What are the treatment differences between Aplastic Anemia (AA) and Myelodysplastic Syndromes (MDS)?

Treatment Differences Between Aplastic Anemia and Myelodysplastic Syndromes

Aplastic anemia and MDS require fundamentally different treatment approaches: AA is treated primarily with immunosuppressive therapy (horse ATG plus cyclosporine) targeting immune-mediated stem cell destruction, while MDS treatment is risk-stratified with lower-risk disease managed by erythropoiesis-stimulating agents or lenalidomide for del(5q), and higher-risk disease treated with hypomethylating agents or allogeneic stem cell transplantation. 1

Aplastic Anemia Treatment Algorithm

First-Line Therapy for AA

• Immunosuppressive therapy with horse ATG (40 mg/kg/day for 4 days) plus cyclosporine is the standard first-line treatment for patients not eligible for allogeneic hematopoietic stem cell transplantation 1
• Cyclosporine must be continued for at least 6 months 1
• Dose-attenuated ATG (15 mg/kg/day for 5 days) produces similar response rates (71% vs 64%) and overall survival in older patients (>60 years) with fewer infectious complications, making it appropriate for those with comorbidities 2, 3
• Response assessment occurs at 3 months, with overall response rates of approximately 44-64% by this timepoint 4, 5

Transplant Considerations for AA

• Allogeneic stem cell transplantation is first-line for younger patients with matched sibling donors 1
• Patients failing initial immunosuppressive therapy should be considered for alternative donor transplantation 1

Myelodysplastic Syndrome Treatment Algorithm

Lower-Risk MDS (IPSS Low/Intermediate-1)

Treatment priority is managing cytopenias and improving quality of life, not preventing AML transformation 6

For Patients WITHOUT del(5q):

• First-line: Erythropoiesis-stimulating agents (ESAs) - EPO 30,000-80,000 units weekly or darbepoetin 150-300 μg weekly achieve 60% erythroid response rates when baseline EPO is low and transfusion requirements are limited 6

• ESAs provide independent favorable prognostic factor for survival without impacting AML progression 6

• G-CSF addition improves ESA efficacy 6

• Response occurs within 8-12 weeks with median duration of 2 years 6

• Second-line after ESA failure:

  • Anti-thymocyte globulin (ATG) with or without cyclosporine yields 25-40% erythroid response in select patients: age <65 years, transfusion history <2 years, normal karyotype or trisomy 8, no excess blasts, HLA DR15 genotype, with thrombocytopenia or marrow hypocellularity 6
  • Hypomethylating agents (HMAs) achieve RBC transfusion independence in 30-40% 6
  • Lenalidomide achieves 25-30% RBC transfusion independence, with higher rates when combined with ESA 6

For Patients WITH del(5q):

• First-line: Lenalidomide 10 mg/day, 3 weeks out of 4 achieves 60-65% RBC transfusion independence with median duration of 2-2.5 years 6
• Cytogenetic response occurs in 50-75% (30-45% complete) 6
• Grade 3-4 neutropenia and thrombocytopenia occur in ~60% during first weeks, requiring close monitoring and potential dose reduction with G-CSF support 6
• TP53 mutations (present in ~20%) confer lenalidomide resistance and higher AML progression risk, requiring more aggressive treatment 6

Higher-Risk MDS (IPSS Intermediate-2/High)

• Hypomethylating agents (azacitidine or decitabine) are standard therapy, with azacitidine showing survival benefit particularly in patients with chromosome 7 alterations 6
• Allogeneic stem cell transplantation is indicated for intermediate- and poor-risk patients with HLA-identical sibling or matched unrelated donor, provided age and performance status permit 6
• Reduced-intensity conditioning regimens are appropriate for patients >50 years 6

Hypoplastic MDS Overlap

• Hypoplastic MDS with low bone marrow cellularity may be treated with immunosuppressive therapy (ATG) similar to aplastic anemia, though with limited success 6
• This represents a critical diagnostic and therapeutic overlap between the two conditions 6

Key Distinguishing Features

Pathophysiology Drives Treatment Choice

• AA results from immune-mediated stem cell destruction, hence immunosuppression is curative in many cases 1
• MDS is a clonal stem cell disorder with dysplasia and malignant potential, requiring risk-stratified approaches targeting either cytopenias (lower-risk) or preventing AML transformation (higher-risk) 6

Common Pitfalls

• Do not use intensive chemotherapy for lower-risk MDS—it does not improve survival and worsens quality of life 6
• Recognize that 15-20% of AA patients develop secondary MDS/AML by 10 years, requiring ongoing surveillance 7
• Hypoplastic MDS can mimic AA; bone marrow morphology showing dysplasia distinguishes MDS from AA 6
• In older AA patients, dose-attenuated ATG reduces infectious complications without compromising efficacy 2, 3

Supportive Care Overlap

• Both conditions require transfusion support, infection management during neutropenia, and monitoring for iron overload with chronic transfusions 6
• Growth factors (G-CSF, ESAs) are used supportively in both, but their role in natural history modification differs 6