Peripheral Blood Stem Cell Mobilization by G-CSF Alone and Engraftment Kinetics Following Autologous Transplantation in Children and Adolescents with Solid Tumor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5197-5197
Author(s):  
Hiroyoshi Watanabe ◽  
Tsutomu Watanabe ◽  
Hiroko Suzuya ◽  
Yoshifumi Wakata ◽  
Toshihiro Onishi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Platelet Recovery ◽  
Irradiation Group ◽  
Cd34 Cells ◽  
Pediatric Cancer Patients ◽  
Group 3 ◽  
Cell Mobilization

Abstract The purpose of this study was to examine the yield of PBSC, mobilized with G-CSF alone, and engraftment kinetics after autologous transplantation in pediatric cancer patients. In 55 patients (median age; 7 years, range 0–21) with various pediatric and adolescent solid tumors, PBSC were mobilized with G-CSF alone, and the yields of PBSC and engraftment following autologous PBSCT were evaluated retrospectively. Patients were categorized according to prior treatment; patients who had received less than 4 or 4 cycles of chemotherapy with/without local irradiation (Group 1: N= 21), patients who received more than 4 cycles of chemotherapy or 3 or more cycles of chemotherapy with extended irradiation (Group 2: N= 23), and patients who received high-dose chemotherapy with stem cell support (Group 3: N= 11). Ten microgram per kg of G-CSF was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for five days. The peaks of CD34+ cells and CFU-GM were observed on day 5 of G-CSF administration essentially in all patients. Aphereses were performed on days 5 and 6 of G-CSF treatment. Mobilization failure was observed in four patients in all groups. Compared with the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in those mobilized with G-CSF alone. However, there were no significant differences in WBC engraftment speed compared to the chemotherapy plus G-CSF mobilization group, although platelet recovery was delayed in patients with G-CSF alone, especially in patients in Group 3. The median time taken for ANC and platelet counts to reach 500 and 20K was 12 days (range 8–28) and 15 days (8–55), respectively, in all patients who were mobilized by G-CSF alone except for patients with progressive disease. In summary, mobilization with G-CSF alone can mobilize a sufficient number of CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric patients with cancer, even in heavily pre-treated patients. Mobilization with G-CSF alone might offer some advantages, such as ease of determining a collection schedule without a daily determination of CD34+ cells in the blood, and the avoidance of neutropenic fever and additional transfusion.

Autologous transplantation of granulocyte colony-stimulating factor–primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1595-1600 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Antonio de Vivo ◽  
Daniela Damiani ◽  
Alessandro Isidori ◽  
Monica Tani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
High Dose Chemotherapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Myeloablative Chemotherapy ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stimulating Factor

AbstractWe assessed the hematopoietic recovery and transplantation-related mortality (TRM) of patients who had failed peripheral blood stem cell mobilization and subsequently received high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF)–primed bone marrow (BM). Studied were 86 heavily pretreated consecutive patients with acute leukemia (n = 21), refractory/relapsed non-Hodgkin lymphoma (n = 41) and Hodgkin disease (n = 17), and multiple myeloma (n = 7). There were 78 patients who showed insufficient mobilization of CD34+ cells (< 10 cells/μL), whereas 8 patients collected less than 1 × 106 CD34+ cells/kg. BM was primed in vivo for 3 days with 15 to 16 μg/kg of subcutaneous G-CSF. Median numbers of nucleated cells, colony-forming unit cells (CFU-Cs), and CD34+ cells per kilogram harvested were 3.5 × 108, 3.72 × 104, and 0.82 × 106, respectively. Following myeloablative chemotherapy, median times to achieve a granulocyte count higher than 0.5 × 109/L and an unsupported platelet count higher than 20 and 50 × 109/L were 13 (range, 8-24), 15 (range, 12-75), and 22 (range, 12-180) days, respectively, for lymphoma/myeloma patients and 23 (range, 13-53), 52 (range, 40-120), and 90 (range, 46-207) days, respectively, for leukemia patients. Median times to hospital discharge after transplantation were 17 (range, 12-40) and 27 (range, 14-39) days for lymphoma/myeloma and acute leukemia patients, respectively. TRM was 4.6%, whereas 15 patients died of disease. G-CSF–primed BM induces effective multilineage hematopoietic recovery after high-dose chemotherapy and can be safely used in patients with poor stem cell mobilization.

Steady State Mobilization of Autologous Blood Stem Cells Using G-CSF and AMD3100 in Patients with Multiple Myeloma (MM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5219-5219
Author(s):  
Gerhard Ehninger ◽  
Stefan Fruehauf ◽  
Kai Hubel ◽  
Uwe Platzbecker ◽  
Karin Badel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autologous Blood ◽  
Fold Increase ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Growth Factors ◽  
Platelet Recovery ◽  
Significant Toxicity ◽  
Cd34 Cells

Abstract Background: High dose chemotherapy with autologous stem cell transplantation (ASCT) improves disease free and overall survival in pts with MM; tandem ASCT may further enhance clinical benefits. Mobilization with G-CSF alone fails to yield sufficient CD34+ cells for a tandem ASCT in the majority of MM pts. A mobilization regimen including G-CSF and cyclophosphamide is more effective, but associated with significant toxicity. This phase II study evaluated the efficacy and safety of a non-cytotoxic mobilization regimen of AMD3100 plus G-CSF for ASC mobilization in pts with MM. Methods: Mobilization treatment consisted of subcutaneous G-CSF (Filgrastim 10 μg/kg) given in the morning on 5 consecutive days and a single dose of AMD3100 (240 μg/kg) in the evening of day 4, 10–11 hours prior to leukapheresis. These procedures could be repeated for up to 5 additional days in order to collect an adequate number of cells for transplantation. Monitoring of CD34+ cells in peripheral blood (PB) was performed immediately prior to each AMD3100 administration and prior to the aphereses. Patients were treated with high dose chemotherapy in preparation for transplantation according to local standard of care guidelines. Pts did not receive hematopoietic growth factors following ASCT. The primary endpoint of the study was safety; secondary endpoints included 1) % of pts with >2-fold increase of CD34+ cells following AMD3100, and 2) % of pts in with hematopoietic recovery between day 14 and day 21. Results: 31 pts were evaluable, including 19 males (median age: 57 yrs, range: 40–73) and 12 females (median age: 61 yrs, range: 53–67). Pts had received a maximum of 4 prior chemotherapy cycles. The cumulative proportion of pts reaching a target of 5×10^6/kg CD34+ cells was 60% on day 1, 87% on day 2, and 93% on day 3. For the initial mobilization, AMD3100 increased absolute CD34+ counts ≥ 2-fold in 78% of pts (median fold increase: 2.8; range: 1.1–15.2). Additional aphereses showed a ≥ 2-fold increase in 21% of cases (median fold increase: 1.4; range: 0.7–6.5). Overall, the median number of CD34+ cells yielded was 7.1×10^6/kg (range: 3–28×10^6/kg). The majority of pts (n=19) underwent only a single apheresis, whereas additional procedures were needed in 12 cases. Nineteen pts received a single transplant, 11 pts a tandem transplant. Autografts contained a median of 3.1×10^6/kg CD34+ cells (range 2.4–9.2×10^6/kg). After first transplant, median time to neutrophil and platelet engraftment was 14 and 13 days, respectively. All patients had complete engraftment within 20 days except 1 pt who had neutrophil recovery at day 34 (single transplant) and 1 had platelet recovery at day 27 after the 2nd transplant. AMD3100 was well tolerated, drug-related adverse events (AEs) were limited to 2 cases of mild nausea/vomiting. Conclusions: The addition of AMD3100 to G-CSF doubled the number of mobilized CD34+ cells in the majority of pts, allowing the collection of sufficient CD34+ cells for tandem ASCT in 1–2 aphereses. Unlike chemotherapeutics commonly used to enhance stem cell mobilization, AMD3100 was not associated with any significant toxicity.

Kinetics of Autologous Stem Cell Mobilization Failure: Comparison of AMD3100/G-CSF, G-CSF, GM-/G-CSF, and Chemotherapy/G-CSF on Remobilization Success.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3380-3380 ◽  
Author(s):  
John F. DiPersio ◽  
Angela Smith ◽  
Dianne Sempek ◽  
Albert Baker ◽  
Steven Jiang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Surrogate Marker ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Disease State ◽  
High Dose ◽  
Factors Associated ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Kinetics Of

Abstract Background: No standard approach for the mobilization of peripheral hematologic stem and progenitor cells (HSPCs) has been established. High levels of circulating CD34+ cells, a surrogate marker for mobilization efficiency, are associated with less apheresis days. A higher dose of CD34+ cell transfused after high-dose chemotherapy decreases time to hematologic recovery. Consequently, a better understanding of variables associated with mobilization kinetics may further optimize stem cell collection and reduce complications associated with autologous stem cell transplants. Methods: The Washington University (St. Louis, MO) transplantation database includes clinical parameters from 407 multiple myeloma (MM), 567 non-Hodgkin’s Lymphoma (NHL), and 164 Hodgkin’s disease (HD) pts who received an ASCT between 1995 and 2006. A retrospective analysis of this large pt population was conducted to determine factors associated with the mobilization kinetics of CD34+ cells. Results: Figure 1 summarizes the mobilization kinetics as defined by number of days to reach a target of 2 × 10^6 CD34+ cells/kg. Overall, the median number of aphereses to reach the target were 1, 2, and 2 in MM, NHL, and HD, respectively. Daily median CD34+ yields in MM pts were 3.8, 1.2, and 0.5 × 10^6 on day 1–3, respectively. In NHL pts, yields were 1.4, 0.8, and 0.4 × 10^6 on day 1–3. In HD pts, yields were 1.8, 0.8, and 0.3 × 10^6 on day 1–3, respectively. The addition of chemotherapy increased the % of pts requiring only a single apheresis to reach the mobilization target. Figure 2 summarizes the mobilization kinetics for each re-mobilization regimen. In general, a limited number of cells was collected with each aphereses; >70% of pts failed to mobilize 2 × 10^6 CD34+ cells/kg. In contrast, remobilization with AMD3100 allowed the collection of sufficient CD34+ cells in 67% of pts; median number of apheresis to reach the target was 3. Conclusions: Factors associated with mobilization kinetics of CD34+ cells include disease state and mobilization regimen. Re-mobilization is associated with high failure rates, re-mobilization regimens including AMD3100 are more successful. Figure 1: Mobilization kinetics by disease state Figure 1:. Mobilization kinetics by disease state Figure 2: Mobilization kinetics by re-mobilization regimen Figure 2:. Mobilization kinetics by re-mobilization regimen

DCEP (Dexamethasone, Cyclophosphamide, Etoposide, Cisplatin) Followed by High-Dose G-CSF Is a Highly Efficient and Safe Regimen for Stem Cell Mobilization for Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3284-3284
Author(s):  
Jason P. Gonsky ◽  
Nikoletta Lendvai ◽  
Michele L. Donato ◽  
Scott D. Rowley ◽  
Andrew L. Pecora ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Yield ◽  
High Dose ◽  
Outpatient Basis ◽  
Stem Cell Rescue ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Related Mortality

Abstract High dose chemotherapy with autologous stem cell rescue remains a standard therapy for multiple myeloma patients who can tolerate it. A mobilizing regimen for multiple myeloma should ideally allow for a high yield of CD34+ cells, provide anti-myeloma activity, be well tolerated, and have predictable kinetics regarding initiation of collection of stem cells. Higher numbers of infused autologous CD34+ cells allow for more rapid engraftment and lower incidence of transplant-related morbidity and mortality. The goal for patients with myeloma is to harvest enough CD34+ cells to provide at least two autologous transplants. Previous mobilization regimens utilized G-CSF alone or high-dose cyclophosphamide with G-CSF. However, high-dose cyclophosphamide (4–7g/m2) has only modest efficacy against myeloma and is associated with significant morbidity and up to 1–2% treatment-related mortality. DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) is a well established regimen with good efficacy as salvage treatment for myeloma. Additionally, the use of DCEP with G-CSF for mobilization in myeloma has previously been reported to provide an average yield of approximately 6x106 CD34+ cells. We report our experience with DCEP and high-dose G-CSF in mobilizing 88 multiple myeloma patients since 2006. Our regimen consisted of 40 mg dexamethasone IV over 15 minutes x 4 days, cyclophosphamide 500 mg/m2, etoposide 40 mg/m2 (capped at 75 mg), and cisplatin 15 mg/m2 (capped at 25 mg), all continuous IV infusions over 24h x 4 days, with G-CSF starting 24–48h after completion of chemotherapy, administered SQ at 5 mcg/kg x 6 days followed by 10 mcg/kg daily until pheresis is completed. Over 80% of our patients were ready to initiate collection on day 14. Our goal for collection is 10–12x106 CD34+ cells to allow for two or three transplants using at least 4x106 CD34+ cells per transplant. Yields were excellent with a mean yield of 27x106 CD34+ cells, with a range of 7.3–130.5x106 CD34+ cells. 37/88 (42%) of patients required only one day of pheresis, with a mean yield of 34x106 CD34+ cells. 38/88 (43%) of patients required two days of pheresis. Only 15% of patients required more than two days of pheresis. Only 3 patients yielded fewer than 10x106 CD34+ cells (3%), and none yielded fewer than 5x106 CD34+ cells. In conclusion, this regimen is highly efficacious, offers excellent stem cell yields and predictable collection kinetics, can be administered on an outpatient basis, and is safe and well tolerated.

scholarly journals High CD34+ Cell Counts Decrease Hematologic Toxicity of Autologous Peripheral Blood Progenitor Cell Transplantation

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3148-3155 ◽  
Author(s):  
Nicolas Ketterer ◽  
Gilles Salles ◽  
Michel Raba ◽  
Daniel Espinouse ◽  
Anne Sonet ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Progenitor Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Lymphoproliferative Diseases ◽  
High Group ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Intermediate Group ◽  
Cd34 Cells

Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

scholarly journals High CD34+ Cell Counts Decrease Hematologic Toxicity of Autologous Peripheral Blood Progenitor Cell Transplantation

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3148-3155 ◽  
Author(s):  
Nicolas Ketterer ◽  
Gilles Salles ◽  
Michel Raba ◽  
Daniel Espinouse ◽  
Anne Sonet ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Progenitor Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Lymphoproliferative Diseases ◽  
High Group ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Intermediate Group ◽  
Cd34 Cells

Abstract Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 2169-2174 ◽  
Author(s):  
Patrick Stiff ◽  
Bohao Chen ◽  
Wilbur Franklin ◽  
David Oldenberg ◽  
Eric Hsi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Ex Vivo ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Small Aliquot

Abstract The collection of small aliquots of bone marrow (BM), followed by ex vivo expansion for autologous transplantation may be less morbid, and more cost-effective, than typical BM or blood stem cell harvesting. Passive elimination of contaminating tumor cells during expansion could reduce reinoculation risks. Nineteen breast cancer patients underwent autotransplants exclusively using ex vivo expanded small aliquot BM cells (900-1200 × 106). BM was expanded in media containing recombinant flt3 ligand, erythropoietin, and PIXY321, using stromal-based perfusion bioreactors for 12 days, and infused after high-dose chemotherapy. Correlations between cell dose and engraftment times were determined, and immunocytochemical tumor cell assays were performed before and after expansion. The median volume of BM expanded was 36.7 mL (range 15.8-87.0). Engraftment of neutrophils greater than 500/μL and platelets greater than 20 000/μL were 16 (13-24) and 24 (19-45) days, respectively; 1 patient had delayed platelet engraftment, even after infusion of back-up BM. Hematopoiesis is maintained at 24 months, despite posttransplant radiotherapy in 18 of the 19 patients. Transplanted CD34+/Lin−(lineage negative) cell dose correlated with neutrophil and platelet engraftment, with patients receiving greater than 2.0 × 105 CD34+/Lin− cells per kilogram, engrafting by day 28. Tumor cells were observed in 1 of the 19 patients before expansion, and in none of the 19 patients after expansion. It is feasible to perform autotransplants solely with BM cells grown ex vivo in perfusion bioreactors from a small aliquot. Engraftment times are similar to those of a typical 1000 to 1500 mL BM autotransplant. If verified, this procedure could reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which small stem cell doses are available, eg, cord blood transplants.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

High Dose Thiotepa, Busulfan, Cyclophosphamide (TBC) and Autologous Hematopoietic Stem Cell Transplantation (ASCT) without Whole Brain Radiotherapy (WBRT) for Primary Central Nervous System Lymphoma (PCNSL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 911-911 ◽  
Author(s):  
Douglas A. Stewart ◽  
Peter Forsyth ◽  
Ahsan Chaudhry ◽  
Oluyemi Jeje ◽  
Donald Morris ◽  
...  
Keyword(s):  
Stem Cell ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cranial Radiotherapy ◽  
Hematopoietic Stem ◽  
Prognostic Features ◽  
Brain Radiotherapy ◽  
Cell Mobilization

Abstract Introduction: Treatment of PCNSL with high dose methotrexate (HD-MTX)-based chemotherapy and WBRT is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. Patients and Methods: In an attempt to improve upon these dismal results, we treated eleven PCNSL pts aged 40–68 years (median=55) with TBC/ASCT without WBRT. These pts all received prior induction therapy with HD-MTX 3.5 or 5g/m2 q14d x 4-5 cycles +/− procarbazine 100mg/m2 po d1-7 q28d x 2 cycles concurrently with HD-MTX, and then underwent stem cell mobilization with Ara-C 3g/m2 IV d1 and 2, G-CSF d7-14, and apheresis d15 or 16. The TBC regimen consisted of thiotepa 300mg/m2 d-8 and -7, busulfan 3.2mg/kg IV daily d-6 to -4, and cyclophosphamide 2g/m² d-3 and -2. Poor prognostic features included relapsed/progressive disease (n=2), immune-deficiency (SLE, Imuran/Prednisone = 1), ECOG 2-4 (n=9), age >60 yrs (n=4), deep brain involvement (n=8), elevated LDH (n=2), elevated CSF protein (n=2). Results: Stem Cell Collection and Engraftment: A median of 24 (5–45) x 106 CD34+ cells/kg were collected with a median 14.1L (8.5-30L) apheresis. Engraftment to ANC>0.5 and platelet>20 both occurred at a median of day +9 (7–12). TBC Toxicity: Two early treatment-related deaths occurred in pts 65 and 66 years of age, who both originally presented with ECOG of 4. In addition, a 68 yr old man developed Bearman grade 3 regimen-related toxicity (RRT) requiring ICU admission for encephalopathy and respiratory failure. He survived and returned home to function independently. The remaining pts experienced significant Bearman grade 1–2 RRT including generalized skin rash, peripheral edema, mucositis, delirium and asthenia. All surviving pts experienced improvement in neurological function and ECOG. Six pts returned to work including a 62 yr old pianist. Only one pt developed late neurotoxicity with symptoms of mild dementia. Survival: One patient relapsed 30 months post-TBC and died 1 month post-cranial radiotherapy. Eight pts (73%) are currently alive and relapse-free at 9, 15, 17, 18, 25, 43, 52, and 55 months post-TBC/ASCT. Two pts received TBC/ASCT as the only treatment after rapid disease progression following initial chemotherapy. One of these pts relapsed 7 mo after prior HD-MTX/Ara-C and BEAM/ASCT, and the other progressed within 1 mo of completing induction HD-MTX/Ara-C. Both these 2 pts remain relapse-free 43 and 52 months post-TBC/ASCT. Conclusion: TBC/ASCT is capable of inducing prolonged remissions in pts with poor prognosis PCNSL, but is poorly tolerated in pts over 65 years. High dose chemotherapy for PCNSL should include drugs that penetrate the CNS well such as busulfan and thiotepa rather than standard lymphoma regimens such as BEAM.

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