VitalMatch · Data summary

Scleroderma does not shorten life after lung transplant. It front-loads the risk.

Recipients with systemic sclerosis survive as long as everyone else once age is accounted for. Their excess risk sits in the first year: more severe graft dysfunction, more early rejection, longer admissions. No regimen can be shown to be better for them specifically, but the one associated with better survival in everyone, tacrolimus rather than cyclosporine, shows the same association in them.

Source: OPTN/UNOS STAR, Dec 2025 release · 42,925 adult first lung transplants since May 2005 · 819 with scleroderma · question posed by A. Iacono

1.01adjusted hazard ratio for death, scleroderma vs not

95% CI 0.91–1.12, centre-stratified, 21,540 deaths. In the first year alone: 1.21 (1.00–1.47). After it: 0.95 (0.84–1.07).

01 · The data

1.83 million recorded values from four registry tables

1,825,759

recorded values analysed

5.6M

data cells read, blanks included

258,346

records across 4 STAR tables

127

registry variables used

188,658

patient-years of follow-up, 21,540 deaths

819

scleroderma recipients: 432 ILD, 385 PH

STAR table	Records in registry	Records analysed	Variables	Values recorded	Cells read
THORACIC_DATA Transplant record	237,532	42,925	32	1,226,185	1,373,600
DECEASED_DONOR_DATA Donor age, smoking	316,248	42,909	2	85,818	85,818
THORACIC_IMMUNO_DISCHARGE_DATA Discharge immunosuppression	163,775	42,925	91	280,212	3,906,175
THORACIC_FOLLOWUP_DATA Follow-up forms (BOS)	1,174,689	129,587	2	233,544	259,174
Total		258,346	127	1,825,759	5,624,767

A value is a non-missing cell of a variable read, in a record that belongs to the analysis. Cells read counts blanks too, which matters for the immunosuppression form: there a blank means “not given”, so 3,906,175 cells carry information although only 280,212 record a drug. Linkage keys are counted once. Core fields are near-complete (age, sex, procedure, centre 100%; survival time 98.7%; ischaemic time 97.2%). The weak point is 72-hour blood gases (PaO₂ 42% complete), so severe PGD is gradeable in only part of the cohort.

02 · Survival

The curves track each other for a decade

Patient survival, Kaplan–Meier at yearly intervals Scleroderma No scleroderma IPF

Years after transplant. Five-year survival 63.0% with scleroderma, 59.0% without, 56.7% for IPF.

Scleroderma vs comparison	Hazard ratio (95% CI)	p	Deaths
Overall, unadjusted	0.89 (0.80–0.98)	0.02	21,540
Overall, adjusted + centre strata	1.01 (0.91–1.12)	0.80	21,540
First year only	1.21 (1.00–1.47)	0.05	4,920
After year 1, if alive at 1 year	0.95 (0.84–1.07)	0.41	16,620
Graft survival, adjusted	0.98 (0.89–1.09)	0.75	22,436
SSc-ILD vs IPF, adjusted	1.03 (0.85–1.26)	0.76	8,499
SSc-PH vs IPAH, adjusted	0.96 (0.83–1.12)	0.63	647

The crude advantage is age. Scleroderma recipients are a median 53 years old against 61. After adjustment there is no difference overall, and none against the disease-matched comparators. The hazard is not flat: a borderline excess in year one, nothing after. That is the pattern the last UNOS analysis (through 2012) and single-centre series described, and it holds here in 819 recipients, although the first-year excess is borderline.

03 · Where the risk is

The first admission is harder

Early outcomes, % of recipients Scleroderma No scleroderma

Outcome	SSc	No SSc	Adjusted RR (95% CI)	p
Severe PGD 72h	42.2%	32.4%	1.26 (1.14–1.41)	<0.001
Acute rejection	10.6%	7.3%	1.31 (1.08–1.59)	0.007
Stay >30 days	33.0%	24.1%	1.20 (1.09–1.32)	<0.001
Dialysis	9.8%	7.3%	1.11 (0.90–1.37)	0.32
Treated rej. 1y	22.0%	22.7%	0.99 (0.79–1.23)	0.90

Severe primary graft dysfunction, acute rejection before discharge and admissions over 30 days are all more common after adjustment. Dialysis before discharge, the renal-crisis concern, is not significantly raised. By one year, treated rejection is identical. Severe PGD was gradeable in 415 scleroderma and 15,526 other recipients.

04 · Chronic rejection

Bronchiolitis obliterans is not more common

BOS grade ≥1, cumulative incidence with death competing Scleroderma No scleroderma IPF

Years after transplant. Transplants before July 2019, follow-up to 30 June 2020, when the field was discontinued.

Cause-specific hazard ratio 0.88 (0.74–1.05); SSc-ILD vs IPF 0.75 (0.60–0.93). The obvious artefact is ruled out: scleroderma recipients are reported on as often as anyone (94.3% vs 94.9% with a follow-up form; 1.46 vs 1.52 forms per patient-year). Read it as “not higher”, not “protective”: grading is centre-reported and the successor CLAD fields are not in this release.

05 · Immunosuppression

Same drugs as everyone else, and the same associations

At discharge	SSc	No SSc	SSc 2005-2011	SSc 2012-2019	SSc 2020+
IL-2RA induction	65.4%	64.2%	29%	64%	84%
Depleting induction	15.9%	9.8%	33%	19%	5%
No induction	18.6%	26.0%	38%	17%	11%
Tacrolimus	94.2%	93.1%	·	·	·
Cyclosporine	2.3%	3.6%	·	·	·
Mycophenolate	86.0%	82.7%	62%	92%	92%
Azathioprine	7.3%	11.5%	23%	4%	3%

Depleting induction in scleroderma fell from 33% to 5% across eras while IL-2 receptor antagonists rose to 84%.

Regimen and survival Scleroderma No scleroderma

Maintenance comparisons use a 90-day landmark to avoid immortal-time bias. Scleroderma models: centre-clustered errors, reduced adjustment set; others: full adjustment, centre strata.

Comparison	SSc HR	SSc deaths	No SSc HR	Interaction p
Cyclosporine vs tacrolimus	1.94 (1.21–3.10)	327	1.34 (1.24–1.44)	·
Depleting induction vs none	1.18 (0.91–1.55)	364	0.88 (0.83–0.93)	0.49
IL-2RA induction vs none	0.98 (0.75–1.29)	364	0.94 (0.91–0.98)	0.77
Azathioprine vs mycophenolate	1.07 (0.70–1.64)	327	0.95 (0.90–1.00)	0.34

Tacrolimus is the one consistent signal. Among recipients alive at 90 days, cyclosporine is associated with higher mortality in scleroderma (1.94 (1.21–3.10), only 19 patients and 12 deaths) and in everyone else (1.34 (1.24–1.44)), matching a randomised trial in which cyclosporine doubled the risk of BOS (Treede 2012). For induction and the antimetabolite, scleroderma does not modify the association (interaction p = 0.49, 0.77, 0.34).

06 · The question asked

What regimen optimises outcome?

No data, including these, identify a regimen that is better for scleroderma specifically. No trial or registry study has compared regimens within scleroderma lung recipients, and here a within-scleroderma difference would need a hazard ratio of about 1.5 to be detected. What the registry supports:

• Tacrolimus over cyclosporine: consistent in scleroderma, in other recipients, in trial and registry evidence.
• Standard induction: associated with modestly better survival overall (0.94 (0.91–0.98) IL-2RA; 0.88 (0.83–0.93) depleting), with no sign scleroderma differs. No basis to prefer depleting agents; within scleroderma they come with more treated rejection (1.69 (1.21–2.35)), most likely because they go to higher-risk recipients.
• Mycophenolate or azathioprine: no survival difference either way.
• Concentrate on the first year: that is where scleroderma-specific risk sits, and perioperative care is where a difference could be made.

Not answerable from STAR: steroid dose and renal crisis (the low-dose advice is expert opinion), calcineurin-inhibitor levels and kidney-sparing strategies, and reflux, dysmotility and fundoplication.