Generation and clinical useofleuimiaderived dendritic cell activated lymphocytes in patients with chronic myelogenous leukemia (CML)

David Claxton, John McMannis, Marcos Delima, Richard Champlin, Aniruddha Choudhury

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have previously shown that dendritic cells (DC) may be generated from patients with chronic myelogenous leukemia and acute myelogenous leukemia. These DC may be used to activate autologous anti-leukemic lymphocytes (DC/AL). A clinical trial has been initiated exploring the feasibility, toxicity and therapeutic potential of these activated cells in patients with CML. In four patients Ficoll separated apheresis cells were collected and placed in culture for 14-16 days in serum free medium containing GM-CSF, IL-4, TNFa in gas permeable bags. In three of these patients GM-CSF was administered prior to the apheresis so as to raise the leukocyte count above 20,000/ul, providing relative enrichment of myeloid cells. In the third patient, myeloid leukocytosis obviated the need for this systemic cytokine. In three of four patients cultures yielded 6000-10,000 X 10e6 cells which were 20-30% positive for CD la and CD86. In the fourth patient this DC culture failed, yielding 60% CD3 positive cells because of a high starting number of these cells. In the other three apheresis mononuclear cells were cultured 7 days in serum free medium with OKT3 and IL-2 to yield T-cells which were co-cultured 3:1 with autologous DC without cytokines. After three days of coculture, cells (DC/AL) were cryopreserved in clinical scale aliquots. Two patients received infusions of these cells. Initial cell doses 10e6 Cells/KgBW - were administered 3 days after priming doses of Cyclophosphamide 2Gm/M2. Beginning 4-6 hours after DC/AL infusion, patients received IL-2 0.5MU SC q12h for 10 doses. Therapy was well tolerated in both. One subsequently received a second dose of 107 Cells/KgBW, while the other received two doses of 1 Oe7 Cells/KgBW and 5 X 10e7 Cells/KgBW respectively. In each case DC/AL infusion was followed by IL2. The only toxicities seen were cytopenias related to the chemotherapy, low grade fever (<38.5 C) and transient redness at the site of the IL-2 injections. The second of these patients showed loss of trisomy 8 in the leukemic clone after the second cycle of therapy. Dendritic Cell Activated Lymphocyte infusions are feasible and safe in patients with CML. Accrual of additional patients may allow assessment of clinical efficacy.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000

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Lymphocytes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Dendritic Cells
Interleukin-2
Blood Component Removal
Serum-Free Culture Media
Granulocyte-Macrophage Colony-Stimulating Factor
Toxicity
Cytokines
Muromonab-CD3
Ficoll
Chemotherapy
T-cells
Cell culture
Interleukin-4
Cyclophosphamide
Leukocytosis
Myeloid Cells
Coculture Techniques
Gases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Claxton, David ; McMannis, John ; Delima, Marcos ; Champlin, Richard ; Choudhury, Aniruddha. / Generation and clinical useofleuimiaderived dendritic cell activated lymphocytes in patients with chronic myelogenous leukemia (CML). In: Blood. 2000 ; Vol. 96, No. 11 PART I.
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abstract = "We have previously shown that dendritic cells (DC) may be generated from patients with chronic myelogenous leukemia and acute myelogenous leukemia. These DC may be used to activate autologous anti-leukemic lymphocytes (DC/AL). A clinical trial has been initiated exploring the feasibility, toxicity and therapeutic potential of these activated cells in patients with CML. In four patients Ficoll separated apheresis cells were collected and placed in culture for 14-16 days in serum free medium containing GM-CSF, IL-4, TNFa in gas permeable bags. In three of these patients GM-CSF was administered prior to the apheresis so as to raise the leukocyte count above 20,000/ul, providing relative enrichment of myeloid cells. In the third patient, myeloid leukocytosis obviated the need for this systemic cytokine. In three of four patients cultures yielded 6000-10,000 X 10e6 cells which were 20-30{\%} positive for CD la and CD86. In the fourth patient this DC culture failed, yielding 60{\%} CD3 positive cells because of a high starting number of these cells. In the other three apheresis mononuclear cells were cultured 7 days in serum free medium with OKT3 and IL-2 to yield T-cells which were co-cultured 3:1 with autologous DC without cytokines. After three days of coculture, cells (DC/AL) were cryopreserved in clinical scale aliquots. Two patients received infusions of these cells. Initial cell doses 10e6 Cells/KgBW - were administered 3 days after priming doses of Cyclophosphamide 2Gm/M2. Beginning 4-6 hours after DC/AL infusion, patients received IL-2 0.5MU SC q12h for 10 doses. Therapy was well tolerated in both. One subsequently received a second dose of 107 Cells/KgBW, while the other received two doses of 1 Oe7 Cells/KgBW and 5 X 10e7 Cells/KgBW respectively. In each case DC/AL infusion was followed by IL2. The only toxicities seen were cytopenias related to the chemotherapy, low grade fever (<38.5 C) and transient redness at the site of the IL-2 injections. The second of these patients showed loss of trisomy 8 in the leukemic clone after the second cycle of therapy. Dendritic Cell Activated Lymphocyte infusions are feasible and safe in patients with CML. Accrual of additional patients may allow assessment of clinical efficacy.",
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Generation and clinical useofleuimiaderived dendritic cell activated lymphocytes in patients with chronic myelogenous leukemia (CML). / Claxton, David; McMannis, John; Delima, Marcos; Champlin, Richard; Choudhury, Aniruddha.

In: Blood, Vol. 96, No. 11 PART I, 01.12.2000.

Research output: Contribution to journalArticle

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T1 - Generation and clinical useofleuimiaderived dendritic cell activated lymphocytes in patients with chronic myelogenous leukemia (CML)

AU - Claxton, David

AU - McMannis, John

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AU - Choudhury, Aniruddha

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N2 - We have previously shown that dendritic cells (DC) may be generated from patients with chronic myelogenous leukemia and acute myelogenous leukemia. These DC may be used to activate autologous anti-leukemic lymphocytes (DC/AL). A clinical trial has been initiated exploring the feasibility, toxicity and therapeutic potential of these activated cells in patients with CML. In four patients Ficoll separated apheresis cells were collected and placed in culture for 14-16 days in serum free medium containing GM-CSF, IL-4, TNFa in gas permeable bags. In three of these patients GM-CSF was administered prior to the apheresis so as to raise the leukocyte count above 20,000/ul, providing relative enrichment of myeloid cells. In the third patient, myeloid leukocytosis obviated the need for this systemic cytokine. In three of four patients cultures yielded 6000-10,000 X 10e6 cells which were 20-30% positive for CD la and CD86. In the fourth patient this DC culture failed, yielding 60% CD3 positive cells because of a high starting number of these cells. In the other three apheresis mononuclear cells were cultured 7 days in serum free medium with OKT3 and IL-2 to yield T-cells which were co-cultured 3:1 with autologous DC without cytokines. After three days of coculture, cells (DC/AL) were cryopreserved in clinical scale aliquots. Two patients received infusions of these cells. Initial cell doses 10e6 Cells/KgBW - were administered 3 days after priming doses of Cyclophosphamide 2Gm/M2. Beginning 4-6 hours after DC/AL infusion, patients received IL-2 0.5MU SC q12h for 10 doses. Therapy was well tolerated in both. One subsequently received a second dose of 107 Cells/KgBW, while the other received two doses of 1 Oe7 Cells/KgBW and 5 X 10e7 Cells/KgBW respectively. In each case DC/AL infusion was followed by IL2. The only toxicities seen were cytopenias related to the chemotherapy, low grade fever (<38.5 C) and transient redness at the site of the IL-2 injections. The second of these patients showed loss of trisomy 8 in the leukemic clone after the second cycle of therapy. Dendritic Cell Activated Lymphocyte infusions are feasible and safe in patients with CML. Accrual of additional patients may allow assessment of clinical efficacy.

AB - We have previously shown that dendritic cells (DC) may be generated from patients with chronic myelogenous leukemia and acute myelogenous leukemia. These DC may be used to activate autologous anti-leukemic lymphocytes (DC/AL). A clinical trial has been initiated exploring the feasibility, toxicity and therapeutic potential of these activated cells in patients with CML. In four patients Ficoll separated apheresis cells were collected and placed in culture for 14-16 days in serum free medium containing GM-CSF, IL-4, TNFa in gas permeable bags. In three of these patients GM-CSF was administered prior to the apheresis so as to raise the leukocyte count above 20,000/ul, providing relative enrichment of myeloid cells. In the third patient, myeloid leukocytosis obviated the need for this systemic cytokine. In three of four patients cultures yielded 6000-10,000 X 10e6 cells which were 20-30% positive for CD la and CD86. In the fourth patient this DC culture failed, yielding 60% CD3 positive cells because of a high starting number of these cells. In the other three apheresis mononuclear cells were cultured 7 days in serum free medium with OKT3 and IL-2 to yield T-cells which were co-cultured 3:1 with autologous DC without cytokines. After three days of coculture, cells (DC/AL) were cryopreserved in clinical scale aliquots. Two patients received infusions of these cells. Initial cell doses 10e6 Cells/KgBW - were administered 3 days after priming doses of Cyclophosphamide 2Gm/M2. Beginning 4-6 hours after DC/AL infusion, patients received IL-2 0.5MU SC q12h for 10 doses. Therapy was well tolerated in both. One subsequently received a second dose of 107 Cells/KgBW, while the other received two doses of 1 Oe7 Cells/KgBW and 5 X 10e7 Cells/KgBW respectively. In each case DC/AL infusion was followed by IL2. The only toxicities seen were cytopenias related to the chemotherapy, low grade fever (<38.5 C) and transient redness at the site of the IL-2 injections. The second of these patients showed loss of trisomy 8 in the leukemic clone after the second cycle of therapy. Dendritic Cell Activated Lymphocyte infusions are feasible and safe in patients with CML. Accrual of additional patients may allow assessment of clinical efficacy.

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