Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma.

1997 ◽  
Vol 15 (2) ◽  
pp. 535-546 ◽  
Author(s):  
M J Watts ◽  
A M Sullivan ◽  
E Jamieson ◽  
R Pearce ◽  
A Fielding ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Cell Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
Cell Mobilization ◽  
Wbc Count ◽  
The Relationship ◽  
Stimulating Factor

PURPOSE To define parameters that predict for rapid engraftment after peripheral-blood stem-cell (PBSC) transplantation, progenitor thresholds, the proportion of patients who achieve these thresholds with a standardized mobilization regimen, and the factors that predict for mobilization efficiency. PATIENTS AND METHODS One hundred and one patients with pretreated lymphoma were mobilized with cyclophosphamide 1.5 g/m2 and granulocyte colony-stimulating factor (G-CSF), with the first apheresis performed when the recovery WBC count was > or = 5.0 x 10(9)/L. The relationship between the number of progenitor cells collected and patient age, sex, diagnosis, prior radiotherapy, and time since last chemotherapy was determined by multivariate analysis. The relationship between these factors, progenitor numbers returned, post-PBSC G-CSF, and hematologic recovery was performed in 81 patients following chemotherapy with carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM protocol). RESULTS No BEAM recipients had delayed neutrophil recovery beyond 28 days. Delayed platelet recovery occurred in 7.4% and minimum and optimum thresholds of 1 x 10(6) and 3.5 x 10(6) CD34+ cells/kg and 1 x 10(5) and 3.5 x 10(5) granulocyte-macrophage colony-forming cells (GM-CFC)/kg were established. Hematologic recovery was adversely affected by prior treatment with mini-BEAM, and neutrophil recovery was accelerated by post-PBSC G-CSF. The minimum GM-CFC threshold was achieved with a single apheresis in 83% of patients and in 90% with two aphereses. The optimal threshold was achieved with two leukaphereses in 69% of patients. Prior radiotherapy adversely affected mobilization. CONCLUSION Hematopoietic recovery following PBSC is dependent on progenitor-cell number infused and affect of previous chemotherapy on progenitor quality. Progenitor-cell mobilization is adversely affected by prior radiotherapy. The minimum threshold of GM-CFC required is achieved in most patients with a single apheresis, but an optimal collection usually requires at least two harvests.

A Randomized Trial Comparing the Effectiveness of Peripheral Blood Stem Cell Mobilization with Chemotherapy and Early vs Delayed Initiation of Granulocyte Colony-Stimulating Factor (G-CSF) in Patients with Lymphoma and Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2929-2929
Author(s):  
Isabelle A. Bence-Bruckler ◽  
Sheryl McDiarmid ◽  
Harold L. Atkins ◽  
Mitchell Sabloff ◽  
Isabelle Gauthier ◽  
...  
Keyword(s):  
Median Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Platelet Recovery ◽  
Prior Chemotherapy ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Group 2 ◽  
Stimulating Factor ◽  
Group 1

Abstract The optimal dose and schedule of granulocyte colony-stimulating factor (G-CSF) for peripheral blood progenitor cell (PBPC) mobilization is unclear. When PBPC mobilization is performed using chemotherapy and growth factor priming, growth factors are often initiated early (day +1) upon completion of chemotherapy. Several small trials report safe and successful PBPC collection after delayed G-CSF initiation. We evaluated two schedules of G-CSF administration in patients with lymphoma and myeloma undergoing PBPC collection. We compared CD34+ cell yields obtained in each group and number of G-CSF doses required. Secondary end points were post-transplant neutrophil and platelet recovery and duration of febrile neutropenia, IV antibiotic administration and hospitalization. We studied patients with lymphoma and myeloma referred for ASCT. Eligible patients had not received more than two prior chemotherapy regimens or pelvic irradiation. Priming chemotherapy was DHAP (lymphoma) or cyclophosphamide 2.5 gm/m2 (myeloma and lymphoma). Rituximab was combined with chemotherapy for certain lymphoma patients for purposes of in vivo purging. G-CSF was initiated either 24 hours (day +1) post completion of chemotherapy (Group 1), or on the 5th day (day +5) after chemotherapy (Group 2). The dose of G-CSF was 300 ug sc daily for patients weighing 70 kg or less, and 480 ug sc daily if > 70 kg. Leukapheresis was initiated when the WBC count was >2.0 x 109/l and the CD34+ count was >10/microliter. Single or serial daily leukaphereses were performed until a minimum of 2 x 106 CD34+ cells/kg were obtained. There were eighty-one consenting patients: 30 with nonHodgkin’s lymphoma, 37 with myeloma and 14 with Hodgkin’s lymphoma. Priming was done with DHAP in 33 and with cyclophosphamide in 46. Forty-two were randomized to day +1 G-CSF initiation (Group1) and 39 to day +5 (Group 2). Diagnosis, prior chemotherapy or priming regimen did not vary among the study groups. Three patients in Group 1 did not proceed to collection (two due to disease progression, the third withdrew consent). All patients in Group 1 were successfuly mobilized, while in group 2, two were not successfully mobilized (p=0.49). Of these patients, one underwent marrow harvest while the other was transplanted with a suboptimal CD34+ cell count. In Group 1, 32 of 39 were mobilized with a single leukapheresis and 7 required two; in Group 2, 25 of 37 were mobilized in 1 day, 11 in 2 days and one patient required 4 days (p=0.2).The median number of CD34+ cells collected was 10.6 x 106/kg in Group 1 versus 7.9 x 106/kg in Group 2 (p=.04). The median number of doses of G-CSF administered was 9 in Group 1 and 6 in Group 2 (p<.0001). The time to neutrophil and platelet recovery were 11 and 11.5 days respectively and did not differ amoung the groups. There was no difference in the number of platelet transfusions, duration of febrile neutropenia, antibiotic use or length of hospitalization. The number of units of RBC transfused in Group 1 was 4 (range; 0–11) versus 2 in Group 2 (range; 0–21; p=.04). Stem cell mobilization using delayed G-CSF initiation was as effective as early initiation, and required a median of 9 vs 6 doses of drug. Despite lower CD34+ yields in the delayed G-CSF group, the outcome of mobilization was not compromised and post-transplant engraftment, infectious complications and hospitalization were comparable.

Chemotherapy with Granulocyte Colony Stimulating Factor (G-CSF) Alone Versus Granulocyte Colony Stimulating Factor (G-CSF) Plus Granulocyte-Macrophage Stimulating Factor (GM-CSF) for Hematopoietic Progenitor Cell Mobilization in Patients with Relapsed Non-Hodgkin’s Lymphomas (NHLs).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1900-1900
Author(s):  
Chitra Hosing ◽  
Mark Munsell ◽  
Uday Popat ◽  
Martin Körbling ◽  
Rosamar Valverde ◽  
...  
Keyword(s):  
Success Rate ◽  
Clinical Outcomes ◽  
Progenitor Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitor ◽  
Gm Csf ◽  
Cell Mobilization ◽  
Stimulating Factor ◽  
Graft Composition

Abstract Both G-CSF and GM-CSF (alone or in combination) may be used for mobilization of hematopoietic progenitor cells in patients undergoing autologous stem cell transplantation (ASCT). It has been suggested that GM-CSF use during mobilization may impact graft composition and therefore clinical outcomes. METHODS: We prospectively evaluated patients ≤ 70 years old with relapsed CD20+ NHL who were candidates for ASCT. Additional eligibility criteria included adequate marrow and organ function. Patients with history of pelvic radiation, > 3 prior chemoregimens or > 6 cycles of fludarabine chemotherapy were excluded. Patients recieved chemotherapy with ifosfamide 3.33 g/m2 daily × 3 days, etoposide 150 mg/m2 × 6 doses and rituximab (375 mg/m2 on day 1 and 1 g/m2 on day 8). Using a Bayesian adaptive randomization based on treatment outcomes, patient’s were randomized to receive G-CSF 12 μg/kg/d (Group G) or G-CSF 12 μg/kg/d plus GM-CSF 500 μg/d (Group G/GM). We assumed that the success rate for each treatment arm had a β prior distribution with mean 0.90 and variance 0.03. Cytokines started 24 hours after completion of chemotherapy and continued until completion of apheresis. RESULTS: Forty-three patients were randomized to Group G and 41 patients to Group G/GM. In each arm 1 patient withdrew consent after randomization. Baseline characteristics were similar in the 2 groups (Table 1). Both regimens were equally well tolerated. Data are presented as intent to treat analysis. Thirty-nine patients (90.7%) in Group G and 35 patients (85.4%) in Group G/GM collected ≥ 4 × 106 CD34+ cells/kg. The probability that Group G has a higher success rate than Group G/GM is 0.778. The median CD34+ cell dose collected was 10.3 × 106/kg (range, 0.1–59) and 7.5 × 106/kg (range, 0.7–73) in Groups G and G/GM respectively (P=NS). A median of 2 apheresis procedures were required in both arms. Seventy-three patients have undergone ASCT. After a median follow up time of 14.5 months (range, 0.6–38.5) in Group G and 14.0 months (range, 1.1–39.9) in Group G/GM, the 3 year PFS is 75% (95% CI 57.9–99.4) and 77% (95% CI 65–91.5) respectively (P=0.41). CONCLUSION: Our study does not support the hypothesis that using G-CSF plus GM-CSF versus G-CSF alone for progenitor cell mobilization alters graft composition in a way that impacts clinical outcomes after ASCT for NHLs. Baseline Patient Characteristics *Missing data 1 patient G-CSF, N (%) G-CSF + GM-CSF, N (%) 43 (51) 41 (49) AGE <39 4 (9.3) 3 (7.3) 40–59 29 (57.4) 26 (63.5) >59 10 (23.2) 12 (29.3) GENDER (Male/Female) 29/14 (67.4/32.6) 24/17 (58.5/41.5) HISTOLOGY Low grade 4 (9.3) 7 (17.1) Intermediate grade 39 (90.7) 34 (82.9) ANN ARBOR STAGE >I 18 (41.9) 18 (43.9) LDH>Normal* 15 (34.9) 11 (27.5) Figure Figure

scholarly journals Effects of granulocyte–colony-stimulating factor on progenitor cell mobilization and heart perfusion and function in normal mice

Cytotherapy ◽  
2011 ◽  
Vol 13 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Marie Delgaudine ◽  
Bernard Lambermont ◽  
Patrizio Lancellotti ◽  
Véronique Roelants ◽  
Stéphan Walrand ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Heart Perfusion ◽  
Cell Mobilization ◽  
And Function ◽  
Stimulating Factor

Use of Granulocyte Colony-Stimulating Factor after Allogeneic Peripheral Blood Stem Cell Transplantation in Children with Thalassemia Major: Single Center Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5316-5316
Author(s):  
Gulsun Tezcan ◽  
Alphan Kupesiz ◽  
Vedat Uygun ◽  
Volkan Hazar ◽  
M.Akif Yesilipek
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Thalassemia Major ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Platelet Recovery ◽  
Neutrophil Recovery ◽  
The Mean ◽  
Stimulating Factor

Abstract High dose chemo-radiotherapy followed by either allogeneic or autologous hematopoietic stem cell transplantation (HSCT) is the treatment of choice for an increasing number of congenital or acquired diseases of childhood. One of the major drawbacks of this procedure is the prolonged period of profound neutropenia and complications associated with neutropenia. Although administration of granulocyte colony-stimulating factor (G-CSF) to adult patients undergoing high-dose chemotherapy and HSCT is believed to accelerate neutrophil recovery, the actual clinical benefits of G-CSF in children remain a controversial point requiring controlled studies and also the optimal timing for G-CSF infusion has not been established yet. It is well-known that children frequently recover faster than adults after HSCT and suffer less from life-threatening infections. In addition, studies demonstrating that these cytokines may also modify T-cell and dendritic cell function brought about a question whether the effect is strong enough to alter the risk of graft-versus-host disease (GVHD). In this retrospective three armed study we reviewed our experience at Akdeniz University School of Medicine Pediatric Hematology/Oncology Department to determine whether G-CSF administration on posttransplant period affects neutrophil and platelet engrafment time and alters the risk of acute or chronic GVHD in a relatively homogeneous nonmalignant group, thalassemia major patients. Fortyseven patients transplanted with peripheral blood stem cells were studied. G-CSF, if administered, were started on posttransplant day 1 or day 5. 25 patients in day 1 and 11 patients in day 5 group with other 11 non-administered patients were revealed retrospectively in respect to main outcomes that were hematopoietic recovery (neutrophil and platelet recovery defined by a neutrophil count of ≥0.5x109/L for 3 consecutive days and nontransfused platelet count of ≥20x109/L for 7 consecutive days) and GVHD. They were all given methotrexate combined with cyclosporine as GVHD prophylaxis with ATG in 35 patients. In G-CSF non-administered group neutrophil recovery was delayed compared with G-CSF administered group (16.5±2.8 vs 13.8±3.6 p=0.009) although transplanted MNC count was higher (16.8±3.5 vs 9.4±4.1 p<0.001). Although there was no any significant difference, platelet recovery seems to delay in G-CSF group (15.9±7.1 vs 21.8±14.5 p>0.05). The mean days to neutrophil recovery (14.0 ±3.7 vs 3.7±3.5 p>0.05) and the mean days to platelet recovery (22.7±15.5 vs 19.8±12.6 p>0.05) were not significantly different between day 1 and day 5 group. There were 5 grade II-IV acute and 5 chronic GVHD, both in G-CSF administered group but there were not any statistical differences in respect to GVHD between G-CSF or non-administered group and also within the G-CSF administered group according to administration time. In conclusion, administration of G-CSF after allogeneic PBSCT in children with thalassemia cause faster neutrophil recovery but administration on day 1 seems as if there is no additive effect compared to day 5 and do not alter the risk of acute or chronic GVHD. More studies in larger scales are needed to determine whether greater delay or non-use is feasible or not.

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