ACUTE MYELOID LEUKEMIA: TREATMENT OVER 60

Abstract

Undertreatment of older patients with acute myeloid leukemia (AML) can explain, in part, their inferior outcome when compared to that of younger patients. In agreement with the benefit seen by patients under age 60 from high-dose cytosine arabinoside (Ara-C), there are dose effects in the over 60s, in particular for daunorubicin, in induction treatment and for the duration of postremission treatment. The use of these effects can partly overcome the mostly unfavorable disease biology in older age AML, as expressed by the absence of favorable and the over-representation of adverse chromosomal abnormalities as well as the expression of drug resistance. We recommend an adequate dosage of 60 mg/m2 daunorubicin on 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, and followed by a prolonged monthly maintenance chemotherapy for at least 1 year's duration. Further improvements in supportive care may help to deliver additional antileukemic cytotoxicity. As a novel approach, nonmyeloablative preparative regimens may open up the possibility of allogeneic transplantation for older patients with AML. Other new options like multidrug resistance modulators, antibody targeted therapies and molecular targeting are under clinical investigation. A questionnaire study in patients with AML showed that, according to patients' self-assessment, intensive and prolonged treatment did not result in a diminished quality of life. This finding did not vary by age, under or over 60 years. As the median age in this disease is more than 60 years, the adequate management of AML in older patients remains the major challenge.

Efficacy and safety of imatinib in adult patients with c-kit–positive acute myeloid leukemia

“…Five patients received combination therapy because of high PB blast counts ( PN 13,19,20,21) or because of thrombocytosis (PN 4). Imatinib plus hydroxyurea resulted in resolution of thrombocytosis in patient 4 and in a significant reduction in PB blast counts from 23.4 ϫ 10 9 /L at screening to 4.0 ϫ 10 9 /L on day 28 in patient 21; patients 13, 19, and 20 were refractory.…”

“…[17][18][19][20][21][22][23] More than 70% of patients with AML have blast cells that express c-kit, a receptor tyrosine kinase for the ligand stem cell factor (SCF). 24,25 C-kit is essential for the maintenance of normal hematopoiesis and also plays a role in the biologic aspects of some human malignancies, including gastrointestinal stromal tumors (GISTs), [26][27][28] small cell lung cancer, [29][30][31][32][33] breast cancer, 34 and AML.…”

Immunological Characterization and Antibacterial Function of Persisting Granulocytes in Leukemic Patients Receiving Pulse Cytosine Arabinoside-Consolidation Chemotherapy on Days 1, 3, and 5

“…Induction and consolidation of AML in the elderly is becoming an increasingly important aspect in clinical hematology (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). In fact, the majority of all patients with AML are over 60 years of age at diagnosis, and the percentage of patients with AML Ͼ60 years of age is constantly rising.…”

“…In fact, the majority of all patients with AML are over 60 years of age at diagnosis, and the percentage of patients with AML Ͼ60 years of age is constantly rising. Moreover, because of improved supportive care and general therapeutic facilities, more and more of these patients are nowadays judged candidates for curative therapeutic interventions (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Because these patients cannot tolerate all chemotherapies and therapeutic maneuvers that otherwise can be offered to younger adults (like bone marrow transplantation or very high doses of ARA-C), it seems of great importance to search for alternative treatment strategies for this group of patients.…”

Cytarabine Induction Followed by Imatinib Post-Induction Therapy in Patients with Acute Myeloid Leukaemia - Limited Effects in a Case Series

“…These therapies might include antibodybased therapies, inhibition of angiogenesis or inhibition of intracellular signals that promote proliferation and/or block differentiation. [9][10][11][12] . AML subtype M2 -associated with t(8;21) -and AML M4Eo -associated with inv (16) -so called core binding factor AMLs, have a high incidence of expression of early stem cell markers including kit, a receptor tyrosine kinase for the ligand stem cell factor (SCF) [13][14][15] and a relevant proportion of these patients harbour a mutated c-kit 16 with probably activating mutations.…”