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Winter 2011

Welcome from the Director

Our Research is Your Patient’s Opportunity

Every year, stem cell transplants for children are getting better. We now have safer preparative regimens, novel alternative donor sources, and dozens of carefully designed protocols to help overcome barriers to using mismatched or partially matched donor cells.

Transplantation is still risky, no question, and we still have much to learn. But today, even compared to a few years ago when I first moved to Seattle, we are fortunate to have even more transplant options for our highest risk pediatric patients—those who have failed treatment with standard chemotherapeutic regimens and those who need a transplant but cannot tolerate myeloablative conditioning. We are also at the forefront in the field of transplantation for children with nonmalignant blood diseases, primary immunodeficiencies, and other genetic disorders.

Much of this progress can be attributed to good clinical research. Only with well-designed studies and the continued participation of patients and families can we learn how to make transplantation safer and more effective.

Here at Seattle Cancer Care Alliance, we have never had more pediatric clinical trials underway. This research not only paves the way for future breakthroughs, it also provides hope for many patients and families who have simply run out of options.

One of my goals related to our work at SCCA is to make sure that clinicians who care for children with many of these life-threatening diseases are aware of the advances and opportunities in pediatric transplantation. That’s why this issue of Pediatric BMT Update includes a complete listing of marrow or stem cell transplant trials open to children. We encourage you to scan this list for a quick review of the emerging applications and novel strategies now being explored here at SCCA. We will distribute print versions of this full list once each year and it will be available online at all times.

Please contact us at 800-804-8824 if you have a patient who might be appropriate for one or more of these trials. Early referral for transplant consideration can be a critical factor in eligibility for study protocols and in long-term outcomes. We are always available to discuss transplant and non-transplant treatments for any pediatric patient.

Also in this issue, you will find an update on a clinical study evaluating a promising new conditioning agent—treosulfan—in transplantation for nonmalignant diseases.  Here in Seattle, we have already performed nearly 400 marrow or stem cell transplants for children with nonmalignant disease. In coming years, increasing numbers of children with immunodeficiencies, sickle cell disease, aplastic anemia, marrow failure, and other such serious, noncancer disorders will benefit from stem cell or marrow transplantation. In future issues, we will update you on new protocols and progress in this exciting area.

K. Scott Baker, MD, MS
Director, Pediatric Blood and Marrow Transplantation and Survivorship Programs,
Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital
Professor of Pediatrics, University of Washington School of Medicine

Update on Pediatric Transplantation at SCCA:

Excellent Survival Rates, Even in Children Lacking Related Donors

New statistics on children receiving transplants at the SCCA document a high volume and diversity of patients, as well as outstanding survival outcomes.

The recently-updated registry data show that since 1969 the SCCA has performed 2,386 bone marrow transplants in children and teens. More than 2,000 were allogeneic transplants, and nearly 25 percent of these were of the more difficult “unrelated donor” variety. Nearly 400 transplants were for nonmalignant conditions.

Every year SCCA starts treatment for about 100 children with leukemia, lymphoma, or rare, genetic nonmalignant diseases,and we perform transplants in about half of these children. Many are high-risk patients.

Overall, the SCCA registry data for pediatric transplantation show:

  • 100-day survival percentage rates in the five years 2006 - 2010: 96, 94, 91, 92, and 100 percent 
  • One-year survival percentage rates in the years 2005 - 2009: 82, 89, 76, 81, and 78 percent 

One striking trend in the SCCA data is the increasing use of alternative donors in stem cell transplantation, either unrelated donors (489 total) or cord blood (88). In this category of growing importance, SCCA consistently ranks among the top U.S. transplant centers in one-year survival; for example, in children 0-19 years of age, our one-year survival rate for 2004-2009 was 76 percent after an unrelated donor transplant (NMDP 2011 data, www.marrow.org).

Outstanding transplant outcomes with the toughest cases at SCCA no doubt contributed to Seattle Children’s recent selection as one of the country’s Top Ten Pediatric Hospitals for Cancer; in the US News Best Children’s Hospitals 2011-2012 rankings, Seattle Children’s was rated “Superior” in Bone Marrow Transplant Services as well as in Commitment to Involving Parents and Family. (U.S. News & World Report 2011 http://health.usnews.com/best-hospitals/pediatric-rankings/cancer)

For the full update on Seattle Children’s Cancer Survival Rates, see:
http://www.seattlechildrens.org/clinics-programs/cancer/statistics  

Can Treosulfan Pave the Way to Safer Transplantation in Nonmalignant Diseases?

A new transplant study at SCCA is tackling several big challenges all at once.

  • Treosulfan, the drug being tested as a reduced-toxicity conditioning agent, is currently available only in Europe and transplant data in children are limited.
  • The 20 or so nonmalignant diseases targeted in the trial are exceedingly rare, most with few treatment options other than supportive care.
  • A transplant is often the only known cure for nonmalignant diseases, such as primary immune deficiency disorders, bone marrow failure syndromes, metabolic disorders, and sickle cell disease. However the health issues facing these patients – including organ damage and underlying infections – make it difficult for them to tolerate the powerful drugs and/or radiation used in standard transplant regimens.

For Dr. Lauri Burroughs, a pediatric blood and marrow transplantation specialist at SCCA who heads up the treosulfan trial, these challenges are exactly what make the study so important.

“The genetic conditions we’re studying are rare,” she said. “There’s much less research on these diseases compared to pediatric malignancies like leukemia.”

The SCCA study, which will recruit more than 30 children from around the United States, will provide the nation’s first prospective evaluation of this promising drug’s safety and efficacy in stem cell transplantation for nonmalignant diseases.

The Dilemma with Transplants in Nonmalignant Disease:
High Risks, Leading to Avoidance and Delay, Leading to Even Higher Risks

“Because the risks of transplant used to be so great, patients often didn’t come to transplant until their disease had progressed to the point that they didn’t have other options,” Dr. Burroughs said. “Unfortunately, if you wait too long, you miss the best opportunity for a successful transplant.”

“These patients often have underlying problems, like infections or organ disease,” she explained. “When you give them aggressive regimens, they are especially prone to toxicities and the mortality rates have been prohibitively high.”

The Goals: Intense Conditioning Without the Side Effects, Earlier Transplant

Now, with treosulfan, the SCCA pediatric transplant group hopes to lower the toxicity of the conditioning regimen and thereby avoid delays in transplantation referral.

“Lowering the toxicity, and therefore the mortality, associated with transplantation allows us to consider transplantation earlier in the course of their disease,” Dr. Burroughs said. “This gives more patients a chance to receive this potentially life saving therapy, and that means more children get a chance to live a long and productive life. Everyone deserves that.”

Preliminary evidence with treosulfan supports this hope. Studies across Europe show that this busulfan analog has markedly reduced transplant-related mortality risk. One main reason is that, unlike busulfan, treosulfan is not metabolized in the liver and thus avoids the common liver toxicity known as veno-occlusive disease.

“It is still a powerful myeloablative drug,” Dr. Burroughs explained. “Treosulfan still wipes out the immune system, but it has fewer side effects. Patients get the benefits of a full intensity regimen, but with significantly reduced risk of acute complications.”

Now Available: Options for Any Child Who Needs a Transplant

The treosulfan protocol is just the latest addition to the wide selection of safer protocols available at the SCCA suited for practically any patient situation.

“We’ve come tremendously far in the past 10 years in terms of developing safer transplant regimens as well as expanding donor choices,” Dr. Burroughs said. “This progress has been very important in overcoming many of the historical barriers to transplantation.”

Today, in addition to the treosulfan protocol, SCCA has a full spectrum of transplant treatment options that are tailored to the specific disease and donor stem cell source.

“We also offer bone marrow, peripheral, and cord blood donors,” Dr. Burroughs said. “And in terms of HLA matching, we have related, unrelated, and haploidentical. With all these options, we can offer transplantation for nearly all patients with nonmalignant diseases who need this potentially life saving therapy.”

To provide a lasting forum for developing more patient-specific transplant treatment options, Dr. Burroughs and colleagues established the Nonmalignant Board. “Patients with nonmalignant diseases have unique underlying medical problems that require the expertise of multiple subspecialists,” Dr. Burroughs said, who leads the group. The Nonmalignant Board now meets twice a month and is teleconferenced to eight collaborating institutions across the U.S.

“The only way we are going to improve the care of patients with rare nonmalignant diseases is if we work together,” Dr. Burroughs said. “Every patient is discussed at the Nonmalignant Board. Therefore, every patient has multiple experts weighing in on the best possible treatment options.”

Asked what key message she wants to convey to pediatricians, Dr. Burroughs replied: “We are developing safer treatment options for patients with nonmalignant diseases. As a result more children and young adults are surviving and leading healthy productive lives. Early treatment is essential for successful outcomes. We would like to see these patients as early as possible in their disease course so we can help their physicians navigate treatment options.”

For more information about pediatric transplants, please go to www.seattlecca.org/bonemarrowtransplant or call our intake office at (800) 804-8824 and ask for a pediatric transplant doctor. You can reach Dr. Lauri Burroughs directly at (206) 667-2396 or email lburroug@fhcrc.org.

Facts About the Treosulfan Clinical Trial

Title: Allogeneic HCT for Nonmalignant Inherited Disorders w/ Treosulfan (FHCRC-2256).

ClinicalTrials.gov identifier: NCT00919503

Objective: This phase II study will determine efficacy and safety of treosulfan and fludarabine with or without radiation followed by allogeneic HCT.

Patients: At least 30 patients, age <55 years, with nonmalignant inherited disease such as: 

  • Primary immunodeficiency diseases or disorders (eg, chronic granulomatous disease, IPEX syndrome, Wiskott Aldrich Syndrome); 
  • Metabolic storage diseases (eg, mucopolysaccharidosis type 1, Hurler syndrome, adrenal leukodystrophy); 
  • Sickle cell disease and other hemoglobulinopathies (eg, thalassemia); 
  • Osteopetrosis; 
  • Hemophagocytic lymphohistiocytosis; 
  • Inherited marrow failure syndromes (eg, dyskeratosis congenita, Shwachman-Diamond syndrome, Diamond Blackfan anemia).

Excluded: patients with Fanconi’s anemia.

Participating Study Centers: Seattle Cancer Care Alliance (Seattle, WA); Oregon Health and Science University (Portland, OR); Children’s Hospital of Wisconsin (Milwaukee, WI), Children’s Hospital at Vanderbilt (Nashville, TN).

For more information, visit www.seattlecca.org/clinical-trials/transplant-2256.cfm.

Questions regarding eligibility or protocol information should be directed to the Principal Investigator, Dr. Lauri Burroughs (206) 667-2396 or email lburroug@fhcrc.org.

SCCA Transplant Trials for Pediatric Patients

If you have a patient who may benefit from one of these clinical trials, please call (800) 804-8824 to determine the exact eligibility requirements and to inquire if even newer studies may be more appropriate for your patient. Please remember that many other standard and/or investigational and combination treatment options are available at the SCCA for your patients.

See specific trial details in the online Clinical Trials Database for the Seattle Cancer Care Alliance: www.seattlecca.org/clinicaltrials

The following SCCA clinical trials are open to most children under 18 years of age. 

Related Documents:

01-17-2012 Peds_BMT_News_Nov_2011.pdf (6880kb)
PDF of this issue of Pediatric Bone Marrow Transplant Newsletter.

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