CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer

Kyriakos P. Papadopoulos, Janet Ayello, Robert F. Reiss, Andrea Troxel, Elizabeth Kaufman, Linda T. Vahdat, Karen H. Antman, Charles S. Hesdorffer

Research output: Contribution to journalArticle

Abstract

Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD346+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 109/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 109/L (range 6 x 109/L- 176 x 109/L). Eight patients (12%) had platelet nadir 9/L, and all recovered their counts to >20 x 109/L on day 7. There was no clinical difference in days to engraftment between women receiving 6 CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of ≥1 x 1066 CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 109/L was 10 days (range 9-15), and platelet recovery to >20 X 109/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving ≥2 x 106 CD34+/kg versus 6 CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p <0.01). Ninety-eight percent of patients infused with ≥2 x 106 CD346+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of ≥2 x 106 CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than 6 CD34+ cells/kg (9 days versus 10 days, p = 0.01), but a dose ≥3 X 106 CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.

Original languageEnglish (US)
Pages (from-to)357-363
Number of pages7
JournalJournal of Hematotherapy and Stem Cell Research
Volume8
Issue number4
DOIs
StatePublished - Aug 1999
Externally publishedYes

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Thiotepa
Melphalan
Carboplatin
Paclitaxel
Cyclophosphamide
Breast Neoplasms
Drug Therapy
Neutrophils
Blood Platelets
Granulocyte Colony-Stimulating Factor
Platelet Count
Bone Marrow

ASJC Scopus subject areas

  • Hematology
  • Immunology

Cite this

CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer. / Papadopoulos, Kyriakos P.; Ayello, Janet; Reiss, Robert F.; Troxel, Andrea; Kaufman, Elizabeth; Vahdat, Linda T.; Antman, Karen H.; Hesdorffer, Charles S.

In: Journal of Hematotherapy and Stem Cell Research, Vol. 8, No. 4, 08.1999, p. 357-363.

Research output: Contribution to journalArticle

Papadopoulos, Kyriakos P. ; Ayello, Janet ; Reiss, Robert F. ; Troxel, Andrea ; Kaufman, Elizabeth ; Vahdat, Linda T. ; Antman, Karen H. ; Hesdorffer, Charles S. / CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer. In: Journal of Hematotherapy and Stem Cell Research. 1999 ; Vol. 8, No. 4. pp. 357-363.
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abstract = "Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD346+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 109/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 109/L (range 6 x 109/L- 176 x 109/L). Eight patients (12{\%}) had platelet nadir 9/L, and all recovered their counts to >20 x 109/L on day 7. There was no clinical difference in days to engraftment between women receiving 6 CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of ≥1 x 1066 CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 109/L was 10 days (range 9-15), and platelet recovery to >20 X 109/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving ≥2 x 106 CD34+/kg versus 6 CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p <0.01). Ninety-eight percent of patients infused with ≥2 x 106 CD346+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of ≥2 x 106 CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than 6 CD34+ cells/kg (9 days versus 10 days, p = 0.01), but a dose ≥3 X 106 CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.",
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T1 - CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer

AU - Papadopoulos, Kyriakos P.

AU - Ayello, Janet

AU - Reiss, Robert F.

AU - Troxel, Andrea

AU - Kaufman, Elizabeth

AU - Vahdat, Linda T.

AU - Antman, Karen H.

AU - Hesdorffer, Charles S.

PY - 1999/8

Y1 - 1999/8

N2 - Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD346+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 109/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 109/L (range 6 x 109/L- 176 x 109/L). Eight patients (12%) had platelet nadir 9/L, and all recovered their counts to >20 x 109/L on day 7. There was no clinical difference in days to engraftment between women receiving 6 CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of ≥1 x 1066 CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 109/L was 10 days (range 9-15), and platelet recovery to >20 X 109/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving ≥2 x 106 CD34+/kg versus 6 CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p <0.01). Ninety-eight percent of patients infused with ≥2 x 106 CD346+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of ≥2 x 106 CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than 6 CD34+ cells/kg (9 days versus 10 days, p = 0.01), but a dose ≥3 X 106 CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.

AB - Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD346+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 109/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 109/L (range 6 x 109/L- 176 x 109/L). Eight patients (12%) had platelet nadir 9/L, and all recovered their counts to >20 x 109/L on day 7. There was no clinical difference in days to engraftment between women receiving 6 CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of ≥1 x 1066 CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 109/L was 10 days (range 9-15), and platelet recovery to >20 X 109/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving ≥2 x 106 CD34+/kg versus 6 CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p <0.01). Ninety-eight percent of patients infused with ≥2 x 106 CD346+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of ≥2 x 106 CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than 6 CD34+ cells/kg (9 days versus 10 days, p = 0.01), but a dose ≥3 X 106 CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.

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