Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization

Abstract

This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 microg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 microg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached > or = 2 x 10(9)/L; leukapheresis was continued until acquisition of a target dose of > or = 5 x 10(6) CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 x 10(6) CD34 cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 x 10(6) cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after high-dose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 x 10(9)/L and a platelet count of 20 x 10(9)/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.

Mobilization, collection, and immunomagnetic selection of peripheral blood CD34 cells in recovered aplastic anemia patients

“…Other agents have been used to increase mobilization of CD34 cells from normal individuals, either alone or in combination 15,16 . Stem cell factor (SCF) and G‐CSF when given together appear to result in higher yields of CD34 cells than G‐CSF alone 17 .…”

“…Other agents have been used to increase mobilization of CD34 cells from normal individuals, either alone or in combination. 15,16 Stem cell factor (SCF) and G-CSF when given together appear to result in higher yields of CD34 cells than G-CSF alone. 17 The small but significant incidence of anaphylaxis associated with SCF administration makes this agent less attractive for clinical use.…”

Effect of hematopoietic growth factors on severity of experimental autoimmune encephalomyelitis

“…27 When TPO was added to G-CSF and chemotherapy as a part of the mobilizing regimen in patients with breast cancer, enhanced mobilization of HSC was observed. 29 Murray et al 14 demonstrated that TPO alone can efficiently mobilize primitive hematopoietic progenitor and stem cells with long-term repopulating ability into peripheral blood. Our data showed that administration of TPO in mice resulted in the same level of WBC increase as seen following G-CSF treatment and higher WBC count than post Flt-3L injections.…”

Coleta de células progenitoras hematopoéticas de sangue periférico após administração de ciclofosfamida e fator estimulador de colônias de granulócitos (G-CSF): uma análise de 307 pacientes

“…Outras citocinas com capacidade de recrutamento de CPH da medula óssea para o sangue periférico têm sido reconhecidas (Gajewski et al, 2002 (Stiff et al, 2000). Dawson et al (2005) (Liles et al, 2003).…”