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PubMed1999

Cyclophosphamide and paclitaxel as initial or salvage regimen for the mobilization of peripheral blood progenitor cells.

Peripheral blood progenitor cells are now commonly used for hematologic reconstitution after myelosuppressive chemotherapy for hematologic and solid malignancies. The purpose of this study was to evaluate the activity of paclitaxel 170 mg/m2 and cyclophosphamide 2 g/m2 (CP) with filgrastim (human G-CSF) for mobilization of PBPCs as the first or second maneuver after failure with filgrastim alone. Sixty-four patients with stage II-IV breast cancer received (CP) followed by filgrastim (10 microg/kg/day). In 35 (55%) this was the first maneuver while it was for salvage in 29 (45%) patients. The median number of aphereses was two (range, 1-7). In 83% of the patients apheresis was initiated on days 10-11 following chemotherapy. The median numbers of CD34+ cells/kg, CD34+ cells/apheresis/kg and total nucleated cells/kg collected were 8.7 x 10(6) (2.11-73.5), 3.97 x 10(6) (0.3-36.75) and 164.15 x 10(8) (9-660), respectively. All the patients yielded at least 2 x 10(6) CD34+ cells/kg. CP mobilization salvaged the 29 patients who failed mobilization with filgrastim alone. When used as first-line mobilization the yield of CD34+ cells x 10(6)/kg was higher than in the salvage group (16.93 vs 3.94, P < 0.001). Patients receiving CP as salvage reached the target of 5 x 10(6) CD34+ cells/kg in only 45% (13/29) of cases vs 94.3% as first maneuver. CP followed by filgrastim is a safe and effective regimen for the mobilization of PBPCs in patients with breast cancer and shows significant activity in patients who failed to mobilize with filgrastim, suggesting a higher mobilization potential.

Adult↗

PubMed2000

Mobilization of hematopoietic progenitor cells with paclitaxel (taxol) as a single chemotheraupetic agent, associated with rhG-CSF.

We assessed the mobilization capacity of taxol with rhG-CSF, both as a single chemotherapeutic agent and in the presence of cyclophosphamide (CY), and compared the effect with yields achieved when mobilization was performed solely with rhG-CSF. Fifteen patients with breast cancer received taxol 170 mg/m2 (continuous infusion, day 1) and rhG-CSF (8 microg/kg/day, from day 2 until the end of apheresis) (T-G group), while seven breast cancer patients were additionally treated with CY (4 g/m2) on day 2, followed by rhG-CSF starting at similar doses on day 3 (T-CY-G group). The PBSC collections after taxol with/without CY were compared with those of 30 breast cancer patients who had received rhG-CSF (8 microg/kg/day) for mobilization. No differences were found in the characteristics of patients included in any of the three mobilization groups. The median yield of CD34+ cells from all patients included in taxol containing schedules was 9 x 106/kg (range 2-26) collected with a median of one apheresis procedure (range 1-4). Leukaphereses began earlier in the T-G group (median day 8, range 7-10) than in the T-CY-G group (median day 13, range 11-17). In most patients (20 out of 22) who received taxol containing regimens, more than 2.5 x 106 CD34+ cells/kg, a threshold considered to be sufficient for hematopoietic reconstitution, were collected with a single apheresis. Those patients in the T-G group experienced less neutropenic and thrombocytopenic days, with all neutropenic fever episodes developing in patients treated with the T-CY-G schedule (43%). When considering priming with rhG-CSF alone in our historical cohort of 30 breast cancer patients, a significant detrimental effect was observed in comparison with taxol mobilizing schedules, in the number of aphereses performed, in the total yield CD34+cells and in the number of patients who achieved the target dose of 2.5 x 106/kg CD34+ cells within the first collection procedure. We conclude that taxol containing schedules are effective in mobilizing PBSC and facilitate the collection of high yields of CD34+ cells (usually more than 5 x 106/kg recipient body weight) with a reduced number of apheresis procedures. Taxol, as a single agent with rhG-CSF, exhibits less hematological toxicity than the combination chemotherapy mobilization regimen including CY. Bone Marrow Transplantation (2000) 25, 231-235.

Adult↗

PubMed2001

Synergistic effects of pegylated recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor on mobilization of hematopoietic progenitor and stem cells with long-term repopulating ability into peripheral blood in mice.

We investigated the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on peripheral blood progenitor cell (PBPC) mobilization and the combined effect of PEG-rHuMGDF plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) in C57BL/6 mice. Treatment of mice with PEG-rHuMGDF increased the numbers of day 8 and day 12 spleen colony-forming units (CFU-S), and pre-CFU-S in the PB. Ten days administration of PEG-rHuMGDF could mobilize higher numbers of days 8 and day 12 CFU-S than 5 days administration. An optimal dose of PEG-rHuMGDF mobilized a higher number of committed progenitor cells (day 8 CFU-S) and a lower number of immature progenitor cells (pre-CFU-S) into PB than rhG-CSF. The combined administration of optimal or suboptimal doses of PEG-rHuMGDF and rhG-CSF induced synergistic effects on mobilization of CFU-S and pre-CFU-S into PB compared to either factor alone. Four months after sex-mismatched PBPC transplantation, long-term donor-derived engraftment was observed in all recipients that had been transplanted with PBPCs mobilized by rhG-CSF and/or PEG-rHuMGDF, as determined by Y-chromosome polymerase chain reaction (PCR) analysis. Our data suggest that cytokine-induced pathways for PBPC mobilization may be different between PEG-rHuMGDF and rhG-CSF and indicate that PEG-rHuMGDF alone or the combination with rhG-CSF may be useful in effective PBPC mobilization.

Animals↗

PubMed2002

Peripheral blood stem cell collection in children with acute leukemia: effectiveness of the 'DIAVE' mobilizing regimen.

Few experiences of peripheral blood (PB) hematopoietic stem cell mobilization for autologous transplantation have been reported to date in children with acute leukemia (AL). The five-drug-chemotherapy 'DIAVE' (dexamethazone, idarubicine, cytosine-arabinoside, vincristine, etoposide), followed by G-CSF, previously reported as consolidation, was adopted as a mobilization regimen in 29 children (median age: 8 years, range: 3-21; median weight: 34 kg, range: 15-73) with ALL in second remission (CR2: 21), in CR3 (2) or ANLL in CR1 (6). A median peak of 94 x 10(6) CD34(+)cells/l (range: 10-604) was reached at a median time of 12 days (range: 10-18) after the beginning of the mobilizing regimen, which was well tolerated. A median of 10.9 x 10(6) CD34(+)cells/kg (range: 2.4-56.6) were collected in 25 patients (86%), approaching 40 x 10(6)/l CD34(+) cells in the PB (ALL in CR2: 20/21, in CR3: 0/2; ANLL: 5/6) by means of one (20) or two (5) leukaphereses; a median of 2.5 blood volumes was processed. Patients with ANLL mobilized more cells than patients with ALL; moreover, the shorter the interval between remission and mobilizing therapy, the higher was the yield. The products collected underwent purification, aiming at achieving complete removal of possibly contaminating leukemic cells, in 21 cases; also, unmanipulated aliquots were stored as rescues for all but one patient. All the 23 patients undergoing transplantation engrafted (ANC >0.5 x 10(9)/l) at a median of 12 days. In conclusion, the DIAVE regimen compares favorably with conventional mobilizing regimens, usually containing cyclophosphamide, in terms of low toxicity, collection time predictability, and efficacy, as shown by the high proportion of patients mobilizing, the large amounts of stem cell collected by means of one or two leukaphereses only, and the prompt engraftment after infusion.

Acute Disease↗

PubMed2004

Good and poor CD34+ cells mobilization in acute leukemia: analysis of factors affecting the yield of progenitor cells.

SUMMARY: The factors possibly affecting the collection of peripheral blood stem cells (PBSC) were evaluated in 104 de novo acute leukemia patients (66 myeloid and 38 lymphoblastic leukemias) in first cytological complete remission (CR); all patients achieved CR after first-line induction chemotherapy. The acute myeloid leukemia patients (AML) were given consolidation-mobilization chemotherapy with cytarabine, and daunoblastin or mitoxantrone or idarubicin; the acute lymphoblastic leukemia patients (ALL) were given consolidation-mobilization chemotherapy with cytarabine and etoposide. In all patients, the collection of PBSC was performed during recovery after giving consolidation chemotherapy and granulocyte colony-stimulating factor (G-CSF). Two main groups were considered according to the CD34+ cells x 10(6)/kg b.w. collected, that is, poor mobilizers (PM), with a collection of <2 x 10(6)/kg and good mobilizers, with a collection of >2 x 10(6)/kg. Of 104 patients, 27 (25.9%) were PM; 20/27 had AML and 7/27 had ALL. At multivariate analysis, a lower CD34+ cells count premobilization chemotherapy (CD34 steady state), the presence of FUO (fever of unknown origin) or infection, and a lower number of CD34+ cells on the first day of collection correlated with poor mobilization. These results may enable early recognition of patients who may have poor mobilization, and aid selection of patients for different mobilization regimens.

Acute Disease↗

PubMed1998

A combination of low-dose cyclophosphamide and colony-stimulating factors is more cost-effective than granulocyte-colony-stimulating factors alone in mobilizing peripheral blood stem and progenitor cells.

BACKGROUND: The use of peripheral blood progenitor cells (PBPCs) instead of autologous bone marrow leads to more rapid engraftment following high-dose chemotherapy. Mobilization regimens differ with respect to toxicity, efficiency, and cost. STUDY DESIGN AND METHODS: Two cohorts of patients with breast cancer received one of two mobilization regimens: granulocyte-colony-stimulating factor (G-CSF) at 10 micrograms per kg was given subcutaneously for 5 days, with leukapheresis begun on Day 6, or low-dose cyclophosphamide followed by sequential granulocyte-macrophage-CSF (GM-CSF) at 5 micrograms per kg for 5 days and by G-CSF at 10 micrograms per kg, with leukapheresis begun on Day 11. Results of CD34+ cell collection, engraftment, and costs of mobilization were determined. RESULTS: The combination chemotherapy and growth factor regimen was more efficient in mobilizing CD34+ cells. Sixty-six percent of patients reached a target 4 x 10(6) CD34+ cells per kg in a single leukapheresis session with the combination regimen, compared to 14 percent who received G-CSF alone (p < 0.01). The mean number of leukapheresis sessions required to reach a target of 4 x 10(6) CD34+ cells per kg was 1.3 for the combination regimen and 2.7 for the regimen of G-CSF alone (p < 0.01). One patient in the chemotherapy and growth factor group developed febrile neutropenia. Engraftment was similar in both cohorts of patients. The cost of mobilization, including all supplies and cryopreservation, was $7381 for the G-CSF regimen and $5508 for the chemotherapy regimen (p < 0.05). This reduction was attributed to the lower number of leukapheresis and cryopreservation sessions, which outweighed the slight increase in expense for chemotherapy and growth factor in the combination regimen. CONCLUSION: This combination mobilization regimen allowed the predictable and efficient collection of CD34+ cells from the peripheral blood in a limited number of leukapheresis sessions, which reduced the cost of mobilization by approximately 25 percent.

Adult↗

PubMed2002

Equivalent mobilization and collection of granulocytes for transfusion after administration of glycosylated G-CSF (3 microg/kg) plus dexamethasone versus glycosylated G-CSF (12 microg/kg) alone.

BACKGROUND: The aim of this study was to find a regimen for mobilization and collection of granulocytes that combines low-dose G-CSF administration with satisfactory PMN mobilization and apheresis at a low rate of donor adverse reactions. STUDY DESIGN AND METHODS: In a prospective study, 52 healthy unrelated volunteers received a single subcutaneous injection of glycosylated G-CSF (Lenograstim Chugai-Pharma, Frankfurt, Germany) at medians of 3.1 (range, 2.4-3.6) microg per kg plus dexamethasone (8 mg orally; n = 29) or at 11.8 (7.1-18.5) microg of lenograstim per kg (p < or = 0.0001) without dexamethasone (n = 23) and underwent standard apheresis using the PMN program of a cell separator (Spectra, COBE [now Gambro] BCT). WBC and PMN mobilization results and apheresis yields were compared and the severity and clinical significance of donor adverse reactions was evaluated. RESULTS: For the low-dose G-CSF plus dexamethasone versus the high-dose G-CSF alone group, similar mobilization results were observed for WBCs with 31.3 (19.1-44.9) x 10(9) per L versus 27.5 (19.2-44.0) x 10(9) per L (p = 0.21, NS) and PMNs with 29.0 (17.6-42.2) x 10(9) per L versus 25.2 (16.2-39.0) x 10(9) per L (p = 0.08, NS). The PMN apheresis yields were equal with 70 (39-139) x 10(9) per unit with low-dose G-CSF versus 68 (33-120) x 10(9) per unit in the high-dose G-CSF group (p = 0.83, NS). Regarding donor adverse reactions, 7 out of 29 (24%) and 8 out of 23 donors (35%) reported moderate or severe symptoms. The character of these reactions was different; symptoms of greater clinical significance and a higher need for analgesics were observed in the high-dose G-CSF group. CONCLUSIONS: A Lenograstim dose of 3 microg per kg plus DXM assures effective PMN mobilization and acceptable apheresis components. The combination of glycosylated G-CSF with DXM allows a significant dose reduction in G-CSF for PMN mobilization and collection as compared with higher G-CSF doses alone. In the high-dose G-CSF mobilization group, adverse reactions were more severe and required more analgesics.

Adult↗

PubMed2002

The composition of leukapheresis products impacts on the hematopoietic recovery after autologous transplantation independently of the mobilization regimen.

BACKGROUND: Effects of mobilization regimen on the composition of leukapheresis products (LPs) and on hematopoietic reconstitution after autologous peripheral blood progenitor cell transplantation (PBPCT) are not well known. STUDY DESIGN AND METHODS: The effects of three different mobilization regimens--stem cell factor (SCF) plus granulocyte colony stimulating factor (G-CSF) plus cyclophosphamide (CCP), G-CSF alone, and G-CSF plus CCP--on the composition of LPs from patients with nonhematologic PBPC malignancies compared to LPs from G-CSF-mobilized healthy donors and normal marrow (BM) samples were analyzed. The impact of LP composition on both short- and long-term engraftment after autologous PBPCT was also evaluated. RESULTS: The most effective regimen for mobilization of CD34+ hematopoietic progenitor cells (HPCs) into peripheral blood was SCF, G-CSF, and CCP, providing the highest numbers of all CD34+ HPCs subsets analyzed. Patients mobilized with SCF plus G-CSF plus CCP showed the highest numbers of neutrophils and monocytes, whereas the highest numbers of lymphocytes and NK cells were observed in LPs from G-CSF-mobilized patients. The overall number of CD34+ HPCs was the strongest factor for predicting recovery of platelets, whereas the number of myelomonocytic-committed CD34+ precursors was the most powerful independent prognostic factor for WBC and neutrophil recovery. The overall number of CD4+ T cells returned showed an independent prognostic value for predicting the occurrence of infections, during the first year after transplant. CONCLUSIONS: The use of different mobilization regimens modifies the overall number of CD34+ HPCs obtained during leukapheresis procedures, and also affects both the absolute and the relative composition of the LPs in different CD34+ and CD34- cell subsets.

Adult↗

PubMed2000

Mobilization of stem/progenitor cells by sulfated polysaccharides does not require selectin presence.

Employing carbohydrate ligands, which have been extensively used to block selectin function in vitro and in vivo, we have examined the involvement of such ligands in stem/progenitor cell mobilization in mice and monkeys. We found that sulfated fucans, branched and linear, are capable of increasing mature white cells in the periphery and mobilizing stem/progenitor cells of all classes (up to 32-fold) within a few hours posttreatment in a dose-dependent manner. To elicit the effect, the presence of sulfate groups was necessary, yet not sufficient, as certain sulfated hexosamines tested (chondroitin sulfates A or B) were ineffective. Significant mobilization of stem/progenitor cells and leukocytosis was elicited in selectin-deficient mice (L(-/-), PE(-/-), or LPE(-/-)) similar to that of wild-type controls, suggesting that the mode of action of sulfated fucans is not through blockade of known selectins. Other mechanisms have been entertained, in particular, the release of chemokines/cytokines, including some previously implicated in mobilization. Significant increases were documented in the levels of seven circulating chemokines/cytokines within a few hours after fucan sulfate treatment and support such a proposition. Additionally, an increase was noted in plasma metalloproteinase (MMP) 9, which might independently contribute to the mobilization process by enzymatically facilitating chemokine/cytokine release. Mobilization by sulfated polysaccharides provides a distinct paradigm in the mobilization process and uncovers an additional novel in vivo biological role for sulfated glycans. As similarly sulfated compounds were ineffective in vivo, the data also underscore the fact that polysaccharides with similar structures may elicit diverse in vivo effects.

Animals↗

PubMed2006

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase.

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.

Adjuvants, Immunologic↗

PubMed2003

Phenotypic and immunologic characteristics of docetaxel-mobilized peripheral blood stem cells in mice.

Effective mobilization of peripheral blood stem cells is vital for transplantation of patients after high-dose chemotherapy and provides a convenient source of stem cells for genetic engineering and other studies, but optimal mobilization strategies have not been defined. Recent studies show that in the presence of recombinant human granulocyte colony-stimulating factor (rhG-CSF), docetaxel (DXT) is an effective mobilization agent. This study was performed to evaluate the phenotype and immunologic properties of DXT-mobilized stem cells. Administration of DXT + rhG-CSF to normal C57Bl/6 mice induced a 75-fold increase in blood hematopoietic progenitors and a significant increase in both CD3(+) (T cell) and DX5(+) [natural killer (NK)] cells when compared to untreated mice. The cytotoxicity of DXT + rhG-CSF-mobilized cell populations against YAC-1 and B16F10 cell lines was not significantly different from that of untreated mice. When compared to cyclophosphamide + rhG-CSF, DXT + rhG-CSF-mobilized cell populations yielded a greater number of T and NK cells, with significantly higher cytotoxic effector function. These results suggest that DXT + rhG-CSF-mobilized PBSCs retain potent immunologic capacity with a high number of the functional cellular subsets than those normally present in peripheral blood, which may be important in maintaining the antitumor immunity after transplantation.

Animals↗

PubMed2004

A population study of the association between hospitalization for alcoholism among employees in different socio-economic classes and the risk of mobility out of, or within, the workforce.

BACKGROUND: Alcohol problems can increase the risk of downward mobility within, or mobility out of, the workforce. The magnitude of this risk has been unclear, as has also been the question whether the risk is different for men and women, for different socio-economic classes, and for single-living compared with co-habiting people. METHODS: The study period was 1970-1980, when unemployment was low in Sweden. Information about socio-economic status from censuses was linked to hospitalization for alcoholism, alcohol psychosis and alcohol intoxication (AAA) over the period 1970-1975 in Stockholm County in persons aged 20-49 years in 1970 and gainfully employed in the same socio-economic category in both 1970 and 1975, and to general population data. The standardized rate ratio for mobility out of the workforce and for downward socio-economic mobility was calculated for those hospitalized with AAA. RESULTS: There was a statistically significant risk of mobility out of the workforce over the period 1976-1980 in both sexes and in all socio-economic groups. The relative risk was 6.63 for male skilled and semi-skilled manual workers and 9.52 for non-manual employees at medium and high level, while the corresponding figures were lower for women. The absolute risk of leaving the workforce was lowest in non-manual employees at medium and high level. The relative risk was reduced in persons who were co-habiting. CONCLUSIONS: Severe alcohol problems are powerful determinants of downward mobility within, or mobility out of, the workforce in both sexes and in all socio-economic categories.

Alcoholism↗

PubMed1999

Mechanisms underlying hematopoietic stem cell mobilization induced by the CXC chemokine interleukin-8.

The CXC chemokine interleukin-8 induces rapid mobilization of hematopoietic progenitor cells in mice and monkeys. Antibodies against the beta 2-integrin leukocyte function-associated antigen-1 completely blocked interleukin-8-induced mobilization. This was not due to a direct effect on the hematopoietic progenitor cells, as leukocyte function-associated antigen-1 was found not to be expressed on hematopoietic progenitor cells. Additional experiments showed that interleukin-8 induces the rapid release of the metalloproteinase gelatinase B, concurrent with the mobilization of hematopoietic progenitor cells. Mobilization could be completely prevented by anti-gelatinase B antibodies. Because neutrophils express leukocyte function-associated antigen-1 and high affinity interleukin-8 receptors, and release gelatinase B upon stimulation with interleukin-8, we hypothesized that neutrophils are key mediators in interleukin-8-induced stem cell mobilization. Further studies showed that mobilization by interleukin-8 was completely absent in mice rendered neutropenic with anti-granulocytic antibodies. Taken together, these data are consistent with an essential role for neutrophils in interleukin-8-induced stem cell mobilization.

Animals↗

PubMed2002

Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor.

Hematopoietic progenitor cells can be mobilized from the bone marrow to the blood by a wide variety of stimuli, including hematopoietic growth factors, chemotherapy, and chemokines. Increasingly, mobilized peripheral blood hematopoietic progenitor cells instead of bone marrow hematopoietic progenitor cells have been used to reconstitute hematopoiesis after myeloablative therapy because of their reduced engraftment times and relative ease of collection. A striking feature of hematopoietic progenitor cell mobilization is the ability of hematopoietic growth factors with distinct cellular targets and biologic activities to mobilize a similar spectrum of pluripotent and lineage-committed hematopoietic progenitor cells into the blood. Recent studies have identified some of the key adhesive interactions that regulate hematopoietic progenitor cell trafficking in the bone marrow. In addition, pathways linking mobilizing agents to hematopoietic progenitor cell mobilization have begun to be elucidated. This review summarizes these advances, emphasizing the mechanisms regulating granulocyte colony-stimulating factor-induced mobilization.

Animals↗

PubMed2005

Peripheral blood progenitor cell mobilization and collection in 42 patients with primary systemic amyloidosis.

BACKGROUND: High-dose chemotherapy followed by an inoculum of autologous peripheral blood progenitor cells (PBPCs) can improve survival in patients affected with primary systemic amyloidosis (AL). It has been documented, however, that the morbidity and mortality of PBPC mobilization and collection in this setting are higher than in patients with other diseases. To minimize the mobilization and collection-related risks, we developed a multidisciplinary approach involving different specialists to manage AL patients with predominant heart and renal involvement. STUDY DESIGN AND METHODS: We report our experience in 42 patients (23 men, 19 women; median age, 51.2 years; range, 28-68 years) with AL who underwent PBPC mobilization and collection. Twenty of the 42 patients (47.6%) had cardiac involvement and 35 of 42 (83.3%) renal involvement. Thirty-three patients (78.5%) were mobilized with granulocyte-colony-stimulating factor (G-CSF) alone (10 microg/kg) and 9 (21.4%) with cyclophosphamide (CTX) (3 g/m(2)) plus G-CSF (10 microg/kg). RESULTS: The median number of collections per patient after either G-CSF or CTX plus G-CSF was 1.8 (range, 1-3). The median number of CD34+ cells collected in patients mobilized with G-CSF alone was 8.2 x 10(6) per kg (range, 1.35 x 10(6)-21.3 x 10(6)/kg) and in patients mobilized with CTX plus G-CSF it was 8.9 x 10(6) per kg (range, 5.5 x 10(6)-14.9 x 10(6)/kg). Forty of the 42 (95.2%) patients produced the minimum required CD34+ cell target dose (4 x 10(6)/kg). The overall rate of morbidity during the collections was 50 percent (21/42 patients): 18 patients (42.8%) had asymptomatic hypotension, 1 (2.4%) had symptomatic hypotension with nausea and vomiting, and 2 (4.7%) experienced a life-threatening hypotensive episode. There were no procedure-related deaths. CONCLUSION: Our multidisciplinary approach was effective in limiting the serious side effects related to PBPC mobilization and collection in AL patients.

Adult↗

PubMed2005

Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist.

BACKGROUND: AMD3100, a selective antagonist of CXCR4, rapidly mobilizes CD34+ hematopoietic progenitor cells (HPCs) from marrow to peripheral blood with minimal side effects. STUDY DESIGN AND METHODS: To further investigate potential clinical utility of AMD3100 for CD34+ cell mobilization and collection, a Phase I study in normal volunteers was performed examining single-dose administration of AMD3100 alone and in combination with a standard 5-day granulocyte-colony-stimulating factor (G-CSF) regimen. RESULTS: AMD3100 (160 microg/kg x 1 on Day 5) significantly increased both G-CSF-stimulated (10 microg/kg/day) mobilization of CD34+ cells (3.8-fold) and leukapheresis yield of CD34+ cells. Moreover, collection of CD34+ cells was comparable between individuals mobilized by a single-dose regimen of AMD3100 (240 microg/kg) and individuals mobilized with a 5-day regimen of G-CSF. AMD3100-mobilized leukapheresis products contained significantly greater numbers of T and B cells compared to G-CSF-stimulated leukapheresis products. CONCLUSION: These findings indicate that AMD3100 can be used alone or as an adjunct to G-CSF to mobilize cells for HPC transplantation.

Anti-HIV Agents↗

PubMed2006

CD34+ cell adhesion molecule profiles differ between patients mobilized with granulocyte-colony-stimulating factor alone and chemotherapy followed by granulocyte-colony-stimulating factor.

BACKGROUND: High-dose therapy with autologous peripheral blood progenitor cell support is widely utilized but requires successful CD34+ cell mobilization and collection. Chemotherapy plus growth factors appear to mobilize more CD34+ cells than growth factors alone. Because alterations in expression of adhesion molecules are important in the trafficking of hematopoietic progenitors, the possibility was explored that the mechanism of this superior mobilization may be greater down regulation of adhesion molecules. STUDY DESIGN AND METHODS: The expression of eight adhesion molecules (CD11a, b, and c; 15s; 49d and e; 54; and 62L) on the collected CD34+ cells from 15 patients undergoing mobilization with chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) was compared with those of 14 concomitant patients receiving G-CSF alone. RESULTS: Patients receiving chemotherapy plus G-CSF mobilized more CD34+ cells and did not differ in prior chemotherapy or radiation. There were no significant differences in the percentage of CD34+ cells expressing any of the adhesion molecules examined between the two groups. The chemotherapy plus G-CSF-mobilized cells consistently showed higher expression intensity, and this showed significance or a strong trend for CD11a and c, CD15s, and CD54. Despite these higher expression levels, there were no differences in engraftment kinetics. CONCLUSIONS: CD34+ cells mobilized by chemotherapy plus growth factors appear to have higher intensities of expression of several adhesion molecules. The significance of this observation will require further study.

Adult↗

PubMed2001

Increase in circulating SDF-1 after treatment with sulfated glycans. The role of SDF-1 in mobilization.

SDF-1 is a potent chemoattractant for mature white blood cells and hemopoietic stem/progenitor cells (HPCs). An important role for this chemokine in mobilization has been postulated, but in vivo studies directly addressing its effects are lacking. After one injection of fucan sulfate (FucS) or dextran sulfate, plasma levels of SDF-1 are greatly increased in mice or primates. Increases are dose-dependent and correlate with mobilization of HPCs. Elevated levels of circulating SDF-1 appear to be uniquely associated with this treatment, as it was not seen with cytokine or anti-integrin antibody treatments that induce mobilization. In vitro, these sulfated glycans specifically bind to SDF-1 and inhibit SDF-1/heparin binding, suggesting a mechanism of release from sequestration on heparan sulfate proteoglycans in vivo. Although other chemokines including IL8 and cytokines like G-CSF also increase, evidence in GCSFR-deficient mice suggests that at least these two factors are unlikely participants in FucS-induced mobilization. Likewise, although the activity of the metallo-protease MMP9 increases after FucS treatment, experiments in MMP9-/- mice indicate its presence is dispensable for mobilization or SDF-1 release. However, effects of other proteases cannot be ruled out by these experiments. Finally, anti-SDF-1 antibodies partially inhibit FucS-induced mobilization, supporting a causative relationship. Our data offer a unique insight into the mechanism of sulfated glycan-induced mobilization and suggest a novel way of disturbing SDF-1 gradients between bone marrow and peripheral blood.

Animals↗