IKZF1plus alterations are not associated with outcomes in Philadelphia-positive acute lymphoblastic leukemia patients enrolled in the FBMTG ALL/MRD2008 trial

Yoshikiyo Ito; Hidetoshi Ozawa; Tetsuya Eto; Toshihiro Miyamoto; Tomohiko Kamimura; Ryosuke Ogawa; Naoyuki Uchida; Atsusi Wake; Tomoaki Fujisaki; Yuju Ohno; Ken Takase; Hirokazu Okumura; Yasushi Takamatsu; Noriaki Kawano; Koichi Akashi; Koji Nagafuji

doi:10.1111/ejh.13972

IKZF1^plus alterations are not associated with outcomes in Philadelphia-positive acute lymphoblastic leukemia patients enrolled in the FBMTG ALL/MRD2008 trial

Eur J Haematol. 2023 Jul;111(1):103-112. doi: 10.1111/ejh.13972. Epub 2023 Apr 8.

Authors

Yoshikiyo Ito¹, Hidetoshi Ozawa², Tetsuya Eto³, Toshihiro Miyamoto^{4

5}, Tomohiko Kamimura⁶, Ryosuke Ogawa⁷, Naoyuki Uchida⁸, Atsusi Wake⁹, Tomoaki Fujisaki¹⁰, Yuju Ohno¹¹, Ken Takase¹², Hirokazu Okumura^{13

14}, Yasushi Takamatsu¹⁵, Noriaki Kawano¹⁶, Koichi Akashi⁴, Koji Nagafuji²

Affiliations

¹ Department of Hematology, Imamura General Hospital, Kagoshima, Japan.
² Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
³ Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
⁴ Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
⁵ Division of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
⁶ Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.
⁷ Department of Hematology and Oncology, Japan Community Health Care Organization (JCHO) Kyushu Hospital, Kitakyushu, Japan.
⁸ Department of Hematology, Toranomon Hospital, Tokyo, Japan.
⁹ Department of Hematology, Toranomon Hospital Kajigaya, Kawasaki, Japan.
¹⁰ Department of Hematology, Matsuyama Red Cross Hospital, Matsuyama, Japan.
¹¹ Department of Hematology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
¹² Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
¹³ Department of Hematology, Toyama Prefectural Central Hospital, Toyama, Japan.
¹⁴ Department of Hematology, Minamisoma Municipal General Hospital, Minamisoma, Japan.
¹⁵ Division of Medical Oncology, Hematology and Infectious Diseases, Department of Internal Medicine, Fukuoka University Hospital, Fukuoka, Japan.
¹⁶ Department of Hematology, Miyazaki Prefectural Hospital, Miyazaki, Japan.

PMID: 36991564
DOI: 10.1111/ejh.13972

Abstract

Objective: The prognostic significance of IKZF1^plus in adult Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients had remained to be clarified.

Methods: We conducted a prospective, multicenter study, the ALL/MRD2008 trial, and investigated the clinical significance of IKZF1^plus .

Results: From December 2008 to November 2013, 38 untreated Ph+ ALL patients were enrolled. At the end of the induction, 97.4% of patients (37/38) achieved complete hematological remission, with MRD-negativity of 48.6% (18/37). There were 19 patients with IKZF1^plus , 13 with IKZF1 deletion alone (ΔIKZF1) and 4 with no IKZF1 deletions (no ΔIKZF1). The probability of 3-year DFS and OS in these Ph+ ALL patients were 50% (95% confidence interval [CI], 33-65) and 55% (95% CI, 38-69), respectively. There was no significant difference between IKZF1^plus , ΔIKZF1, and no ΔIKZF1 in DFS (47%, 54%, 75% [p = .63]) or OS (47%, 62%, NA [p = .39]).

Conclusions: We revealed no relationship between IKZF1^plus status and survival outcomes in Ph+ ALL patients treated with imatinib/dasatinib combination chemotherapy. Further investigations are warranted to clarify the prognostic significance of IKZF1^plus in adult Ph+ ALL patients.

Keywords: IKZF1plus; Philadelphia-positive ALL.

Publication types

Multicenter Study

MeSH terms

Adult
Dasatinib / therapeutic use
Humans
Ikaros Transcription Factor* / genetics
Imatinib Mesylate / therapeutic use
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
Prognosis
Prospective Studies

Substances

Ikaros Transcription Factor
Imatinib Mesylate
Dasatinib