Tables

Supplementary Table 1. Characteristics and outcomes of studies that compared first ATG treatments

Design / ATG preparation / ATG Dose / n / Early mortality
at 3 months (n) / Overall response
at 6 months (n) / Decision
Xie,
2014 [1] / Retrospective / Thymoglobulin / 3.75 mg/kg/day
for 5 days / 29 / N/A / N/A / Excluded – study of ATG-fresenius
ATG fresenius / 5 mg/kg/day
for 5 days / 24 / N/A / N/A
Jeong,
2014 [2] / Retrospective / Thymoglobulin / 2.3-5.0 mg/kg/day
for 5 days / 158 / 4 / 87 / Included
Lymphoglobuline / 15 mg/kg/day
for 5 days / 297 / 3 / 178
Shao,
2013 [3] / Retrospective / Thymoglobulin / 3.5-5.0 mg/kg/day
for 5 days / 175 / 11 / 99 / Included
Lymphoglobuline / 12 mg/kg/day
for 5 days / 29 / 6 / 13
ATG fresenius / 3.5-5.0 mg/kg/day
for 5 days / 94 / 15 / 24
Yoshimi,
2013 [4] / Retrospective1 / Thymoglobulin / 3.75 mg/kg
for 5days / 32 / 0 / 11 / Included
Lymphoglobuline / 15 mg/kg
for 8 days / 96 / 4 / 62
Shin,
2013 [5] / Retrospective / Thymoglobulin / 2.5 mg/kg
for 5days / 53 / 5 / 24 / Included
Lymphoglobuline / 15 mg/kg
for 5 days / 46 / 2 / 18
Vallejo,
2013 [6] / Retrospective / Thymoglobulin / 2.5-4 mg/kg/day
for 5days / 165 / 20 / N/A / Included
Lymphoglobuline / 15 mg/kg/day
for 5 days / 47 / 2 / N/A
Marsh,
2012 [7] / Prospective Cohort / Thymoglobulin / 3.75 mg/kg
for 5days / 35 / 2 / N/A / Included
Lymphoglobuline / N/A / 105 / 3 / N/A
Scheinberg,
2011 [8] / RCT / Thymoglobulin / 3.5 mg/kg
for 5days / 60 / 3 / 22 / Included
ATGAM / 40 mg/kg
for 4days / 60 / 0 / 41
Afable,
2011 [9] / Retrospective1 / Thymoglobulin / 3.5 mg/kg/day
for 5days / 20 / 2 / 9 / Included
ATGAM / 40 mg/kg/day
for 4days / 67 / 6 / 39
Serefhanoglu,
2011 [10] / Retrospective / Thymoglobulin / 2.5-5 mg/kg/day
for 5days / 7 / 1 / N/A / Included
Lymphoglobuline / 15 mg/kg/day
for 5 days / 9 / 2 / N/A
ATG fresenius / 3-5 mg/kg/day
for 5 days / 8 / 4 / N/A
Hochsmann,
2011 [11] / Retrospective / Thymoglobulin / 3.5 mg/kg/day
for 5days / 56 / N/A / N/A / Excluded – Study of ATG-fresenius
ATG fresenius / N/A / 5 / N/A / N/A
Biju,
2011 [12] / Retrospective / ATGAM / 40 mg/kg/day
for 4 days / 131 / N/A / N/A / Excluded – Refered to neither survival rate nor response rate
Lymphoglobuline / 15 mg/kg/day
for 5 days / 191 / N/A / N/A
Yamazaki,
2011 [13] / Retrospective / Thymoglobulin / N/A / 57 / N/A / N/A / Excluded – Refered to neither survival rate nor response rate
Lymphoglobuline / N/A / N/A / N/A / N/A
Pawelec,
2011 [14] / Retrospective / Thymoglobulin / 3.75 mg/kg/day
for 5 days / 55 / N/A / 28 / Included
Lymphoglobuline / 15 mg/kg/day
for 5 days / 49 / N/A / 34
Halkes,
2011 [15] / Retrospective / Thymoglobulin / 5 mg/kg/day
for 5 days / 9 / N/A / 3 / Included
Lymphoglobuline / N/A / 13 / N/A / 9
Atta,
2010 [16] / Retrospective / Thymoglobulin / 2.5 mg/kg
for 5days / 29 / 7 / 10 / Included
Lymphoglobuline / 15 mg/kg
for 5 days / 42 / 5 / 25
Chang,
2010 [17] / Retrospective / Thymoglobulin / 3.5 mg/kg/day
for 5days / 33 / N/A / 16 / Included
ATGAM / 40 mg/kg/day
for 5days / 29 / N/A / 15
Feng,
2010 [18] / Retrospective / Rabbit ATG2 / N/A / 25 / N/A / N/A / Excluded – Did not report the ATG preparations
Horse ATG2 / N/A / 27 / N/A / N/A
Zheng,
2006 [19] / RCT / ATG fresenius / 5 mg/kg
for 5 days / 32 / 6 / N/A / Excluded – Study of ATG fresenius
Lymphoglobuline / 12 mg/kg/
for 4days / 30 / 2 / N/A
Maschan,
2004 [20] / RCT / ATG fresenius / 40 mg/kg / 17 / 0 / N/A / Excluded – Study of ATG fresenius
ATGAM / 160 mg/kg / 15 / 1 / N/A

RCT: randomized controlled trial; N/A: not available

1 Retrospective studies with historical controls

2 Type of ATG was not shown

Supplementary Table 2. Sensitivity analysis of the early mortality rate at 3 months

Omitted Study / Model / Relative Risk / 95% confidence interval / P value
Jeong,
2014 / Fixed effect model / 1.28 / 0.81-2.02 / 0.29
Random effects model / 1.24 / 0.61-2.53 / 0.56
Shao,
2013 / Fixed effect model / 1.90 / 1.13-3.21 / 0.016
Random effects model / 1.87 / 1.09-3.20 / 0.023
Shin,
2013 / Fixed effect model / 1.30 / 0.83-2.05 / 0.25
Random effects model / 1.27 / 0.62-2.61 / 0.52
Vallejo,
2013 / Fixed effect model / 1.19 / 0.76-1.88 / 0.44
Random effects model / 1.21 / 0.60-2.43 / 0.60
Yoshimi,
2013 / Fixed effect model / 1.45 / 0.93-2.25 / 0.10
Random effects model / 1.43 / 0.72-2.83 / 0.31
Marsh,
2012 / Fixed effect model / 1.33 / 0.85-2.09 / 0.21
Random effects model / 1.29 / 0.63-2.65 / 0.49
Afable,
2011 / Fixed effect model / 1.39 / 0.88-2.19 / 0.16
Random effects model / 1.38 / 0.66-2.89 / 0.40
Scheinberg, 2011 / Fixed effect model / 1.27 / 0.81-1.98 / 0.29
Random effects model / 1.24 / 0.64-2.40 / 0.53
Serefhanoglu, 2011 / Fixed effect model / 1.41 / 0.90-2.20 / 0.13
Random effects model / 1.42 / 0.70-2.87 / 0.33
Atta,
2010 / Fixed effect model / 1.26 / 0.78-2.04 / 0.35
Random effects model / 1.25 / 0.59-2.66 / 0.56

Figures

Supplementary Figure 1. Subgroup analysis of (a) early mortality rate at 3 months and (b) overall response rate at 6 months with Thymoglobulin vs. Lymphoglobuline/ATGAM.

Studies are grouped according to the horse ATG preparation as Lymphoglobuline or ATGAM. Results are shown in forest plots.

Supplementary Figure 2. Meta-regression analysis of early mortality.

(a) Patient median or mean age (b) ANC before ATG administration, (c) ARC before ATG administration, (d) Percentage of male patients, (e) Platelet count before ATG administration, (f) Percentage of VSAA patients.

ANC: absolute neutrophil count; ARC: absolute reticulocyte count; ATG: antithymocyte globulin; VSAA: very severe aplasticanemia

Supplementary Figure 3. Forest plot for early mortality at 3 months with the studies which include only new cohort.

Meta-analysis of early mortality at 3 months with the studies which includes only patients who were treated after 2000.


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