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ASH Annual Meeting and Exposition

An analysis of data from the Bone Marrow Transplant Survivor Study (BMTSS) suggests that long-term survivors of hematopoietic cell transplantation (HCT) have a much higher risk of chronic psychological, and physical health conditions than was previously assumed.

At 15 years post-transplant, the cumulative incidence of any chronic health condition in survivors was 71%, while the incidence of severe or life-threatening conditions or death was 40%.

“Although we have observed these rather sobering realities for 15-year post-transplant survival,” said study coauthor, Smita Bhatia, MD, MPH, chair of the department of Population Sciences, City of Hope, Duarte, CA, “we need to remember that transplant continues to be life saving, and possibly the only curative option for a large number of our patients with hematologic malignancies.” The focus of the present analysis is to determine the scope of the price paid for these successes.

Previously, Bhatia’s group had shown that patients who had HCT and who had survived 2 or more years were at increased risk of developing a wide range of chronic physical health and psychological conditions. However, as Bhatia noted, there was a lack of information regarding the burden of morbidity for survivors of much longer term.

Using resources offered by the BMTSS, Bhatia and colleagues looked at the psychological and physical health status of 366 patients with >10 years post-transplant survival, and compared these data with survivor siblings. Severity scores ranging from grade 1 (mild) to 5 (death due to chronic health condition) were assigned to each health condition. The Brief Symptom Inventory instrument was used to describe adverse psychological health.

Results for the study cohort showed that the mean age was 22 years at the time of HCT, and 37 years of age for study participation. The mean length of follow-up time was 15 years.

Regarding survivor health, at least one chronic health condition was reported by 74% survivors of HCT, as compared to 29% of the survivor’s siblings (

<0.001). Further, 25% of the survivors reported a severe life-threatening condition, compared to only 8% of their siblings (

Considered on the whole, the analysis showed that survivors had a greater than 5-fold likelihood of developing a severe, potentially life-threatening condition as compared to their age-matched siblings. Incidence of morbidity did not differ by malignancy type.

The most commonly reported severe/life-threatening chronic health conditions included stroke, myocardial infarction, diabetes, musculoskeletal problems, and subsequent malignancies. Survivors also reported a far higher incidence of anxiety and depression than their siblings.

Commenting on the study, HCT transplant specialist, Stephanie Lee, MD, MPH, professor of medicine, University of Washington School of Medicine, Seattle, WA, emphasized the need for greater awareness of the potential confounders of long-term survival. “We have a lot more HCT survivors now than we used to,” she said. “We’re thankful for that of course, but it’s important to realize that once the transplant is over, it’s not really over.” Lee stressed the need for awareness on the part of healthcare providers, their patients, and even third-party payors, of the reality that long-term, aggressive follow-up will be essential in cutting the rates of serious morbidities in patients with HCT.

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Bone Marrow Transplant Survivor Study analysis suggests long-term survivors of HCT have high risk of chronic psychological, and physical health conditions

Burden of Morbidity Reported for Long-term Survivors of Hematopoietic Cell Transplantation 

Laurie H. Sehn, MD, MPH, clinical associate professor in the division of medical oncology at the University of British Columbia and the British Columbia Cancer Agency, discusses bioengineered monoclonal antibodies and their promising future in treating patients with lymphoma. At the 53rd Annual Meeting of the American Society of Hematology, held in San Diego, Sehn presented phase II data on GA101, a monoclonal antibody that targets CD20, and how it might perform even better than rituximab, a practice-changing therapy for patients with non-Hodgkin lymphoma.

Dr. Laurie Sehn from the British Columbia Cancer Agency Discusses the Efficacy of the CD20 Agent GA101

Dr. Sehn Discusses the Efficacy of the CD20 Agent GA101

The addition of fractionated doses of gemtuzumab ozogamicin (GO) to a standard chemotherapy regimen improved both event-free, and overall survival (OS) of newly diagnosed patients with acute myeloid leukemia (AML), aged 50 to 70 years, according to results from a Phase III trial reported at the 53rd Annual Meeting of the American Society of Hematology.

“With this research we are encouraged that gemtuzumab may be able to deliver better overall outcomes for these AML patients with limited alternatives,” said lead investigator, Sylvie Castaigne, MD, professor, Department of Hematology at Hôpital de Versailles,Versailles, France.

Gemtuzumab ozogamicin (GO), a humanized monoclonal antibody linked to a cytotoxic agent, is targeted to the CD33 cell surface antigen that is present on roughly 90% of blast cells in AML. When the drug was first developed it was seen as a promising agent in treating AML; however, studies performed after the drug’s approval in 2000 raised questions about excess toxicity. These concerns persisted, and in June of 2010, the manufacturer voluntarily withdrew GO from the US market.

“In its initial development, gemtuzumab was dosed 9 mg/m

,” said Castaigne, “but this dose was so toxic we were unable to combine it with standard chemotherapy.” This led Castaigne and her colleagues to develop a new fractionated regimen. “We give 3 mg/m

 on day 1, 4, and 7, which allows us to combine it with chemotherapy. Using it this way we were able to demonstrate more efficacy,” and with less toxicity than that observed with the 9-mg bolus dose. The approach was validated in 2 previous Phase II trials.  

In the current investigation, the research team at the Acute Leukemia French Association designed a Phase III, prospective, open-label, randomized trial, enrolling treatment naïve, 

 patients with AML, ages 50 to 70 years. Study participants were randomized to 1 of 2 treatment arms — either standard chemotherapy with daunorubicin/ara-C (DC: n=134) or DC plus GO (DCGO, n=137). Study endpoints were event-free survival (EFS), disease-free survival (DFS), OS, and safety over a 3-year follow-up period.

Response rates to treatment were as follows: overall, CR+CRp was achieved in 220/271 patients (77%): 100/134 (75%) in the DC arm (control) versus 110/137 (80%) in the DCGO arm (

=0.31). Significantly, primary resistant AML rate was 29/134 (22%) after DC versus 18/137 (13%) after DCGO (

=0.08). Regarding safety at induction, there were 5/134 (4%) induction deaths in the DC arm and 9/137 (6%) in the DCGO arm (

Adding gemtuzumab to chemotherapy improved event-free and OS of newly diagnosed patients with acute myeloid leukemia.

Minimal Dosing Strategy With Gemtuzumab Ozogamicin Improves Survival in Older Patients With Acute Myeloid Leukemia 

A new study has found that peripheral blood stem cell (PBSC) transplants from unrelated donors increase the incidence of graft-versus-host disease (GVHD), thereby putting into question the validity of using a form of transplantation that had previously been shown to be clinically beneficial.

The phase III, prospective, randomized, multicenter trial, which was presented at the 53rd Annual Meeting of the American Society of Hematology, held in San Diego, California, found that 53% of patients receiving PBSC transplants experienced overall chronic GVHD, compared to 40% of patients who had received bone marrow transplants (

=0.02). The study also found that 46% of patients had chronic extensive GVHD, compared to 31% of patients who received bone marrow stem cells.

Peripheral blood stem cells are stem cells that are found in bone marrow, which have been moved into the bloodstream through a special regimen such as apheresis, which collects PBSCs through a tube inserted into the vein. This method has been used more frequently in the transplant setting, because about 70% of patients receiving transplants who cannot find a donor within their family are able to find an unrelated donor who can supply them with PBSCs. Previous studies that examined patients who received PBSCs from related donors showed that patients had better engraftment after the transplant, lower relapse rates, and increased survival rates compared to patients who had received bone marrow transplants. However, those trials also showed an increased incidence in GVHD.		

Claudio Anasetti, MD, chair of the department of Blood and Marrow Transplant at H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida and lead author of the study, said that there has been a 75% increased use of PBSCs from unrelated donors without any appropriate study. Researchers from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducted the trial to compare 2-year survival probabilities in patients who had received PBSC transplants or bone marrow transplants. Patients were randomized to receive bone marrow transplants (n=278) or PBSCs (n=273) as the graft source.

While the trial found no differences in overall survival, relapse, nonrelapse mortality, or acute GVHD between patients who had received these grafts from unrelated donors, the differences in GVHD proved to be a major point of concern.

"The increase was significant," said Anasetti at the meeting. "Why would anyone want to have a 16% increase of living with graft-versus-host disease?"

Graft-versus-host disease often results from slight differences between the cells of the donor and the recipient, which cause T-cells from the newly transplanted organ to attack the recipient's body. Chronic GVHD can be managed by immunosuppressive drugs, which can lower the body's ability to fight infection. The National Institutes of Health estimate that between 30% and 40% of patients who receive a donated organ from a related donor experience GVHD, while 60% to 80% of patients who receive an organ from an unrelated donor experience the disease.

Anasetti said that the results of this trial will, most likely, cause many transplant physicians to rethink treatment strategies for patients, including whether or not bone marrow transplants are a more appropriate method for patients with various forms of blood cancer. However, Anasetti said PBSCs may still be a treatment option despite the trial, because bone marrow transplants are less likely to achieve engraftment.

"More effective strategies to prevent graft-versus-host disease are needed to improve outcomes for all patients receiving unrelated donor transplants," Anasetti said.

Study finds that peripheral blood stem cell (PBSC) transplants increase the incidence of graft-versus-host disease (GVHD).

Peripheral Blood Stem Cell (PBSC) Transplants Increase the Incidence of Graft-Versus-Host Disease (GVHD)

James N. Kochenderfer, MD, Experimental Transplantation and Immunology Branch, National Cancer Institute in Bethesda, MD, discusses the B-cell antigen CD19 and its role in chemotherapy-resistant B-cell malignancies. At the 53rd Annual Meeting of the American Society of Hematology, held at the San Diego Convention Center, Kochenderfer presented data on 8 patients treated with an anti-CD19 chimeric antigen receptor. While the agent did cause some toxicity in patients, it was able to eliminate targeted cells.

Dr. James Kochenderfer from the National Cancer Institute Discusses the B-cell Antigen CD19

Dr. Kochenderfer Discusses the B-cell Antigen CD19

Tatyana Feldman, MD, a hematologist and oncologist who specializes in lymphoma at John Theurer Cancer Center at Hackensack University Medical Center in Hackensack, NJ, discusses how difficult it is to treat rare forms of lymphoma. Many of these cases are diagnosed in early stages and pose more of a nuisance to the patient, but later stages are very serious, and there are not as many good therapies that exist for treating this relatively small population of patients.

Dr. Tatyana Feldman from John Theurer Cancer Center Discusses the Difficulties of Rare Lymphomas

ASH Annual Meeting and Exposition | Conference

Burden of Morbidity Reported for Long-term Survivors of Hematopoietic Cell Transplantation

Dr. Sehn Discusses the Efficacy of the CD20 Agent GA101

Minimal Dosing Strategy With Gemtuzumab Ozogamicin Improves Survival in Older Patients With Acute Myeloid Leukemia

Peripheral Blood Stem Cell (PBSC) Transplants Increase the Incidence of Graft-Versus-Host Disease (GVHD)

Dr. Kochenderfer Discusses the B-cell Antigen CD19

Dr. Feldman Discusses the Difficulties of Rare Lymphomas