Management and treatment results in patients with acute promyelocytic leukaemia (APL) not enrolled in clinical trials.
OBJECTIVE
Acute promyelocytic leukaemia (APL) therapy with all-trans retinoic acid and chemotherapy is associated with a high cure rate in clinical trials. As some patients are not enrolled in these trials due to early severe events, these results might be overestimated. To address this issue, we reviewed all APL patients referred to the Hospital Saint-Louis within the 2000-2010 period, with a special focus on inclusion in recruiting trials.


METHODS
One hundred patients (including eight children) with newly diagnosed APL were admitted during this period, which covered two consecutive APL trials conducted by the French-Belgian-Swiss APL group.


RESULTS
The rate of patients not enrolled within recruiting trials was 29%. The main reason for non-inclusion was protocol ineligibility related to disease severity at diagnosis. Non-enrolled patients more frequently had white blood cell count (WBC) . or =50×10(9)/L (31% versus 8%; p=.01), platelet count<40×10(9)/L (97% versus 65%; p=.001) and microgranular variant APL (38% versus 11%; p=.004) and were more frequently admitted in intensive care unit during induction (41% versus 24%; p=.094). Early mortality rate was higher in non-enrolled patients (21% versus 3%; p=.007), translating into a lower complete remission rate (79% versus 96%; p=.007) and lower event-free survival (65% versus 84% at 5 years; p=.05), while disease-free survival was similar in both non-enrolled and enrolled patient groups (81% versus 88% at 5 years; p=.68).


CONCLUSIONS
Initial APL severity leads to a significant proportion of patients non-registered within clinical trials, which may underestimate the real early mortality, which remained nonetheless less than 10% in this study.
Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), University Paris Diderot, Paris, France.
Jean Baptiste
JB
Micol
Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), University Paris Diderot, Paris, France.
Emmanuel
E
Raffoux
Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), University Paris Diderot, Paris, France.
Nicolas
N
Boissel
Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), University Paris Diderot, Paris, France.
Etienne
E
Lengliné
Medical Intensive Care Unit, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), Paris, France.
Emmanuel
E
Canet
Laboratory of Hematology, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), Paris, France.
Marie Thérèse
MT
Daniel
Laboratory of Hematology, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), Paris, France.
Adrienne de
Ad
Labarthe
Laboratory of Hematology, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), Paris, France.
Odile
O
Maarek
Laboratory of Cellular Biology, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), Paris, France.
Bruno
B
Cassinat
Department of Hematology, Hôpital Avicenne (Assistance Publique - Hôpitaux de Paris), Bobigny, France.
Lionel
L
Adès
Department of Pediatric Hematology, Hôpital Robert Debré (Assistance Publique - Hôpitaux de Paris), Paris, France.
André
A
Baruchel
Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), University Paris Diderot, Paris, France.
Laurent
L
Degos
Medical Intensive Care Unit, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), Paris, France.
Elie
E
Azoulay
Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris), University Paris Diderot, Paris, France. Electronic address: herve.dombret@sls.aphp.fr.
Hervé
H
Dombret
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010343:Patient Admission / Q000706:statistics & numerical data*; D018579:Patient Selection; D010976:Platelet Count; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
D014212:Tretinoin
Acute promyelocytic leukaemia; Early deaths; Enrollment in clinical trials