Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation

Arnold Freedman, Donna Neuberg, Peter Mauch, John Gribben, Robert Soiffer, Kenneth Anderson, Michael Robertson, David C. Fisher, Robert Schlossman, Mary Kroon, Catherine Rhuda, Caroline Kuhlman, Jerome Ritz, Lee Nadler

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem calls recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony- stimulating factor [G-CSF]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blond cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP end G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.

Original languageEnglish (US)
Pages (from-to)4996-5001
Number of pages6
JournalBlood
Volume90
Issue number12
StatePublished - Dec 15 1997
Externally publishedYes

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Autologous Transplantation
Vincristine
Granulocyte Colony-Stimulating Factor
Prednisone
Stem cells
Bone Marrow Transplantation
Doxorubicin
Cyclophosphamide
Bone
Stem Cells
Intercellular Signaling Peptides and Proteins
Chemotherapy
Drug Therapy
Neutrophils
Therapeutics
Blood Platelets
Platelets
Bone Marrow
Follicular Lymphoma
Retreatment

ASJC Scopus subject areas

  • Hematology

Cite this

Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation. / Freedman, Arnold; Neuberg, Donna; Mauch, Peter; Gribben, John; Soiffer, Robert; Anderson, Kenneth; Robertson, Michael; Fisher, David C.; Schlossman, Robert; Kroon, Mary; Rhuda, Catherine; Kuhlman, Caroline; Ritz, Jerome; Nadler, Lee.

In: Blood, Vol. 90, No. 12, 15.12.1997, p. 4996-5001.

Research output: Contribution to journalArticle

Freedman, A, Neuberg, D, Mauch, P, Gribben, J, Soiffer, R, Anderson, K, Robertson, M, Fisher, DC, Schlossman, R, Kroon, M, Rhuda, C, Kuhlman, C, Ritz, J & Nadler, L 1997, 'Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation', Blood, vol. 90, no. 12, pp. 4996-5001.
Freedman, Arnold ; Neuberg, Donna ; Mauch, Peter ; Gribben, John ; Soiffer, Robert ; Anderson, Kenneth ; Robertson, Michael ; Fisher, David C. ; Schlossman, Robert ; Kroon, Mary ; Rhuda, Catherine ; Kuhlman, Caroline ; Ritz, Jerome ; Nadler, Lee. / Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation. In: Blood. 1997 ; Vol. 90, No. 12. pp. 4996-5001.
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abstract = "Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem calls recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony- stimulating factor [G-CSF]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blond cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP end G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.",
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AU - Mauch, Peter

AU - Gribben, John

AU - Soiffer, Robert

AU - Anderson, Kenneth

AU - Robertson, Michael

AU - Fisher, David C.

AU - Schlossman, Robert

AU - Kroon, Mary

AU - Rhuda, Catherine

AU - Kuhlman, Caroline

AU - Ritz, Jerome

AU - Nadler, Lee

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