Immunosuppressive therapy (IST) can improve cytopenias in selected patients with myelodysplastic syndrome (MDS). Between 1998 and 2004, 129 patients with MDS [94 int-1, 13 int-2, 16 low and 6 high International Prognostic Scoring System (IPSS) stage] were given IST on investigational protocols: 116 received ATG 160mg/kg, 42 with additional cyclosporine (CsA); 13 received CsA alone for up to 6 months. Mean follow-up was 47 (range 0.7–120) months. Previously, we reported a score, using HLA-DR15 type, age and duration of red cell transfusion-dependence to segregate patients into high probability (HP), intermediate probability (IP), and low probability (LP) of hematological response to IST. Here we compare survival, response, and leukemic progression in HP and LP/IP NIH IST-treated patients and in non-IST controls enrolled in the International MDS Risk Analysis Workshop (IMRAW) (
). Overall, 29% of NIH IST patients responded: HP patients (median ages for HP and the combined LP/IP] were 49 and 65 yr, respectively) were more likely to respond to IST than LP patients 38/55 (69%) vs 0/71 plus 0/3 IP; p<0.0001) (IP was included in LP group for analysis of survival), with better responses to ATG/CsA than with ATG alone (p=0.015). Neither abnormal cytogenetics nor bone marrow cellularity affected the response rate independent of IPSS int-1 or HP status. Seven of eight (87%) int-1 patients ≤ 60 with trisomy 8 as the sole abnormality and 16/34 with normal cytogenetics (47%) responded to one course of ATG; all 11 int-1 patients with 5q- were >60 years of age and none responded to IST. Marrow cellularity did not influence response to IST. Only two responders relapsed and required re-treatment with ATG; both responded to the second treatment. All but one patient with trisomy 8 increased the percentage of these cells in the marrow following therapy; the two responding monosomy 7 patients showed normal cytogenetics and FISH analysis following response to therapy. Age and IPSS stage were the major factors affecting survival in both treated and untreated patients. The actuarial survival of the 44 IST int-1 patients (median age 54) age ≤ 60 was superior to the untreated 87 int-1 IMRAW patients age ≤ 60 years (median age 48); the projected median survival was >16.4 years for the IST group and 5.2 years for the IMRAW group (p=0.0016), while there was no difference in survival between IST and IMRAW int-1 patients > 60 years of age (p=NS). Leukemic evolution was also decreased in the int-1 IST treated group ≤ 60 years of age compared to the comparable conservatively treated IMRAW group (projected time for 25% pts to develop AML was >16.4 years for IST patients vs 6.9 years for the IMRAW group) (p<0.001). These findings indicate that our IPSS int-1 patients ≤age 60 who received IST had improved survival compared to an untreated historical control group and that combined ATG/CsA gave superior responses compared to ATG alone.
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