Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning

The effect of postgrafting mycophenolate mofetil dosing

Michael B. Maris, Brenda M. Sandmaier, Barry E. Storer, David G. Maloney, Judith A. Shizuru, Edward Agura, Constanze Kliem, Michael Pulsipher, Richard Maziarz, Peter A. McSweeney, James Wade, Amelia A. Langston, Thomas R. Chauncey, Benedetto Bruno, Karl G. Blume, Rainer Storb

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m2, 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.

Original languageEnglish (US)
Pages (from-to)454-465
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume12
Issue number4
DOIs
StatePublished - Apr 2006

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Mycophenolic Acid
Unrelated Donors
Cell Transplantation
Granulocyte Colony-Stimulating Factor
Blood Cells
Graft Rejection
Graft vs Host Disease
Cyclosporine
Transplants
Whole-Body Irradiation
Hematologic Neoplasms
Immunosuppression
Disease-Free Survival
Half-Life
Pharmacokinetics

Keywords

  • Graft-versus-tumor effect
  • Hematologic malignancy
  • Hematopoietic cell transplantation
  • Nonmyeloablative conditioning
  • Reduced-intensity conditioning
  • Unrelated donor allografting

ASJC Scopus subject areas

  • Transplantation

Cite this

Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning : The effect of postgrafting mycophenolate mofetil dosing. / Maris, Michael B.; Sandmaier, Brenda M.; Storer, Barry E.; Maloney, David G.; Shizuru, Judith A.; Agura, Edward; Kliem, Constanze; Pulsipher, Michael; Maziarz, Richard; McSweeney, Peter A.; Wade, James; Langston, Amelia A.; Chauncey, Thomas R.; Bruno, Benedetto; Blume, Karl G.; Storb, Rainer.

In: Biology of Blood and Marrow Transplantation, Vol. 12, No. 4, 04.2006, p. 454-465.

Research output: Contribution to journalArticle

Maris, MB, Sandmaier, BM, Storer, BE, Maloney, DG, Shizuru, JA, Agura, E, Kliem, C, Pulsipher, M, Maziarz, R, McSweeney, PA, Wade, J, Langston, AA, Chauncey, TR, Bruno, B, Blume, KG & Storb, R 2006, 'Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: The effect of postgrafting mycophenolate mofetil dosing', Biology of Blood and Marrow Transplantation, vol. 12, no. 4, pp. 454-465. https://doi.org/10.1016/j.bbmt.2005.12.030
Maris, Michael B. ; Sandmaier, Brenda M. ; Storer, Barry E. ; Maloney, David G. ; Shizuru, Judith A. ; Agura, Edward ; Kliem, Constanze ; Pulsipher, Michael ; Maziarz, Richard ; McSweeney, Peter A. ; Wade, James ; Langston, Amelia A. ; Chauncey, Thomas R. ; Bruno, Benedetto ; Blume, Karl G. ; Storb, Rainer. / Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning : The effect of postgrafting mycophenolate mofetil dosing. In: Biology of Blood and Marrow Transplantation. 2006 ; Vol. 12, No. 4. pp. 454-465.
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abstract = "We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m2, 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15{\%}; the cumulative probability of acute graft-versus-host disease (GVHD) was 52{\%}. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5{\%}, whereas acute GVHD remained at 53{\%}. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19{\%}, 58{\%}, and 49{\%} versus 20{\%}, 48{\%}, and 37{\%}, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95{\%} durable engraftment of unrelated donor G-PBMC grafts.",
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AU - Wade, James

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