Reduced Intensity Transplant Using Extracorporeal Photopheresis
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Cancer, Blood Cancer, Leukemia |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/2/2016 |
| Start Date: | July 2005 |
| End Date: | January 2010 |
| Contact: | Jennifer Schneiderman, MD, MS |
| Email: | jschneiderman@childrensmemorial.org |
| Phone: | 773-880-4562 |
Reduced Intensity Stem Cell Transplant in Children and Young Adults Utilizing Photopheresis, Fludarabine, and Busulfan
Stem cell transplantation may be used to cure childhood cancers, and other diseases.
Traditionally, stem cell transplants use high doses of chemotherapy and radiation. This
regimen may cause significant problems after transplant such as infertility, infection, and
graft versus host disease (GVHD).
Reduced intensity transplant (RIT) uses medications which weaken the immune system, allowing
donor cells to take over. The goal of a RIT is to reduce the risk for complications after
transplant. Usually medication is used to weaken the immune system, but there are other
options such as extracorporeal photopheresis (ECP) that may be less toxic.
ECP is currently used for the treatment of GVHD and certain lymphomas. ECP uses a machine
that filters white blood cells from the blood, treats them with ultraviolet (UV) light, and
then gives all the cells back to the patient. The patient's immune system becomes weaker,
allowing the donor cells to replace those of the patient. Studies involving the use of ECP
for conditioning have shown fewer side effects than the use of medications.
The primary purpose of this clinical research trial is to evaluate the safety and
feasibility of ECP as part of a preparative regimen for RIT in children and young adults.
Traditionally, stem cell transplants use high doses of chemotherapy and radiation. This
regimen may cause significant problems after transplant such as infertility, infection, and
graft versus host disease (GVHD).
Reduced intensity transplant (RIT) uses medications which weaken the immune system, allowing
donor cells to take over. The goal of a RIT is to reduce the risk for complications after
transplant. Usually medication is used to weaken the immune system, but there are other
options such as extracorporeal photopheresis (ECP) that may be less toxic.
ECP is currently used for the treatment of GVHD and certain lymphomas. ECP uses a machine
that filters white blood cells from the blood, treats them with ultraviolet (UV) light, and
then gives all the cells back to the patient. The patient's immune system becomes weaker,
allowing the donor cells to replace those of the patient. Studies involving the use of ECP
for conditioning have shown fewer side effects than the use of medications.
The primary purpose of this clinical research trial is to evaluate the safety and
feasibility of ECP as part of a preparative regimen for RIT in children and young adults.
This study tests the feasibility of a reduced intensity preparative regimen for stem cell
transplant including extracorporeal photopheresis (ECP), busulfan, and fludarabine in
patients with leukemia, lymphoma, and certain non-malignant diseases. The current reduced
intensity protocol includes busulfan, fludarabine, and anti-thymocyte immunoglobulin. ECP is
currently used in diseases such as chronic GVHD and cutaneous T cell lymphoma. The mechanism
of ECP has not been defined. It is hypothesized that exposure of white blood cells to
ultraviolet light with 8-methoxypsoralen initiates an apoptotic cellular cascade. Apoptotic
cells are recognized and removed by the reticuloendothelial system, initiating the secretion
of anti-inflammatory cytokines and the reduction of proinflammatory cytokines. Antigen
presenting cells then regulate immune responses through the induction of tolerance.
Here we incorporate the use of ECP, fludarabine, and busulfan in the preparative regimen,
followed by ECP as prophylaxis for acute graft versus host disease. We hypothesize that
photopheresis is safe and feasible, and patients will have similar rates of engraftment with
less GVHD as those treated with current reduced intensity protocols. The use of ECP prior to
transplant provides immunosuppression promoting host engraftment. Furthermore, the
introduction of ECP following transplant may be able to induce tolerance thereby reducing
rates of GVHD.
transplant including extracorporeal photopheresis (ECP), busulfan, and fludarabine in
patients with leukemia, lymphoma, and certain non-malignant diseases. The current reduced
intensity protocol includes busulfan, fludarabine, and anti-thymocyte immunoglobulin. ECP is
currently used in diseases such as chronic GVHD and cutaneous T cell lymphoma. The mechanism
of ECP has not been defined. It is hypothesized that exposure of white blood cells to
ultraviolet light with 8-methoxypsoralen initiates an apoptotic cellular cascade. Apoptotic
cells are recognized and removed by the reticuloendothelial system, initiating the secretion
of anti-inflammatory cytokines and the reduction of proinflammatory cytokines. Antigen
presenting cells then regulate immune responses through the induction of tolerance.
Here we incorporate the use of ECP, fludarabine, and busulfan in the preparative regimen,
followed by ECP as prophylaxis for acute graft versus host disease. We hypothesize that
photopheresis is safe and feasible, and patients will have similar rates of engraftment with
less GVHD as those treated with current reduced intensity protocols. The use of ECP prior to
transplant provides immunosuppression promoting host engraftment. Furthermore, the
introduction of ECP following transplant may be able to induce tolerance thereby reducing
rates of GVHD.
Inclusion Criteria:
- Weight > 25 kg
- Patients with acute lymphoblastic leukemia (ALL) who are in CR (complete remission; <
5% blasts in bone marrow and no active central nervous system disease) who:
- Are in second remission with an initial remission of < 36 months.
- Patients with "high risk" disease in CR1, defined by karyotype abnormalities
such as presence of (9;22) translocation, monosomy 7, or monosomy 5; and/or
patients with slow initial response (initial remission not reached within four
weeks from diagnosis).
- Are in third (or subsequent) remission
- Experience isolated extramedullary relapse while on therapy
- Have experienced relapse following myeloablative stem cell transplant
- Are WT1+ following induction therapy
- Patients with acute myelogenous leukemia (AML) who:
- Are in first remission and remain WT1 positive.
- Are in second remission
- Are in initial partial remission (< 20% blasts in bone marrow)
- Experience relapse following myeloablative stem cell transplant
- Patients with relapsed lymphoma whose residual disease appears to be chemo-responsive
and non-bulky (< 5 cm largest diameter)
- Patients with chronic myelogenous leukemia (CML) in chronic phase who:
- Don't achieve remission (molecular or cytogenetic) by 1 year of diagnosis with
therapy (imatinib mesylate or interferon)
- Have a rising quantitative bcr/abl on imatinib mesylate (molecular relapse)
- Had developed accelerated phase regardless of therapy but are now back in second
chronic phase
- Patients with recurrent solid tumors (neuroblastoma, Ewing's sarcoma, melanoma,
rhabdomyosarcoma)
- Patients with myelodysplastic syndrome
- Patients with refractory anemia (RA) and refractory anemia with excess blasts (RAEB)
are eligible, but refractory anemia with excess blasts in transformation (RAEB-T)
patients are only eligible if treated to < 20% blasts with chemotherapy
- Patients with selected immunodeficiencies such as Wiskott-Aldrich syndrome or
hyper-IgM syndrome
- Patients with metabolic diseases such as Niemann-Pick or adrenoleukodystrophy
- Patients with bone marrow failure syndromes, including aplastic anemia
- Adequate venous access
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