BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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. INTERPRETATION AND 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.
RCT Entities:
BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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. INTERPRETATION AND 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.
Authors: Wendy Stock; Jeffrey L Johnson; Richard M Stone; Jonathan E Kolitz; Bayard L Powell; Meir Wetzler; Peter Westervelt; Guido Marcucci; Daniel J DeAngelo; James W Vardiman; Diane McDonnell; Krzysztof Mrózek; Clara D Bloomfield; Richard A Larson Journal: Cancer Date: 2012-06-28 Impact factor: 6.860
Authors: Raquel Malumbres; Vicente Fresquet; Jose Roman-Gomez; Miriam Bobadilla; Eloy F Robles; Giovanna G Altobelli; M José Calasanz; Erlend B Smeland; Maria Angela Aznar; Xabier Agirre; Vanesa Martin-Palanco; Felipe Prosper; Izidore S Lossos; Jose A Martinez-Climent Journal: Haematologica Date: 2011-04-01 Impact factor: 9.941
Authors: Nicholas J Short; Hagop M Kantarjian; Koji Sasaki; Jorge E Cortes; Farhad Ravandi; Deborah A Thomas; Guillermo Garcia-Manero; Issa Khouri; Partow Kebriaei; Richard E Champlin; Sherry Pierce; Ghayas C Issa; Marina Konopleva; Tapan M Kadia; Carlos Bueso-Ramos; Joseph D Khoury; Nitin Jain; Susan M O'Brien; Elias Jabbour Journal: Cancer Date: 2016-08-10 Impact factor: 6.860
Authors: Amaia Vilas-Zornoza; Xabier Agirre; Vanesa Martín-Palanco; José Ignacio Martín-Subero; Edurne San José-Eneriz; Leire Garate; Sara Álvarez; Estíbaliz Miranda; Paula Rodríguez-Otero; José Rifón; Antonio Torres; María José Calasanz; Juan Cruz Cigudosa; José Román-Gómez; Felipe Prósper Journal: PLoS One Date: 2011-02-28 Impact factor: 3.240
Authors: J Roman-Gomez; A Jimenez-Velasco; X Agirre; J A Castillejo; G Navarro; M Barrios; E J Andreu; F Prosper; A Heiniger; A Torres Journal: Br J Cancer Date: 2004-08-16 Impact factor: 7.640