Childhood acute promyelocytic leukemia: no benefit of all-trans-retinoic acid administered in a short-course schedule.
From January 1990 to August 1997, 29 consecutive patients were treated with newly diagnosed primary acute promyelocytic leukemia (APL) at the authors' Institution. Of these, 27 (16 boys and 11 girls) were evaluable. Median age at diagnosis was 6.3 (range: 1.9-15.7) years. This population was treated with two consecutive protocols: 13 patients were included in the AML-HPG-90 protocol and 14 in the AML-HPG-95. The initial treatment was the same for both protocols: an induction 8-day phase with cytarabine, idarubicin, and etoposide was followed by a consolidation with cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, doxorubicin, and prednisone. Two courses of intensification with high-dose (HD) cytarabine and etoposide were given in the first study. Only one intensification course was administered in the second study, with HD cytarabine plus idarubicin or etoposide decided by randomization. Complete remission was achieved in 67% (18/27) of cases. Mortality on induction was quite high, 30% (8/27) mainly due to hemorrhages from disseminated intravascular coagulation (DIC). The event-free survival estimate for all patients was 0.47 (SE: 0.1). From April 1994, all-trans-retinoic acid (ATRA) was administered just during the first days of the induction phase (median: 9, range: 2-27) to stop or prevent DIC. Eighteen patients received ATRA and 9 did not. Three patients developed signs of ATRA syndrome during the first days of administration but no one died due to this toxicity. The impact of a short course of ATRA on early control of DIC was studied by analyzing the number of platelet, cryoprecipitate, and fresh frozen plasma transfusions during the induction phase in both groups. No statistical differences in complete remission rate, early mortality, need of transfusion of blood components for DIC, and survival estimates could be established between patients who received ATRA and those who did not. ATRA used in a short-course schedule during induction of APL did not stop early mortality due to DIC. Moreover, survival results did not improve with this method of ATRA usage. Longer periods of ATRA administration during APL therapy are strongly recommended.
Zubizarreta
P A
PA
Hematology-Oncology Department, Hospital de Pediatría SAMIC Professor Dr. J. P. Garrahan, Buenos Aires, Argentina. pzubizar@cvtci.com.ar
Rose
A B
AB
Felice
M S
MS
Alfaro
E
E
Delfino
S
S
Cygler
A M
AM
Sackmann-Muriel
F
F
D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D003582:Cytogenetics; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000150:complications; D004334:Drug Administration Schedule; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology; D006474:Hemorrhagic Disorders / Q000517:prevention & control; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D010976:Platelet Count; D012189:Retrospective Studies; D012307:Risk Factors; D013534:Survival; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage* / Q000633:toxicity
D000970:Antineoplastic Agents; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014212:Tretinoin; D003907:Dexamethasone; D005340:Fibrinogen