Adult Bone Marrow Transplant NewsOutcomes Studies Reveal Patients’ Post-Transplant Experiences
Adult Bone-Marrow Transplant News
Outcomes Studies Reveal Patients’ Post-Transplant Experiences
“Recovering from a bone-marrow or stem-cell transplant doesn’t end when you come home from the transplant center, or even in the first year or the first five years. Recovery is ongoing. We’re trying to enhance health and wellbeing for the rest of the transplant recipient’s lifespan,” says Stephanie Lee, MD, MPH. She is among the many researchers studying hematopoietic cell transplant outcomes at Fred Hutchinson Cancer Research Center.
Read about important outcomes research at the Hutchinson Center that may benefit your patients:
Unraveling Chronic Graft-vs.-Host Disease
Hutchinson Center leads an NIH-funded, multi-center study of 700 patients to understand and better treat this potentially devastating complication.
One-Year Follow-Up: What Is It Good For?
A review of records from comprehensive follow-up visits by patients one year after transplant reveals the frequency of abnormal findings and how often treatment changes because of these findings.
Increased Risk for Second Cancer After Transplant
To advise transplant survivors about cancer screenings, we need to better understand why they’re at increased risk for a second cancer. Researchers are looking for the factors that matter.
Examining the Many Dimensions of Post-Transplant Life
Outcomes research runs the gambit, examining everything from musculoskeletal complications, to sexual function, to emotional distress, to return-to-work time.
Does Transplant Raise Risk of Heart Problems?
With data from Washington State about heart-related hospitalizations, researchers are checking whether transplant recipients face increased risk for heart problems later in life.
Using Imatinib and Nilotinib to Prevent Post-Transplant Relapse
Very early after transplant, leukemia patients can tolerate imatinib, which may help prevent relapse. Now researchers are set to test a related drug many times more powerful.
Progress of GVHD
Hutchinson Center research focuses on graft-vs.-host disease (GVHD), both preventing and treating it — which leads to an interest in improving methods used assess it.
A multi-center observational study of chronic graft-vs.-host disease (GVHD), which opened to enrollees in fall 2007 at the Hutchinson Center and elsewhere, may help dispel the frustration of doctors and patients struggling to understand this complication and how to treat it with only the results of small, fragmented studies to guide them.
Centers Unite for a Common Cause
“There’s been a big effort around the country to take a closer look at chronic graft-versus host disease,” explains Stephanie Lee, MD, MPH. But small sample sizes at individual institutions have limited the data researchers could gather and the conclusions they could draw. Three years ago, the National Institutes of Health (NIH) assembled transplant experts from around the country, including several from Hutchinson Center, to meet and devise standard definitions and protocols for transplant researchers. The current project grew out of those efforts to establish a subgroup to spearhead multi-center studies.
"We will both study what the physicians say about their patients’ health and ask the patients how they’re doing. What’s important to the doctor is not always what’s important to the patient.”
Hutchinson Center is the lead center for Study 2192: Improving Outcomes Assessment in Chronic GVHD, which is funded by NIH and aims to follow 700 adults and children for five years, using comprehensive measures to document how GVHD does or does not affect them over time. “We will both study what the physicians say about their patients’ health and ask the patients how they’re doing, such as asking about symptoms and quality of life. What’s important to the doctor is not always what’s important to the patient. The two types of data are very complementary,” says Lee.
Refining GVHD Treatment
Lee hopes the study will help researchers learn who’s destined to have more problems with GVHD, how to identify these patients as early as possible, and how not to undertreat patients who need interventions but also not overtreat those who don’t. Because the seven centers involved in the study offer somewhat different therapies, researchers may also be able to determine which therapies are more effective.
“Both adults and children will be enrolled at all centers, which also offers us the ability to compare GVHD in these two populations,” says Lee. The same measurement tools will be used to evaluate adults and children. This should give researchers greater insight into whether GVHD is the same syndrome regardless of patients’ age.
“We’re hoping this study is going to form the backbone for other studies,” says Lee, including investigations into the biology of GVHD and approaches that may help prevent it.
On or near the first anniversary of their hematopoietic cell transplant, most patients make a pilgrimage back to the Hutchinson Center for a comprehensive follow-up visit. Recently researchers at the Center reviewed one year’s worth of records from these visits, looking for clues to how to make the visits as useful as possible for patients, their long-term follow-up team, and their community doctors.
Records of 118 patients who received an allogeneic transplant in 2005 revealed a high percentage of patients who had abnormal test results leading the long-term follow-up team to recommend a change in their therapy, such as taking a different medicine or taking it in a different way. The researchers looked at which abnormalities occurred, which therapeutic changes the team recommended, and which kinds of tests or other evaluations had been most useful to them in assessing patients’ health.
Consensus guidelines based on expert opinion, much of it from doctors at Hutchinson Center, have shaped transplant follow-up visits for years. By continuing such records review and collaborating with other transplant centers, the Hutchinson Center team intends to refine its guidelines on the basis of data, provide recommendations to other centers that are developing follow-up programs, and create a standard packet of information about one-year follow-up visits for patients across centers.
- Read about our long-term follow-up program
- Download our post-transplant guidelines for referring physicians
- Visit our frequently asked questions about long-term follow-up for patients and families.
Why do some patients whose cancer was successfully treated with a hematopoietic cell transplant go on to develop a second cancer? The answer matters so doctors can advise transplant survivors about the cancer screenings they need.
Which Factors Influence Risk?
Researchers know that certain cancer treatments increase patients’ risk for a second cancer, says Debra Friedman, MD, director of the Hutchinson Center Survivorship Program. But many patients who get these treatments don’t develop second cancers, which leads researchers to speculate that some people are predisposed to develop cancer again thanks to certain as-yet-unidentified risk factors. It’s a speculation Friedman is investigating in Study 2023: “Radiation Sensitivity, DNA Repair and Second Cancers.”
“The goal of this study is to try to tease out other factors that may interact with treatment factors to increase risk,” explains Friedman. “We’ll be looking at many factors, including genetic factors, such as variations in genes necessary for metabolizing chemotherapy or for repairing DNA damaged by radiation or chemotherapy; whether the patients have an inherited sensitivity to radiation; whether they have exposures that might increase their risk for certain cancers, such as tobacco use, which might increase risk for mouth cancer; and whether they have a family history of cancer.”
Enrolling Transplant Survivors with Second Cancers
The research team started enrolling subjects in 2004, contacting SCCA transplant survivors whom we know have developed a second cancer to invite them to participate. If you know transplant survivors who have had a second cancer and not yet been invited to join the study, please invite them to contact Melissa Alvendia, the study coordinator at the Hutchinson Center for information at 206-667-3777 or toll-free at 866-429-7709. The team will also be recruiting controls, people who have had the same disease and transplant but no second cancer.
Read some publications on second cancer after transplant by Friedman and other researchers at the Hutchinson Center:
- Friedman DL et al. “Increased Risk of Breast Cancer Among Survivors of Allogeneic Hematopoietic Cell Transplantation: A Report from the FHCRC and the EBMT-Late Effect Working Party.” Blood, January 2008, vol. 111, no. 2, p. 939-44. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/17911386]
- Leisenring W et al. “Nonmelanoma Skin and Mucosal Cancers After Hematopoietic Cell Transplantation.” Journal of Clinical Oncology, March 2006, vol. 24, no. 7, p. 1119-1126. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/16461782]
- Friedman DL et al. “Second Malignant Neoplasms Following Hematopoietic Stem Cell Transplantation.” International Journal of Hematology, April 2004, vol. 79, no. 3, p. 229-234. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/15168589]
“Outcomes” after a hematopoietic cell transplant can refer to numerous, diverse dimensions of patients’ physical as well as cognitive and psychosocial health. Researchers like psychologist Karen Syrjala, PhD, director of Biobehavioral Sciences and co-director of the Hutchinson Center Survivorship Program, explore these many dimensions, seeking to understand and improve post-transplant life.
What’s Happening 5 and 10 Years Out
Syrjala’s research includes a study of two cohorts of adult transplant recipients, both evaluated starting before transplant, one followed for 5 years and the other followed for 10. The research team has collected patient reports of how they are doing in quality of life, symptoms, function, and psychological state. Then they’ve evaluated outcomes ranging from muscle, joint and bone complications, to sexual function, to emotional distress or worry, to return-to-work time.“Transplant recipients who are doing well may think they don’t need to be in studies. But, yes, we do need to hear from you so we can see that you’re doing well and learn why.”
The investigation has yielded interesting results. “The slowest areas of recovery are in the distress that people experience and the time it takes them to return to work,” says Syrjala. “We also find they have higher rates of musculoskeletal complaints than the average U.S. adult population of the same age. They have more aches, cramps, and stiffness. They feel weaker. Some don’t recover fully in stamina and energy as we might hope.”
Ways Survivors Are Doing Well
“Emotionally our survivors are doing very well. At three years out from their transplant, they look very much like the average population,” says Syrjala. This contrasts with results from studies of national samples of transplant recipients not including patients from the Hutchinson Center. Those studies tend to show that patients have significantly poorer psychosocial functioning than case-matched controls.
“I think there are two reasons,” says Syrjala. “One is that we stay in touch with our survivors and provide them with ongoing long-term support. The other is that when we do our research we make a very concerted effort to get a full representation of our population of transplant recipients—including people who are doing well.” Other transplant centers are more likely to collect data only from survivors with poorer function because they are more likely to receive follow-up care and participate in research.
“Transplant recipients who are doing well may think they don’t need to be in studies,” says Syrjala. “But, yes, we do need to hear from you so we can see that you’re doing well and learn why.”
Read about a new study of survivors called “INSPIRE: Internet Program for a Randomized Controlled Trial (RCT) on Fatigue and Distress for Long-Term Cancer Survivors.” At press time, INSPIRE is in the IRB approval process. Syrjala, who is the principal investigator, expects to begin enrolling participants in the summer of 2008, at which time the public Web site INSPIREforsurvivors.org will be up and running online.
Learn about active research projects in Biobehavioral Sciences at Hutchinson Center.
Read some of Syrjala’s transplant outcomes publications:
- Syrjala KL et al. “Sexual Function Changes During the 5 Years After High-Dose Treatment and Hematopoietic Cell Transplantation for Malignancy, with Case-Matched Controls at 5 Years.” Blood, February 2008, vol. 111, no. 3, p. 989-96. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/17878404]
- Hammond C et al. “Fertility and Risk Factors for Elevated Infertility Concern in 10-Year Hematopoietic Cell Transplant Survivors and Case-Matched Controls.” Journal of Clinical Oncology, August 2007, vol. 25, no. 23, p. 3511-7. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/17646668]
- Syrjala KL et al. “Late Effects of Hematopoietic Cell Transplantation Among 10-Year Adult Survivors Compared with Case-Matched Controls.” Journal of Clinical Oncology, September 2005, vol. 23, no. 27, p. 6596-606. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/16170167]
- Syrjala KL et al. “Neuropsychologic Changes from Before Transplantation to 1 Year in Patients Receiving Myeloablative Allogeneic Hematopoietic Cell Transplant.” Blood, November 2004, vol. 104, no. 10, p. 3386-92. Abstract on PubMed [http://www.ncbi.nlm.nih.gov/pubmed/15251983]
Data collected by the State of Washington will help Eric Chow, MD, MPH, trace whether children and adults who receive a hematopoietic cell transplant are at increased risk for heart problems later in life.
All hospitals in the state are required to report the kinds of hospitalizations that occur there every year for every patient. Washington State now has more than 20 years of such data. By teasing out which patients were hospitalized for heart problems and then linking this data to data from the Hutchinson Center about our transplant recipients in an anonymous way, Chow will be able to see whether transplant recipients are at greater risk than the general population.
Many transplant recipients do very well, but some develop secondary health problems. Our scientists are researching how to prevent and treat these problems.
Studies published so far about a possible link have involved small numbers of patients over a limited follow-up period, says Chow. The method described here will allow him to look at a relatively large group of patients over a longer follow-up period. It also eliminates the challenges associated with locating and enrolling eligible participants. Chow expects to begin analyzing the data in the summer of 2008.
“Many people who’ve had a transplant do very well,” says Chow. “Within months, they’re able to be off medicines and go back to a fairly normal life. Others have a lot of secondary problems. We’re trying to make most people fall into first category, of course. But we’re also looking into the secondary problems to learn how we might prevent or treat them.”
Very early after hematopoietic cell transplants, patients were able to tolerate doses of imatinib mesylate (Gleevec®) comparable to doses used in primary therapy, according to study published in Blood in 2007. The findings may be important to help prevent disease relapse.
Lead author Paul Carpenter, MD, of the Hutchinson Center, and colleagues tested imatinib in 22 patients, most with acute lymphoblastic leukemia (ALL), to show that this use of the drug is feasible. A follow-up study at the Hutchinson Center, expected to begin recruiting patients in early summer 2008, will take a similar look at nilotinib (Tasigna®).
“We’re going to see whether this new drug — which is related to Gleevec but is at least 20 times more powerful — might also be tolerated very early after transplant,” explains Carpenter. “There is reason to believe that certain side effects might occur less frequently than with Gleevec. If it is well tolerated, we expect it to be even more effective at preventing relapse.”
Survival Data “Very Encouraging”
The imatinib study involved 15 patients with Philadelphia chromosome-positive ALL and seven with high-risk chromic myelogenous leukemia; 19 adults and three children. They received the drug for one year, starting at the time of engraftment.
Though the researchers’ primary question was whether it is possible to give imatinib safely very early after transplant, they also looked at survival data, and Carpenter calls the results “very encouraging.” Since the study closed, the team has treated several more patients with the same protocol. More than three-quarters of them, including all 10 children treated, are alive at press time.
More About These Studies
- Check the Hutchinson Center clinical trials search [http://www.fhcrc.org/patient/treatment/trials/] page for Protocol 2223 to get information about the upcoming nilotinib study once it’s open for enrollment.
- Read about the imatinib study here: Carpenter PA et al. “Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia.” Blood, April 1, 2007, vol. 109, no. 7, p. 2791-3. Abstract [http://www.ncbi.nlm.nih.gov/pubmed/17119111] on Pubmed
In addition to reducing relapse, Carpenter’s research focuses on graft-vs.-host disease (GVHD), both preventing and treating it — which leads to an interest in improving methods used assess it.
The individual physicians treating patients with GVHD have largely defined assessment of how well the treatment is working, says Carpenter. Ideally, researchers would like standardized, objective measures. “But these are hard to establish,” says Carpenter, “because GVHD affects many different organs. There are many signs and symptoms that factor into the analysis.” He and other researchers are working to develop methods to quantify whether a particular treatment improves GVHD or not.
Carpenter is involved in several other research efforts related to GVHD, including these:
- A clinical trial, known as BMT CTN Protocol 0801, under development by the Blood and Marrow Transplant Clinical Trials Network, [https://web.emmes.com/study/bmt2/] to test a new treatment for chronic GVHD from its earliest stages in both children and adults
- An investigation comparing the initial treatment of acute GVHD using steroids and mesenchymal stem cells with standard therapy using steroids plus placebo (FHCRC Protocol 2229)
- A Children’s Oncology Group (COG) [http://www.childrensoncologygroup.org/] study called ASCT0631 to evaluate whether transplants with G-mobilized bone marrow are more successful than standard bone marrow transplants from matched related sibling donors
- A COG study called ASCT0431 testing use of the immunosuppressant drug sirolimus (Rapamune®) to prevent GVHD in children undergoing transplant for acute lymphoblastic leukemia
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