Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell'Adulto.
OBJECTIVE
Recent reports of extramedullary disease (EMD) at recurrence in acute promyelocytic leukemia (APL) have raised increasing concern about a possible role of retinoic acid (RA) therapy.


METHODS
We analyzed the risk of developing EMD localization at relapse in APL patients enrolled onto two consecutive studies of the Gruppo Italiano Malattie Ematologiche dell'Adulto. The studies investigated chemotherapy alone (LAP0389) versus RA plus chemotherapy (AIDA).


RESULTS
When all relapse types were taken into account, 94 (51%) of 184 patients and 131 (18%) of 740 patients who attained hematologic remission underwent relapse in the LAP0389 and AIDA studies, respectively (P < .0001). EMD localization was documented in five (5%) of 94 and 16 (12%) of 131 patients (P = .08). Hematologic and/or molecular relapse was diagnosed concomitantly in all but two patients with EMD in the AIDA study. For patients in the LAP0389 and AIDA series, the probability of EMD localization of any type at relapse was 3% and 4.5%, respectively (P = .79), while the probability of CNS involvement was 0.6% and 2% (P = .28). No significant differences were found with regard to mean WBC count and promyelocytic leukemia/retinoic acid receptor-alpha junction type in comparisons of patients with EMD and hematologic relapse.


CONCLUSIONS
APL patients receiving all-trans retinoic acid in addition to chemotherapy have no increased risk of developing EMD at relapse as compared with those treated with chemotherapy alone.
Specchia
G
G
Department of Hematology, University of Bari, Bari, Italy. emadhba@cimedoc.uniba.it
Lo Coco
F
F
Vignetti
M
M
Avvisati
G
G
Fazi
P
P
Albano
F
F
Di Raimondo
F
F
Martino
B
B
Ferrara
F
F
Selleri
C
C
Liso
V
V
Mandelli
F
F
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006411:Hematopoiesis, Extramedullary; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics; D012008:Recurrence; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D012313:RNA