title: 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.
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 CD34+ 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 10(9)/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 10(9)/L (range 6 x 10(9)/L-176 x 10(9)/L). Eight patients (12%) had platelet nadir <20 x 10(9)/L, and all recovered their counts to >20 x 10(9)/L on day 7. There was no clinical difference in days to engraftment between women receiving <2 or > or =2 x 10(6) CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of > or =1 x 10(6) 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 10(9)/L was 10 days (range 9-15), and platelet recovery to >20 x 10(9)/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving > or =2 x 10(6) CD34+/kg versus <2 x 10(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 > or =2 x 10(6) CD34+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of > or =2 x 10(6) CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than <2 x 10(6) CD34+ cells/kg (9 days versus 10 days,p = 0.01), but a dose > or =3 X 10(6) CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.
authors.affiliation: Division of Medical Oncology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Papadopoulos
authors.forename: J
authors.initials: J
authors.lastname: Ayello
authors.forename: R F
authors.initials: RF
authors.lastname: Reiss
authors.forename: A
authors.initials: A
authors.lastname: Troxel
authors.forename: E
authors.initials: E
authors.lastname: Kaufman
authors.forename: L T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: K H
authors.initials: KH
authors.lastname: Antman
authors.forename: C S
authors.initials: CS
authors.lastname: Hesdorffer
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001772:Blood Cell Count; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D017239:Paclitaxel; D008558:Melphalan