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Biology of Blood and Marrow... Aug 2012Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation; however, a proportion of patients fail to collect the... (Review)
Review
Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation; however, a proportion of patients fail to collect the minimum number of cells required. We summarized the efficacy and safety of HSC mobilization strategies. We performed a systematic review of randomized controlled trials comparing HSC mobilization strategies before autologous transplantation for hematologic malignancies. The primary outcome was CD34+ cell yield. Secondary outcomes included number of aphereses, proportion of failures, rate of count recovery, and adverse events. We identified 28 articles within 3 broad strategies. Using a cyclophosphamide with growth factor strategy (10 articles), CD34+ cell yield is improved by addition of molgramostim to cyclophosphamide (1.4 vs 0.5 × 10(6)/kg; P = .0165), addition of cyclophosphamide to filgrastim (7.2 vs 2.5 × 10(6)/kg; P = .004), and addition of ancestim to cyclophosphamide and filgrastim (12.4 vs 8.3 × 10(6)/kg; P = .007). Within a growth factor-based strategy (6 articles), addition of plerixafor improves CD34+ cell yield over filgrastim alone in multiple myeloma (MM; 11.0 vs 6.2 × 10(6)/kg; P < .001) and non-Hodgkin lymphoma (5.69 vs 1.98 × 10(6)/kg; P < .01). With combination or noncyclophosphamide-based chemotherapy (12 articles), higher-dose filgrastim (8.2 vs 4.7 × 10(6)/kg for 16 vs 8/mcg/kg daily of filgrastim, respectively; P < .0001) and addition of rituximab to etoposide and filgrastim (9.9 vs 5.6 × 10(6)/kg; P = .021) improve CD34+ cell yield. Growth factor alone after chemotherapy, ancestim, or plerixafor provide adequate autologous HSC grafts for the majority of patients. Although some strategies result in higher CD34+ cell yield, this potentially comes at the expense of increased toxicity. As all strategies are reasonable, programmatic, and patient-specific considerations must inform the approach to autologous graft mobilization.
Topics: Antigens, CD34; Benzylamines; Cyclams; Cyclophosphamide; Hematologic Neoplasms; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Heterocyclic Compounds; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Transplantation, Autologous
PubMed: 22261379
DOI: 10.1016/j.bbmt.2012.01.008 -
Bone Marrow Transplantation Jul 2011Ancestim (r-MetHuSCF) is available in France for compassionate use in patients who are candidates for high-dose chemotherapy and autologous transplantation, and who...
Ancestim (r-metHuSCF) plus filgrastim and/or chemotherapy for mobilization of blood progenitors in 513 poorly mobilizing cancer patients: the French compassionate experience.
Ancestim (r-MetHuSCF) is available in France for compassionate use in patients who are candidates for high-dose chemotherapy and autologous transplantation, and who failed in previous attempts at mobilization and collection. We report here data from 513 adult patients who benefited from this program, between January 1998 and July 2007. Given with systematic premedication, ancestim was generally well tolerated, although severe but not life-threatening adverse events were reported in 12 individuals. Overall, a graft was obtained or completed for 235 patients (46%). The median number of collected CD34+ cells was 3.00 × 10(6)/kg (range: 0.03-39.50). The target threshold of 2 × 10(6) CD34+ cells/kg was reached in 161 patients (31%). Factors associated with collection were diagnosis of myeloma, no previous autologous transplant, no more than one previous failed attempt and a mobilization regimen including cytotoxic agents. A total of 207 patients (40%) proceeded to high-dose chemotherapy and autologous transplantation. The median time to reach 0.5 × 10(9)/L neutrophils and 20 × 10(9)/L platelets was 12 (6-40) and 13 (0-31) days, respectively. We conclude that a combination of ancestim with filgrastim successfully mobilized CD34+ cells in peripheral blood, and allowed adequate collection in preparation for autologous transplantation in approximately one-third of poorly mobilizing patients.
Topics: Adolescent; Adult; Compassionate Use Trials; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Neoplasms; Recombinant Proteins; Stem Cell Factor; Transplantation, Autologous; Young Adult
PubMed: 20956952
DOI: 10.1038/bmt.2010.231 -
Bone Marrow Transplantation Jan 2011SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment.
SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial very unlikely may challenge chemotherapy plus r-metHuG-CSF priming in candidates for high-dose therapy.
Topics: Adult; Aged; Antigens, CD34; Drug Therapy, Combination; Female; Filgrastim; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Lymphoma; Male; Middle Aged; Neutropenia; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Recombinant Proteins; Stem Cell Factor; Thrombocytopenia; Transplantation Conditioning; Transplantation, Autologous; Young Adult
PubMed: 20436517
DOI: 10.1038/bmt.2010.84 -
Expert Opinion on Biological Therapy Jan 2010The mobilization and collection of hematopoietic stem and progenitor cells (HSPC) is central to many potentially curative treatments for cancer and some non-malignant... (Review)
Review
The mobilization and collection of hematopoietic stem and progenitor cells (HSPC) is central to many potentially curative treatments for cancer and some non-malignant conditions. Recombinant human cytokines have been the mainstay of therapeutic HSPC mobilization, particularly G-CSF. Even with currently used mobilization regimens using G-CSF with or without chemotherapy, up to 60% of patients can fail to mobilize enough HSPC for a transplant procedure. Recombinant human stem cell factor (ancestim, rhSCF, Stemgen) is another such cytokine, which has shown promising synergy when used in combination with G-CSF for HSPC mobilization. It provides a useful second-line option for prior failed-mobilizer patients and those who are anticipated to mobilize poorly due to recognised risk factors. It may also have utility in promoting bone marrow recovery in cases of refractory bone marrow failure such as aplastic anaemia and prolonged non-engraftment after allogeneic HSPC transplantation. We review the literature supporting the use of rhSCF in the context of HSPC mobilization and bone marrow failure. The emergence of other novel agents for HSPC mobilization such as plerixafor (AMD3100, Mozobil) will further demarcate the role of Ancestim as a second- or third-line mobilization agent for the mobilization-refractory patient.
Topics: Animals; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Stem Cell Factor
PubMed: 19947895
DOI: 10.1517/14712590903473123 -
Pediatric Blood & Cancer Jan 2010Pegfilgrastim, the long acting agent of rh-GCSF, has been shown to be as effective as Filgrastim in children undergoing cytotoxic chemotherapy by reducing the duration...
BACKGROUND
Pegfilgrastim, the long acting agent of rh-GCSF, has been shown to be as effective as Filgrastim in children undergoing cytotoxic chemotherapy by reducing the duration of neutropenia. Recent studies in adults have also shown that Pegfilgrastim is effective to mobilize CD34+ stem cells, resulting in earlier peripheral stem cell collections (PSCC). The aim of the study was to compare the efficacy of Pegfilgrastim with Filgrastim for CD34+ stem cell mobilization in children.
PROCEDURE
Three groups of patients were compared: Group 1: six patients with Ewing Sarcoma stimulated with Filgrastim; Group 2: five patients with Ewing Sarcoma, Ependymoma, and Neuroblastoma; Group 3: four patients with relapsed neoplasm. Patients of Group 2 and 3 were stimulated with Pegfilgrastim followed by peripheral stem cell collection. Two patients in Group 3 needed further cytokine stimulation with Filgrastim combined with stem cell factor, Ancestim.
RESULTS
In Groups 1-3, a median of 4, 3, and 3 PSCC between day 12-24, 6-13, and 8-30 were performed, yielding a median of 14.2, 24.0, and 10.3 x 10(6) CD34+ stem cells/kg BW, respectively.
CONCLUSIONS
Group 2 data show that stem cell mobilization with Pegfilgrastim in children when performed during primary or without previous long lasting chemotherapy seems to produce earlier CD34+ peaks and better CD34+ yields than in Group 1. CD34+ cell mobilization with Pegfilgrastim in Group 3-patients with previous long lasting chemotherapy was possible.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Male; Neoplasm Recurrence, Local; Neoplasms; Neutropenia; Peripheral Blood Stem Cell Transplantation; Polyethylene Glycols; Prognosis; Prospective Studies; Radiotherapy Dosage; Recombinant Proteins; Survival Rate; Treatment Outcome; Young Adult
PubMed: 19785023
DOI: 10.1002/pbc.22304 -
Leukemia & Lymphoma Oct 2008
Successful treatment of partial graft failure after matched unrelated donor stem cell transplantation by a combination of ancestim (stem cell factor) and granulocyte colony stimulating factor in a patient with heavily pre-treated chronic lymphocytic leukemia.
Topics: Drug Therapy, Combination; Graft Rejection; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Stem Cell Factor; Treatment Outcome
PubMed: 18728966
DOI: 10.1080/10428190802304958 -
International Journal of Hematology Jun 2006We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte...
We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia refractory to immunosuppressive therapy. In one patient, hemoglobin levels increased from 6.4 g/dL to 11.3 g/dL after 36 weeks of SCF/G-CSF treatment. Thereafter, the platelet count (24.0 x 10(9)/L) began to improve without the therapy, and as of week 272, the platelet count was 125.0 x 10(9)/L with a leukocyte count of 8.4 x 10(9)/L and a hemoglobin level of 12.9 g/dL. In the other patient, more than 3 years of SCF/G-CSF treatment ameliorated hemoglobin levels and platelet counts from 5.8 g/dL to 15.9 g/dL and 8.0 x 10(9)/L to 50.0 x 10(9)/L, respectively. After cessation of SCF/G-CSF treatment, the positive response was sustained, and the platelet count improved further to 71.0 x 10(9)/L as of week 242. These observations suggest the clinical benefit of SCF/G-CSF administration to patients with refractory aplastic anemia.
Topics: Aged; Anemia, Aplastic; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Male; Middle Aged; Platelet Count; Recombinant Proteins; Recovery of Function; Stem Cell Factor
PubMed: 16787870
DOI: 10.1532/IJH97.05098 -
Bone Marrow Transplantation May 2005
Topics: Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Recombinant Proteins; Stem Cell Factor; Stem Cells
PubMed: 15806123
DOI: 10.1038/sj.bmt.1704950 -
Bone Marrow Transplantation Oct 2004Up to a third of autologous transplantation candidates fail to mobilize hematopoietic progenitors into the peripheral blood with chemotherapy and/or growth factor...
Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection.
Up to a third of autologous transplantation candidates fail to mobilize hematopoietic progenitors into the peripheral blood with chemotherapy and/or growth factor treatment, thus requiring innovative mobilization strategies. In total, 20 cancer patients unable to provide adequate PBPC products after a previous mobilization attempt were treated with ancestim (20 microg/kg/day s.c.) and filgrastim (10 microg/kg/day s.c.). In 16 patients, the pre-study mobilization was with filgrastim alone. Eight patients underwent single large volume leukapheresis (LVL) and 12 multiple standard volume leukaphereses (SVL) in both mobilizations. Pairwise comparison of peripheral blood CD34(+) cell concentrations on the day of first leukapheresis failed to document synergism - median CD34(+)/microl of 3.2 (<0.1 to 15.4) and 4.5 (1-28.56) for the pre-study and on-study mobilizations (P = 0.79, sign test), and 4.2 (<0.1-15.4) and 5 (1-28.56), respectively, for the 16 patients previously mobilized with filgrastim alone (P = 1, sign test). The number of CD34(+) cells/kg collected per unit of blood volume (BV) processed was similar in both mobilizations - median 0.1 x 10(6)/kg/BV and 0.09 x 10(6)/kg/BV, respectively (P = 1, sign test). In this phase II study, the combination of ancestim and filgrastim did not allow adequate PBPC mobilization and collection in patients with a previous suboptimal PBPC collection.
Topics: Adult; Antigens, CD34; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Leukapheresis; Leukocytes, Mononuclear; Male; Middle Aged; Recombinant Proteins; Stem Cell Factor; Stem Cells; Time Factors; Transplantation, Autologous
PubMed: 15322567
DOI: 10.1038/sj.bmt.1704602 -
Bone Marrow Transplantation Mar 2003This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield... (Clinical Trial)
Clinical Trial
Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim.
This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield 0.5-1.9 x 10(6)/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20 microg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20 microg/kg/day plus filgrastim 5-10 microg/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of >or=3 x 10(6) CD34(+) cells/kg. In both groups, CD34(+) yield (x 10(6)/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 10(6)/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 10(6)/kg BW in the prior mobilization as in those with 0.76-1.99 x 10(6)/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34(+) cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.
Topics: Adult; Aged; Antigens, CD34; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Proto-Oncogene Proteins c-kit; Recombinant Proteins; Stem Cell Factor
PubMed: 12634728
DOI: 10.1038/sj.bmt.1703860