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3008 Reduced-Intensity Allogeneic HSCT for Children and Adolescents/Young Adults with CML: A Study from the Adult and Pediatric CML Working Group of the Japan Society for Hematopoietic Cell Transplantation

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster II
Hematology Disease Topics & Pathways:
Diseases, Biological, CML, Therapies, Pediatric, Young Adult, Study Population, Clinically relevant, Myeloid Malignancies, transplantation, TKI
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Hiroyuki Shimada, MD, PhD1*, Akihiko Tanizawa, MD, PhD2*, Takeshi Kondo, MD, PhD3, Hideki Muramatsu, MD, PhD4, Masahiro Yasui, MD5, Arinobu Tojo, MD, PhD6, Tokiko Nagamura-Inoue, MD, PhD7, Tetsuya Eto, MD, PhD8*, Aiko Igarashi, MD9*, Heiwa Kanamori, MD, PhD10, Maho Sato, MD5*, Maiko Noguchi, MD11*, Tatsuo Ichinohe, MD, PhD12, Masami Inoue, MD5, Koji Kato, MD, PhD13*, Yoshiko Atsuta, MD, PhD14* and Kazuteru Ohashi, MD, PhD9*

1Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
2Department of Human Resource Development for Cancer, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
3Department of Hematology, Aiiku Hospital, Sapporo, Japan
4Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
5Department of Hematology/Oncology, Osaka Women's and Children's Hospital, Osaka, Japan
6Division of Molecular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
7Department of Cell Processing and Transfusion, IMSUT Cell Resource Center, Research Hospital,The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
8Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
9Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
10Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan
11Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan
12Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
13Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
14The Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

Background: The introduction of tyrosine kinase inhibitor (TKI) has reduced the indications for allogeneic hematopoietic stem cell transplants (HSCT) in patients with chronic myeloid leukemia (CML). In children and adolescents/young adults (AYA), however, the long-term side effects of TKI and financial burden could become a future issue. Thus, the role of HSCT with reduced intensity conditioning (RIC) as an alternative to TKI especially in the first chronic phase (CP1) should be defined for children and AYA with CML. However, less is well-known about the efficacy of RIC regimens on children and AYA with CML, in chronic phase (CP) as well as advanced phase.

Aims: To describe the long-term outcomes of children and AYA with all phases of CML treated with a RIC HSCT and to define potential prognostic factors for outcome.

Patients and Methods: We retrospectively analyzed 3796 patients with CML using data from the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation and included children and AYA under 30 years old at HSCT who underwent allo-HSCT between 2001 and 2014 and received TKI before HSCT. The myeloablative conditioning regimen was defined as TBI ≥ 8 Gy, busulfan > 8mg/kg, or melphalan > 180 mg/m2.

Result: The characteristics of patients are summarized in Table 1. RIC was selected preferentially in patients with better status. The median follow-up of survivors was 64 months (3­ - 171 months). There was no significant difference in 5-year overall survival (OS) among CP (124 cases), accelerated phase (AP) (23 cases) and blastic phase (BP) (53 cases) at diagnosis, 83%, 71% and 73%, respectively. In CP at diagnosis, 5-year OS was significantly higher in CP1 (89 cases) at HSCT than in CP2≤/AP/BP (35 cases) (89% versus 66%, p = 0.0004), and in CP1 at HSCT, there was no difference in 5-year OS between myeloablative conditioning (MAC) (58 cases) and RIC (31 cases) (both 89%) (Figure 1). However, 5-year OS in RIC was significantly higher in children (0-14 years old, 23 cases) than in AYA (15-29 years old, 8 cases) (95% versus 75%, p = 0.0495). Two of eight AYA patients with CP1 died after RIC HSCT due to grade IV acute GVHD-related complications without disease relapse, suggesting that the indications for RIC in AYA with CP1 should be carefully judged. In AP/BP at diagnosis, 5-year OS was significantly higher in the second chronic phase (CP2) (48 cases) at HSCT than in the third chronic phase (CP3)≤/AP/BP (28 cases) (82% versus 56%, p = 0.0073). However, the rate of major cytogenetic response (MCyR) at HSCT was significantly higher in CP2 than in CP3≤/AP/BP, and when focusing only on MCyR at HSCT in AP/BP at diagnosis, there was no difference in 5-year OS between CP2 at HSCT (40 cases) and CP3≤/AP/BP (13 cases) (83% versus 78%). On condition of MCyR at HSCT in AP/BP at diagnosis, regardless of the phase at HSCT, there was no difference in 5-year OS between MAC (46 cases) and RIC (7 cases: 2 in children and 5 in AYA) (79% versus 100%) (Figure 2), suggesting that even in AP/BP at diagnosis, RIC could be indicated for the patients with good response to TKI. On multivariate analysis, disease phase at HSCT and time from diagnosis to HSCT were independent predictors of OS in CP at diagnosis (Table 2), and cytogenetic response at HSCT and stem cell source in AP/BP at diagnosis (Table 3). There was no significant difference of OS between MAC and RIC.

Conclusion: In HSCT for CML after TKI administration, the indications for RIC in children under 15 years old with CP1 are appropriate. In RIC HSCT for AYA patients under 30 years old with CP1, caution should be exercised in transplant-related mortality rather than disease progression. Furthermore, even in AP/BP at diagnosis, RIC could be indicated for children and AYA patients with MCyR at HSCT.

Disclosures: Ichinohe: Eisai Co.: Research Funding; Mundipharma: Honoraria; Bristol-Myers Squibb: Honoraria; Kyowa Hakko Kirin Co.: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Otsuka Pharmaceutical Co.: Research Funding; Zenyaku Kogyo Co.: Research Funding; MSD: Research Funding; Celgene: Honoraria; Takeda Pharmaceutical Co.: Research Funding; JCR Pharmaceuticals: Honoraria; Taiho Pharmaceutical Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Astellas Pharma: Research Funding; Novartis.: Honoraria; Alexion Pharmaceuticals: Honoraria; Chugai Pharmaceutical Co.: Research Funding; CSL Behring: Research Funding; Ono Pharmaceutical Co.: Research Funding; Pfizer: Research Funding; Nippon Shinyaku Co.: Research Funding; Repertoire Genesis Inc.: Research Funding.

*signifies non-member of ASH