Aplastic Anemia, Pesticide Exposure and Response to Cyclosporine Monotherapy: A Single Institution Case Controlled Study

Introduction:The present study is a prospective, hospital-based, case-controlled study of 19 patients of acquired Aplastic Anaemia (AA) from the SMS Medical College Hospital, Jaipur, India.

Patients & Methods:All newly diagnosed patients of Aplastic Anaemia over a one year period starting from Jan 2005 were included in the study. Detailed demographic parameters including a careful evaluation for pesticide exposure, haematological profile, serum organochlorine levels and response to oral Cyclosporine-A (Cyc-A) were recorded as per a preset Performa. Patients were followed for a minimum of 12 months. Patients receiving stem cell transplantation (SCT) and anti-thymocyte globulin (ATG) were excluded from the study. Serum quantitative and qualitative estimation of organochlorine pesticide levels by gas chromatography were done in all patients at study entry and compared with age and sex matched normal control.

Observations & Results:

1. Of the 19 patients included in the study, 15 (78%) were males and the mean age was 23 years (range 7 to 64 years) in the study.

2. Thirteen of the 19 patients (68.4%) were from rural versus urban habitat and 9/19 (47.4%) gave a history of pesticide exposure. All these were from rural background.

3. Six patients (31.6%) had non-severe AA, 9/19 (47.4%) had severe AA and 4/19 (21%) had very severe AA.

4. Overall response to Cyc-A at 3 months was 47.4% [complete response (CR) 10.6%] and at 6 months was 47.4% (CR 21.1%).

5. Non-severe AA patients had a response rate of 83.3% versus 33.3% in the severe AA and 25% in the very severe AA group.

6. Cyc-A was generally well tolerated with mild toxicity. No patient was taken off the drug because of toxicity. No patient required serum Cyc-A level monitoring.

7. Serum organocholorine levels were significantly higher (p<0.005) in the AA patients (mean 0.35 ppm) versus controls (0.22 ppm).

8. Mean serum organoclorine levels appear to correlate with the severity of AA.

9. Patients with higher serum organochlorine levels were less likely to respond to Cyc-A therapy.

Conclusions:Even though this is a relatively small, single-institution study, the following conclusions can be drawn:

1. Single agent Cyc-A can produce a response in close to half of AA patients within 3 months of starting treatment.

2. Considering the ease of administration and the low toxicity, Cyc-A could be considered as initial therapy in all patients of AA in a resource-limited setting (as compared to ATG and SCT).

3. Pesticide exposure may play a role in the aetiopathogenesis of AA, particularly in patients with occupational exposure to the agent.

4. Pesticide exposure and elevated serum pesticide levels may identify patients of AA who will not respond to immunotherapy (Cyc-A).