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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-05-1340.
Submitted May 6, 2002
Accepted September 20, 2002
Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases
Dietger Niederwieser*, Michael Maris, Judith A Shizuru, Effie Petersdorf, Ute Hegenbart, Brenda M Sandmaier, David G Maloney, Barry Storer, Thoralf Lange, Thomas Chauncey, Michael Deininger, Wolfram Poenisch, Claudio Anasetti, Ann Woolfrey, Marie-Terese Little, Karl G Blume, Peter A McSweeney, and Rainer F Storb
Hematology and Oncology, University of Leipzig, Leipzig, Germany
Fred Hutchinson Cancer Research Center, Seattle, WA, USA; School of Medicine, University of Washington, Seattle, WA, USA
Stanford University, Stanford, CA, USA
Fred Hutchinson Cancer Research Center, Seattle, WA, USA; School of Medicine, University of Washington, Seattle, WA, USA; Veterans Administration Medical Center, Seattle, WA, USA
University of Colorado Health Sciences Center, Denver, CO, USA
* Corresponding author; email: dietger{at}medizin.uni-leipzig.de.
Background: Toxicities of high-dose conditioning regimens have limited the use of conventional unrelated donor hematopoietic cell transplantation (HCT) to younger, medically fit patients. Based on preclinical studies, an HCT approach has been developed for elderly or medically infirm patients with HLA-matched or mismatched unrelated donors. Methods: Fifty-two patients with hematological diseases were included. Most (88%) had preceding unsuccessful conventional HCT or refractory/advanced disease. Patients were treated with fludarabine 30 mg/m2/day from days -4 to -2, 2 Gy TBI on day 0, cyclosporine at 6.25 mg/kg twice daily from day -3 and MMF at 15 mg/kg twice daily from day 0. Results: Durable donor chimerism was attained in 88% of the patients. By day 28, a median of 100% of CD56+ cells were of donor origin. Granulocyte and T-cell donor chimerism increased to medians of 100% on day 56 and day 180 (range 55-100%) respectively. Acute GVHD, grade II, was seen in 42% (CI 29-56%), grade III in 8% (CI 0-15%), and grade IV in 13% (CI 4-23%) of patients; it was fatal in 9%. The 100 day transplant related mortality was 11%. Complete remissions, including molecular remissions, were seen in 45% of patients with measurable disease pretransplant. Mortality from disease progression was 27% at one year. With a median follow-up of 19 months, 18 of the 52 patients (35%) were alive and 25% were in remission. Conclusions: HCT from HLA-matched or mismatched unrelated donors can be performed with a reduced intensity conditioning regimen in patients ineligible for conventional HCT.
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