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Adult Bone Marrow Transplant News

Nonmyeloablative Regimens and Mini-Transplants Provide Transplant Options

Nonmyeloablative regimens open marrow or blood stem cell transplant to more patients while mini-transplants may be an option for elderly or medically compromised patients. Read detailed information in the links below:

Nonmyeloablative regimens open marrow or blood stem cell transplants to more patients

“Mini,” or nonmyeloablative, transplants may be appropriate and successful in some patients who aren’t eligible for a conventional hematopoietic cell transplant because of their advanced age or poor health — even if they don’t have a related, HLA-matched donor. Experts at Fred Hutchinson Cancer Research Center, where the procedure was developed a decade ago, have performed hundreds of mini-transplants, and they consult with physicians and patients interested in this option.

Call for mini-transplant information
Call our Intake office at 800-804-8824 to reach our clinical coordinator, a senior physician who can speak with you about whether a mini-transplant (or conventional transplant) may be appropriate for your patient. You can also refer patients to Seattle Cancer Care Alliance (SCCA) for a second opinion, including evaluation of whether transplantation is a suitable option, using our online Patient Referral Form.

“We are really open minded, especially since SCCA is not only a transplant clinic but also a chemotherapy clinic. We give a very balanced evaluation as to which treatment options might be most appropriate,” says Rainer Storb, MD, head of the Hutchinson Center’s transplantation biology program and member of the clinical research division.

Consider a transplant sooner than later

Recommended timing for a mini-transplant varies depending on the disease. But in general, Storb encourages physicians to investigate transplantation, along with any new agents or other experimental options you might consider, sooner rather than later after standard therapies fail. Mini-transplants have the potential to be curative, but the window of opportunity may close in the latest stages of illness.

Promising mini-transplant research

Eventually mini-transplants may become the preferred transplant even for some younger, healthier patients if studies show the outcomes of this less-toxic procedure are equivalent to the outcomes of conventional transplants. For example, in one current multi-center clinical trial, younger patients with acute myelogenous leukemia are being randomized to receive either a mini and conventional transplant on the basis of retrospective comparisons suggesting outcomes will be similar. Read about this clinical trial.

Among the most interesting recently published findings about mini-transplants is a report on newly diagnosed multiple myeloma published by Italian investigators in cooperation with the Hutchinson Center. Researchers compared an autologous transplant followed by a mini-transplant in patients with an HLA-matched sibling donor to the standard of care, a double autologous transplant, in those without a match. Survival rates were significantly higher in the mini-transplant group. See this study.

Researchers at the Hutchinson Center have also begun carrying out and studying the results of mini-transplants using donors, related or unrelated, who are not perfectly matched to the patient and mini-transplants using two units of cord blood. Read our previous newsletter about cord blood transplants [need link].

What is a mini-transplant?

The crucial difference between conventional transplants and nonmyeloablative transplants is that in the former doctors destroy the patient’s bone marrow using high-dose chemotherapy and total body irradiation, a process called conditioning, before they infuse donor stem cells to “rescue” the patient. In the latter they use low-dose radiation and immunosuppressive drugs instead. The immunosuppression allows infused donor cells a chance to engraft and then target and destroy the patient’s diseased cells.

The intensity of and toxicities associated with conventional conditioning make myeloablative transplants too risky for some patients, particularly the elderly and those with serious health problems besides the disease for which they might be transplanted. So typically transplant centers restrict myeloablative transplants to younger patients and those less medically compromised.

“Not that long ago transplants were limited to patients age 50 to 60 at the latest, and that’s clearly changed with nonmyeloablative transplants,” says Storb. The same goes for patients with kidney, heart or other organ-related conditions that disqualify them from conventional transplants. “Those patients are now often in the position to get and survive a mini-transplant. That includes children who may have other serious medical problems.”

Diseases treated with mini-transplant

Mini-transplant may be an option for patients with the following conditions, depending in part on the severity of their disease and their response to previous treatment:

  • Chronic leukemias (myeloid or lymphocytic)
  • Acute myeloid leukemias
  • High-risk acute lymphocytic leukemias
  • Hodgkin or non-Hodgkin lymphomas
  • Multiple myelomas
  • Myelodysplastic or myeloproliferative syndromes
  • Myelofibrosis
  • Genetic diseases, such as Fanconi anemia, congenital aplastic anemias or immunodeficiency diseases
  • Acquired aplastic anemia

More information

Clinical trials

Search for mini-transplant clinical trials at the Hutchinson Center.

Patient profiles

Edwin Sedan — Mini-transplant success in a younger patient with chronic myeloid leukemia who was not eligible for a conventional transplant because of liver complications.

Chris Christiansen — The experience of an older patient with a rare form of lymphoma who had a mini-transplant, with more about efforts to mobilize T cells and antibodies against cancer.

Options for donor cells for hematopoietic stem cell transplants

Of the 30 percent of candidates for a hematopoietic stem cell transplant in the United States who cannot find a matched donor for a bone marrow or peripheral blood stem cell (PBSC) transplant, almost all can receive stem cells derived from umbilical cord blood because the donor’s relatively naïve immune cells are less likely to identify the recipient’s tissues as foreign and worthy of attack.

“Cord blood transplant has the advantage of allowing greater tissue-matching disparity,” says Dr. Colleen Delaney, the Hutchinson Center researcher who leads our cord blood expansion trial.

“So what’s the problem? Why aren’t we doing it more?” asks Delaney. She explains: The number of stem cells per unit of cord blood is much smaller than the number per unit of donated bone marrow or PBSCs. In other words, cord blood provides a smaller cell dose (the number of transplanted stem cells per kilogram of body weight of the recipient) — the main predictor of post-transplant outcome. A lower cell dose usually means a poorer outcome because when fewer stem cells are transplanted, these cells take longer to engraft and the recipient goes longer without the white blood cells that guard against infection.

“Stay a Stem Cell!”

Delaney’s solution is to culture stem cells from cord blood in the lab before the transplant in order to expand the cell dose and spur faster engraftment. The activity in our own bones provides the model. Healthy bone marrow constantly makes new stem cells, each of which either divides or matures. Culturing stem cells means placing the cells on a suitable growth medium to prompt the same division that normally happens in vivo.

Up until now, when researchers tried this, the cells tended to mature rather than divide, and although these cells could be infused into patients, they were not clinically beneficial. The challenge has been to find a way to prevent this maturation. “We want to give them the right signal to say ‘Stay a stem cell! Stay a stem cell!’” says Delaney.

For earlier animal experiments and now for the human trial, Delaney is culturing the cells in the presence of a specially manufactured protein known to regulate stem cell choices in the marrow and other hematopoietic tissues. In this environment, the cultured stem cells do tend to stay young and to divide—and they seem primed for quicker engraftment than a typical unit of cord blood. Researchers make the protein and culture the cells in facilities at the Hutchinson Center. All subjects receive two units of cord blood, one of which has been expanded. The trial is open to both adults and children.

Banking on a Breakthrough

Delaney and her group hypothesize that the expanded unit will engraft sooner, providing a first wave of defense against pathogens more quickly than an unexpanded unit. After several weeks, the cells from the expanded unit may begin to burn out, but by then the unexpanded unit should have engrafted and be ready to take over.

Though researchers at other facilities are exploring other ways to expand cord blood, says Delaney, so far no one has found a technique that’s shown benefit to patients. “This has been tried before, but never has it been shown to be clinically effective,” she says. “If it works, it’s going to be the first time anyone’s done this.”

Get study details

  • Study 2044: A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors with an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies

Other cord blood studies at SCCA

  • Study 2010: Transplantation of Unrelated Umbilical Cord Blood for Patients with Hematological Diseases with Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen
  • Study 2012: Transplantation of Unrelated Donor Umbilical Cord Blood In Patients With Hematological Malignancies Using a Non-Myeloablative Preparative Regimen
  • Fred Hutchinson Cancer Research Center Web site

Long Term Follow Up Program

Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center have a dedicated long-term follow-up (LTFU) program designed to provide life-long support to people who have had a hematopoietic cell transplant—including telephone consultations for transplant recipients and their physicians, so you have access to our transplant experts for advice. Our medical staff can talk with you about transplant-related issues such as management of side effects, chronic graft-versus-host-disease, and late complications, as well as alternatives to address recurrence of the patient’s original disease, if this occurs.

Who We Serve

Our LTFU program serves people who received a bone marrow or stem cell transplant through SCCA or through the Hutchinson Center before SCCA was formed in 1998. This includes approximately 4,500 patients, both children and adults, some of whom had a transplant more than 25 years ago. Our telephone consultation service is free to these patients and their doctors.

How to Contact Us

To contact the LTFU team for a consultation, call 206-667-4415. Our hours are Monday through Friday from 8:30 a.m. to 4 p.m. (Pacific time). If you do not reach someone in person, please leave a voicemail message.

For an emergency consultation, if you do not reach a person at the regular consultation line or it is after hours, call 206-667-7600 and ask for the charge nurse.

Who Will Respond to Your Call

Nurses and middle-level practitioners with expertise in long-term follow-up care respond to calls to the consultation line. After collecting needed medical information from the physician (or patient) who called, they present the case to the LTFU attending physician to determine appropriate recommendations. (Depending on the situation, the attending physician may also want to speak directly with you about your patient’s case.) We are able to return most calls within 48 to 72 hours. We do prioritize calls based on the urgency of the situation.


Adult Bone Marrow Transplant News

The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.

Pediatric Bone Marrow Transplant News

Read about important outcomes research at the Fred Hutch that may benefit your patients.

Clinical Trials Monthly

Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.

The Leading Edge Newsletter

Each quarterly Leading Edge newsletter will highlight a new topic to give you the latest news on leading-edge therapies that SCCA physicians are offering.