Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide.
OBJECTIVE
Arsenic trioxide, like all-trans-retinoic acid (RA), induces differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of APL patients with all-trans RA is commonly associated with leukocytosis, and approximately 50% of patients develop the RA syndrome. We reviewed our clinical experience with arsenic trioxide to determine the incidence of these two phenomena.


METHODS
Twenty-six patients with relapsed or refractory APL were treated with arsenic trioxide for remission induction at daily doses that ranged from 0.06 to 0.17 mg/kg.


RESULTS
Twenty-three patients (88%) achieved complete remission. Leukocytosis was observed in 15 patients (58%). The median baseline leukocyte count for patients with leukocytosis was 3,900 cells/microL (range, 1,200 to 72,300 cells/microL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/microL; range, 500 to 5,400 cells/microL; P =.01). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in eight patients (31%). Patients who developed leukocytosis were significantly more likely to develop the RA syndrome (P <.001), and no patient without a peak leukocyte count greater than 10,000 cells/microL developed the syndrome. Among the patients with leukocytosis, there was no observed relation between the leukocyte peak and the probability of developing the syndrome (P =.37).


CONCLUSIONS
Induction therapy of APL with all-trans RA and arsenic trioxide is associated with leukocytosis and the RA syndrome. These clinical effects seem to be intrinsically related to the biologic responsiveness and the differentiation process induced by these new agents.
Camacho
L H
LH
Leukemia and Developmental Chemotherapy Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Soignet
S L
SL
Chanel
S
S
Ho
R
R
Heller
G
G
Scheinberg
D A
DA
Ellison
R
R
Warrell
R P
RP
D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects*; D004417:Dyspnea / Q000139:chemically induced; D005334:Fever / Q000139:chemically induced; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D007964:Leukocytosis / Q000139:chemically induced*; D010087:Oxides / Q000009:adverse effects*; D010996:Pleural Effusion / Q000139:chemically induced; D013577:Syndrome; D014212:Tretinoin / Q000009:adverse effects*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide