Prognostic value of karyotypic analysis in children and adults with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 trial.
OBJECTIVE
Cytogenetic analysis is one of the most reliable prognostic factors in acute lymphoblastic leukemia. The objective of this study was to analyze the prognostic value of cytogenetic analysis in children and adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a prospective multicenter trial.


METHODS
One hundred and thirty patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93 trial had an adequate cytogenetic study after review. Cytogenetic subgroups were established according to the cancer and acute leukemia group B criteria (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining chromosome abnormalities) and their main clinicobiological features were compared. Univariable and multivariable analyses for complete remission (CR) attainment, event-free survival (EFS) and overall survival (OS) were performed.


RESULTS
The mean SD age was 26 14 years. Two were infants (<1 year), 42 were children and 86 adults (19-50 years). The cytogenetic study was normal in 44 (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34 cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the remaining cases, whereas those with 11q23 rearrangements were younger and had higher WBC counts. Multivariable analyses showed two associated factors in adults with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response to therapy (assessed by a percentage of blast cells higher than 10% in bone marrow study on day 14). For children with very high-risk ALL, only slow response to therapy (assessed by the presence of blast cells in peripheral blood on day 8) was associated with a negative impact on CR, EFS and OS.


CONCLUSIONS
In adult patients with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a useful independent prognostic marker. The poorest prognosis for patients with t(9;22) justifies the development of specific treatments for these patients. In this small subgroup of children with very high-risk ALL no cytogenetic characteristics was found to influence the results of therapy, slow response to therapy being the only prognostic factor.
Ribera
Josep-Maria
JM
Hematology Department and Hematopoietic Progenitor Transplant Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. jmribera@ns.hugtip.scs.es
Ortega
Juan-José
JJ
Oriol
Albert
A
Granada
Isabel
I
Hernández-Rivas
Jesús-Maria
JM
Parody
Ricardo
R
Bethencourt
Concepción
C
Rivas
Concepción
C
Bastida
Pilar
P
del Potro
Eloy
E
González-Valentín
Maria-Elvira
ME
Moreno
María-José
MJ
Besalduch
Joan
J
Fernández-Calvo
Javier
J
Tormo
Mar
M
Arias
Jesús
J
Molinés
Antonio
A
Sanz
Miguel Angel
MA
Maldonado
Juan
J
Millá
Fuensanta
F
Feliu
Evarist
E
San Miguel
Jesús-Fernando
JF
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007621:Karyotyping; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome