Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors

Naoto T. Ueno, Yee Chung Cheng, Gabriela Rondón, Nizar M. Tannir, James L. Gajewski, Daniel R. Couriel, Chitra Hosing, Marcos J. De Lima, Paolo Anderlini, Issa F. Khouri, Daniel J. Booser, Gabriel N. Hortobagyi, Lance C. Pagliaro, Eric Jonasch, Sergio A. Giralt, Richard E. Champlin

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Abstract

We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.

Original languageEnglish (US)
Pages (from-to)3829-3836
Number of pages8
JournalBlood
Volume102
Issue number10
DOIs
StatePublished - Nov 15 2003
Externally publishedYes

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Chimerism
Melphalan
Stem Cell Transplantation
Stem cells
Grafts
Tumors
Tissue Donors
Graft vs Host Disease
Neoplasms
Renal Cell Carcinoma
Lymphocytes
Tacrolimus
Time measurement
Methotrexate
Breast Neoplasms
Unrelated Donors
Cells
fludarabine
Stem Cells
Transplants

ASJC Scopus subject areas

  • Hematology

Cite this

Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors. / Ueno, Naoto T.; Cheng, Yee Chung; Rondón, Gabriela; Tannir, Nizar M.; Gajewski, James L.; Couriel, Daniel R.; Hosing, Chitra; De Lima, Marcos J.; Anderlini, Paolo; Khouri, Issa F.; Booser, Daniel J.; Hortobagyi, Gabriel N.; Pagliaro, Lance C.; Jonasch, Eric; Giralt, Sergio A.; Champlin, Richard E.

In: Blood, Vol. 102, No. 10, 15.11.2003, p. 3829-3836.

Research output: Contribution to journalArticle

Ueno, NT, Cheng, YC, Rondón, G, Tannir, NM, Gajewski, JL, Couriel, DR, Hosing, C, De Lima, MJ, Anderlini, P, Khouri, IF, Booser, DJ, Hortobagyi, GN, Pagliaro, LC, Jonasch, E, Giralt, SA & Champlin, RE 2003, 'Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors', Blood, vol. 102, no. 10, pp. 3829-3836. https://doi.org/10.1182/blood-2003-04-1022
Ueno, Naoto T. ; Cheng, Yee Chung ; Rondón, Gabriela ; Tannir, Nizar M. ; Gajewski, James L. ; Couriel, Daniel R. ; Hosing, Chitra ; De Lima, Marcos J. ; Anderlini, Paolo ; Khouri, Issa F. ; Booser, Daniel J. ; Hortobagyi, Gabriel N. ; Pagliaro, Lance C. ; Jonasch, Eric ; Giralt, Sergio A. ; Champlin, Richard E. / Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors. In: Blood. 2003 ; Vol. 102, No. 10. pp. 3829-3836.
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abstract = "We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100{\%} donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39{\%}) had grades II to IV acute GVHD and 10 patients (43{\%}) had chronic GVHD. Five patients (22{\%}) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45{\%}), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.",
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T1 - Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors

AU - Ueno, Naoto T.

AU - Cheng, Yee Chung

AU - Rondón, Gabriela

AU - Tannir, Nizar M.

AU - Gajewski, James L.

AU - Couriel, Daniel R.

AU - Hosing, Chitra

AU - De Lima, Marcos J.

AU - Anderlini, Paolo

AU - Khouri, Issa F.

AU - Booser, Daniel J.

AU - Hortobagyi, Gabriel N.

AU - Pagliaro, Lance C.

AU - Jonasch, Eric

AU - Giralt, Sergio A.

AU - Champlin, Richard E.

PY - 2003/11/15

Y1 - 2003/11/15

N2 - We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.

AB - We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.

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