Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation

John E. Levine, Thomas Braun, Samuel L. Penza, Patrick Beatty, Kenneth Cornetta, Rodrigo Martino, William R. Drobyski, A. John Barrett, David L. Porter, Sergio Giralt, Jose Leis, Houston E. Holmes, Matthew Johnson, Mary Horowitz, Robert H. Collins

Research output: Contribution to journalArticle

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Abstract

Purpose: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs. Patients and Methods: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided. Results: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A post-transplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission. Conclusion: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.

Original languageEnglish (US)
Pages (from-to)405-412
Number of pages8
JournalJournal of Clinical Oncology
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2002
Externally publishedYes

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Stem Cell Transplantation
Leukocytes
Tissue Donors
Recurrence
Drug Therapy
Neoplasms
Graft vs Host Disease
Bone Marrow Transplantation
Granulocyte Colony-Stimulating Factor
Survival
Transplants
Salvage Therapy
Mortality
Cytarabine
Homologous Transplantation
Immunosuppression
Siblings
Survival Rate
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. / Levine, John E.; Braun, Thomas; Penza, Samuel L.; Beatty, Patrick; Cornetta, Kenneth; Martino, Rodrigo; Drobyski, William R.; Barrett, A. John; Porter, David L.; Giralt, Sergio; Leis, Jose; Holmes, Houston E.; Johnson, Matthew; Horowitz, Mary; Collins, Robert H.

In: Journal of Clinical Oncology, Vol. 20, No. 2, 15.01.2002, p. 405-412.

Research output: Contribution to journalArticle

Levine, JE, Braun, T, Penza, SL, Beatty, P, Cornetta, K, Martino, R, Drobyski, WR, Barrett, AJ, Porter, DL, Giralt, S, Leis, J, Holmes, HE, Johnson, M, Horowitz, M & Collins, RH 2002, 'Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation', Journal of Clinical Oncology, vol. 20, no. 2, pp. 405-412. https://doi.org/10.1200/JCO.20.2.405
Levine, John E. ; Braun, Thomas ; Penza, Samuel L. ; Beatty, Patrick ; Cornetta, Kenneth ; Martino, Rodrigo ; Drobyski, William R. ; Barrett, A. John ; Porter, David L. ; Giralt, Sergio ; Leis, Jose ; Holmes, Houston E. ; Johnson, Matthew ; Horowitz, Mary ; Collins, Robert H. / Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 2. pp. 405-412.
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abstract = "Purpose: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs. Patients and Methods: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided. Results: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56{\%} of the patients. Treatment-related mortality was 23{\%}. Overall survival at 2 years for the entire cohort was 19{\%}. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51{\%} and 41{\%}, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5{\%}. A post-transplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission. Conclusion: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.",
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T1 - Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation

AU - Levine, John E.

AU - Braun, Thomas

AU - Penza, Samuel L.

AU - Beatty, Patrick

AU - Cornetta, Kenneth

AU - Martino, Rodrigo

AU - Drobyski, William R.

AU - Barrett, A. John

AU - Porter, David L.

AU - Giralt, Sergio

AU - Leis, Jose

AU - Holmes, Houston E.

AU - Johnson, Matthew

AU - Horowitz, Mary

AU - Collins, Robert H.

PY - 2002/1/15

Y1 - 2002/1/15

N2 - Purpose: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs. Patients and Methods: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided. Results: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A post-transplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission. Conclusion: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.

AB - Purpose: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs. Patients and Methods: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided. Results: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A post-transplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission. Conclusion: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.

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