Allogeneic Hematopoietic Stem Cell Transplantation for Management of Histiocytic Sarcoma: A Systemic Review
Authors: Shahzad Moazzam , Khan Abat , Amin Muhammad Kashif , Higginbotham Aaron , Akram Umar , Khan Muhammad Atif , Ishaq Muhammad Uzair , Saif Nooria , Akram Fatima , Shahani Javeria , Chaudhary Sibgha Gull , Anwar Iqra , Singh Anurag , McGuirk Joseph P. , Mushtaq Muhammad Umair 
Published: December 2024

Introduction: Histiocytic sarcoma (HS) is an exceptionally rare and aggressive tumor of hematolymphoid lineage, constituting less than 1% of hematolymphoid neoplasms and affecting only about 1 in 5.88 million individuals. Its rarity and severity underscore the urgent need for tailored therapeutic approaches. Currently, there is no established standard of care for HS, with management typically involving surgery and radiotherapy, chemotherapy, or targeted therapy in various combinations. While these regimens can sometimes be successful, a diagnosis of HS generally indicates a poor prognosis, especially in cases of systemic disease.

Method: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was performed on PubMed, Cochrane, and Embase using MeSH terms and keywords relevant to HS from inception until April 2024. We screened 460 articles, removing duplicates. Original studies (clinical trials, retrospective and prospective studies), case reports, and case series, including patients with a confirmed diagnosis of HS above 18 years of age, were considered eligible. Studies lacking treatment information or individual patient data, review articles, and non-English studies were excluded. We included 99 studies in the systematic review. Data was extracted, including country, age, gender, ethnicity, clinical presentation and stage, site, diagnostic criteria, immunohistochemistry (IHC) markers, treatment, follow-up, and outcomes.

Results: A total of 185 patients with HS were included, with nearly equal gender distribution. The median age of patients was 55 years (range 18-82). The most commonly reported chemotherapy regimen was CHOP (cyclophosphamide, hydroxydaunorubicin/doxorubicin, oncovin/vincristine, and prednisone), followed by ICE (ifosfamide, carboplatin, and etoposide). Less frequently reported regimens included HIPEC (hyperthermic intraperitoneal chemotherapy), DHAP (dexamethasone and high-dose cytarabine), and AEVD (doxorubicin, etoposide, vinblastine, and dacarbazine). The median follow-up period was 12 months (range 0.5-144). Immunotherapy with agents such as nivolumab and pembrolizumab was used in cases with PD-L1 (programmed cell death ligand 1) mutations, showing potential benefits. A total of 64 patients were treated with surgery (± radiotherapy). Most of these patients had unifocal disease, resulting in a favorable survival rate in approximately half of these cases. Ten patients underwent stem cell transplantation - five allogeneic and five consolidative autologous transplants. Three of the five patients in each transplant group achieved remission. We present a case of a 33-year-old male diagnosed with systemic HS, successfully treated at the University of Kansas Medical Center. Despite initial disease progression following treatment with ICE, CHOP, and CLAG-M (Cladribine, Ara-C, mitoxantrone, and G-CSF) chemotherapies and no targetable mutations, allogeneic haploidentical peripheral blood stem cell transplantation effectively curtailed tumor growth and reduced metastases, leading to a remission lasting more than a year after the transplant.

Conclusion: This systematic review and case report underscore the heterogeneous clinical behavior of histiocytic sarcoma, necessitating tailored therapeutic approaches and comprehensive management strategies to address its aggressive nature and potential for systemic involvement. Allogeneic hematopoietic stem cell transplantation can be considered in refractory cases.