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Immunosuppressive therapy in myelodysplastic syndromes
A pre-specified subgroup analysis showed that the ORR was highest with ATG + Etanercept at 58.1% (95%CI: 37.8-75.9%; I2=27%), followed by other IST at 52.5% (95%CI: 30.4-73.7%; I2=76%), CsA at 47.3% (95%CI: 33- 62%; I2=7%), ATG at 37.4% (95%CI: 29.1-46.6%; I2=11%), and ATG + CsA at 35.2% (95%CI: 18.9-55.9%; I2=86%), respectively (Figure 2A).
Complete remission rates were reported by 16 studies (Figure 2B). Overall, the CR rate was 12.5% (95%CI: 9.3- 16.6%). Heterogeneity among the various studies was low, with a Cochran’s Q statistic of 17 (P=0.32) and an I2 statistic of 12%.
A pre-specified subgroup analysis for patients, who received ATG, ATG + CsA, ATG + Etanercept, CsA and other IST, showed that the CR was 9.2% (95%CI: 4.0- 19.6%; I2=0%), 12.6% (95%CI: 8.6-18.1%; I2=0%), 10.2% (95%CI: 3.3-27.8%; I2=2%), 4.9% (95%CI: 1.0-21.1%; I2=0) and 22.1% (95%CI: 10.6-40.4%; I2=46%), respec- tively (Figure 2B).
Hematologic improvement and transfusion independence
Erythroid hematologic improvement rates were report- ed by 16 studies (Figure 3A). Overall, the HI-E rate was 41.8% (95%CI: 33.3-50.8%). Heterogeneity among the various studies was high, with a Cochran’s Q statistic of 53.1 (P<0.001) and an I2 statistic of 72%.
A pre-specified subgroup analysis showed that the HI-E rate was highest with ATG + Etanercept at 51.8% (95%CI: 29.8-73.1%; I2=42%), followed by CsA at 50% (95%CI: 32.7-67.3%; I2=0), ATG + CsA at 44.8% (95%CI: 14.3-79.8%; I2=92%), other IST agents at 43.1% (95%CI: 24.0-64.4%; I2=70%), and ATG at 31.7% (95%CI: 20.3- 45.8%; I2=29%), respectively (Figure 3A).
The rates of TI were reported by 14 studies (Figure 3B).
Overall, the TI was 33.4% (95%CI: 25.1-42.9%). There was a significant heterogeneity among the various studies, with a Cochran’s Q statistic of 35.1 (P=0.001) and an I2 sta- tistic of 63%.
A pre-specified subgroup analysis showed that the TI rate was highest with CsA at 44.8% (95%CI: 28.8-61.9%; I2=9%) followed by ATG + Etanercept at 38.5% (95%CI: 17-65.6%; I2=0%), ATG at 25.2% (95%CI: 13.3-42.5%; I2=50%), ATG + CsA at 28.4% (95%CI: 10.0-58.6%; I2=86%), and other IST at 25.9% (95%CI: 11.7-48.0; I2=27%), respectively (Figure 3B).
Acute myeloid leukemia progression rate and adverse events
The rates of progression to AML were reported by 11 studies (Figure 4). Overall, the AML progression rate per person year of follow up was low (8.6%; 95%CI: 3.3- 13.9%). There was a significant heterogeneity among the various studies, with a Cochran’s Q statistic of 45.2 (P<0.001) and an I2 statistic of 78%. Pre-specified sub- group analysis showed an AML transformation rate per patient year of 13.7% (95%CI: 1.4-25.9%; I2=73%), 13.5% (95%CI: 0-31.3; I2=91%), 7.0% (95%CI: 0-22.4%; I2=71%), and 6.7% (95%CI: 0-13.5%; I2=0%) for patients who received ATG, ATG + CsA, CsA and other IST, respectively.
Only 10 of the 22 studies reported grade 3/4 side effects.16,18,19,30,32,35,37,39-41 The data included in these papers were insufficient to conduct any further meta-analysis on the safety of IST in LR-MDS.
Sensitivity analysis
Separate sensitivity analyses for ORR, HI, TI and AML progression rate showed that exclusion of any one study did not change the overall effect direction but did change
AB
Figure 3. Rate of hematologic improvement in the erythroid lineage (HI-E) and red blood cell transfusion independence. Forest plots of odds ratios (squares, pro- portional to study weights used in meta-analysis, 95% confidence intervals) for various forms of immunosuppressive therapy (IST), with the summary measure (center line of diamond) and associated confidence intervals (lateral tips of diamond) for hematologic improvement in the erythroid lineage (HI-E) and achievement of red blood cell transfusion independence (TI) are shown in panel (A) and (B), respectively.
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