Clinico-pathological profile and treatment patterns of immune mediated aplastic anemia in resource constrained settings – an analysis from the aplastic anemia registry of India

Abstract

Abstract Introduction: The Aplastic Anemia Registry of India was initiated by a group of hematologists representing major institutions in the country to collect data on the clinic-pathological profile and treatment outcomes of aplastic anemia. IRB approval was obtained from each institution. Methodology: Data on consecutive patients were collected which included demographic details, clinical symptoms at presentation, laboratory investigations including blood counts, viral serology, liver and renal function tests, serum LDH, presence of PNH clone, stress cytogenetics, NGS if available and bone marrow studies. Data was also collected on the various lines of treatment that the patient undertook, follow up and final outcomes at last follow up. A cloud based software was used for data entry and storage. Results: A total of 2869 patients were seen at 8 participating institutions between 2013 and 2024. Patients with a diagnosis of inherited bone marrow failure was excluded from this analysis. The median age at diagnosis was 36 years (range: 1- 89). There were 409 children aged < 15 years [14.2%]. This included 1722 males and 1147 females. Anemia was the predominant symptom in 88.3% while bleeding was seen in 44.3% and fever in 41.3%. Gum bleeding, menorrhagia and epistaxis were the main sites of bleeding. A history of preceding jaundice was noted in 108 [3.7%]. Based on the modified Camitta criteria, 976 patients [34%] were diagnosed to have non-severe aplastic anemia [NSAA], 1452 [50.6%] had severe aplastic anemia [SAA] while 441 [15.4%] had very severe aplastic anemia [VSAA]. A PNH clone was detected in 13.6% of patients tested. The median number of lines of treatment received was 2 [range: 1-4]. First line treatment consisted of androgens [Danazol/Stanazolol] in 50.2% followed by Cyclosporine [CSA] in 38.8%, ATG in 6.9% and BMT in 2.4%. About 15% of these patients were on combination therapy – Cyclosporine with Danazol or Cyclosporine with Eltrombopag. As second line treatment, Cyclosporine was mainly used [50.2%] followed by androgens [22.9%], TPO agonists [14.1%], ATG in 7.7% and BMT in 2.6%. TPO agonists were the main agents used in both 3rd and 4th line [34 and 31% respectively], followed by androgens [14 and 21%], Cyclosporine [21 and 10%] and ATG [10 and 16%]. The overall response rate was 33% with androgens, 38% with Cyclosporine, 58.4% with ATG and 68.2% with BMT. Responses were seen in 60.5% of patients with NSAA, 45.6% with SAA and 28.4% with VSAA. The overall survival was 70.5% with NSAA, 60.9% with SAA and 42.5% with VSAA Conclusions: Majority of patients [>65%] in India present to the hospital with Severe or Very Severe aplastic anemia. Androgens and Cyclosporine continue to remain the mainstay of treatment though increasingly TPO agonists are being used in the relapsed refractory setting. Strategies to improve access to curative treatment options such as ATG and BMT need to be explored.