Allogeneic hematopoietic stem cell transplantation overcome the poor prognosis of patients with IKZF1plus CD20–a very high-risk subtype in B-cell acute lymphoblastic leukemia

Tang, Bingqing; Cai, Zihong; Wang, Zhixiang; Lin, Danna; He, Xianjun; Li, Qiuli; Liang, Xiaojie; Huang, Kangyu; Zhou, Xuan; Lin, Ren; Xu, Nuo; Zhang, Fan; Huang, Fen; Sun, Jing; Liu, Xiaoli; Liu, Qifa; Zhou, Hongsheng

doi:10.1038/s41409-022-01797-1

Cited by 6 publications

(7 citation statements)

References 30 publications

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“… 20 In adult B‐ALL, our previous study demonstrated that IKZF1 deletions plus CD20 positivity correlated with a very poor prognostic profile. 11 These findings characterize the subgroups with poor prognoses in B‐ALL and refine the IKZF1 ‐based prognostic stratification. In the current study, we revealed a synergistic effect of CRLF2/EPOR/JAK2/p‐CRKL/p‐STAT5 and IKZF1 in Ph‐like ALL, which resulted in poor outcomes and shaped the Ph‐like classification into HR and SR subgroups.…”

Section: Discussionmentioning

confidence: 64%

“…Patients received chemotherapy or targeted drugs (TKIs and ruxolitinib) along with chemotherapy as frontline treatment. The chemotherapy regimens included Precision‐Classification‐Directed‐Target‐Total‐Therapy (PDT)‐ALL‐2016 11 , 14 , 15 (for NFH) and the Chinese guideline for the treatment of adult ALL 5 (for the other four SCHC centers). Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) was recommended for patients who achieved complete remission (CR) if a donor was available.…”

Section: Methodsmentioning

confidence: 99%

“…Emerging evidence has shown that IKZF1 aberrations confer resistance to conventional chemotherapy, targeted therapy, blinatumomab, and chimeric antigen receptor T (CAR‐T) cell immunotherapy. 7 , 8 , 9 , 10 , 11 , 12 In addition, IKZF1 plus (defined as IKZF1 deletions that co‐occur with deletions in CDKN2A , CDKN2B , PAX5 , or PAR1 in the absence of an ERG deletion) is associated with worse outcomes in pediatric patients with B‐ALL 8 and has been incorporated into the 2023 National Comprehensive Cancer Network (NCCN) guidelines. However, the prognostic implications of combining IKZF1 aberrations and oncogenic activation in Ph‐like ALL have been marginally addressed.…”

Section: Introductionmentioning

confidence: 99%

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An integrated classification of tumor suppressor IKZF1 inactivation and oncogenic activation in Philadelphia chromosome‐like acute lymphoblastic leukemia

Huang,

Zhang,

Gong

et al. 2024

HemaSphere

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Philadelphia chromosome (Ph)‐like acute lymphoblastic leukemia (ALL) is recognized for its genetic and clinical diversity. In this study, we identified a novel high‐risk subset of Ph‐like ALL, characterized by the activation of oncogenic signaling and the inactivation of the tumor suppressor gene IKZF1, resulting in a dismal outcome. The association between cytogenetic aberrations and clinical features was assessed on a cohort of 191 patients with Ph‐like ALL. Our findings revealed that patients with inactivation of IKZF1 combined with activation of oncogenic signaling (CRLF2/EPOR/JAK2 rearrangements or p‐CRKL/p‐STAT5 high expression) had the worst outcome (3‐year overall survival [OS] of 28.8% vs. 80.1% for others, p < 0.001; 2‐year event‐free survival [EFS] of 6.5% vs. 57.0% for others, p < 0.001). Multivariable analysis demonstrated that this high‐risk feature was an independent inferior prognostic factor (adjusted hazard ratio for OS = 4.55, 95% confidence interval [CI]: 2.35–8.81, p < 0.001; adjusted hazard ratio for EFS = 3.27, 95% CI: 1.99–5.39, p < 0.001). Allogeneic hematopoietic stem cell transplantation was associated with improved prognoses in patients within the high‐risk subgroup. In conclusion, this study identified a clinically distinct entity that possesses effective prognostic features and provides potential guidance for refining risk stratification in Ph‐like ALL.

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Section: Discussionmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An integrated classification of tumor suppressor IKZF1 inactivation and oncogenic activation in Philadelphia chromosome‐like acute lymphoblastic leukemia

Huang,

Zhang,

Gong

et al. 2024

HemaSphere

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“…Paediatric‐inspired regimen in this study is population‐based and peg‐asparaginase‐intensified protocol of PDT‐ALL‐2016 15 (Table S1). Adult regimen was performed according to the Chinese guidelines for the diagnosis and treatment of ALL (2016) as described in the CALLG‐2008 protocol 16 (Table S2).…”

Section: Methodsmentioning

confidence: 99%

PASS‐ALL study of paediatric‐inspired versus adult chemotherapy regimens on survival of high‐risk Philadelphia‐negative B‐cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation

Wang,

Fan,

et al. 2023

Br J Haematol

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SummaryThis PASS‐ALL study was designed to explore the effect of paediatric‐inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high‐risk Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukaemia (HR PH‐ve B‐cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo‐HSCT). The PASS‐ALL study is a multicentre, observational cohort study, and 143 patients with HR B‐cell PH‐ve ALL were enrolled from five centres—77 patients allocated in the paediatric‐inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo‐HSCT. Three‐year leukaemia‐free survival (LFS) in the paediatric‐inspired cohort was 72.2% (95% CI 60.8%–83.6%) compared with 44.6% (95% CI 31.9%–57.3%; p = 0.001). Furthermore, time‐to‐positive minimal residual disease (TTP‐MRD) post‐HSCT was marked different, 3‐year cumulative incidence of relapse was 25.9% (95% CI 15.8%–37.2%) in paediatric cohort and 45.4% (95% CI 40.0%–57.9%) in adult cohort (p = 0.026). Finally, the 3‐year OS rate was 75.3% (95% CI 64.9%–85.7%) for the paediatric‐inspired cohort and 64.1% (95% CI 51.8%–76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric‐inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327–4.862, p = 0.005). Collectively, our data suggest that paediatric‐inspired chemotherapy pre‐HSCT results in deeper and durable MRD response reduces relapse post‐HSCT and improves survival in HR B‐cell PH‐ve ALL patients with allo‐HSCT.

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“…Patients in this study were enrolled from PDT-ALL-2016 pediatric-inspired cohort, a GRAALL-2003 backbone, PEG-asparaginase-intensi ed, pediatric-inspired regimen [15,16] , whose detailed protocol was attached in the supplemental data. PDT-ALL-2016 cohort contain a total of 411 adult ALL patients, all of whom were diagnosed at Nanfang Hospital from January 2016 to December 2021, with outcomes updated in January 2023.…”

Section: Pdt-all-2016 Cohortmentioning

confidence: 99%

Superior Survival with Allogeneic Hematopoietic Stem Cell Transplantation versus Chemotherapy for High-Risk Adult Acute Lymphoblastic Leukemia in PDT-ALL-2016 Pediatric-Inspired Cohort

Zhou,

Chen,

Cai

et al. 2024

Preprint

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The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult high-risk acute lymphoblastic leukemia (HR-ALL) remained elusive in the pediatric-inspired regimen era. We conducted a cohort study on the outcome of allo-HSCT post-consolidation versus chemotherapy for HR-ALL in the first complete remission in PDT-ALL-2016 pediatric-inspired cohort. A total of 245 patients with HR-ALL were enrolled, according to donor availability and patients’ preferences, among which 159 received allo-HSCT after consolidation therapy, and 86 received post-remission chemotherapy. With a median follow-up of 43.6 months, the 3-year overall survival (OS) in allo-HSCT cohort was 77.1% (70.6–84.2%), and 51.7% (41.7–64.1%) in chemotherapy cohort, respectively (p < .001). In multivariate analysis, allo-HSCT cohort showed superior OS (HR = 0.33, 0.21–0.54, p < .001), event-free-survival (EFS, HR = 0.36, 0.23–0.56, p < .001), cumulative incidence of relapse (CIR, HR = 0.13, 0.07–0.22, p < .001), and increased non-relapse mortality (NRM, HR = 4.06, 1.23–13.4, p = .021), compared to chemotherapy cohort. Notably, allo-HSCT improved the outcome of minimal residue disease (MRD)-positive subset (OS, HR = 0.42,0.20–0.90, p = .025), as well as MRD-negative subset (OS, HR = 0.21, 0.10–0.43, p < .001). Our study demonstrates that allo-HSCT post-consolidation, compared to chemotherapy, could further improve survival of HR-ALL in pediatric-inspired cohort, regardless of MRD status.

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Allogeneic hematopoietic stem cell transplantation overcome the poor prognosis of patients with IKZF1plus CD20–a very high-risk subtype in B-cell acute lymphoblastic leukemia

Cited by 6 publications

References 30 publications

An integrated classification of tumor suppressor IKZF1 inactivation and oncogenic activation in Philadelphia chromosome‐like acute lymphoblastic leukemia

An integrated classification of tumor suppressor IKZF1 inactivation and oncogenic activation in Philadelphia chromosome‐like acute lymphoblastic leukemia

PASS‐ALL study of paediatric‐inspired versus adult chemotherapy regimens on survival of high‐risk Philadelphia‐negative B‐cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation

Superior Survival with Allogeneic Hematopoietic Stem Cell Transplantation versus Chemotherapy for High-Risk Adult Acute Lymphoblastic Leukemia in PDT-ALL-2016 Pediatric-Inspired Cohort

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