Comparative Study of Treatment Outcomes of Patients of Aplastic Anemia with Combination Therapy Cyclosporine a + Danazol+ Eltrombopag Versus Cyclosporine a + Danazol + High Dose Romiplostim

Introduction

In aplastic anemia (AA), pancytopenia and hypocellular bone marrow occur without aberrant infiltration or reticulin. Acquired AA frequently comes from an autoimmune attack on hematopoietic stem/progenitor cells, while inherited versions include Fanconi anemia, Dyskeratosis Congenita, etc. Symptoms of peripheral blood cytopenia include tiredness, bruising, and bleeding. Blood counts, bone marrow biopsy, and exclusion of Paroxysmal Nocturnal Hemoglobinuria (PNH) and hypoplastic Myelodysplastic Syndrome (hMDS) establish the diagnosis. Immunosuppressive therapy (IST) and hematopoietic stem-cell transplantation (HSCT) are frequent therapies. However, socioeconomic constraints can limit access. Recently, thrombopoietin receptor agonists (TPO-RAs) such as Eltrombopag and Romiplostim have shown potential in AA hematopoiesis. This pilot trial compared the treatment outcomes of Cyclosporine A + Danazol + Eltrombopag vs. high-dose Romiplostim in patients not choosing HSCT and ATG.

Methodology

The hospital-based open-labeled clinical trial was started after proper registration in the Clinical Trial Registry of India. Patients were allocated into two groups as per their choice. Group A (n=10) received Eltrombopag, Cyclosporine A, and Danazol, while Group B (n=6) received Romiplostim, Cyclosporine A, and Danazol. All consenting adult patients diagnosed with AA were included, and those who had undergone HSCT or had viral infections or significant PNH clones were excluded. The primary outcomes measured were changes in hemoglobin (Hb), total leukocyte count (TLC), and platelet count (PLC) at 3 and 6 months.

Results

This prospective pilot study included 16 newly diagnosed AA patients divided into two groups. Ten patients recruited in Group A had a median age of 42 years, and that of Group B was 58 years [16 -70 years]. 4/10 were females in Group A (40%), and all were males in Group B. At baseline, Group A had median Hb of 5.7gm/dl [2.5-7.2gm/dl], TLC of 1600/cumm [830-3910/cumm] and PLC of 26,000/cumm [4000-45,000/cumm]. For Group B the median baseline Hb was 4.2gm/dl [3.2-6.1gm/dl], TLC of 1250/cumm [800-2100/cumm] and PLC of 12,000/cumm [10000-16,000/cumm]. At the 3-month follow-up, Group A showed a 0.2 times increase in PLC, while Group B was doubled. At the 6-month follow-up, Group A showed a 1.2 times increase compared to 3 months and a 1.6 times increase compared to baseline. Group B showed a 1.2 times increase compared to 3 months and a 3.6 times increase compared to baseline. Hemoglobin and TLC values followed similar trends, with both groups showing increases at 3 and 6 months but without significant differences between the groups. The median counts at 6 months, of Group A was Hb 9.45gm/dl [6.4-12.1gm/dl], TLC 3065/cumm[ 2170-8000/cumm], and PLC 57,000/cumm [16000-140000/cumm]. While the median counts for Group B was Hb 7.8gm/dl[7.2-8.4gm/dl], TLC 4100/cumm [3600-5280/cumm] and PLC 60,000/cumm [ 46,000-70,000/cumm]. However, the change in both groups was not statistically significant on Mann-Whitney Test and Kruskal-Wallis Test. Kolmogorov was also done since the arms were mismatched. Both groups showed a marked reduction in transfusion dependency from 90% and 100% at induction to 20% and 50% at 6 months. Two patients expired in Group A and one in Group B.

Discussion

The study found that both combination therapies led to significant increases in Hb, TLC, and PLC over six months, with no significant differences between Group A and Group B. Financial and logistical constraints often precluded patients from receiving HSCT and ATG therapy. Previous studies have shown varying response rates to these therapies, with some reporting higher efficacy for Romiplostim. The current study, however, did not find a significant difference in response between the two groups. Notably, none of the patients experienced significant adverse effects requiring dose modification or treatment interruption. The injectable nature and higher cost made romiplostim a poorer choice among patients.

Conclusion

This pilot study demonstrated that Eltrombopag and high-dose Romiplostim effectively managed AA patients. Given the socioeconomic barriers, these findings suggest that alternative IST regimens can provide viable and effective treatment options for patients. Further research with larger cohorts and longer follow-ups is needed to validate these results and assess long-term outcomes.

No relevant conflicts of interest to declare.