Stem Cell Transplantation for Advanced Myelodysplastic Syndrome

Hematopoietic Stem Cell Transplantation for Advanced

Myelodysplastic Syndrome After Conditioning With

Busulfan and Fractionated Total Body Irradiation

Is Associated With Low Relapse Rate but

Considerable Nonrelapse Mortality

Manuel Jurado, H. Joachim Deeg, Barry Storer, Claudio Anasetti, Jeanne

E. Anderson, Eileen Bryant, Thomas Chauncey, Kris Doney, Mary E. D.

Flowers, John Hansen, Paul J. Martin, Richard A. Nash, Effie Petersdorf,

Jerry Radich, George Sale, Brenda M. Sandmaier, Rainer Storb, James

Wade, Robert Witherspoon, Frederick R. Appelbaum

Biology of Blood and Marrow Transplantation 8:161-169 (2002)

ABSTRACT

The objectives of this study were to develop transplantation regimens

for patients with advanced myelodysplastic syndrome (MDS) that would be

associated with low transplantation-related mortality and improved

relapse-free survival. Sixty patients with advanced MDS or acute myeloid

leukemia evolving from MDS (sAML), 12 to 62 years old (median, 40

years), were conditioned with busulfan (7 mg/kg) and TBI (6 x 200 cGy)

(BU/TBI) and received transplants from related (n = 20) or unrelated

donors (n = 40). By French-American-British (FAB) criteria, 21 patients

had refractory anemia with excess blasts (RAEB), 16 had RAEB in

transformation (RAEB-T), 15 had sAML, and 8 had chronic myelomonocytic

leukemia (CMML). By International Prognostic Scoring System (IPSS)

criteria, 1 patient had low, 10 had intermediate-1, 13 had

intermediate-2, and 31 had high-risk MDS (5 patients had proliferative

CMML). All evaluable patients achieved sustained engraftment. The

cumulative incidence (CI) of acute GVHD grades II to IV was 83% with

unrelated donors and 85% with related donors. The CI of relapse was 25%

at 3 years. The incidence of nonrelapse mortality (NRM) at 100 days was

38%. The Kaplan-Meier estimate of survival was 26% at 3 years. Major

causes of death were relapse, organ failure, GVHD, and infection. In

multivariate analysis, improved relapse-free survival was associated

with good cytogenetic risk (P = .002) and shorter disease duration (P =

.004). NRM was increased with longer disease duration (P = .0002),

positive cytomegalovirus serology (P = .02), and male sex (P = .02).

Relapse was associated with poor cytogenetic risk (P = .0004). Thus,

BU/TBI conditioning as used in this trial was associated with relapse

rates comparable to those observed with a previously used more intensive

regimen combining BU/TBI with cyclophosphamide. However, despite the

omission of cyclophosphamide, transplantation-related morbidity and

mortality were considerable, particularly with transplants from

unrelated donors. Future trials should explore the efficacy and

tolerability of reduced-intensity conditioning regimens.

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