Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McSweeney, P. A.
Right arrow Articles by Storb, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McSweeney, P. A.
Right arrow Articles by Storb, R. F.
Related Collections
Right arrow Neoplasia
Right arrow Transplantation
Right arrow Clinical Trials and Observations
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

Blood, 1 June 2001, Vol. 97, No. 11, pp. 3390-3400

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects

Peter A. McSweeney, Dietger Niederwieser, Judith A. Shizuru, Brenda M. Sandmaier, Arthur J. Molina, David G. Maloney, Thomas R. Chauncey, Theodore A. Gooley, Ute Hegenbart, Richard A. Nash, Jerald Radich, John L. Wagner, Steven Minor, Frederick R. Appelbaum, William I. Bensinger, Eileen Bryant, Mary E. D. Flowers, George E. Georges, F. Carl Grumet, Hans-Peter Kiem, Beverly Torok-Storb, Cong Yu, Karl G. Blume, and Rainer F. Storb

From the Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, and Veterans Affairs Medical Center, Seattle, WA; Stanford University, Stanford, CA; and University of Leipzig, Germany.

Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies.

© 2001 by The American Society of Hematology.
 

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
BloodHome page
R. Marks, K. Potthoff, J. Hahn, G. Ihorst, H. Bertz, A. Spyridonidis, E. Holler, and J. M. Finke
Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies
Blood, July 15, 2008; 112(2): 415 - 425.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
P. Anderlini and R. E. Champlin
Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges
Blood, February 15, 2008; 111(4): 1767 - 1772.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
R. Conrad, M. Remberger, K. Cederlund, O. Ringden, and L. Barkholt
A comparison between low intensity and reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation for solid tumors
Haematologica, February 1, 2008; 93(2): 265 - 272.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
E. Castermans, F. Baron, E. Willems, N. Schaaf-Lafontaine, N. Meuris, A. Gothot, J.-F. Vanbellighen, C. Herens, L. Seidel, V. Geenen, et al.
Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning
Haematologica, February 1, 2008; 93(2): 240 - 247.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. L. Sorror, B. E. Storer, D. G. Maloney, B. M. Sandmaier, P. J. Martin, and R. Storb
Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia
Blood, January 1, 2008; 111(1): 446 - 452.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
E. Olavarria, S. Siddique, M. J. Griffiths, S. Avery, J. L. Byrne, K. P. Piper, A. L. Lennard, L. Pallan, J. M. Arrazi, J. B. Perz, et al.
Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia
Blood, December 15, 2007; 110(13): 4614 - 4617.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
P. Kebriaei, M. A. Detry, S. Giralt, A. Carrasco-Yalan, A. Anagnostopoulos, D. Couriel, I. F. Khouri, P. Anderlini, C. Hosing, A. Alousi, et al.
Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia
Blood, November 1, 2007; 110(9): 3456 - 3462.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Kahl, B. E. Storer, B. M. Sandmaier, M. Mielcarek, M. B. Maris, K. G. Blume, D. Niederwieser, T. R. Chauncey, S. J. Forman, E. Agura, et al.
Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning
Blood, October 1, 2007; 110(7): 2744 - 2748.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
M. E. King and J. M. Rowe
Recent Developments in Acute Myelogenous Leukemia Therapy
Oncologist, October 1, 2007; 12(suppl_2): 14 - 21.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
M. L. Sorror, B. M. Sandmaier, B. E. Storer, M. B. Maris, F. Baron, D. G. Maloney, B. L. Scott, H. J. Deeg, F. R. Appelbaum, and R. Storb
Comorbidity and Disease Status Based Risk Stratification of Outcomes Among Patients With Acute Myeloid Leukemia or Myelodysplasia Receiving Allogeneic Hematopoietic Cell Transplantation
J. Clin. Oncol., September 20, 2007; 25(27): 4246 - 4254.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
M Devetten and J. Armitage
Hematopoietic cell transplantation: progress and obstacles
Ann. Onc., September 1, 2007; 18(9): 1450 - 1456.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
A. E.C. Broers, M. Bruinsma, S. J. Posthumus-van Sluijs, E.-J. Wils, H. Spits, B. Lowenberg, E. Braakman, and J. J. Cornelissen
IL-7 mediated protection against minor antigen-mismatched allograft rejection is associated with enhanced recovery of regulatory T cells
Haematologica, August 1, 2007; 92(8): 1099 - 1106.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. S. Graves, W. Hogan, C. S. Kuhr, R. Diaconescu, M. A. Harkey, G. E. Georges, G. E. Sale, E. Zellmer, S. Baran, C. Jochum, et al.
Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning
Blood, July 1, 2007; 110(1): 418 - 423.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
D. G. Maloney
Follicular NHL: From Antibodies and Vaccines to Graft-versus-Lymphoma Effects
Hematology, January 1, 2007; 2007(1): 226 - 232.
[Abstract] [Full Text] [PDF]


Home page
Br Med BullHome page
J. Aschan
Allogeneic haematopoietic stem cell transplantation: current status and future outlook
Br. Med. Bull., October 5, 2006; (2006) ldl005v2.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
F. Baron, R. Storb, B. E. Storer, M. B. Maris, D. Niederwieser, J. A. Shizuru, T. R. Chauncey, B. Bruno, S. J. Forman, P. A. McSweeney, et al.
Factors Associated With Outcomes in Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning After Failed Myeloablative Hematopoietic Cell Transplantation
J. Clin. Oncol., September 1, 2006; 24(25): 4150 - 4157.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
H. J. Deeg, M. O'Donnell, J. Tolar, R. Agarwal, R. E. Harris, S. A. Feig, M. C. Territo, R. H. Collins, P. A. McSweeney, E. A. Copelan, et al.
Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy
Blood, September 1, 2006; 108(5): 1485 - 1491.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
N.-C. Gorin, M. Labopin, J.-M. Boiron, N. Theorin, T. Littlewood, S. Slavin, H. Greinix, J. Y. Cahn, E. P. Alessandrino, A. Rambaldi, et al.
Results of Genoidentical Hemopoietic Stem Cell Transplantation With Reduced Intensity Conditioning for Acute Myelocytic Leukemia: Higher Doses of Stem Cells Infused Benefit Patients Receiving Transplants in Second Remission or Beyond--The Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation
J. Clin. Oncol., August 20, 2006; 24(24): 3959 - 3966.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Schmid, M. Schleuning, R. Schwerdtfeger, B. Hertenstein, E. Mischak-Weissinger, D. Bunjes, S. v. Harsdorf, C. Scheid, U. Holtick, H. Greinix, et al.
Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation
Blood, August 1, 2006; 108(3): 1092 - 1099.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
L. Barkholt, M. Bregni, M. Remberger, D. Blaise, J. Peccatori, G. Massenkeil, P. Pedrazzoli, A. Zambelli, J.-O. Bay, S. Francois, et al.
Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe
Ann. Onc., July 1, 2006; 17(7): 1134 - 1140.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
L. Pirson, F. Baron, N. Meuris, O. Giet, E. Castermans, R. Greimers, I. Di Stefano, A. Gothot, and Y. Beguin
Despite Inhibition of Hematopoietic Progenitor Cell Growth In Vitro, the Tyrosine Kinase Inhibitor Imatinib Does Not Impair Engraftment of Human CD133+ Cells into NOD/SCID{beta}2mNull Mice
Stem Cells, July 1, 2006; 24(7): 1814 - 1821.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
F. Carnevale-Schianca, A. Cignetti, A. Capaldi, K. Vitaggio, A. Vallario, A. Ricchiardi, E. Sperti, R. Ferraris, M. Gatti, G. Grignani, et al.
Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD
Blood, May 1, 2006; 107(9): 3795 - 3803.
[Abstract] [Full Text] [PDF]


Home page
NEJMHome page
E. A. Copelan
Hematopoietic stem-cell transplantation.
N. Engl. J. Med., April 27, 2006; 354(17): 1813 - 1826.
[Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. Ohashi, A. Kobayashi, H. Hara, Y. Miura, K. Yoshida, M. Kushida, Y. Ikarashi, M. Mandai, M. Kitajima, T. Yoshida, et al.
Allogeneic MHC gene transfer enhances antitumor activity of allogeneic hematopoietic stem cell transplantation without exacerbating graft-versus-host disease.
Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2208 - 2215.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
U. Hegenbart, D. Niederwieser, B. M. Sandmaier, M. B. Maris, J. A. Shizuru, H. Greinix, C. Cordonnier, B. Rio, A. Gratwohl, T. Lange, et al.
Treatment for Acute Myelogenous Leukemia by Low-Dose, Total-Body, Irradiation-Based Conditioning and Hematopoietic Cell Transplantation From Related and Unrelated Donors
J. Clin. Oncol., January 20, 2006; 24(3): 444 - 453.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
B. L. Scott and B. M. Sandmaier
Outcomes with Myeloid Malignancies
Hematology, January 1, 2006; 2006(1): 381 - 389.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
F. Locatelli
Reduced-Intensity Regimens in Allogeneic Hematopoietic Stem Cell Transplantation for Hemoglobinopathies
Hematology, January 1, 2006; 2006(1): 398 - 401.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
B. L. Abbott
Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment
Oncologist, January 1, 2006; 11(1): 21 - 30.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. C. Zimring, G. A. Hair, S. S. Deshpande, and J. T. Horan
Immunization to minor histocompatibility antigens on transfused RBCs through crosspriming into recipient MHC class I pathways
Blood, January 1, 2006; 107(1): 187 - 189.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
L. Giaccone, J. S. McCune, M. B. Maris, T. A. Gooley, B. M. Sandmaier, J. T. Slattery, S. Cole, R. A. Nash, R. F. Storb, and G. E. Georges
Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation
Blood, December 15, 2005; 106(13): 4381 - 4388.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. J. Wu, L. Krishnamurti, J. L. Kutok, M. Biernacki, S. Rogers, W. Zhang, J. H. Antin, and J. Ritz
Evidence for ineffective erythropoiesis in severe sickle cell disease
Blood, November 15, 2005; 106(10): 3639 - 3645.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
D. Caballero, J. A. Garcia-Marco, R. Martino, V. Mateos, J. M. Ribera, J. Sarra, A. Leon, G. Sanz, J. de la Serna, R. Cabrera, et al.
Allogeneic Transplant with Reduced Intensity Conditioning Regimens may Overcome the Poor Prognosis of B-Cell Chronic Lymphocytic Leukemia with Unmutated Immunoglobulin Variable Heavy-Chain Gene and Chromosomal Abnormalities (11q- and 17p-)
Clin. Cancer Res., November 1, 2005; 11(21): 7757 - 7763.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Crawley, R. Szydlo, M. Lalancette, A. Bacigalupo, A. Lange, M. Brune, G. Juliusson, A. Nagler, A. Gratwohl, J. Passweg, et al.
Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT
Blood, November 1, 2005; 106(9): 2969 - 2976.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. Stelljes, M. Bornhauser, M. Kroger, J. Beyer, M. C. Sauerland, A. Heinecke, B. Berning, C. Scheffold, G. Silling, T. Buchner, et al.
Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia
Blood, November 1, 2005; 106(9): 3314 - 3321.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. L. Sorror, M. B. Maris, R. Storb, F. Baron, B. M. Sandmaier, D. G. Maloney, and B. Storer
Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT
Blood, October 15, 2005; 106(8): 2912 - 2919.
[Abstract] [Full Text] [PDF]


Home page
NEJMHome page
R. Lowsky, T. Takahashi, Y. P. Liu, S. Dejbakhsh-Jones, F. C. Grumet, J. A. Shizuru, G. G. Laport, K. E. Stockerl-Goldstein, L. J. Johnston, R. T. Hoppe, et al.
Protective conditioning for acute graft-versus-host disease.
N. Engl. J. Med., September 29, 2005; 353(13): 1321 - 1331.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
P. Corradini, F. Zallio, J. Mariotti, L. Farina, M. Bregni, P. Valagussa, F. Ciceri, A. Bacigalupo, A. Dodero, M. Lucesole, et al.
Effect of Age and Previous Autologous Transplantation on Nonrelapse Mortality and Survival in Patients Treated With Reduced-Intensity Conditioning and Allografting for Advanced Hematologic Malignancies
J. Clin. Oncol., September 20, 2005; 23(27): 6690 - 6698.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
C. Schmid, M. Schleuning, G. Ledderose, J. Tischer, and H.-J. Kolb
Sequential Regimen of Chemotherapy, Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation, and Prophylactic Donor Lymphocyte Transfusion in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
J. Clin. Oncol., August 20, 2005; 23(24): 5675 - 5687.
[Abstract] [Full Text] [PDF]