J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://www.thejh.org

Original Article

Volume 11, Number 4, August 2022, pages 131-141

Experiences of a Single Center in One Hundred Ninety-Four Adult Patients With Langerhans Cell Histiocytosis

Figure 1. Histology of LCH in the lungs. Staining with hematoxylin and eosin (H&E, a), CD1a (b), CD207 (Langerin, c). LCH: Langerhans cell histiocytosis.

Figure 2. Mucocutaneous manifestations of LCH with maculopapular brownish exanthema in the area of the anterior sweat groove and in the groin region (a, indicated by arrows) and ulcerative change of the gums (b, indicated by arrows) with already tooth loss. LCH: Langerhans cell histiocytosis.

Figure 3. Reticulonodular compaction (a, indicated by an arrow) and cystic changes (b, indicated by an arrow) especially in the upper and middle lung fields bilaterally in LCH. CT of the thorax native, transverse sections. LCH: Langerhans cell histiocytosis; CT: computed tomography.

Figure 4. Osteolysis due to LCH in the mandible (a, indicated by an arrow) and petrous bone and temporal bone with mastoid (b, indicated by an arrow). CT of the skull native, sagittal and coronal sections. LCH: Langerhans cell histiocytosis; CT: computed tomography.

Figure 5. LCH infiltration of the hypothalamus bilaterally. MRI of the skull (FLAIR, transverse sections) with contrast medium before (a, indicated by an arrow) and 9 months later (b, indicated by an arrow) after cytostatic chemotherapy with high-dose cytarabine and cladribine for 3 months. LCH: Langerhans cell histiocytosis; MRI: magnetic resonance imaging.

**Table 1.** Distribution of the Organs Involved at the Time of Diagnosis
Organs	Single system disease	Multisystem disease	Altogether
Lungs	39 (20.1)	40 (20.6)	79 (40.7)
Bones	62 (32)	50 (25.8)	112 (57.7)
Unifocal	44 (22.7)	18 (9.3)	62 (32)
Multifocal	18 (9.3)	32 (16.5)	50 (25.8)
Skin	15 (7.7)	19 (9.8)	34 (17.5)
Unilocular	7 (3.6)	0	7 (3, 6)
Multilocular	8 (4.1)	19 (9.8)	27 (13, 9)
Oral mucosa	0	6 (3.1)	6 (3.1)
Genital mucosa	2 (1)	3 (1.5)	5 (2.6)
Central nervous system	0	5 (2.6)	5 (2.6)
Pituitary gland	1 (0.5)	29 (14.9)	30 (15.5)
Neurohypophysis	0	18 (9.3)	18 (9.3)
Neuro- and adenohypophysis	1 (0.5)	11 (5.7)	12 (6.2)
Lymph nodes	4 (2.1)	7 (3.6)	11 (5.7)
Spleen	0	1 (0.5)	1 (0.5)
Liver	0	7 (3.6)	7 (3.6)
Gastrointestinal tract	2 (1)	5 (2.6)	7 (3.6)
Esophagus	0	2 (1)	2 (1)
Stomach	0	2 (1)	2 (1)
Colon	2 (1)	1 (0.5)	3 (1.5)
Sclera	1 (0.5)	0	1 (0.5)
Retrobulbar space	0	1 (0.5)	1 (0.5)
Heart	0	1 (0.5)	1 (0.5)
Kidneys	1 (0.5)	1 (0.5)	2 (1)
Adrenal glands	0	1 (0.5)	1 (0.5)

Table 1. Distribution of the Organs Involved at the Time of Diagnosis

Organs

Single system disease

Multisystem disease

Altogether

127 patients, n (%)

67 patients, n (%)

194 patients, n (%)

Lungs

39 (20.1)

40 (20.6)

79 (40.7)

Bones

62 (32)

50 (25.8)

112 (57.7)

Unifocal

44 (22.7)

18 (9.3)

62 (32)

Multifocal

18 (9.3)

32 (16.5)

50 (25.8)

Skin

15 (7.7)

19 (9.8)

34 (17.5)

Unilocular

7 (3.6)

7 (3, 6)

Multilocular

8 (4.1)

19 (9.8)

27 (13, 9)

Oral mucosa

6 (3.1)

Genital mucosa

2 (1)

3 (1.5)

5 (2.6)

Central nervous system

5 (2.6)

Pituitary gland

1 (0.5)

29 (14.9)

30 (15.5)

Neurohypophysis

18 (9.3)

Neuro- and adenohypophysis

1 (0.5)

11 (5.7)

12 (6.2)

Lymph nodes

4 (2.1)

7 (3.6)

11 (5.7)

Spleen

1 (0.5)

Liver

7 (3.6)

Gastrointestinal tract

2 (1)

5 (2.6)

7 (3.6)

Esophagus

2 (1)

Stomach

2 (1)

Colon

2 (1)

1 (0.5)

3 (1.5)

Sclera

1 (0.5)

Retrobulbar space

1 (0.5)

Heart

1 (0.5)

Kidneys

1 (0.5)

2 (1)

Adrenal glands

1 (0.5)

Table 2. Cytostatic Chemotherapy Regimens Used

Chemotherapy (cytostatic drugs)

Evaluable patients (cytostatic pretreated)

Organ involvement (SS, MS)

Therapy response (ORR%)

Median duration, therapy response (months)

MS: multisystem disease; SS: single system disease; ORR: overall remission rate; CR: complete regression; PR: partial regression; SD: stable course or mixed response.

Cladribine

29 (13)

SS 9

PR 22 (76%)

MS 20

SD 6 (21%)

PD 1 (3%)

(ORR 76%)

Cladribine plus cytarabine

4 (1)

SS 1

PR 3 (75%)

MS 3

SD 1 (25%)

(ORR (75%)

Cytarabine

16 (3)

SS 3

PR 7 (44%)

MS 13

SD 5 (31%)

PD 4 (25%)

(ORR 44%)

Etoposide

5 (5)

SS 1

PR 3 (60%)

MS 4

SD 2 (40%)

(ORR 60%)

Methotrexate

12 (4)

SS 8

CR 1 (8%)

MS 4

PR 5 (42%)

SD 5 (42%)

PD 1 (8%)

(ORR 50%)

Vinblastine plus prednisone

14 (2)

SS 6

PR 5 (36%)

MS 8

SD 9 (64%)

(ORR 36%)

Vinblastine plus prednisone plus 6-mercaptopurine

24 (3)

SS 8

CR 2 (8%)

MS 16

PR 8 (33%)

SD 11 (46%)

PD 3 (12%)

(ORR 41%)

Vinblastine plus cyclophosphamide plus 6-mercaptopurine

2 (0)

MS 2

SD 2 (100%)

Vinblastine plus etoposide plus 6-mercaptopruine

2 (0)

SS 1

SD 2 (100%)

MS 1

**Table 3.** Long-Term Effects After Disease and Therapy
Permanent consequences	Patients, n (%)
ECD: Erdheim-Chester disease; LCH: Langerhans cell histiocytosis.
Endocrine dysfunction	36 (18.6)
Neurohypophysis	21 (10.8)
Neuro- and adenohypophysis	15 (7.7)
Pulmonary dysfunction	15 (7.7)
Neurological dysfunction	9 (4.6)
Hearing loss and balance disorders	6 (3.1)
Tooth loss	5 (2.6)
Death	4 (2.1)
LCH/ECD	2 (1)
Therapy induced sepsis	2 (1)
Blindness of one eye	2 (1)
Malignant disease	1 (0.5)
Liver cirrhosis	1 (0.5)
Skin ulcerations	1 (0.5)

Table 3. Long-Term Effects After Disease and Therapy

Permanent consequences

Patients, n (%)

ECD: Erdheim-Chester disease; LCH: Langerhans cell histiocytosis.

Endocrine dysfunction

36 (18.6)

Neurohypophysis

21 (10.8)

Neuro- and adenohypophysis

15 (7.7)

Pulmonary dysfunction

15 (7.7)

Neurological dysfunction

9 (4.6)

Hearing loss and balance disorders

6 (3.1)

Tooth loss

5 (2.6)

Death

4 (2.1)

LCH/ECD

2 (1)

Therapy induced sepsis

2 (1)

Blindness of one eye

2 (1)

Malignant disease

1 (0.5)

Liver cirrhosis

1 (0.5)

Skin ulcerations

1 (0.5)