Chronic myelomonocytic leukemia (CMML) is a highly heterogeneous myeloid malignancy in which early identification of high-risk patients is critical for timely referral to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, a collaborative team led by Professor Zheng Ge of Zhongda Hospital, Southeast University, and Professor Shuqian Xu of Qilu Hospital, Shandong University, published a study in Blood Cancer Journal entitled "BLAST demonstrates higher prognostic accuracy for survival than CPSS in Chinese patients with chronic myelomonocytic leukemia."This study is the first to systematically validate and compare the prognostic performance of four risk models—BLAST, BLAST-mol, CPSS, and CPSS-mol—in a Chinese CMML cohort. The findings demonstrate that the clinically simple BLAST model, based on only a few readily available clinical variables, provides superior prognostic discrimination for overall survival compared with the traditional CPSS model, offering a valuable new tool for precision risk stratification and transplantation decision-making in CMML.
Oncology Frontier – Hematology Frontier invited Professor Zheng Ge and Professor Shuqian Xu to discuss the clinical significance of these findings and their future implications for CMML management.
Oncology Frontier – Hematology Frontier: CMML is a highly heterogeneous myeloid malignancy, and existing prognostic systems such as CPSS and CPSS-mol have shown limited discriminatory ability in certain risk subgroups. What motivated your team to systematically compare the BLAST model with these traditional prognostic systems in a multicenter Chinese cohort? What do you consider the major limitations of current prognostic assessment for CMML?
Professor Zheng Ge:
The BLAST and BLAST-mol models were originally developed by Professor Ayalew Tefferi’s team at the Mayo Clinic using large Western patient cohorts, where they demonstrated excellent prognostic performance. However, they had never been validated in Chinese patients.
Because CMML is an extremely heterogeneous disease, Chinese patients may differ from Western populations in terms of clinical characteristics, mutational profiles, and treatment patterns. Applying prognostic models developed exclusively in Western cohorts without validation introduces uncertainty.
Therefore, we aimed to systematically evaluate the applicability of all four prognostic models—BLAST, BLAST-mol, CPSS, and CPSS-mol—using multicenter Chinese data, thereby providing evidence-based guidance specifically for Chinese patients.
Current prognostic assessment systems have several important limitations.
First, although CPSS remains the most widely used prognostic model in China, its ability to distinguish certain intermediate-risk groups is limited. In our study, patients classified as CPSS Intermediate-1 and Intermediate-2 showed no significant difference in median overall survival.
Second, CMML carries a substantial risk of transformation to acute myeloid leukemia (AML), yet there is currently no consensus regarding which prognostic model most accurately predicts leukemic transformation.
Finally, although CPSS-mol incorporates molecular and genetic information beyond the original CPSS model and has gained some clinical use in China, its molecular component remains incomplete and has several limitations.
These shortcomings collectively motivated us to conduct this study.
Oncology Frontier – Hematology Frontier: In your study, the BLAST model clearly separated patients into low-, intermediate-, and high-risk groups with significant survival differences, while outperforming both CPSS and CPSS-mol in predicting two- and three-year survival. How do you explain the superior predictive performance of a model built using only a few simple clinical variables?
Professor Shuqian Xu:
The BLAST model relies on only three readily available clinical variables—peripheral blood blast percentage, white blood cell count, and severity of anemia—yet achieved better prognostic discrimination than CPSS.
Its advantages can be understood from three perspectives.
First, the selected variables are highly representative of disease biology.
Blast percentage, leukocytosis, and anemia are key manifestations of CMML progression and bone marrow failure. Together, they accurately reflect disease burden and hematopoietic function while possessing clear biological and clinical relevance.
Second, the model was specifically designed with clinical practicality in mind.
Because BLAST requires only three routinely available laboratory parameters and does not depend on cytogenetic or molecular sequencing data, it minimizes the impact of missing information, resulting in greater stability and broader applicability.
Third, its risk stratification aligns more closely with clinical reality.
BLAST classifies patients into three risk groups, avoiding the limited discrimination observed between adjacent CPSS categories such as Intermediate-1 and Intermediate-2.
Our receiver operating characteristic analyses confirmed this advantage, with BLAST demonstrating higher area under the curve (AUC) values than CPSS for predicting both two-year and three-year survival.
In essence, BLAST achieves more accurate risk stratification using the simplest possible clinical variables, embodying the principle that effective prognostic models do not necessarily require increasing complexity.
Oncology Frontier – Hematology Frontier: Your study also demonstrated that BLAST identified a subset of high-risk patients underestimated by CPSS, while BLAST-mol further improved risk reclassification compared with CPSS-mol. What practical implications could this risk reclassification have for determining the optimal timing of allogeneic stem cell transplantation?
Professor Zheng Ge:
This is an extremely important question.
Our study systematically compared four different prognostic systems. Before Professor Tefferi’s group formally introduced the BLAST and BLAST-mol scoring systems in August 2025, CPSS and CPSS-mol had been the predominant prognostic tools used in China.
When we directly compared the four models, we found that approximately 76% of patients—roughly three-quarters of the cohort—were reassigned to different risk categories after moving from CPSS to BLAST.
Among these reclassified patients, 96.8% were assigned to a higher-risk category.
More importantly, after excluding patients originally classified as high risk by CPSS, those whose risk category was upgraded by BLAST experienced significantly shorter median overall survival.
These findings confirm that BLAST can successfully identify high-risk patients whose prognosis is underestimated by CPSS.
This has several important implications for transplantation.
First, it supports earlier transplantation assessment.
Allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment for CMML. However, because transplantation carries substantial treatment-related mortality, determining the optimal timing remains one of the most challenging clinical decisions.
BLAST identifies patients who should undergo transplant evaluation earlier than would be suggested by CPSS. Relying solely on CPSS may delay transplantation and cause clinicians to miss the optimal therapeutic window.
Second, BLAST may improve clinical trial enrollment.
Many ongoing clinical studies—including MDS-related trials at our own center—primarily enroll high-risk patients. Under CPSS, some patients with genuinely aggressive disease may not qualify for enrollment. BLAST can identify these patients earlier, allowing them access to investigational therapies.
Furthermore, our study demonstrated that BLAST-mol, which incorporates molecular information, provides even better prognostic discrimination than CPSS-mol, enabling more accurate patient selection and improving the quality of future clinical trials.
Third, BLAST facilitates personalized treatment decisions.
Because the model requires only three readily available clinical variables—peripheral blood blast percentage, white blood cell count, and anemia severity—it can be easily applied even in community hospitals or outpatient clinics.
Clinicians no longer need to wait for cytogenetic or molecular testing before identifying high-risk patients and initiating transplant evaluation, enabling a streamlined clinical pathway of early identification, early assessment, and timely transplantation.
Oncology Frontier – Hematology Frontier: Looking toward broader clinical implementation, what additional validation will be required before BLAST and BLAST-mol can become widely adopted in CMML management in China and internationally? Do you believe these models could eventually be incorporated into clinical guidelines and real-world decision-making?
Professor Shuqian Xu:
Several important validation steps remain before BLAST and BLAST-mol can be fully integrated into routine CMML practice.
First, we need larger prospective multicenter studies.
Although our retrospective analysis of 127 Chinese patients provides the first evidence supporting these models in a Chinese population, larger prospective cohorts will be necessary to further confirm their predictive performance and generalizability.
Second, the models should be validated across different treatment settings.
Because patients in our cohort received a variety of therapies, future studies should evaluate BLAST separately among patients receiving different treatment approaches, particularly hypomethylating agents and targeted therapies, to determine whether its prognostic value remains consistent.
Third, BLAST should be evaluated within real clinical decision-making pathways.
Prospective interventional studies are needed to determine whether treatment strategies guided by BLAST—such as transplantation timing or treatment intensity—can improve patient survival rather than simply provide superior statistical risk discrimination.
Despite these remaining challenges, BLAST already possesses several characteristics that make it highly attractive for routine clinical practice.
The model requires only three simple clinical variables, making it easy to use, inexpensive, and highly applicable in real-world settings.
In fact, BLAST and BLAST-mol have already begun influencing decisions regarding the timing of allogeneic stem cell transplantation. By incorporating molecular genetic information, BLAST-mol further improves prognostic accuracy.
As additional validation studies accumulate, we believe both models have strong potential to be incorporated into future CMML guidelines and become practical, reliable tools for routine risk assessment.
Of course, achieving that goal will require continued collaboration and validation by investigators worldwide.
Expert Profiles
Professor Zheng Ge
Zhongda Hospital, Southeast University
Professor Zheng Ge is Chair of the Department of Hematology at Zhongda Hospital, Southeast University, Director of the Southeast University Institute of Hematology, and Director of the Jiangsu Provincial Regional Hematology Medical Center.
She is a Second-Class Professor, Chief Physician, PhD Supervisor, and Postdoctoral Mentor. She earned her doctoral degree from the Karolinska Institutet in Sweden and serves as an Adjunct Associate Professor at the Pennsylvania State University College of Medicine. She is also Director of the International Collaborative Laboratory for Hematologic Diseases, Director of the Nanjing Zhongda Leukemia and MDS Center, and Director of the Precision Diagnosis and Translational Innovation Center for Hematologic Malignancies of the Jiangsu Research Hospital Association.
Professor Ge has received funding from the MMAAP Medical Foundation (USA), five National Natural Science Foundation of China (NSFC) grants, and more than 20 national and provincial research projects. As corresponding author, she has published original research in leading journals including Blood, Leukemia, Blood Cancer Journal, Science Advances, and Advanced Science. She has been invited to deliver lectures at internationally renowned universities, medical centers, and scientific conferences.
She is recognized as a Leading Young and Middle-Aged Talent under Jiangsu Province’s “333 High-Level Talent Program” and is a Jiangsu Provincial Key Medical Talent.
She serves on numerous national and provincial academic organizations, including the Hematology Branch of the Chinese Medical Doctor Association, the Hematology Branch of the Chinese Association of Integrative Medicine, the Hematologic Malignancies Committee and the Hematologic Oncology Committee of the Chinese Anti-Cancer Association, the Hematology Branch of the China International Exchange and Promotive Association for Medical and Health Care, the Hematology Branch of the Chinese Association of Chinese Medicine, the Hematology Branch of the Chinese Geriatrics Society, the China MDS and MPN Working Group, and several hematology societies in Jiangsu Province.
Professor Shuqian Xu
Qilu Hospital, Shandong University
Professor Shuqian Xu is Director of the Department of Hematology, Deputy Director of the Office of International Cooperation and Exchange, and Director of the Cell Immunotherapy Center at Qilu Hospital, Shandong University.
She is a Chief Physician, Professor, PhD Supervisor, Taishan Scholar Young Expert, and Qilu Young Scholar of Shandong University. She completed research training as a Visiting Scholar and Postdoctoral Fellow at Harvard Medical School.
She currently serves as:
- Chair, Hematology Branch, Shandong Young Medical Workers Association
- Deputy Leader, Hematologic Critical Care Group, Chinese Society of Hematology, Chinese Medical Association
- Secretary and Committee Member, Red Blood Cell Disorders Group, Chinese Society of Hematology, Chinese Medical Association
- Vice Chair, Hematology Institutions Branch, Chinese Hospital Association
- Secretary-General, Experimental Hematology Committee, Chinese Association of Pathophysiology
- Standing Committee Member, Leukemia Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Standing Committee Member, Hematologic Malignancies Committee, Chinese Anti-Cancer Association
- Standing Committee Member, Hematologic Immunology Branch, Chinese Society for Immunology
- Deputy Leader, National Hematology Group, Committee of Integrative Medicine Expert Volunteers
- Head, Shandong PNH Collaborative Group
Professor Xu is the principal investigator of subprojects under China’s National Key Research and Development Program and National Natural Science Foundation of China (NSFC). She has published numerous SCI-indexed papers in journals including Nature Genetics, Blood, Leukemia, Autoimmunity Reviews, and Genes & Diseases.
