Gene-modified hematopoietic stem cells for cancer immunotherapy.

The rapid expansion of available cancer immunotherapies has resulted in favorable early outcomes. Specifically the use of gene therapy to introduce chimeric antigen receptors (CARs) and T cell receptors (TCRs) in T cells creates new immunotherapy options for patients. While showing early success with these approaches, limitations remain that can be overcome by the use of modification of hematopoietic stem cells (HSCs) to express CARs and TCRs. With modern gene therapy technologies, increased safety and control of the modification of the HSCs can be achieved through the use of a suicide gene

Gene-modified hematopoietic stem cells for cancer immunotherapy.

The rapid expansion of available cancer immunotherapies has resulted in favorable early outcomes. Specifically the use of gene therapy to introduce chimeric antigen receptors (CARs) and T cell receptors (TCRs) in T cells creates new immunotherapy options for patients. While showing early success with these approaches, limitations remain that can be overcome by the use of modification of hematopoietic stem cells (HSCs) to express CARs and TCRs. With modern gene therapy technologies, increased safety and control of the modification of the HSCs can be achieved through the use of a suicide gene

In Vitro Generation of Human NK Cells Expressing Chimeric Antigen Receptor Through Differentiation of Gene-Modified Hematopoietic Stem Cells.

NK cells represent a very promising source for adoptive cellular approaches for cancer immunotherapy, and extensive research has been conducted, including clinical trials. Gene modification of NK cells can direct their specificity and enhance their function, but the efficiency of gene transfer techniques is very limited. Here we describe two protocols designed to generate mature human NK cells from gene-modified hematopoietic stem cells. These protocols use chimeric antigen receptor as the transgene, but could potentially be modified for the expression any particular transgene in human NK cells

Use of Rapamycin in a Patient With Juvenile Myelomonocytic Leukemia: A Case Report.

The relapse rate for children with juvenile myelomonocytic leukemia (JMML) status post hematopoietic stem cell transplantation (HSCT) approaches 50% within 5 years. Graft-versus-leukemia (GVL) is thought to play important role in the treatment of JMML. For this reason, careful management of immunosuppressive drugs after HSCT is crucial. This case report demonstrates that rapamycin and GVL represent a viable medical strategy for the management of pediatric patients with JMML who relapse following status post-HSCT

Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant.

BackgroundPatients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect.Design/methodCase Series and review of the literature.ResultsWe present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient.ConclusionsAlthough a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft-versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement

Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant.

BackgroundPatients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect.Design/methodCase Series and review of the literature.ResultsWe present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient.ConclusionsAlthough a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft-versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement

Use of Rapamycin in a Patient With Juvenile Myelomonocytic Leukemia: A Case Report

The relapse rate for children with juvenile myelomonocytic leukemia (JMML) status post hematopoietic stem cell transplantation (HSCT) approaches 50% within 5 years. Graft-versus-leukemia (GVL) is thought to play important role in the treatment of JMML. For this reason, careful management of immunosuppressive drugs after HSCT is crucial. This case report demonstrates that rapamycin and GVL represent a viable medical strategy for the management of pediatric patients with JMML who relapse following status post-HSCT