Newly proposed threshold and validation of white blood cell count at diagnosis for Philadelphia chromosome-positive acute lymphoblastic leukemia: risk assessment of relapse in patients with negative minimal residual disease at transplantation—a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSTCT

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 11; pp. 2842 - 2848
• Main Authors: Akahoshi, Yu, Arai, Yasuyuki, Nishiwaki, Satoshi, Tachibana, Takayoshi, Shinohara, Akihito, Doki, Noriko, Uchida, Naoyuki, Tanaka, Masatsugu, Kanda, Yoshinobu, Shiratori, Souichi, Ozawa, Yukiyasu, Shono, Katsuhiro, Katayama, Yuta, Tanaka, Junji, Fukuda, Takahiro, Atsuta, Yoshiko, Kako, Shinichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2021; Nature Publishing Group
• Subjects: 38; 38/77; 631/67/1990/283/2125; 692/499; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Blood; Blood cell count; Cell Biology; Chromosomes; Derivation; Diagnosis; Health aspects; Hematology; Hematopoietic Stem Cell Transplantation; Humans; Internal Medicine; Leukemia; Leukocyte Count; Leukocytes; Lymphatic leukemia; Medicine; Medicine & Public Health; Minimal residual disease; Neoplasm, Residual - diagnosis; Philadelphia Chromosome; Physiological aspects; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prognosis; Public Health; Recurrence; Remission; Risk Assessment; Stem cell transplantation; Stem Cells; Transplantation; Japan
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-021-01422-7

White blood cell count (WBC) at diagnosis is the conventional prognostic factor in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Nevertheless, little is known about the impact of WBC at diagnosis considering the minimal residual disease (MRD) status at allogeneic hematopoietic cell transplantation (HCT). We evaluated adult patients with Ph + ALL who achieved negative-MRD and received HCT in first complete remission between 2006 and 2018. The entire cohort was temporally divided into derivation ( n  = 258) and validation cohorts ( n   =  366). Using a threshold of 15,000/μL, which was determined by a receiver operating characteristic curve analysis in the derivation cohort, high WBC was associated with an increased risk of hematological relapse in both the derivation cohort (25.3% vs. 11.6% at 7 years, P  = 0.004) and the validation cohort (16.2% vs. 8.5% at 3 years, P  = 0.025). In multivariate analyses, high WBC was a strong predictor of hematological relapse in the derivation cohort (HR, 2.52, 95%CI 1.32–4.80, P  = 0.005) and in the validation cohort (HR, 2.32, 95%CI, 1.18–4.55; P  = 0.015). In conclusion, WBC at diagnosis with a new threshold of 15,000/μL should contribute to better risk stratification in patients with negative-MRD at HCT.