Untreated Adult Acute Myeloid Leukemia
A long-term follow-up of 30 patients who had AML that was in remission for at least 10 years has demonstrated a 13% incidence of secondary malignancies. Of 31 long-term female survivors of AML or acute lymphoblastic leukemia younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, 2 congenital problems occurred.
Acute Promyelocytic Leukemia
Special consideration must be given to induction therapy for acute promyelocytic leukemia (PML). Oral administration of tretinoin (all-trans-retinoic acid (ATRA); 45 mg/mm2 /day) can induce remission in 70% to 90% of patients with M3 AML. (ATRA is not effective in patients with AML that resembles M3 morphologically but does not demonstrate the t(15;17) or typical PML-RAR? gene rearrangement.)[25,26,27,28,29,30,31] ATRA induces terminal differentiation of the leukemic cells followed by restoration of nonclonal hematopoiesis. Administration of ATRA leads to rapid resolution of coagulopathy in most patients, and heparin administration is not required in patients receiving ATRA. However, randomized trials have not shown a reduction in morbidity and mortality during ATRA induction when compared with chemotherapy. Administration of ATRA can lead to hyperleukocytosis as well as a syndrome of respiratory distress now known as the differentiation syndrome. Prompt recognition of the syndrome and aggressive administration of steroids can prevent severe respiratory distress. The optimal management of ATRA-induced hyperleukocytosis has not been established; neither has the optimal postremission management of patients who receive ATRA induction. However, two large cooperative group trials have demonstrated a statistically significant relapse-free and overall survival (OS) advantage to patients with M3 AML who receive ATRA at some point during their antileukemic management.[33,34]
A randomized study has shown that the relapse rate was reduced in patients treated with concomitant ATRA and chemotherapy compared with ATRA induction followed by chemotherapy given in remission (relative risk [RR] of relapse at 2 years, 0.41; P = .04).[Level of evidence: 1iiDii] This trial also showed a disease-free survival benefit to maintenance therapy, which consisted of either 6-mercaptopurine plus methotrexate (RR of relapse = 0.41), intermittent ATRA (RR of relapse = 0.62), or a combination of all three drugs. The use of 6-mercaptopurine and methotrexate also produced an improvement in OS (RR of relapse = 0.36; P = .005). Two concurrent clinical trials separately conducted in Italy and Spain included ATRA plus anthracycline induction followed by three cycles of postremission and maintenance therapy. The two treatment protocols differed only in the addition of nonanthracycline drugs during postremission therapy cycles in the Italian study; doses of anthracyclines were identical between the two trials. Essentially identical relapse-free survival suggests that the nonanthracycline drugs (i.e., cytarabine, etoposide, and 6-thioguanine) may not contribute significantly to the outcome of patients with acute promyelocytic leukemia induced with ATRA plus anthracycline.[Level of evidence: 3iiiDii]