Myelodysplastic Syndromes Medical Services in China

Myelodysplastic Syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective blood cell production, peripheral cytopenias, and an increased risk of progression to acute myeloid leukemia (AML). Pathogenically, MDS arises from acquired somatic mutations in hematopoietic stem or progenitor cells—commonly affecting genes involved in RNA splicing (e.g., SF3B1, SRSF2), DNA methylation (TET2, DNMT3A), chromatin modification (ASXL1), transcription regulation (RUNX1), and signal transduction (RAS pathway). These mutations disrupt normal differentiation and promote apoptosis in the bone marrow, leading to dysplastic morphology across one or more myeloid lineages (erythroid, granulocytic, megakaryocytic). The bone marrow is typically hypercellular, though hypocellular variants exist. Disease progression correlates with accumulating genetic lesions and worsening cytogenetic abnormalities—particularly complex karyotypes or monosomy 7. Epidemiologically, MDS predominantly affects older adults, with a median age at diagnosis of 70–75 years. Incidence rises sharply after age 60, estimated at 3–5 per 100,000 persons annually in Western populations; however, recent epidemiologic studies in China suggest incidence may be underreported but is likely comparable—approximately 2–4 per 100,000 among those aged ≥65. Risk factors include prior exposure to chemotherapy (especially alkylating agents and topoisomerase II inhibitors), radiation therapy, benzene and other organic solvent exposures, smoking, and inherited bone marrow failure syndromes (e.g., Fanconi anemia, telomere biology disorders). Age remains the strongest non-modifiable risk factor. Quality of life in MDS is significantly impaired—not only due to fatigue, shortness of breath, recurrent infections, and bleeding tendencies stemming from anemia, neutropenia, and thrombocytopenia—but also from psychological burden, treatment-related side effects (e.g., transfusion iron overload, immunosuppression), and uncertainty around disease evolution. Patients frequently report reduced physical functioning, social withdrawal, anxiety about AML transformation, and diminished capacity for daily activities and employment. Supportive care—including red blood cell and platelet transfusions, growth factor use (e.g., erythropoietin analogs), and iron chelation—is foundational, yet does not alter disease biology. Higher-risk MDS requires disease-modifying therapies such as hypomethylating agents (azacitidine, decitabine), lenalidomide (particularly in del(5q) cases), or allogeneic hematopoietic stem cell transplantation—the only potentially curative option, albeit limited by age, comorbidities, and donor availability. Comprehensive management demands multidisciplinary coordination between hematologists, transfusion medicine specialists, psychologists, and palliative care teams to optimize both survival and patient-centered outcomes.

Myelodysplastic Syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplasia in one or more myeloid lineages, and an increased risk of progression to acute myeloid leukemia (AML). Management is highly individualized, guided by prognostic scoring systems—including the Revised International Prognostic Scoring System (IPSS-R)—which integrate cytogenetics, blast percentage, and severity of cytopenias. Treatment strategies span supportive care, disease-modifying pharmacotherapy, and potentially curative interventions, with goals ranging from symptom control and transfusion independence to long-term remission or cure.

Conservative (supportive) treatment remains foundational for all MDS patients, particularly those with lower-risk disease (IPSS-R Very Low, Low, or Intermediate). It focuses on mitigating complications of cytopenias without directly targeting the underlying clone. Red blood cell (RBC) transfusions alleviate anemia-related fatigue, dyspnea, and cardiac strain; however, iron overload—especially after >20 units—is monitored via serum ferritin and MRI-based liver iron concentration, with iron chelation (e.g., deferasirox) initiated when indicated. Platelet transfusions are reserved for active bleeding or procedural support in thrombocytopenic patients (platelets <10 × 10⁹/L), avoiding routine prophylaxis due to alloimmunization risk. Granulocyte colony-stimulating factor (G-CSF), often combined with erythropoiesis-stimulating agents (ESAs) like epoetin alfa or darbepoetin, may improve hemoglobin levels in select low-risk patients with low endogenous erythropoietin (<500 U/L) and minimal transfusion dependence. Antibiotic prophylaxis is not routinely recommended, but prompt evaluation and broad-spectrum empiric therapy are critical for febrile neutropenia. Vaccination against influenza, pneumococcus, and hepatitis B is strongly advised.

Pharmacologic therapy targets disease biology and modifies natural history. Hypomethylating agents (HMAs)—azacitidine and decitabine—are standard first-line therapy for higher-risk MDS (IPSS-R High or Very High) and selected intermediate-risk patients. Azacitidine improves overall survival, reduces AML transformation, and achieves hematologic improvement in ~40–50% of patients; decitabine shows comparable efficacy with alternative dosing schedules. Lenalidomide is uniquely effective in del(5q) MDS, inducing transfusion independence in ~67% of patients and cytogenetic responses in ~50%, with durable responses often lasting >2 years. Immunosuppressive therapy (IST), including antithymocyte globulin (ATG) and cyclosporine, may benefit a subset of younger, HLA-DR15-positive, hypocellular MDS patients with features overlapping aplastic anemia. Emerging agents include luspatercept—a transforming growth factor-beta (TGF-β) superfamily trap approved for ring sideroblast-positive (RS+) MDS with anemia refractory to ESAs—demonstrating robust transfusion reduction and hemoglobin increases. Venetoclax combinations are under active investigation in higher-risk MDS, particularly with TP53 mutations, though data remain preliminary. All pharmacotherapies require vigilant monitoring for myelosuppression, infection, and secondary malignancies.

Surgical treatment is limited to allogeneic hematopoietic stem cell transplantation (allo-HSCT), the only potentially curative modality. Indicated primarily for fit patients with higher-risk MDS and suitable donors, allo-HSCT offers 5-year overall survival rates of 30–50%, heavily influenced by age, comorbidity burden (HCT-CI score), donor type (matched sibling vs. matched unrelated vs. haploidentical), and disease status at transplant. Reduced-intensity conditioning (RIC) regimens have expanded eligibility to older adults (up to age 70–75 in select centers), improving tolerability while preserving graft-versus-leukemia effects. Post-transplant management includes immunosuppression tapering, surveillance for relapse (via chimerism analysis and flow cytometry), and aggressive intervention for graft-versus-host disease (GVHD). Despite its curative potential, allo-HSCT carries significant risks—including treatment-related mortality (15–25%), chronic GVHD (30–50%), and late effects such as endocrine dysfunction and secondary cancers—necessitating comprehensive pre-transplant assessment and lifelong follow-up.

China offers distinct advantages in MDS management, anchored in rapidly advancing infrastructure and innovation. Over 200 accredited bone marrow transplant centers—including Peking University People’s Hospital, the First Affiliated Hospital of Sun Yat-sen University, and Ruijin Hospital—perform >10,000 allo-HSCTs annually, representing the world’s largest national transplant program. China pioneered widespread adoption of haploidentical HSCT using post-transplant cyclophosphamide, enabling near-universal donor availability and achieving outcomes comparable to matched donors. Domestic development of biosimilar HMAs (e.g., azacitidine generics) and novel agents—including the oral HMA ASTX727 (cedazuridine/decitabine) and the anti-CD47 antibody magrolimab in clinical trials—enhances accessibility and affordability. Integrated multidisciplinary teams (hematologists, transplant physicians, molecular pathologists, genetic counselors, and supportive care specialists) operate within tiered hospital networks, ensuring standardized diagnostics—including next-generation sequencing panels covering SF3B1, TET2, ASXL1, TP53, and splicing factors—and rapid turnaround for cytogenetics and molecular profiling. Moreover, China’s National Medical Products Administration (NMPA) has accelerated approval pathways for breakthrough therapies, shortening time-to-access for global innovations.

Recovery and long-term management emphasize proactive, patient-centered strategies. Patients should maintain rigorous infection prevention: hand hygiene, avoidance of crowded settings during neutropenia, and immediate reporting of fever (>38.0°C). Nutritional optimization—including iron- and folate-rich foods for non-transfused anemia, and protein supplementation during recovery from cytopenias or transplant—is essential. Physical activity tailored to energy levels (e.g., daily walking) combats fatigue and preserves functional capacity. Psychosocial support—including counseling, peer-led support groups, and cognitive-behavioral interventions—is integral, given high rates of anxiety and depression. Regular surveillance includes complete blood counts every 1–3 months (depending on risk and stability), annual bone marrow examinations for higher-risk patients or those with new cytopenias, and periodic assessment of iron stores, renal/hepatic function, and endocrine parameters post-transplant. Smoking cessation and alcohol moderation are strongly encouraged. Finally, shared decision-making—grounded in updated prognostic models, patient values, and realistic expectations—is paramount: for example, clarifying that HMAs aim for disease control rather than cure, while allo-HSCT entails substantial trade-offs between longevity and quality-of-life impact. With evolving therapeutic paradigms and growing expertise across Chinese hematology centers, outcomes for MDS continue to improve, underscoring the importance of timely referral to specialized hematologic care.