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Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens.
Abstract: Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate.
Publication Date: 2006-07-08 PubMed ID: 16830141DOI: 10.1007/s00277-006-0152-yGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Clinical Trial
- Journal Article
Summary
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This research aimed to understand the long-term outcome of aplastic anemia (AA) treatment using horse antilymphocyte globulin (ALG) given at an increased dose, combined with androgens. The findings indicate a higher overall response rate and survival rate after 5 years with this approach. It also reduced the occurrence of therapy-related acute myeloid leukemia/myelodysplastic syndromes (t-AML/MDS).
Overview of Aplastic Anemia and its Treatment
- Aplastic Anemia (AA) is a severe condition that arises from the malfunctioning of hematopoietic stem cells (cells responsible for blood production).
- Existing treatment approaches involve the use of Horse Antilymphocyte Globulin (ALG), especially for patients for whom bone transplantation is not feasible.
- However, the use of ALG has limitations like initiating therapy-related acute myeloid leukemia or myelodysplastic syndromes (t-AML/MDS) in some patients.
Research Approach
- The researchers conducted a single institutional retrospective study involving 87 AA patients.
- These patients were given a higher than usual dose of ALG, akin to doubling the standard dosage, in conjunction with androgens.
Key Findings
- Combination of higher doses of ALG with androgens led to better response rates (77%) and 5-year survival rates (78%). This suggests that it might be a promising treatment approach.
- The androgen combination was correlated with reduced cases of therapy-related t-AML/MDS.
- However, 6% of AA patients had abnormal karyotypes at the time of diagnosis using traditional cytogenetic techniques, unrelated to any time-to-event. Two patients developed secondary malignancies, suggesting a cytogenetic conversion.
Conclusion
- The research concludes that combining a higher dose of ALG with androgens is possible and effective – showing outcomes similar to those from the immunosuppressive treatments containing ALG and cyclosporine.
- It also brings out the potential of this combination in reducing the risk of severities such as SMD/AML.
Cite This Article
APA
Leleu X, Terriou L, Duhamel A, Moreau AS, Andrieux J, Dupire S, Coiteux V, Berthon C, Micol JB, Guieze R, Facon T, Bauters F.
(2006).
Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens.
Ann Hematol, 85(10), 711-716.
https://doi.org/10.1007/s00277-006-0152-y Publication
Researcher Affiliations
- Service des Maladies du Sang, Hôpital Huriez, CHU Lille, France. xavier_leleu@dfci.harvard.edu
MeSH Terms
- Adolescent
- Adult
- Aged
- Androgens / administration & dosage
- Androgens / adverse effects
- Anemia, Aplastic / diagnosis
- Anemia, Aplastic / drug therapy
- Anemia, Aplastic / mortality
- Animals
- Antilymphocyte Serum / administration & dosage
- Antilymphocyte Serum / adverse effects
- Chromosome Aberrations
- Disease-Free Survival
- Female
- Follow-Up Studies
- Horses
- Humans
- Immunosuppressive Agents / administration & dosage
- Immunosuppressive Agents / adverse effects
- Incidence
- Male
- Middle Aged
- Recurrence
- Remission Induction
- Retrospective Studies
- Survival Rate
- Time Factors
Citations
This article has been cited 3 times.- Fassel H, Sheth S. Bone Marrow Failure in Children: Approach to Diagnosis and Treatment. Indian J Pediatr 2020 Feb;87(2):141-149.
- Shahani S, Braga-Basaria M, Maggio M, Basaria S. Androgens and erythropoiesis: past and present. J Endocrinol Invest 2009 Sep;32(8):704-16.
- Piekarska A, Pawelec K, Szmigielska-Kapłon A, Ussowicz M. The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults. Front Immunol 2024;15:1378432.
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