Final analysis of the JALSG Ph+ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph+ALL.

Abstract

The Japan Adult Leukemia Study Group (JALSG) Ph+ALL202 study reported a high complete remission (CR) rate for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients treated with imatinib-combined chemotherapy. However, the long-term treatment efficacy remains uncertain. Here, we report a final analysis of the JALSG Ph+ALL202 study. The outcomes were compared with those of the JALSG ALL93 and ALL97 studies, which were conducted in the pre-imatinib era. Ninety-nine newly diagnosed Ph+ALL patients were enrolled in Ph+ALL202 (median age, 45 years; median follow-up, 4.5 years). CR was achieved in 96/99 (97%) patients. Fifty-nine of these 96 patients (61%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in their first CR (CR1). The 5-year overall and disease-free survival (DFS) rates were 50 and 43%, respectively, which were significantly higher compared to those in the pre-imatinib era (15 and 19%, respectively). Multivariate analysis revealed that imatinib administration, allo-HSCT in CR1, and a white blood cell count < 30 × 109/L were favorable independent prognostic factors for long-term DFS. Improved odds of receiving allo-HSCT and a lower relapse rate leaded to good long-term outcomes. The 3-year DFS tended to be higher in PCR-negative than that in PCR-positive patients (29 vs. 14%) in the non-HSCT patients, and this tendency was also seen in the allo-HSCT patients (59 vs. 50%). The higher rate of CR upon imatinib use may have contributed to these improvements.

• Authors: Yoshihiro Hatta, Shuichi Mizuta, Keitaro Matsuo, Shigeki Ohtake, Masako Iwanaga, Isamu Sugiura, Noriko Doki, Heiwa Kanamori, Yasunori Ueda, Chikamasa Yoshida, Nobuaki Dobashi, Tomoya Maeda, Toshiaki Yujiri, Fumihiko Monma, Yoshikazu Ito, Fumihiko Hayakawa, Jin Takeuchi, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe
• Journal: Annals of hematology (Ann Hematol) Vol. 97 Issue 9 Pg. 1535-1545 (Sep 2018) ISSN: 1432-0584 [Electronic] Germany
• PMID: 29694642 (Publication Type: Journal Article)

Chemical References

• Protein Kinase Inhibitors
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cohort Studies
• Combined Modality Therapy
• Female
• Fusion Proteins, bcr-abl (genetics)
• Hematopoietic Stem Cell Transplantation
• Humans
• Imatinib Mesylate (therapeutic use)
• Japan (epidemiology)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics, mortality, therapy)
• Male
• Middle Aged
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics, mortality, therapy)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Remission Induction
• Survival Analysis
• Transplantation, Homologous
• Treatment Outcome
• Young Adult