Durable remission of renal cell carcinoma in conjuncture with graft versus host disease following allogeneic stem cell transplantation and donor lymphocyte infusion: rule or exception?
Allogeneic stem cell transplantation (alloSCT) followed by donor lymphocyte infusion (DLI) can be applied as immunotherapeutic intervention to treat malignant diseases. Here, we describe a patient with progressive metastatic clear cell renal cell carcinoma (RCC) who was treated with T cell depleted non-myeloablative alloSCT and DLI resulting in disease regression accompanied by extensive graft versus host disease (GVHD). We characterized the specificity of this immune response, and detected a dominant T cell population recognizing a novel minor histocompatibility antigen (MiHA) designated LB-FUCA2-1V. T cells specific for LB-FUCA2-1V were shown to recognize RCC cell lines, supporting a dominant role in the graft versus tumor (GVT) reaction. However, coinciding with the gradual disappearance of chronic GVHD, the anti-tumor effect declined and 3 years after alloSCT the metastases became progressive again. To re-initiate the GVT reaction, escalating doses of DLI were given, but no immune response could be induced and the patient died of progressive disease 8.5 years after alloSCT. Gene expression studies illustrated that only a minimal number of genes shared expression between RCC and professional antigen presenting cells but were not expressed by non-malignant healthy tissues, indicating that in patients suffering from RCC, GVT reactivity after alloSCT may be unavoidably linked to GVHD.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Cornelis A M
CA
van Bergen
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Elisabeth M E
EM
Verdegaal
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
M Wilhelmina
MW
Honders
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Conny
C
Hoogstraten
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
A Q M Jeanne
AQ
Steijn-van Tol
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Linda
L
de Quartel
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Joan
J
de Jong
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Maaike
M
Meyering
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
J H Frederik
JH
Falkenburg
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Marieke
M
Griffioen
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Susanne
S
Osanto
D002292:Carcinoma, Renal Cell / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000503:physiopathology*; D006801:Humans; D007680:Kidney Neoplasms / Q000628:therapy*; D008875:Middle Aged; D012074:Remission Induction; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous