Drug-induced interstitial lung disease in the treatment of malignant lymphoma as a potential diagnostic marker: a comparison of serum Krebs von Lungen-6 and thymus and activation-regulated chemokine/CC chemokine ligand 17

Figures & data

Figure 1 Demographic characteristics of the study population.

Notes: (A) Pathological diagnosis. The common histological diagnoses were DLBCL (n=17), FL (n=11), MCL (n=3), and others (n=5). Others included AI TL, extranodal marginal-zone B-cell lymphoma MAL T type, and DLBCL transformed from extranodal marginal-zone B-cell lymphoma MAL T type (MAL T-DLBCL). (B) Regimens of the first-line treatment. In this study, 34 of 36 patients with ML received the so-called “CHOP-like” regimen as the first-line chemotherapy. Drug-induced ILD progressed in periods of first-line treatment, and all causative regimens were “CHOP-like.”
Abbreviations: AI TL, angioimmunoblastic T-cell lymphoma; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; IL D, interstitial lung disease; MAL T, mucosa-associated lymphoid tissue; MCL, mantle cell lymphoma; ML, malignant lymphoma; R-B, rituximab and bendamustine; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; R-THP-COP, rituximab, tetrahydropyranyl-adriamycin, cyclophosphamide, vincristine, and prednisolone; THP-COP, tetrahydropyranyl-adriamycin, cyclophosphamide, vincristine, and prednisolone.

Table 1 Patient characteristics (n=36)

Characteristics
Age, mean ± SD, range	69.4 ± 11.9	33–88
Male, n (%)	22	61.10
Smoking, n (%)	16	44.40
Heavy smoking (BI over 600), n (%)	6	16.60
Malignant tumors, n (%)
Past history	9	25.00
Family history	12	33.30
Development of drug induced ILD, n (%)	8	22.20
History of prior ILD, n (%)	1	2.8
Ethnicity (Japanese), n (%)	36	100

Abbreviations: BI, Brinkman Index; ILD, interstitial lung disease.

Figure 2 A comparison of the average concentration of serum TARC/CCL17 and KL-6 before/after the development of drug-induced IL D.

Notes: (A) TARC/CCL17; (B) KL-6. Although no significant difference was observed between the average concentration of the serum TARC/CCL17 level on admission and that after the progression of drug-induced IL D (P=0.439), the average concentration of serum KL-6 after the progression of ILD was significantly higher than that on admission (P=0.0028).
Abbreviations: IL D, interstitial lung disease; KL-6, Krebs von den Lungen-6; TARC/CCL17, thymus and activation-regulated chemokine/CC chemokine ligand 17; NS, not significant.

Figure 3 Radiological subtype and the overall survival of DIL D.

Notes: (A) A radiological subtype of DIL D. Six patients were diagnosed with HP, 1 with DAD, and 1 with AE P. (B) The overall survival of patients with DIL D. The median survival of patients with DIL D was 33.0 months and 1- and 2-year survival rates were 87.5% and 58.3%, respectively.
Abbreviations: AE P, acute eosinophilic pneumonia; DAD, diffuse alveolar damage; DIL D, drug-induced interstitial lung disease; HP, hypersensitivity pneumonitis.

Table 2 Summary of clinical outcome in the patients with drug-induced ILD

Pt ID/age (years)	Radiological subtype of drug-induced ILD	Treatment of ILD	Recovery	Dead/alive	Reason of death	Survival (days)
Pt1/66	DAD	PSL 1.0/kg	Yes	Alive	NR	1,453
Pt2/88	HP	Drug off	Yes	Dead	Heat stroke	994
Pt3/79	HP	PSL 0.5/kg	Yes	Dead	Disease progression	710
Pt4/76	HP	None	Yes	Dead	Pneumonia	531
Pt5/65	AEP	PSL 0.5/kg	Yes	Dead	Hepatic failure	53
Pt6/66	HP	PSL 1.0/kg	Yes	Alive	NR	889
Pt7/75	HP	Drug off	Yes	Alive	NR	801
Pt8/76	HP	None	Yes	Alive	NR	71

Abbreviations: AE P, acute eosinophilic pneumonia; DAD, diffuse alveolar damage; HP, hypersensitivity pneumonitis; IL D, interstitial lung disease; NR, not reported; PSL, prednisolone; Pt, patient.

Table 3 Diagnostic value of measurement of circulating TARC/CCL17 and KL-6

Sensitivity/specificity/prevalence	TARC/CCL17	KL-6	Chi-squared test
Sensitivity	50.0% (4/8)	50.00% (4/8)
From the serum before ILD	20.00% (1/5)	16.70% (1/6)
From the serum after ILD	50.0% (3/6)	57.10% (4/7)
Specificity	80.0% (12/15)	94.40% (17/18)	NS (P=0.465)
Prevalence rate	34.8% (8/23)	30.80% (8/26)

Abbreviations: IL D, interstitial lung disease; KL-6, Krebs von den Lungen-6; TARC/CCL17, thymus and activation-regulated chemokine/CC chemokine ligand 17; NS, not significant.

Figure 4 The ROC curves of TARC/CCL17 and KL-6 as a surrogate diagnostic marker of DIL D. AUC of TARC/CCL17 and KL-6 detecting DIL D proved to be nearly equal.

Abbreviations: AUC, area under the curve; DIL D, drug-induced interstitial lung disease; KL-6, Krebs von den Lungen-6; ROC, receiver operating characteristic; TARC/CCL17, thymus and activation-regulated chemokine/CC chemokine ligand 17; NS, not significant.

Figure S1 The schema of DIL D screening using chest CT scan.

Abbreviation: DIL D, drug-induced interstitial lung disease.