Abstract
Immunosuppressive therapy (IST) can improve cytopenias in selected patients with myelodysplastic syndrome (MDS). Between 1998 and 2004, 133 patients with MDS (FAB classification RA, RA, or RARS ) were enrolled in NHLBI IST protocols: 74 received ATG (Pharmacia, 40mg/kg x 4 days); 43 received a combination of ATG and CsA Fourteen received cyclosporine (CsA) to maintain levels above 100 ng/ml for up to 6 months. Average follow-up was 41 months (range 1 week to 10 years). Previously, we reported that responses to ATG alone were most likely in HLA DR15 individuals of younger age and with a shorter duration of red cell transfusion-dependence. We applied a score based on these factors to assign patients into high probability (HP) and low probability (LP) of response to immunosuppression. Here, we use the score to analyze effectiveness of different IST and compare survival, response, and leukemic progression in HP and LP patients. Patients with HP were more likely to respond to any IST schedule than were patients with LP (85% vs 8%; p<0.0001) and they had longer survival when compared to LP patients (90% vs 38% alive at 3 years; P<0.0001). There were no differences in response or survival between HP patients treated with ATG or with ATG/CsA; CsA-alone treated patients were too few for survival evaluation. Other factors positively affecting survival were response to therapy (p=.0004) and female sex (p=0.03). Neither bone marrow cellularity nor cytogenetics independently affected response or survival; patients with monosomy 7 and 5q- were in the LP group while patients with trisomy 8 predominated in the HP group. In general, patients with trisomy 8 and 5q- survived comparably to patients with normal cytogenetics, but patients with monosomy 7 had statistically shorter survival (p=0.007) than patients with normal cytogenetics or trisomy 8. The scoring system further segregated 95 patients within IPSS int-1 into a HP group with 92% 3 year survival vs 39% for LP patients (p<.0001). Mortality in the HP group was a consequence of cytopenias, while most deaths in the LP were from leukemia: only 2/50 (4%) of patients in the HP group developed leukemia compared with 30% of LP patients followed for a mean of 57 months (hazard ratio = 11; 95% CI 2.566 to 12.18; p< P<0.0001). These findings suggest that immunological characteristics may be independent factors determining the outcome of IST in patients with MDS.
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