In allogeneic transplantation, the patient first undergoes a conditioning regimen to wipe out or dramatically reduce the number of cancer cells in the body; conditioning also destroys or severely reduces the number of blood-forming stem cells in the bone marrow. Next, hematopoietic stem cells from a tissue-matched donor are infused into the patient's bloodstream, with the goal of repopulating the bone marrow and restoring its ability to produce blood cells, including red blood cells, platelets, and immune system cells. Although conditioning and allogeneic transplantation can successfully eradicate cancer in the recipient, the treatment is grueling, and treatment-related deaths do occur.
Featured Clinical Trial
Safety of Stem Cell Transplants for HIV-Positive Cancer Patients
Name of the Trial
Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT-CTN-0903). See the protocol summary.
Dr. Joseph Alvarnas and Dr. Richard Ambinder, Blood and Marrow Transplant Clinical Trials Network
Why This Trial Is Important
The transplantation of hematopoietic, or blood-forming, stem cells from a healthy donor, a procedure known as allogeneic stem cell transplantation, is one of the few treatments that may provide a cure for patients with some blood cancers (leukemias and lymphomas) and myelodysplastic syndromes (MDS).
People infected with HIV tend to develop the types of cancers that can be treated with allogeneic stem cell transplantation. Historically, they were not considered for this potentially curative therapy because HIV would threaten the immune cells produced by the transplanted stem cells and because HIV infection itself was considered a fatal condition. In recent years, however, HIV-targeted treatment with highly active antiretroviral therapy (HAART) has dramatically improved the lives and health of HIV-infected patients. In fact, HAART has improved the outlook for HIV patients so much that doctors are now investigating whether some HIV-infected cancer patients can be treated with allogeneic stem cell transplantation.
"Improved access to this potentially curative therapy may be possible for individuduals with HIV infection if the results of this clinical trial show the treatment can be safely performed," said Dr. Richard Little, head of Adult Hematologic Cancer Therapeutics for NCI's Division of Cancer Treatment and Diagnosis.
In this clinical trial, HIV-positive patients receiving HAART who have a blood cancer or an MDS that may respond to the procedure will be treated with allogeneic stem cell transplantation. These cancers include acute myeloid or acute lymphoblastic leukemia in first or second remission, Hodgkin lymphoma or non-Hodgkin lymphoma beyond first remission that has responded at least partially to the most recent therapy, or an advanced MDS. The safety and feasibility of allogeneic transplantation in this patient population will be assessed using the primary endpoint of 100-day non-relapse mortality, that is, the number of patients who have died of causes other than relapse at 100 days after transplantation.
"In the past, HIV infection was on its own a fatal illness, so it didn't really make sense to subject patients to a very intensive therapy like stem cell transplantation when there was another illness that was imminently life threatening," said Dr. Ambinder. "Clearly, with effective antiretroviral therapy, that has dramatically changed. HIV infection is no longer immediately life threatening and may be more akin to other chronic conditions like diabetes; it requires some special attention but it shouldn't preclude people from having otherwise lifesaving treatment."
As part of this study, an effort will be made to try to identify stem cell donors who have a particular genetic mutation known as the delta 32 mutation in a gene called CCR5. The CCR5 protein is found on immune cells and is often exploited by HIV to infect the cells. In the delta 32 mutation, part of the CCR5 gene is deleted, and, in people with the deletion in both alleles of the gene (that is, a homozygous deletion), the mutation may confer innate resistance to HIV infection.
If a large number of matched donors can be identified for a given patient in this trial, the investigators will conduct further analysis to determine the CCR5 mutation status of those donors in hopes of finding one whose cells may be HIV resistant. "However, these donors are rare, so people considering this trial should do so because they have a cancer that requires treatment with allogeneic transplantation. There may be an added benefit, if such a donor can be found, that the progeny of the donated stem cells are more resistant to HIV, but this is not a trial to treat HIV infection," Dr. Ambinder explained.
For More Information
See the lists of eligibility criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.