What’s New in Transplants

What’s New in Transplants

Doctors and researchers at Seattle Cancer Care Alliance (SCCA) and our founding organizations Fred Hutchinson Cancer Research Center and Seattle Children’s are continually creating the newest and boldest strategies for children with cancer or other serious diseases of the blood or bone marrow. Updates on new bone marrow transplant (BMT) methods and other emerging therapies, such as gene therapy and immunotherapy, are provided here.

Many of our innovations are available to appropriate patients through clinical studies.

For the latest information on new therapies and soon-to-open studies, talk with an SCCA pediatric transplant specialist at (800) 804-8824.


Treosulfan is a reduced-toxicity agent used in transplant conditioning. Preliminary studies in Europe showed that the drug is effective in allowing the new marrow to take hold but with far fewer complications. This has translated into better survival rates.

SCCA is testing treosulfan in young patients with rare non-malignant diseases, such as immunodeficiencies, marrow failure syndromes, and metabolic storage diseases. By lowering transplant-related toxicity, doctors at SCCA hope they will be able to recommend BMT to some children with inherited disorders earlier in the course of their disease—therefore improving their chances for long-term survival.

Treosulfan is also being tested in SCCA studies with children having a BMT or cord blood transplant for acute myeloid leukemia or myelodysplastic syndrome. Treosulfan is just one of many safer SCCA protocols that allow more children to overcome historical barriers to transplantation.

Gene Therapy for Fanconi Anemia

In collaboration with the Hutch, the Fanconi Anemia Center at Seattle Children’s initiated the word’s first-ever clinical trial of lentivirus vector-based gene therapy for patients with Fanconi anemia (FA). This very rare inherited condition affects bone marrow as well as other organs and tissues.

The SCCA gene therapy trial is for young adults who cannot have BMT—the standard treatment—because they are too ill or lack a donor match. In the procedure, stem cells are collected from the patient, and the cells are grown in the lab where the virus acts like a delivery envelope to insert the new gene into the cells. The gene-corrected cells are then infused back into the patient. In addition to this groundbreaking gene therapy option, SCCA also offers several reduced-intensity and radiation-free BMT options for kids with FA. These special low-dose protocols are critical in FA because patients are hypersensitive to chemotherapy and radiation.

T-Cell Depletion to Reduce GVHD

Transplanted donor T-cells (a type of white blood cell) can help prevent infection and fight cancer in patients who’ve had BMT. But they can also provoke graft-versus-host disease (GVHD). Suppressing these T-cells with drugs has been the standard approach for achieving a balance of positive-negative T-cell functions, but many children still develop serious GVHD.

In a new approach at SCCA, doctors are selectively removing the GVHD-causing “naïve” T-cells from the donated cells before they are infused, while keeping the infection-fighting memory T-cells. Antibodies selectively pluck out the targeted T-cells from the donated stem cells. Preliminary results in adults have shown this method reduces GVHD but still prevents infection. Children with acute leukemia or myelodysplastic syndrome may be eligible for the study.

New Drugs to Prevent or Treat GVHD

Researchers at the Hutch and SCCA were the first to perfect drug immunosuppression to prevent the most severe forms of GVHD after BMT. This was a historic advance that opened the BMT door for many more patients, including children.

Today our researchers are still searching for novel drugs and drug combinations to fight GVHD—especially the problematic chronic GVHD, which can require a multi-year course of immunosuppression. Some of the newest prevention strategies are testing post-transplant cyclophosphamide, sirolimus-plus-cyclosporine-plus-mycophenolate mofetil, tacrolimus-plus-mycophenolate mofetil, and statins given to donors. All these new drug regimens are being evaluated by doctors who are highly experienced in the special conditioning regimens and T-cell strategies that can limit GVHD.

Moreover, the specialists in our Pediatric Long Term Follow-Up (LTFU) Program are ready to assist families in understanding and using anti-GVHD approaches properly. Our LTFU doctors and nurses spend hours every day helping parents and their children understand how to stay healthy and reduce GVHD risks. This combination of innovation, clinical experience, and comprehensive long-term follow-up gives your child the best chance of coming back strong after a BMT at SCCA.

Engineered T-Cells to Fight Leukemia

One of the newest SCCA studies aims to reprogram a child’s own T-cells to destroy leukemia cells before the child goes on to have a transplant. Wiping the slate clean of leukemia with T-cell therapy will allow many more children to have a successful transplant. The special techniques for engineering the T-cells were developed by researchers at the Hutch, Seattle Children’s, and the University of Washington. Basically, the techniques retrain the patient’s own immune cells to target and kill tumor cells.

In the first studies, the patient’s own T-cells are collected and then purified and reprogrammed with recombinant DNA techniques to produce a chimeric antigen receptor that seeks out malignant (leukemia) B-cells. The engineered cell binds to and kills the leukemia cell. While this powerful new immunotherapy approach is now being used in children with high-risk leukemias, the hope is that it may eventually help a much wider range of patients with lower-risk blood and solid cancers.

Off-the-Shelf Expanded Cord Blood

Discoveries made at the Hutch have led to a new method of preparing stem cells from umbilical cord blood. In the new technique, a specific protein stimulates the stem cells to divide in the lab—but not to mature into white blood cells, red blood cells, and platelets. This expansion of pure stem cells is a breakthrough because it avoids generating the T-cells that cause GVHD.

Expansion is also important because cord blood tends to have a limited number of stem cells, which slows engraftment and recovery after the transplant. Because the immature stem cells from cord blood are often considered “universal donor” stem cells (meaning that the tissue matching is much less stringent), this new SCCA approach may lead to creation of a vast off-the-shelf supply of cord blood for any child needing a stem cell transplant. Current SCCA studies with expanded cord blood involve children and adults with leukemia and other blood cancers.

Targeted Radiation for High-Risk Neuroblastoma

Bone marrow transplantation is often used in conjunction with other cancer therapies. In children with high-risk neuroblastoma, the aggressive approach typically includes chemotherapy, surgery, high-dose radiation therapy, and then autologous BMT followed by even more local radiation, biological agents, or immunotherapy.

Although survival has improved following such intensive therapy, children coming to Seattle Children’s and SCCA can now receive a new type of targeted radiation: I-131 MIBG (metaiodobenzylguanidine radiolabeled with iodine-131). This radioactive iodine is infused over two hours and is taken up by tumor cells. Seattle Children’s was one of the first sites in the country to build a special facility for giving the MIBG treatment. Several other new drug and immunotherapy treatments for neuroblastoma are being developed at Seattle Children’s and SCCA.

New Methods for Non-Malignant Disease Transplants

The Fred Hutchinson Bone Marrow Transplant Program at SCCA is now one of the highest-volume centers for unrelated donor transplants for non-malignant disorders. These include rare blood diseases such as myelodysplastic and myeloproliferative disorders; histiocytic, plasma cell, or stem cell disorders; inherited erythrocyte/platelet or immune system disorders; and inherited metabolic disorders. Experience in treating rare diseases is rare. We have it. Read about the advances we’re making in treating these rare disorders.