Management of acute promyelocytic leukemia relapse in the ATRA era.
OBJECTIVE
The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA.


METHODS
We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days.


RESULTS
Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed.


CONCLUSIONS
ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.
Castagnola
C
C
Divisione di Ematologia, IRCCS Policlinico S.Matteo di Pavia, Italy. castagnola@smatteo.pv.it
Lunghi
M
M
Corso
A
A
Tajana
M
M
Zappasodi
P
P
Dabusti
M
M
Lazzarino
M
M
Bernasconi
C
C
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D000970:Antineoplastic Agents; D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D008942:Mitoxantrone; D013866:Thioguanine; D015255:Idarubicin; D003630:Daunorubicin