131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission

被引:111
作者
Pagel, JM
Appelbaum, FR
Eary, JF
Rajendran, J
Fisher, DR
Gooley, T
Ruffner, K
Nemecek, E
Sickle, E
Durack, L
Carreras, J
Horowitz, MM
Press, OW
Gopal, AK
Martin, PJ
Bernstein, ID
Matthews, DC
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
[2] Univ Washington, Dept Pediat, Seattle, WA 98195 USA
[3] Univ Washington, Dept Med, Seattle, WA USA
[4] Univ Washington, Dept Radiol, Seattle, WA 98195 USA
[5] Pacific NW Natl Lab, Richland, WA 99352 USA
[6] Med Coll Wisconsin, Milwaukee, WI 53226 USA
关键词
D O I
10.1182/blood-2005-06-2317
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 study in which targeted irradiation delivered by I-131-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/mL) and cyclophosphamide (CY; 120 mg/kg). Fifty-two (88%) of 59 patients receiving a trace I-131-labeled dose of 0.5 mg/kg anti-CD45 murine antibody had higher estimated absorbed radiation in bone marrow and spleen than in any other organ. Forty-six patients were treated with 102 to 298 mCi (3774-11 026 MBq) I-131, delivering an estimated 5.3 to 19 (mean, 11.3) Gy to marrow, 17-72 (mean, 29.7) Gy to spleen, and 3.5 Gy (n = 4) to 5.25 Gy (n = 42) to the liver. The estimated 3-year nonrelapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These, results were compared with those from 509 similar International Bone Marrow Transplant Registry patients who underwent transplantation using BU/CY alone. After adjusting for differences in age and cytogenetics risk, the hazard of mortality among all anti body-treated patients was 0.65 times that of the Registry patients (95% CI 0.39-1.08; P = .09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and phase 2 results are sufficiently encouraging to warrant further study.
引用
收藏
页码:2184 / 2191
页数:8
相关论文
共 64 条
[1]   THE USE OF RADIOLABELED ANTI-CD33 ANTIBODY TO AUGMENT MARROW IRRADIATION PRIOR TO MARROW TRANSPLANTATION FOR ACUTE MYELOGENOUS LEUKEMIA [J].
APPELBAUM, FR ;
MATTHEWS, DC ;
EARY, JF ;
BADGER, CC ;
KELLOGG, M ;
PRESS, OW ;
MARTIN, PJ ;
FISHER, DR ;
NELP, WB ;
THOMAS, ED ;
BERNSTEIN, ID .
TRANSPLANTATION, 1992, 54 (05) :829-833
[2]  
BADGER CC, 1986, CANCER RES, V46, P6223
[3]   REGIMEN-RELATED TOXICITY IN PATIENTS UNDERGOING BONE-MARROW TRANSPLANTATION [J].
BEARMAN, SI ;
APPELBAUM, FR ;
BUCKNER, CD ;
PETERSEN, FB ;
FISHER, LD ;
CLIFT, RA ;
THOMAS, ED .
JOURNAL OF CLINICAL ONCOLOGY, 1988, 6 (10) :1562-1568
[4]  
BUCHSBAUM DJ, 1992, CANCER RES, V52, P6476
[5]   Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome:: results of a phase I-II study [J].
Bunjes, D ;
Buchmann, I ;
Duncker, C ;
Seitz, U ;
Kotzerke, J ;
Wiesneth, M ;
Dohr, D ;
Stefanic, M ;
Buck, A ;
Harsdorf, SV ;
Glatting, G ;
Grimminger, W ;
Karakas, T ;
Munzert, G ;
Döhner, H ;
Bergmann, L ;
Reske, SN .
BLOOD, 2001, 98 (03) :565-572
[6]   Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias [J].
Burke, JM ;
Caron, PC ;
Papadopoulos, EB ;
Divgi, CR ;
Sgouros, G ;
Panageas, KS ;
Finn, RD ;
Larson, SM ;
O'Reilly, RJ ;
Scheinberg, DA ;
Jurcic, JG .
BONE MARROW TRANSPLANTATION, 2003, 32 (06) :549-556
[7]   Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission [J].
Cassileth, PA ;
Harrington, DP ;
Appelbaum, FR ;
Lazarus, HM ;
Rowe, JM ;
Paietta, E ;
Willman, C ;
Hurd, DD ;
Bennett, JM ;
Blume, KG ;
Head, DR ;
Wiernik, PH .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (23) :1649-1656
[8]  
CLIFT RA, 1990, BLOOD, V76, P1867
[9]  
CLIFT RA, 1991, BLOOD, V77, P1660
[10]   MARROW TRANSPLANTATION FOR CHRONIC MYELOID-LEUKEMIA - A RANDOMIZED STUDY COMPARING CYCLOPHOSPHAMIDE AND TOTAL-BODY IRRADIATION WITH BUSULFAN AND CYCLOPHOSPHAMIDE [J].
CLIFT, RA ;
BUCKNER, CD ;
THOMAS, ED ;
BENSINGER, WI ;
BOWDEN, R ;
BRYANT, E ;
DEEG, HJ ;
DONEY, KC ;
FISHER, LD ;
HANSEN, JA ;
MARTIN, P ;
MCDONALD, GB ;
SANDERS, JE ;
SCHOCH, G ;
SINGER, J ;
STORB, R ;
SULLIVAN, KM ;
WITHERSPOON, RP ;
APPELBAUM, FR .
BLOOD, 1994, 84 (06) :2036-2043