The objectives of this review paper are to: Compare acute
leukemia with chronic
leukemia and other forms of
cancer. Review the pathophysiology and discuss the clinical and diagnostic features of M3. Describe the variant of M3 (M3m or M3v). Compare conventional
chemotherapy with
all-trans retinoic acid differentiation
therapy (ATRA) in the treatment of M3. Discuss the future direction of differentiation
therapy.
DATA SOURCES: Current literature.
DATA SYNTHESIS: Until the late 1970s, the methods of diagnosis and treatment of AML-M3 were similar to the other forms of
acute myelocytic leukemia. One notable difference between M3 and other
acute myelocytic leukemias involved the common occurrence of life-threatening consumptive coagulopathies in M3 patients that dramatically affected patient outcomes. In 1977 the method of diagnosis confirmation was altered by the identification of a consistent
chromosomal translocation involving the long arms of chromosomes 15 and 17. Reports in the 1970s and 1980s indicated that certain types of active metabolites of
vitamin A, collectively termed
retinoids, could induce differentiation in a variety of
cancer derived cell lines, in vitro. It was shown in the early 1980s that
13-cis-retinoic acid (13cRA) could stimulate differentiation in bone marrow cells collected from patients with various acute
leukemias, including M3. The first clinical trial of a
retinoid, given as a
remission induction therapeutic regimen, involved
all-trans retinoic acid (ATRA) administered to M3 patients in 1988. Since then, ATRA
therapy has been shown to reduce
tumor burden by stimulating differentiation of the leukemic cells, induce long-term clinical remission when administered in conjunction with
chemotherapy, and lower the incidence of consumptive coagulopathies in patients with AML-M3.
CONCLUSION: The diagnosis and treatment of AML-M3 has improved dramatically in the past decade, which has greatly enhanced the prognosis of patients with this disease. First remission rates have increased to greater than 85% world wide, the incidence of
disseminated intravascular coagulation (
DIC) has declined dramatically, and 60% to 70% of patients with AML-M3 have achieved long term survival and are potentially cured.