Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study

Maurizio Aricò, Valentino Conter, Maria Grazia Valsecchi, Carmelo Rizzari, Marie France Pinta Boccalatte, Elena Barisone, Chiara Messina, Giulio De Rossi, Luca Lo Nigro, Andrea Pession, Franco Locatelli, Concetta Micalizzi, Giuseppe Basso, Giuseppe Masera

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background and Objectives. Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure. Design and Methods. The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm 3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m 2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m 2 and no epipodophyllotoxins or cranial irradiation were employed. Results. Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8% of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0% (1.7) and 86.7% (3.5) at 5 years, and 95.3% (2.4) and 86.7% (3.5) at 7 years. Interpretations and Conclusions. Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.

Original languageEnglish
Pages (from-to)1186-1191
Number of pages6
JournalHaematologica
Volume90
Issue number9
Publication statusPublished - Sep 2005

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Therapeutics
Prednisone
Methotrexate
Disease-Free Survival
Podophyllotoxin
Cranial Irradiation
Asparaginase
Second Primary Neoplasms
Anthracyclines
Residual Neoplasm
Vincristine
Patient Selection
Population
Appointments and Schedules
Leukemia
Drug Therapy
Survival
DNA

Keywords

  • ALL
  • Childhood
  • DNA index
  • Treatment reduction

ASJC Scopus subject areas

  • Hematology

Cite this

Aricò, M., Conter, V., Valsecchi, M. G., Rizzari, C., Pinta Boccalatte, M. F., Barisone, E., ... Masera, G. (2005). Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study. Haematologica, 90(9), 1186-1191.

Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study. / Aricò, Maurizio; Conter, Valentino; Valsecchi, Maria Grazia; Rizzari, Carmelo; Pinta Boccalatte, Marie France; Barisone, Elena; Messina, Chiara; De Rossi, Giulio; Lo Nigro, Luca; Pession, Andrea; Locatelli, Franco; Micalizzi, Concetta; Basso, Giuseppe; Masera, Giuseppe.

In: Haematologica, Vol. 90, No. 9, 09.2005, p. 1186-1191.

Research output: Contribution to journalArticle

Aricò, M, Conter, V, Valsecchi, MG, Rizzari, C, Pinta Boccalatte, MF, Barisone, E, Messina, C, De Rossi, G, Lo Nigro, L, Pession, A, Locatelli, F, Micalizzi, C, Basso, G & Masera, G 2005, 'Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study', Haematologica, vol. 90, no. 9, pp. 1186-1191.
Aricò M, Conter V, Valsecchi MG, Rizzari C, Pinta Boccalatte MF, Barisone E et al. Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study. Haematologica. 2005 Sep;90(9):1186-1191.
Aricò, Maurizio ; Conter, Valentino ; Valsecchi, Maria Grazia ; Rizzari, Carmelo ; Pinta Boccalatte, Marie France ; Barisone, Elena ; Messina, Chiara ; De Rossi, Giulio ; Lo Nigro, Luca ; Pession, Andrea ; Locatelli, Franco ; Micalizzi, Concetta ; Basso, Giuseppe ; Masera, Giuseppe. / Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study. In: Haematologica. 2005 ; Vol. 90, No. 9. pp. 1186-1191.
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abstract = "Background and Objectives. Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure. Design and Methods. The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm 3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m 2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m 2 and no epipodophyllotoxins or cranial irradiation were employed. Results. Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8{\%} of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0{\%} (1.7) and 86.7{\%} (3.5) at 5 years, and 95.3{\%} (2.4) and 86.7{\%} (3.5) at 7 years. Interpretations and Conclusions. Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.",
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T1 - Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study

AU - Aricò, Maurizio

AU - Conter, Valentino

AU - Valsecchi, Maria Grazia

AU - Rizzari, Carmelo

AU - Pinta Boccalatte, Marie France

AU - Barisone, Elena

AU - Messina, Chiara

AU - De Rossi, Giulio

AU - Lo Nigro, Luca

AU - Pession, Andrea

AU - Locatelli, Franco

AU - Micalizzi, Concetta

AU - Basso, Giuseppe

AU - Masera, Giuseppe

PY - 2005/9

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N2 - Background and Objectives. Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure. Design and Methods. The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm 3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m 2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m 2 and no epipodophyllotoxins or cranial irradiation were employed. Results. Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8% of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0% (1.7) and 86.7% (3.5) at 5 years, and 95.3% (2.4) and 86.7% (3.5) at 7 years. Interpretations and Conclusions. Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.

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KW - ALL

KW - Childhood

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