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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2002-03-0704.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2357-2366
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Outcome of treatment in adults with Philadelphia
chromosome-positive acute lymphoblastic leukemia results of the
prospective multicenter LALA-94 trial
Hervé Dombret,
Jean Gabert,
Jean-Michel Boiron,
Françoise Rigal-Huguet,
Didier Blaise,
Xavier Thomas,
André Delannoy,
Agnès Buzyn,
Chrystèle Bilhou-Nabera,
Jean-Michel Cayuela,
Pierre Fenaux,
Jean-Henri Bourhis,
Nathalie Fegueux,
Christiane Charrin,
Claude Boucheix,
Véronique Lhéritier,
Hélène Espérou,
Elizabeth MacIntyre,
Jean-Paul Vernant, and
Denis Fière for the Groupe d'Etude et de
Traitement de la Leucémie Aiguë Lymphoblastique de
l'Adulte (GET-LALA Group)
From the Department of Hematology, Hôpital
Saint-Louis, Paris, France; Department of Biochemistry and Molecular
Biology, Hôpital Nord, Marseille, France; Department of
Hematology, Hôpital Haut-Levêque, Pessac, France;
Department of Hematology, Hôpital Purpan, Toulouse, France;
Department of Hematology, Institut Paoli-Calmettes, Marseille, France;
Department of Hematology, Hôpital Edouard Herriot, Lyon, France;
Department of Hematology, Cliniques Universitaires St Luc, Brussels,
Belgium; Department of Hematology, Hôpital Necker, Paris, France;
Department of Hematology, Hôpital Claude Huriez, Lille, France;
Department of Hematology, Institut Gustave Roussy, Villejuif, France;
Department of Hematology, Hôpital Lapeyronie, Montpellier,
France; INSERM U268, Hôpital Paul Brousse, Villejuif, France; and
Department of Hematology, Hôpital
Pitié-Salpêtrière, Paris, France. Members of the
GET-LALA Group are listed in the "appendix" at the end of this
article.
From 1994 to 2000, 154 adults with Philadelphia
chromosome-positive (Ph+) and/or
BCR-ABL+ acute lymphoblastic leukemia (ALL)
were treated according to a prospective trial (median follow-up, 4.5 years) with the aim to study the prognostic value of early response to
therapy and the role of stem cell transplantation (SCT) in first
complete remission (CR). All patients received a standard induction
course followed by a course of mitoxantrone and intermediate-dose
cytarabine (HAM). After each course, minimal residual disease was
tested by specific reverse transcriptase-polymerase chain reaction
(RT-PCR) (median sensitivity, 10 5). Allogeneic SCT (if a
donor) or autologous SCT (if not) was planned at 3 months in all
patients in CR after HAM. CR rates after induction, after HAM, and at 3 months were 53%, 67%, and 62%, respectively. High leukocyte count
and m-bcr subtype were the 2 identified bad-prognosis factors for CR at
3 months, both superseded by a poor early response assessed at day 8 of
the induction course. HAM-associated salvage rate was higher in
patients with M-bcr than in those with m-bcr ALL (55% vs 30%;
P = .05). In the 103 patients eligible for SCT, the
existence of a donor and the negative BCR-ABL status after
HAM were independently predictive of remission duration
(P < .001 and .01, respectively) and survival (P = .02 and .01, respectively). Relapse was the most
common cause of treatment failure in all patient groups. Allogeneic SCT
in first CR is the current best treatment option in adults with the disease. New strategies must be tested during early phases of therapy
to increase the rate of BCR-ABL remissions.
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