Standard Dose Chemotherapy 3+7 Induces Complete Remission in Patients Over 80 Years Old with Single-Lineage Acute Myeloid Leukemias and Normal Karyotype
Authors: Lemez Petr , Galikova Jirina , Michalova Kyra , MacWhannell Alan , Zemanova Zuzana , Stejskal Jan 
Published: April 2020

Abstract
Survival of elderly patients with de novo acute myeloid leukemia (AML) is poor. A single published study on patients with AML aged 80 years and above (DeLima et al., Br. J. Haematol.1996; 93: 89) concluded that chemotherapy was not indicated since median overall survival (OS) of 29 treated patients was 1 month, 9 patients reached complete remission (CR) of 3 months median duration, and only two survived over 1 year: for 15.5 and &gt;18 months. The aim of our study was to identify the characteristics of elderly AML patients who may reach CR by standard chemotherapy. We analyzed 9 consecutive patients with de novo AML aged 80–90 (median 83) years treated by us in 1992–2007. All bone marrow films were hypercelullar with 48–92 (median 80) % leukemic cells, classified as FAB types: 2 M2, 6 M4, and 1 M5. Six patients, all with hypertension and five with ischaemic heart disease (IHD), received chemotherapy, while 3 patients (82–87 years old) opted for supportive or palliative therapy and survived 1–4 months. Cytosine arabinoside (Ara-C) 100 mg/sqm/12 h in 3-h infusion for 7 days and 3 doses of daunorubicin (DNR) 45 mg/sqm/d i.v. (D+A, 1 case) or mitozantrone (MTZ) 10 mg/sqm/d i.v. (M+A, 3 cases) was given to 4 patients. The remaining two patients received D+A with thioguanine (TG) 100 mg/sqm/12 h p.o. for 7 days (TAD). Their WHO performance status (PS) was 4x PS3, 1x PS2, 1x PS1, and median WBC 58 (17.9–97.8) × 10^9/L. Three patients with AML M4 and normal karyotype reached CR. Maintenance therapy consisted of 4-day courses administered in intervals of 5–12 (median 8) weeks according to the patient’s clinical status and tolerance until relapse. Courses containing Ara-C 60 mg/sqm/12h s.c. with TG 70 mg/sqm/12h p.o. were repeated 3x. The fourth course was 1+4 containing a single dose DNR or MTZ as described and Ara-C. The outcomes: An 85 year-old female with IHD and LVEF 25 % reached CR with TAD. She was on maintenance in CR for 17 months when severe heart arrhythmia developed. She refused a pacemaker implantation and died 3 days later. Her OS was 18.6 months. An 80 year-old male reached CR with M+A and was on maintenance therapy when relapsed after 19.7 months. He refused further chemotherapy and his OS was 28 months. An 80 year-old female (PS1, Flt3-ITD neg.) reached CR after D+A 3+7 and got one cycle D+A 2+5 without further maintenance. Her CR lasted 10.1 months. She was further treated with 2 cycles of low-dose Ara-C and her OS was 16.5 months. Three other patients, two with normal karyotype, did not reach CR after chemotherapy. A 90 year-old male with AML M4 died of mycotic pneumonia on the 24th day of TAD induction. An 83 year-old male with AML M5, PS2, experienced nonQ myocardial infarction after M+A induction and did not reach CR. He was further treated with hydroxyurea with OS of 2.7 months. An 80 year-old female with AML M2, complex karyotype, renal insufficiency and sepsis died after 7th hemodialysis in septic shock on 10th day of M+A induction. All three patients who reached CR did not exhibit dysplasia in erythroblastic or megakaryocytic lineage showing that only granulocyte-macrophage lineage was involved in the leukemic clone (single–lineage AMLs). In contrast, all 3 patients who did not reach CR exhibited megakaryocytic dysplasia in a half or more of megakaryocytes and two had erythroblastic dysplasia in more than 26% erythroblasts. They represent a different biological category of AMLs with multi-lineage involvement. In summary, we defined a biological category of single-lineage AML patients over 80 years of age who may benefit from standard dose chemotherapy in spite of their poor performance status.