Problems existing in differentiation therapy of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA).
A large number of acute promyelocytic leukemia (APL) patients, treated with all-trans retinoic acid (ATRA) and chemotherapy, were studied. The results of the studies are as follows: (1) Among 65 patients investigated for the postremissional therapy, the 5-year survival probabilities were 0.20 +/- 0.13 (mean +/- SE) in the group treated with ATRA alone, 0.47 + 0.10 (mean +/- SE) in the group using chemotherapy alone and 0.42 +/- 0.09 (mean +/- SE) in the group treated with chemotherapy and ATRA. (2) The main severe adverse effects in the ATRA treatment include retinoic acid syndrome, renal failure, and thrombosis. These sequelae were observed more frequently in cases with persistent, marked elevation of white blood cell count without significant maturation of leukemic promyelocytes. (3) APL is not a homogeneous disease in that among 50 patients studied at the molecular level, although a PML-RARA fusion gene was detected in 45 cases, one had a variant translocation t(11;17) bearing fusion gene PLZF-RARA, one presented no obvious structural alteration of the PML gene while the RARA gene was rearranged, and three patients had no rearrangement of either PML or RARA genes. (4) Using RT/PCR to detect minimal residual disease, we found positive rates of 22%, 18.4%, and 11.5%, respectively, 12, 24, and 36 months after CR. This observation justifies the use of chemotherapy for at least 3 years after CR induced by ATRA. (5) It seems likely that the fusion gene PML-RARA plays an important role in APL leukemogenesis and in its response to the ATRA treatment.
Wang
Z Y
ZY
Shanghai Institute of Hematology, Rui-jin Hospital, Shanghai Second Medical University, PR China.
Chen
Z
Z
Huang
W
W
Li
X S
XS
Lu
J X
JX
Huang
L A
LA
Zhang
F Q
FQ
Gu
L J
LJ
Ouyang
R R
RR
Chen
S J
SJ
D000206:Actuarial Analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D016019:Survival Analysis; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D014212:Tretinoin; D015122:Mercaptopurine; D008727:Methotrexate