. The use of multiple chemotherapeutic agents will induce more toxicity and morbidity in patients. Fludarabin- containing therapy (FLAG and FLANG) mostly has been used in the treatment of relapsed or refractory AML patients.
Methods: In this retrospective study, we evaluated the response of treatment in 40 adult leukemia patients treated with these regimens from October 2007 to December 2011 in our center. They took FLAG (fludarabine, cytarabine, GCSF) and FLANG (fludarabine, cytarabine, mitoxantrone) according to the approved protocol. They were taken packed cells or platelets as needed and antibiotics in cases of established or highly suspicious infections. After these therapies, 12 patients with suitable donor made ready for allogeneic hematopoietic stem cell transplantation (HSCT) and one patient without donor underwent autologous HSCT.
Results: The median age of patients was 29.5 (range: 16- 50) years old. The male to female ratio was 30:10. The patients were diagnosed with ALL (15, 37.5%) and AML (25, 62.5%). The most common subtype of leukemia was ALL- L2 and AML- M4. The most common disease treated was AML-M4. Two patients had secondary leukemia (breast cancer and MDS). Except two patients which treated with FLAG regimen, others received FLANG. Most patients were primary refractory (18, 45%), first relapse (17, 42.5%) or second relapse (5, 12.5%) before this treatment. Thirteen patients underwent hematopoietic stem cell transplantation after FLANG. Four patients received FLANG as relapse treatment after transplantation. Pulmonary aspergillus infection occurred in 13 patients and aspergillus sinusitis in two after FLANG/ FLAG treatment. White blood cells and platelet recovery observed in 30 patients with a median time of 20 days after treatment. Treatment resulted in complete response (n=19), partial response (n=1) and no response (n=11) in patients. Early death (before 60 days) after treatment occurred in 9 (22.5%) patients. The most common causes of death were primary disease (relapse) (24, 60%) and infection (5, 12.5%). The one- year overall survival was 21.4% (SE: 7.1%). Among the survivors, only 5 patients received transplantation and 5 patients are alive without transplantation.
Conclusion: The study shows that refractory and relapsed leukemia patients can achieve complete remission with FLAG/ FLANG treatment. The side effects include serious fungal infections and sepsis. Moreover, high mortality during these treatments was observed.