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Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00.
J Clin Oncol. 2010 Aug 01; 28(22):3644-52.JC

Abstract

PURPOSE

Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates.

PATIENTS AND METHODS

Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib.

RESULTS

CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall.

CONCLUSION

This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.

Authors+Show Affiliations

U.S.C. Ematologia, Ospedali Riuniti, Bergamo, Italy. rbassan@ospedaliriuniti.bergamo.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20606084

Citation

Bassan, Renato, et al. "Chemotherapy-phased Imatinib Pulses Improve Long-term Outcome of Adult Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 28, no. 22, 2010, pp. 3644-52.
Bassan R, Rossi G, Pogliani EM, et al. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol. 2010;28(22):3644-52.
Bassan, R., Rossi, G., Pogliani, E. M., Di Bona, E., Angelucci, E., Cavattoni, I., Lambertenghi-Deliliers, G., Mannelli, F., Levis, A., Ciceri, F., Mattei, D., Borlenghi, E., Terruzzi, E., Borghero, C., Romani, C., Spinelli, O., Tosi, M., Oldani, E., Intermesoli, T., & Rambaldi, A. (2010). Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 28(22), 3644-52. https://doi.org/10.1200/JCO.2010.28.1287
Bassan R, et al. Chemotherapy-phased Imatinib Pulses Improve Long-term Outcome of Adult Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00. J Clin Oncol. 2010 Aug 1;28(22):3644-52. PubMed PMID: 20606084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. AU - Bassan,Renato, AU - Rossi,Giuseppe, AU - Pogliani,Enrico M, AU - Di Bona,Eros, AU - Angelucci,Emanuele, AU - Cavattoni,Irene, AU - Lambertenghi-Deliliers,Giorgio, AU - Mannelli,Francesco, AU - Levis,Alessandro, AU - Ciceri,Fabio, AU - Mattei,Daniele, AU - Borlenghi,Erika, AU - Terruzzi,Elisabetta, AU - Borghero,Carlo, AU - Romani,Claudio, AU - Spinelli,Orietta, AU - Tosi,Manuela, AU - Oldani,Elena, AU - Intermesoli,Tamara, AU - Rambaldi,Alessandro, Y1 - 2010/07/06/ PY - 2010/7/8/entrez PY - 2010/7/8/pubmed PY - 2010/8/19/medline SP - 3644 EP - 52 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J Clin Oncol VL - 28 IS - 22 N2 - PURPOSE: Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. PATIENTS AND METHODS: Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. RESULTS: CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. CONCLUSION: This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/20606084/Chemotherapy_phased_imatinib_pulses_improve_long_term_outcome_of_adult_patients_with_Philadelphia_chromosome_positive_acute_lymphoblastic_leukemia:_Northern_Italy_Leukemia_Group_protocol_09/00_ L2 - https://ascopubs.org/doi/10.1200/JCO.2010.28.1287?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -