Cladribine (2-chlorodeoxyadenosine) in frontline chemotherapy for adult Langerhans cell histiocytosis: A single-center study of seven cases

Figures & data

Figure 1. Histological findings of LCH in the right supraclavicular lymph node of Case 6. (1) The node is extensively infiltrated by coalescent, focally necrotized infiltrates with prevailing sinusoidal distribution (a – LCH infiltrates, b – lymph node tissue, c – necrotic foci, d – lymph node capsule). (2) The lesional cells have bland lobular nuclei frequently with indentations and abundant cytoplasm (a – Langerhans cells with reactive eosinophils, b – eosinophilic abscess with necrosis, c – giant multinucleated cells). The immunohistochemical staining causes brown membrane (3) and brown nuclear and cytoplasmatic (4) colorings. White scale line = 50 μm.

Figure 2. T1 weighted MRI scans of the brain in transverse (left) and sagittal (right) planes after application of contrast agent in Case 2. Due to incipient eyesight deterioration and increased tracer uptake in the occipital region on bone scintigraphy, the patient was sent to MRI which revealed an osteolytic lesion infiltrating the meningeal membranes near the occipital lobe. The function of the centre of vision which is located in the occipital lobe was deteriorated in this patient by intracranial propagation of LCH. After cladribine treatment the infiltration receded, which was followed by a complete vision recovery.

Table I. Main demographic and clinical characteristics of seven patients treated with cladribine.

				Disease extent
Case	Sex	Age at diagnosis (years)	Age at cladribine initiation (years)	multifocal (MF)/multisystem (MS)	Sites involved	Main disease symptoms
1	M	21	31	MS	bones, lungs	bone pains
2	M	25	25	MF	bones	eyesight deterioration (Figure 2)
3	M	33	33	MS	gingiva, hypophysis, skin	diabetes insipidus, painful skin lesions, loss of teeth
4	M	40	40	MS	lungs, skin	recurrent pneumothorax (3 times), skin pruritus
5	M	46	46	MS	bones, ear, gingiva, lungs	left-sided deafness, loss of teeth, dyspnea
6	M	35	35	MS	lungs, lymph nodes, skin	cough, dyspnea, B-symptoms (fever, night sweats, weight loss), pruritus
7	M	34	35	MS	ear, hypophysis, lungs	chronic otitis externa, diabetes insipidus

Table II. An overview of cladribine-based treatment and therapy responses in seven adult patients with LCH.

Case	Peripheral blood stem cell collection* prior to cladribine	Number of cladribine courses		Concomitant treatment	Treatment response	Response duration (months)
		Initial monotherapy	Following combination with cyclophosphamide and dexamethasone
1	–	4	–	–	durable CR	92+
2	yes	4	–	–	durable CR	94+
3	–	4	–	radiotherapy of the perianal skin (20 Gy in 10 fr)	durable CR	48+
4	–	3	3	photochemotherapy of the skin	durable CR	24+
5	–	4	–	radiotherapy of the temporal bone (20 Gy in 10 fr)	durable CR	26+
6	yes	3	3	radiotherapy of the perianal skin (20 Gy in 10 fr)	CR with early relapse	2
7	–	6	–	–	durable CR	15+

*In case of an initially aggressive disease; fr, fractions; CR, complete remission; +, continuation of complete remission.

Figure 3. T1 weighted MRI scans of the brain in coronary (left) and sagittal (right) planes after application of contrast agent in Case 3. The ball-shaped enlargement (infiltration of the hypophysis infundibulum by LCH) fully retreated after cladribine monotherapy.

Table III. Hematological treatment-related toxicities during the cladribine-based treatment.

Case	Beginning of the 1^st cycle				Lowest values during the treatment				Beginning of the last cycle
	Leu	Hb	Thrombo	Lympho	Leu	Hb	Thrombo	Lympho	Leu	Hb	Thrombo	Lympho
1	6.75	145	247	1.68	3.81	129	134	0.56	3.81	129	134	0.56
2	4.68	128	296	0.95	1.60	128	155	0.43	5.93	162	204	1.45
3	7.92	149	242	2.52	3.01	125	167	0.23	5.57	132	206	0.76
4	7.84	160	366	1.11	3.30	148	276	0.37	4.75	151	346	0.90
5	5.32	153	238	1.42	4.64	153	188	0.67	6.68	166	194	0.67
6	8.39	125	589	1.14	5.65	125	175	0.38	5.65	130	175	0.69
7	7.40	147	217	1.76	5.26	133	154	0.25	6.69	142	220	0.25

Leu, leukocytes (normal range: 4–10 × 10⁹ cells/l); Hb, hemoglobin (normal range: 130–176 g/l); Thrombo, thrombocytes (normal range: 150–350 × 10⁹ cells/l); Lympho, lymphocytes (normal range: 0.8–4 × 10⁹ cells/l).