Increased Numbers of Progenitor Cells in the Apheresis Product of Patients Randomised to Receive Increasing Doses of Stem Cell Factor (r-metHuSCF) Administered in Combination with Chemotherapy and a Standard Dose of Filgrastim (r-metHuG-CSF)

Weaver, Andrew; Woll, Penella J.; Lind, MJ; Jenkins, Bonnie; Gill, Clarence; Dexter, T. M.; Testa, NG; Crowther, Derek

doi:10.1007/978-3-642-71960-8_45

Cited by 20 publications

(30 citation statements)

References 19 publications

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“…Since prior TF4 exposure independently affects time to engraftment, higher threshold of у2.0 ϫ 10 6 /kg is recommended in these patients to ensure haematopoietic recovery. In those without an adequate cell yield, other strategies such as bone marrow harvest, 15 repeat stem cell collection or alternative mobilisation regimens using novel cytokine combinations, 16 should be considered.…”

Section: Discussionmentioning

confidence: 99%

The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipients

Gandhi

Jestice

Scott

et al. 1998

Bone Marrow Transplant

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Summary:We analysed 57 patients with non-myeloid malignancies who received a non-purged autologous PBSCT. All had similar mobilisation and conditioning regimens. A high prior chemotherapy score and the number of chemotherapy lines used (P = 0.015 and P = 0.01, respectively) were adverse predictors of CD34 cell yields. Lower CD34 values (P = 0.002) were seen in patients treated with potent stem cell toxins (BCNU, melphalan, CCNU and mustine), designated toxicity factor 4 agents (TF4). All patients infused with grafts containing CD34 cell doses between 1.0 and 2.0 ؋ 10 6 /kg (range 1.25-1.90) engrafted by day 51. The only variable associated with slow platelet recovery was exposure to TF4 (P = 0.007). The majority of patients with CD34 Ͼ1.0 ؋ 10 6 /kg achieved rapid and sustained engraftment and the only predictive factor of delayed recovery is prior exposure to stem cell toxins. Potential PBSCT candidates should if possible avoid first line and salvage chemotherapy containing TF4 drugs. We therefore advocate a minimum CD34 threshold of Ͼ1.0 ؋ 10 6 /kg in patients without extensive prior chemoradiotherapy, and у2.0؋ 10 6 /kg in all other patients. Keywords: autologous stem cell transplant; CD34; transplantation; chemotherapy score Prior exposure to specific cytotoxic agents and the number of cycles of chemotherapy given, are associated with a reduced peripheral blood progenitor cell yield. 1,2 However the cumulative effects on long-term haematopoiesis of multiple cycles of combination chemotherapy are less well defined. Drake et al 3 have devised a chemotherapy scoring system (outlined in Table 1) in which each chemotherapy agent used was given a score based on its predicted stem cell toxicity (range 0-4). By multivariate analysis only exposure to stem cell toxicity factor 4 drugs (BCNU, melphalan, CCNU and mustine) prior to PBSC mobilisation was a significant predictor of lower CD34 counts. They did not analyse their data with respect to time to engraftment.In order to study the effect of prior chemoradiotherapy on CD34 levels and the rate of engraftment, we calculated the chemotherapy score 3 and the number of lines of chemo-

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Section: Discussionmentioning

confidence: 99%

The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipients

Gandhi

Jestice

Scott

et al. 1998

Bone Marrow Transplant

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“…35 Confluent cells were trypsinised with 0.05% (w/v) trypsin (Worthington Biochemical Corporation, Lakewood, NJ, USA) containing 5 mm EDTA, counted and resuspended at 10 5 cells/ml in RPMI 1640 medium containing 20% (v/v) FCS and 2 mm l-glutamine. Twenty thousand cells (200 l) were deposited per well in 30 replicates on a 96-well plate and cells incubated at 37°C for 24 to 48 h by which time the wells were 70-90% confluent.…”

Section: Long-term Culture Initiating Cell Assays (Ltc-ic)mentioning

confidence: 99%

NOD/SCID repopulating cells but not LTC-IC are enriched in human CD34+ cells expressing the CCR1 chemokine receptor

et al. 2001

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Human haemopoietic stem and progenitor cells may be distinguished by the pattern of cell surface markers they display. The cells defined as 'stem' cells are heterogeneous and lack specific markers for their detection. However, they may be identified in in vitro assays such as the long-term culture initiating cell (LTC-IC) and in transplant assays involving immunosuppressed NOD/SCID mice. It is still not clear to what extent, if any, these cell populations overlap. The chemokine macrophage inflammatory protein-1␣ (MIP-1␣) prolongs survival of LTC-IC in suspension cultures and we now show that in longterm bone marrow cultures (LTBMC) maintenance of haemopoiesis was significantly better from the CD34 + cells which possess MIP-1␣ receptors (P Ͻ 0.006). We examined one MIP-1␣ receptor, CCR1, which is present on CD34 ؉ cells from haemopoietic tissues. In LTBMC the production of GM-CFC from CD34 ؉ CCR1 ؊ cells was significantly higher (P Ͻ 0.02) than that from CD34 ؉ CCR1 ؉ cultures and the incidence of LTC-IC was 3-to 6-fold higher in the CD34 ؉ CCR1 ؊ cell fraction. In contrast, the cells responsible for high levels of engraftment in NOD/SCID mice were contained in the CD34 ؉ CCR1 ؉ cell fraction. The CD34 ؉ CCR1 ؉ cells engrafted to high levels in NOD/SCID and generated large numbers of progenitor cells. Therefore, we conclude that LTC-IC and SRC may be distinguished on the basis of expression of the chemokine receptor CCR1. Leukemia (2001) 15, 1092-1101.

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“…In vivo, r-metHuSCF has been used in association with G-CSF to induce mobilization of PBPC for autologous trans-plantation 9,10 and there are several randomized studies indicating that the combination of both cytokines mobilizes significantly more CD34 + cells than G-CSF alone. [11][12][13][14] However, it is also clear from these studies that the use of r-metHuSCF is not devoid of toxicity. Although there is experience with the use of G-CSF and r-metHuSCF for mobilization of PBPC, the use of both growth factors in combination with chemotherapy is scant.…”

Section: Introductionmentioning

confidence: 99%

Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy

Prósper

Solá

Hornedo³

et al. 2003

Leukemia

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The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34 + cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II-IV breast cancer received cyclophosphamide (3 g/m 2 ), Filgrastim 5 g/kg daily and r-metHuSCF 20 g/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 × 10 3 / l. Collection was performed between days +9 and +12 and the median number of CD34 + cells collected was 9.9 × 10 6 /kg (1.1-53.1) and 6.6 × 10 6 /kg (1.4-33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34 + cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34 + cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34 + cells which results in shortening of time to engraftment and hospitalization.

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Increased Numbers of Progenitor Cells in the Apheresis Product of Patients Randomised to Receive Increasing Doses of Stem Cell Factor (r-metHuSCF) Administered in Combination with Chemotherapy and a Standard Dose of Filgrastim (r-metHuG-CSF)

Cited by 20 publications

References 19 publications

The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipients

The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipients

NOD/SCID repopulating cells but not LTC-IC are enriched in human CD34+ cells expressing the CCR1 chemokine receptor

Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy

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