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

John M. Pagel, Frederick R. Appelbaum, Janet F. Eary, Joseph Rajendran, Darrell R. Fisher, Ted Gooley, Katherine Ruffner, Eneida Nemecek, Eileen Sickle, Larry Durack, Jeanette Carreras, Mary M. Horowitz, Oliver W. Press, Ajay K. Gopal, Paul J. Martin, Irwin D. Bernstein, Dana C. Matthews

Research output: Contribution to journalArticle

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Abstract

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 131I-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 131I-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) 131I, 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 antibody-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.

Original languageEnglish (US)
Pages (from-to)2184-2191
Number of pages8
JournalBlood
Volume107
Issue number5
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

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Busulfan
Cell Transplantation
Acute Myeloid Leukemia
Cyclophosphamide
Anti-Idiotypic Antibodies
Antibodies
Bone
Irradiation
Transplantation (surgical)
Transplants
Bone Marrow
Liver
Registries
Hazards
Therapeutics
Spleen
Radiation
Mortality
Cytogenetics
Disease-Free Survival

ASJC Scopus subject areas

  • Hematology

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131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. / Pagel, John M.; Appelbaum, Frederick R.; Eary, Janet F.; Rajendran, Joseph; Fisher, Darrell R.; Gooley, Ted; Ruffner, Katherine; Nemecek, Eneida; Sickle, Eileen; Durack, Larry; Carreras, Jeanette; Horowitz, Mary M.; Press, Oliver W.; Gopal, Ajay K.; Martin, Paul J.; Bernstein, Irwin D.; Matthews, Dana C.

In: Blood, Vol. 107, No. 5, 01.03.2006, p. 2184-2191.

Research output: Contribution to journalArticle

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 2006, ' 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission', Blood, vol. 107, no. 5, pp. 2184-2191. https://doi.org/10.1182/blood-2005-06-2317
Pagel, John M. ; Appelbaum, Frederick R. ; Eary, Janet F. ; Rajendran, Joseph ; Fisher, Darrell R. ; Gooley, Ted ; Ruffner, Katherine ; Nemecek, Eneida ; Sickle, Eileen ; Durack, Larry ; Carreras, Jeanette ; Horowitz, Mary M. ; Press, Oliver W. ; Gopal, Ajay K. ; Martin, Paul J. ; Bernstein, Irwin D. ; Matthews, Dana C. / 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. In: Blood. 2006 ; Vol. 107, No. 5. pp. 2184-2191.
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abstract = "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 131I-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 131I-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) 131I, 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 antibody-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.",
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T1 - 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission

AU - Pagel, John M.

AU - Appelbaum, Frederick R.

AU - Eary, Janet F.

AU - Rajendran, Joseph

AU - Fisher, Darrell R.

AU - Gooley, Ted

AU - Ruffner, Katherine

AU - Nemecek, Eneida

AU - Sickle, Eileen

AU - Durack, Larry

AU - Carreras, Jeanette

AU - Horowitz, Mary M.

AU - Press, Oliver W.

AU - Gopal, Ajay K.

AU - Martin, Paul J.

AU - Bernstein, Irwin D.

AU - Matthews, Dana C.

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N2 - 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 131I-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 131I-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) 131I, 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 antibody-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.

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