Case Report: Metagenomic Next-Generation Sequencing Can Contribute to the Diagnosis and Treatment of Disseminated Visceral Kaposi Sarcoma Following Allogeneic Haematopoietic Stem Cell Transplantation

Abstract

Disseminated visceral Kaposi sarcoma (KS) following allogeneic haematopoietic stem cell transplantation (HSCT) is a rare but life-threatening posttransplant complication. A suitable management strategy for disseminated KS involvement in transplant patients is unclear. Here, we reported a patient who developed disseminated visceral KS following HSCT, which was the first detailed report documenting the relationship among KS development, delayed immune reconstitution, and HHV-8 DNA levels by metagenomic next-generation sequencing (mNGS). The HHV-8 viral load peaked at 2071 sequence reads with an absolute lymphocyte count of 0.17×109/L on day +242. On day +536, the HHV-8 viral load became undetectable, with an absolute lymphocyte count of 1.06×109/L and the KS disappearance. HHV-8 load in blood detected by mNGS may be used as an early prediction marker for KS, a guide for early withdrawal of immunosuppression, and a tool to monitor KS treatment response in the setting of HSCT, especially in patients with CMV-seropositive or graft failure postengraftment. Through whole-exome sequencing, we explored the molecular mechanism underlying the patient’s longer latency of haematopoietic or immune reconstitution and recurrent infections. Germline mutations in the FANCI and RAD51 genes might impair the patient’s DNA repair ability, leading to a degree of immunodeficiency and tumour susceptibility. We strongly recommended evaluating the clinical history of the donor and investigating whether there were possible germline mutations suspected for immunodeficiency or familial neoplasms. Disseminated visceral KS patients could likely benefit from chemotherapy, especially if the disease appears to be aggressive.

Disseminated visceral Kaposi’s sarcoma after allogeneic hematopoietic stem cell transplantation: a case report

“…The rise in absolute lymphocyte count was found to be consistent with the remission in clinical symptoms, which is in line with previous findings. 8,12 In conclusion, although HSCT-related KS is very rare, identification remains important and KS should be considered, particularly for visceral lesions, which are more fatal than KS lesions of the skin. Greater caution should be applied when dealing with haploidentical transplant patients because they face more intense immunosuppression.…”

“…Difficulties were encountered in this diagnosis due to lack of experience, and HHV-8 was finally discovered through mNGS of gut lavage fluid. Zhou et al 12 showed that mNGS of blood samples rapidly and accurately identifies pathogens that may help assess the development of KS and dynamically guide treatment decisions. To the best of the authors' knowledge, the present report is the first case study to present mNGS as a guide in the treatment of KS associated with HSCT.…”

“…The rise in absolute lymphocyte count was found to be consistent with the remission in clinical symptoms, which is in line with previous findings. 8 , 12 …”