A Prediction Model for Early Recurrence after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with CMML: A Nationwide Representative Multicenter Study

Zhou, Jianying

Oral and Poster Abstracts
723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster III

Non-Biological therapies, Chronic Myeloid Malignancies, CMML, Diseases, Myeloid Malignancies

Jianying Zhou¹^*, Song Wang^2,3,4,5^*, Ting Niu, MD, PhD^6,7, Ming Jiang⁸^*, Shunqing Wang, M.D., Ph.D.⁹^*, Wen Wang¹⁰^*, Xi Zhang, PhD¹¹, Yujun Dong¹²^*, Dingming Wan¹³^*, Xin Du, PhD¹⁴^*, Xudong Wei¹⁵^*, Han Zhu¹⁶^*, Yuhua Li¹⁷^*, Kehong Bi¹⁸^*, Xianmin Song, phd¹⁹, Yi Chen²⁰^*, Li Liu²¹^*, Yi Luo²²^*, Yuhong Zhou²³^*, Xin Li, MD²⁴^*, Yajing Xu, MD²⁵^*, Yicheng Zhang²⁶^*, Xiaoliang Liu²⁷^*, Hai Yi²⁸^*, Xiaobing Huang²⁹^*, Zunmin Zhu, MD, PhD³⁰^*, Jianmin Yang³¹^*, Fang Zhou³²^* and Xiaohui Zhang¹^*

¹Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China
²Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China;, Beijing, China
³Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China, Beijing, China
⁴National Clinical Research Center for Hematologic Disease, Beijing, China;, Beijing, China
⁵Collaborative Innovation Center of Hematology, Peking University, Beijing, China, Beijing, China
⁶Department of Hematology, West China Hospital, Sichuan University, Chengdu, CHN
⁷West China Hospital Sichuan University, Chengdu, Sichuan, China
⁸Department of Hematology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
⁹Department of Hematology, Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China
¹⁰Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
¹¹Army medical University affiliated Xinqiao Hospital, Chongqing, China
¹²Department of Hematology, Peking University First Hospital, Beijing, CHN
¹³Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
¹⁴Guangdong Provincial People’s Hospital, Guangzhou, WA, CHN
¹⁵Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
¹⁶Department of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital With Nanjing Medical University, Nanjing, CHN
¹⁷Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
¹⁸Department of Hematology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
¹⁹Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
²⁰Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
²¹Department of Hematology, the Second Affiliated Hospital (Tangdu Hospital) of Air Force Medical University, Xi'an, China
²²Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
²³Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
²⁴The Third Xiangya Hospital of Central South University, Changsha, China
²⁵Department of Hematoogy, Xiangya Hospital, Central South University, Changsha, China
²⁶Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
²⁷Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun, China
²⁸Department of Hematology, Western Theater General Hospital of the People's Liberation Army of China, Chengdu, China
²⁹Department of Hematology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
³⁰Department of Hematology, Henan Provincial People’s Hospital, Zhengzhou, China
³¹Department of Hematology, Changhai Hospital, The Naval Medical University, Shanghai, China
³²Department of Hematology, the 960th Hospital of the People's Liberation Army of China, Jinan, China

Introduction:

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy. Some patients experience prolonged remission after aggressive chemotherapy, but the only current therapy with proven curative potential is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, not all CMML patients benefit from allo-HSCT, and many experience relapse. Relapse is the leading cause of treatment failure for CMML treated with allo-HSCT, and treatment options for patients relapsing after allo-HSCT are limited. This study conducted a nationwide multicenter real-world study to identify risk factors and develop a novel prediction model for early recurrence in CMML patient posttransplantation. Clinicians can improve the survival of CMML patients with a high risk of early recurrence by intervening as early as possible.

Methods:

Patients ≥18 years old with CMML treated with allo-HSCT for the first time between 2005 and 2022 were included in this nationwide, multicenter, real-world study. Twenty-seven medical centers participated in this analysis, including the derivation cohort from 26 centers and the validation cohort from another center. Information collected included demographic and clinical characteristics, previous treatments and responses, and allo-HSCT treatment details. We first calculated the univariable association of each variable with 1-year relapse in the derivation cohort. Second, the variables with p values less than 0.1 in the univariate analysis were further included as candidate predictors in the multivariate analysis using a backward stepwise logistic regression model. The variables that remained in the final model based on the outcomes of the multivariate analysis in the derivation cohort were identified as independent prognostic factors. A scoring system to predict early recurrence after allo-HSCT was also established, and scores were assigned to the prognostic factors based on the regression coefficient.

Results:

Using multivariable logistic regression methods with stepwise variable selection, two highly significant independent prognostic factors for the early recurrence of CMML posttransplantation were identified: bone marrow blast cell count at diagnosis (p=0.026; odds ratio [OR], 1.149; 95% confidence interval [CI], 1.02-1.30), and leukocyte count pretransplantation (p=0.005; odds ratio [OR], 1.212; 95% confidence interval [CI], 1.06-1.39). A risk grading model was constructed according to the regression coefficients. Bone marrow blast cell count 0-5% is 0 point, 5%-10% is 1 point; 10-20% is 2 points, and >20% is 3 points. Leukocyte count 0-10×10⁹/L is 0 point, 10-20×10⁹/L is 2 points, and >20 ×10⁹/L is 4 points. The points scored for each of these two factors were added to yield the overall risk score, which ranged from zero to seven. Patients were stratified into a low-risk group (0-1 point), a intermediate-risk group (2-3 points) and a high-risk group (4-7 points). The validated internal c-statistic was 0.790 (95% CI, 0.657-0.923), and the external c-statistic was 0.710 (95% CI, 0.580-0.840). The early recurrence rates of the derivation cohort in the low-risk, intermediate-risk, and high-risk groups were 5.9%, 17.9% and 31.8% (p<0.05). The Kaplan‒Meier estimations of relapse-free survival revealed good separation between these risk groups, and 91.9%, 79.4% and 66.1% (p<0.05), respectively. According to the calibration plots, the model-predicted probabilities showed a good correlation with the actual observed frequencies. Decision curve analysis indicated that the clinical implementation of the prognostic model could benefit early recurrence CMML patients.

Conclusion:

CMML patients who relapse after allo-HSCT have a poor prognosis. An integrated prediction model based on clinical biomarkers was developed and externally validated, and this is the first straightforward scoring model that incorporates clinical and laboratory risk factors to evaluate the early recurrence of CMML patients after receiving allo-HSCT. This model can be effectively utilized to help improve the survival and prognosis of CMML patients by accelerating the early identification of patients at a high risk of relapse and contributing to the appropriate implementation of urgent medical support.

Disclosures: No relevant conflicts of interest to declare.

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4951 A Prediction Model for Early Recurrence after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with CMML: A Nationwide Representative Multicenter Study