Efficacy of single-agent cytarabine in adult langerhans cell histiocytosis: Short report and summary of treatment data for a rare disease

Suvir Singh; Jagdeep Singh; Davinder Paul; Kunal Jain

doi:10.4103/joah.joah_5_21

CASE REPORT

Year : 2021 | Volume : 12 | Issue : 4 | Page : 220-223

Efficacy of single-agent cytarabine in adult langerhans cell histiocytosis: Short report and summary of treatment data for a rare disease

Suvir Singh¹, Jagdeep Singh², Davinder Paul², Kunal Jain²
¹ Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
² Department of Medical Oncology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission	25-Jan-2021
Date of Decision	11-Apr-2021
Date of Acceptance	17-Apr-2021
Date of Web Publication	18-Jan-2022

Correspondence Address:
Dr. Suvir Singh
Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College, Ludhiana, Punjab
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/joah.joah_5_21

Abstract

Langerhans Cell Histiocytosis (LCH) in adults is rare and has little prospective data to guide therapy. We describe a 36 year old gentleman who presented with a three-month history of isolated cervical lymphadenopathy, from which excision biopsy revealed sheets of large, atypical cells 10-15 um in size, with indented nuclei and fine chromatin along with eosinophilic microabscesses. Immunohistochemistry was positive for CD3, CD20, CD68, CD1a, S100, CD4, Langerin (CD207) and CD45 with a Ki67 index of 10%. PET scan showed FDG-avid uptake in left mastoid air cells, which was confirmed by MRI to indicate bony involvement with disease. Bone marrow and CSF were normal. He was diagnosed as multisystem LCH without risk organ involvement and initiated on single agent cytarabine at 100 mg/m2 five days a month. A PET scan after three cycles showed near complete metabolic resolution. He has completed six cycles of the same and is asymptomatic. He is planned for continuation of Cytarabine for another of 12 to 14 months. Single agent cytarabine appears safe and effective for adult patients with LCH. We provide a short summary of available data: compilation of prospective data will further clarify the utility of this regimen in adult patients with LCH.

Keywords: Blood, cancer, Langerhans cell histiocytosis, lymphoma

How to cite this article:
Singh S, Singh J, Paul D, Jain K. Efficacy of single-agent cytarabine in adult langerhans cell histiocytosis: Short report and summary of treatment data for a rare disease. J Appl Hematol 2021;12:220-3

How to cite this URL:
Singh S, Singh J, Paul D, Jain K. Efficacy of single-agent cytarabine in adult langerhans cell histiocytosis: Short report and summary of treatment data for a rare disease. J Appl Hematol [serial online] 2021 [cited 2023 Feb 3];12:220-3. Available from: https://www.jahjournal.org/text.asp?2021/12/4/220/335945

Introduction

Langerhans cell histiocytosis (LCH) is a clonal myeloid malignancy characterized tissue lesions consisting of dendritic cell proliferation and an accompanying inflammatory infiltrate.^[1] It is a rare disorder with an incidence of 3–5 cases per million in children and 1–2 per million in adults.^[2] The majority of data available on the treatment of LCH comes from pediatric cohorts and is based on prospective clinical trials.^[3] On the contrary, very little data exist for adult patients with LCH, largely due to rarity of disease which precludes clinical trials. This has led to the use of a variety of agents for the treatment of adult LCH including cytarabine, clofarabine, cladribine, and combination agents in leukemia-like regimens.^[2] It is essential to report data on treatment of a rare disease like adult LCH so that a meaningful body of evidence can be accrued to guide therapy. We describe an adult patient who presented with multisystem (MS) LCH and responded favorably to single-agent cytarabine.

Case Report

Mr S, a 37-year-old gentleman presented with left-sided neck swelling for 2 weeks, without any associated systemic symptoms. Initial examination revealed left-sided posterior cervical and postauricular lymphadenopathy with no other significant findings. The patient underwent a fine-needle aspiration from the lymph nodes, which revealed lymphoid cells with numerous histiocytes, plasma cells, and eosinophils. An excision biopsy was performed, revealing effaced architecture with sheets of large neoplastic histiocytic cells, 10–15 μm in size with indented nuclei and inconspicuous nucleoli. Multiple eosinophilic microabscesses were also noted. Immunohistochemistry was positive for S100, CD1a, CD68, CD45, and Langerin in lesional cells, with negative staining for TdT, myeloperoxidase, CD117, and HMB-45, indicating a histologic diagnosis of LCH [Figure 1]. Renal and hepatic function tests and serum electrolytes were normal. Imaging with fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) scan revealed metabolically active cervical, supraclavicular, mediastinal, and portocaval nodes, along with FDG-avid opacification of left mastoid air cells [[Figure 2] and left three images in [Figure 2]]. A magnetic resonance imaging scan of the brain confirmed sclerosis of mastoid air cells, likely due to disease infiltration. The final diagnosis was thus confirmed as MS LCH, involving lymph nodes and bone, with no risk organ involvement. Options for therapy were discussed, and he was initiated on single-agent cytarabine at a dose of 100 mg/m² 5 days a month. He tolerated it well without any complications. A repeat PET scan after three cycles revealed near complete resolution of cervical, preauricular, and portocaval nodes and mastoid lesion, with partial resolution of supraclavicular and mediastinal nodes [[Figure 3]: last three images]. He continues to be asymptomatic and is continued on monthly cytarabine, with a plan to complete a total of 10–12 cycles followed by reassessment.

Figure 1: Photomicrographs showing sheets of large atypical cells along with immunohistochemical staining for S-100, CD1a, CD45 and Ki67 Index of 10%

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Figure 2: Fluorodeoxyglucose-positron emission tomography/computed tomography scan at diagnosis showing fluorodeoxyglucose-avid uptake in left mastoid air cells along with mediastinal and abdominal lymph nodes

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Figure 3: First three images show whole-body fluorodeoxyglucose positron emission tomography/computed tomography with mediastinal and thoracic uptake. The second three images show significant reduction after 3 cycles of chemotherapy

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Discussion

Prospective, long-term data to guide therapy for LCH are predominantly available from studies in pediatric populations. No such data exist for adult LCH and treatment decisions must be made based on case series or expert opinion. Pediatric regimens in adult patients are associated with higher toxicity and lower efficacy, and in some cases demonstrate relapse rates exceeding 80% 1-year following treatment.^[4]

Epidemiological and clinical data on adult LCH are available from limited institutional series, the largest of which are summarized in [Table 1]. Similar to paediatric disease, LCH in adults commonly involves skin, bone, pituitary, or organs of hematopoietic system. An attempt must be made to describe initial extent of disease as completely as possible, with a detailed clinical examination, skeletal survey, and additional investigations as indicated. Sensitivity of picking up skeletal lesions is significantly improved using FDG-PET.^[7] A definitive diagnosis is made by biopsy showing dendritic cells with an attendant inflammatory infiltrate and positive staining for CD1a and S100.^[8] Positive staining for Langerin (CD207) adds to specificity and helps differentiation from inflammatory conditions.^[9]

Table 1: Salient features of two published series on adult langerhans cell histiocytosis

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The therapeutic algorithm of LCH in adult patients is broadly based on pediatric studies and initially guided by extent of disease and organ system involvement. Single-system LCH (SS-LCH) involves one organ or system and is usually treated effectively with local therapy including curettage or local radiation.^[10] MS-LCH involves two or more organs or systems or multifocal involvement of a SS. Although contentious, documentation of risk organ involvement (spleen, liver, brain, and bone marrow) at presentation is recommended so that patients at higher risk of progression are identified.^[11] Patients with MS LCH or SS LCH with multifocal involvement require systemic therapy for adequate disease control.

Due to scarcity of randomized data, there is no single regimen of choice and multiple agents have been described in literature. Case series have reported the use of 2-CDA, cytarabine, etoposide, methotrexate, vemurafenib, and leukemia-based protocols with varying efficacy. The presence of central nervous system or high-risk lesions has been treated with 2-CDA upfront with meaningful efficacy.^[12] Based on the available data and toxicity profile, we selected cytarabine at a dose of 100 mg/m² for 5 days each month, which would ostensibly be less immunosuppressive compared to 2-CDA. [Table 2] summarizes salient features of some agents used in the treatment of adult LCH and approximate response rates noted with the same.

Table 2: Studies evaluating cytarabine, cladribine and other single agents as initial treatment options for adult langerhans cell histiocytosis

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We performed disease reassessment after 3 months as recommended by the Euro Histio-Net guidelines.^[16] In case of a suitable response, guidelines recommend continuation of cytarabine for 6–12 months in most patients. It is interesting to note that the maximum grade of recommendation in the above guidelines is C1, indicating a paucity of clinical trial data. At the end of therapy, 3 monthly clinical and basic laboratory evaluation is recommended. In case of suspicion of relapse, all initial investigations must be repeated to define precise extent of disease involvement.

To summarize, our patient demonstrates clinically meaningful response to single-agent cytarabine, which is easily administered on outpatient basis with minimal toxicity. It will be informative to collate individual case reports and series to generate a body of evidence for guiding therapy for this rare disease.

Acknowledgement

SS performed literature search and prepared the manuscript.

DP, JS, and KJ performed literature search and prepared the manuscript.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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