title: Intrathecal Administration of Tumor-Infiltrating Lymphocytes Is Well Tolerated in a Patient with Leptomeningeal Disease from Metastatic Melanoma: A Case Report.
abstract: Patients with leptomeningeal disease (LMD) from melanoma have very poor outcomes and few treatment options. We present a case of intrathecal (i.t.) administration of autologous tumor-infiltrating lymphocytes (TIL) in a patient with LMD from metastatic melanoma. The patient developed LMD after previous treatments with surgery, high-dose bolus interleukin-2 (HD IL2), and systemic TIL infusion and experienced radiographic progression after intrathecal IL2 (i.t. IL2) therapy. The patient received weekly treatment with increasing numbers of i.t. TIL followed by twice-weekly i.t. IL2. The patient received three i.t. TIL infusions and did not experience any toxicities beyond those expected with i.t. IL2 therapy. Analysis of cerebrospinal fluid demonstrated increased inflammatory cytokines following the i.t.
  
  
  METHODS
  Subsequent imaging demonstrated disease stabilization, and neurological deficits also remained stable. The patient expired 5 months after the initiation of i.t. TIL therapy with disease progression in the brain, liver, lung, and peritoneal and retroperitoneal lymph nodes, but without LMD progression. These results demonstrate the safety of i.t. administration of TIL in melanoma patients with LMD and support the feasibility of conducting a prospective clinical trial to determine this therapy's clinical benefit among these patients.
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. icglitza@mdanderson.org.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: Glitza
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cara
authors.initials: C
authors.lastname: Haymaker
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chantale
authors.initials: C
authors.lastname: Bernatchez
authors.affiliation: Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Luis
authors.initials: L
authors.lastname: Vence
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michelle
authors.initials: M
authors.lastname: Rohlfs
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jessie
authors.initials: J
authors.lastname: Richard
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carol
authors.initials: C
authors.lastname: Lacey
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rahmatu
authors.initials: R
authors.lastname: Mansaray
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Orenthial J
authors.initials: OJ
authors.lastname: Fulbright
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Renjith
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher
authors.initials: C
authors.lastname: Toth
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Seth
authors.initials: S
authors.lastname: Wardell
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sapna P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Radvanyi
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Papadopoulos
authors.affiliation: Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
mesh_terms: D016207:Cytokines / Q000134:cerebrospinal fluid; D018450:Disease Progression; D017809:Fatal Outcome; D006801:Humans; D007278:Injections, Spinal; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy; D055756:Meningeal Carcinomatosis / Q000628:therapy*; D008875:Middle Aged
chemical_list: D016207:Cytokines