The study was designed to evaluate the role of [F]FDG-PET before high- dose chemotherapy followed by stem cell transplants in predicting progression-free survival and overall survival. Due to the improved outcomes of lymphoma patients after induction treatment with the newest generation of chemotherapy agents, non-responding or relapsing patients are becoming harder to treat. Recently, [F]FDG-PET has been identified as the most helpful, non-invasive metabolic imaging technique allowing differentiation between active tumors and fibrosis. It also has demonstrated its important prognostic value after completion of first-line therapy in patients with both Hodgkin's disease and non-Hodgkin's lymphoma.
"While the use of high dose chemotherapy combined with stem cell transplantation has been shown to be the best available treatment for lymphoma patients who do not respond or who relapse after first-line treatment, a portion of these patients will develop recurrent disease after this toxic treatment," according to Karoline Spaepen, M.D., Ph.D., department of Nuclear Medicine, University Hospital Gasthuisberg, Leuven, Belgium, and lead author of the study. "With this study, we hope to identify those patients who would not respond to this treatment, and may benefit from newer experimental regimens."
In the study, researchers conducted a retrospective analysis of the clinical and conventional imaging data of 60 patients scheduled for high dose chemotherapy followed by stem cell transplantation, while simultaneously analyzing the [F]FDG-PET results. Of the 60 scans performed prior to high dose chemotherapy followed by stem cell transplantation, half of the scans were considered negative (not affirming the presence), and half of the scans showed residual abnormal amounts of FDG update (considered positive).
Of the 30 patients with a negative pretransplant scan, 25 are still in complete remission after a median follow-up of 1,510 days. According to conventional diagnostic measures taken at the same time, 16 of these patients achieved a complete response and only nine patients had a partial response. Two patients died after achieving a complete response following high dose chemotherapy followed by stem cell transplantation – one from cardiac arrest, the other from late septic shock due to a fungal infection. Of the three remaining patients who relapsed after a negative pretransplant [F]FDG-PET, two patients relapsed due to low grade lymphoma, and the third had minimal residual disease.
Conversely, of the 30 positive scans, 26 patients relapsed after receiving the high dose chemotherapy followed by stem cell transplants. The median progression-free survival (the time interval from the date of entry into salvage therapy until the first objective evidence of relapse/progression, or the date of last follow-up) was 402 days. Although all of the patients were categorized as chemosensitive to salvage (save by therapeutic measures) chemotherapy based on conventional diagnostic measures, 12 patients in this group achieved a partial response before high dose chemotherapy and stem cell transplantation. In the remaining 14 patients, conventional diagnostic measures showed no evidence of residual lymphoma, therefore only [F]FDG-PET was positive for residual disease. During further treatment, 16 patients died of progressive disease (median overall survival was 480 days); six patients are still under treatment and four patients achieved a complete response after additional high dose chemotherapy and allogeneic stem cell transplantation (stem cells from an unrelated donor). Only four patients with a positive pretransplantation [F]FDG-PET achieved a complete response after high dose chemotherapy followed by stem cell transplantation and sustained a complete response after a median follow-up of 1,326 days.
"As hematologists, we strive to not only identify the best treatments for our patients, but also for ways to identify those patients who will most benefit from these treatments," said Ronald Hoffman, MD, President of the American Society of Hematology and Director of the Cancer Center at University of Illinois Medical Center at Chicago. "The research conducted by Dr. Spaepen and her colleagues brings us one step closer to ensuring that those patients undergoing rigorous treatment with high dose chemotherapy followed by stem cell transplantation will benefit from this often difficult procedure."
Patients in the study had either Hodgkin's disease or non-Hodgkin's lymphoma with induction failure (progression during induction treatment or within 90 days after the end of treatment) or first/subsequent relapse; sensitivity to conventional dose salvage chemotherapy; a follow-up of at least one year; and a [F]FDG-PET scan in addition to conventional diagnostic methods at restaging between salvage therapy with high dose chemotherapy followed by stem cell transplantation performed within an interval of at least three weeks after the last chemotherapy or last irradiation and not more than eight weeks prior to high dose chemotherapy followed by stem-cell transplantation.
According to the American Cancer Society, 61,000 people will be diagnosed with lymphoma in the United States in 2003; of these, 7,600 people will be diagnosed with Hodgkin's disease and more than 53,400 people will be diagnosed with non-Hodgkin's lymphoma. Since the early 1970s, incidence rates for non-Hodgkin's lymphoma have nearly doubled, although the rates stabilized in the 1990s. The incidence rates for Hodgkin's disease have declined significantly since the late 1980s. An estimated 24,700 deaths from lymphoma will occur in 2003 – 1,300 from Hodgkin's disease, and 23,400 from non-Hodgkin's lymphoma.
Blood, the Journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. All articles undergo rigorous peer review and are selected for publication on the basis of the originality and quality of the work described. As a special service to researchers and clinicians, accepted papers are made available online about three months ahead of print as "First Edition Papers." Blood is issued to Society members and other subscribers twice per month, available in print and online.
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