Clinical Response to Oral Low-Dose Cyclosporin in Myelodysplastic Syndrome: Study of 31 Cases from India.

Aim: This prospective, single arm, institutional study was designed to evaluate the response to Cyclosporin A (CsA) in adult patients with primary MDS with cytopenias.

Material and Methods

Patients aged 18 years or more, with primary MDS, normal renal and hepatic functions were eligible for inclusion after informed consent. The diagnosis of MDS was based on demonstrating features of dysplasia in one or more cell lines on peripheral blood smear and bone marrow examination. The criteria for cytopenia were one or more of the following: hemoglobin <10 g/dl; platelets <100x10⁹/L; absolute neutrophil count <1.5x 10⁹/L. Secondary causes of MDS were excluded by clinical and laboratory assessment. Other exclusion criteria were: response to therapeutic trial of vitamin B12 and folic acid, HIV infection and diagnosis of PNH. MDS was considered hypocellular if bone marrow (BM) cellularity was <30%, and in such cases dysplastic features had to be present in more than one cell line, so as to exclude hypoplastic anemia. CsA was used in doses of 3–5 mg/kg/day in 2 divided doses. Response was assessed using the International Working Group criteria for MDS (Cheson et al in Blood 2000, 96:3671–74), after a minimum follow up of 3 months.

Results

A total of 31consecutive patients with MDS who fulfilled inclusion criteria were assessed. Patient characteristics were: median age 38 years (range 20–70); male18, female 13; MDS type: RA-24, RAEB-7; BM: hypocellular-8 (25.8%), normocellular-19 (61.3%), hypercellular-4 (12.9%); transfusion dependent - 26 (83.8%).

Response

There were no remissions. Hematological improvement (HI) was seen in different cell lines. Erythroid response (HI-E) was seen in 18 (58%):

• major response in 10 (32.2%); type- 8 RA, 2 RAEB; cellularity - hypocellular 4, normocellular 6

• minor response in 8 (25.8%); type- 7 RA, 1 RAEB; hypercellular-1, hypocellular-1, normocellular-6 and

• no response in 13 (41.9%); type RA- 9, RAEB-4; hypocellular- 3, normocellular-7, hypercellular-3.

In terms of type of MDS, response occurred in 3/7 (42.8%) of RAEB (major in 2, minor in 1) and 15/24 (62.5%) of RA (major 8, minor 7). Neutropenia at onset was present in 14/31 (45.1%) patients only. Of these, neutrophil response (HI-N) major was seen in 1 (RA, hypocellular) who also showed major erythroid response. Thrombocytopenia at onset was present in 21/31 (67.7%) patients only. Of these, platelet response (HI-P) major was seen in 1 (RA, normocellular) and minor response was seen in 1 (RA, normocellular) and both also showed erythroid response. Median interval between diagnosis and treatment was 1 month (range 1–6). Median length of treatment: was 11 months (range 4–46). Effect in responders was seen in median of 3 months (range 1–6). There were no delayed responses seen after 6 months therapy. Relapse occurred in 9 patients. Two relapsed within 1 and 2 months of stopping treatment. 7 patients relapsed while on treatment at a median time of 6 months. There was no statistically significant difference in responses according to the type of MDS or BM cellularity using the Chi square test (p > 0.05).

Conclusion: Anemia improved in 58% patients of MDS (RA and RAEB) and was sustained in 29% cases, irrespective of bone marrow cellularity. Further experience is needed to determine the duration of treatment, as relapses can occur both during therapy and on cessation of cyclosporin.