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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-05-1340.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1620-1629
TRANSPLANTATION
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 Pönisch,
Claudio Anasetti,
Ann Woolfrey,
Marie-Terese Little,
Karl G. Blume,
Peter A. McSweeney, and
Rainer
F. Storb
From the Division of Hematology and Oncology,
University of Leipzig, Leipzig, Germany; Fred Hutchinson
Cancer Research Center and University of Washington School of Medicine,
Seattle, WA; Stanford University, Stanford, CA; Veterans Administration
Medical Center, Seattle, WA; and University of Colorado Health Sciences
Center, Denver, CO.
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. In this study, 52 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/d from days  4 to 2, 2 Gy total body
irradiation on day 0, cyclosporine at 6.25 mg/kg twice daily from day
3, and mycophenolate mofetil at 15 mg/kg twice daily from day
0. 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 transplantation-related mortality was 11%. Complete
remissions, including molecular remissions, were seen in 45% of
patients with measurable disease before transplantation. 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. 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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