Did we focus on the most important issues in the use of growth factors and stem-cell transplantation?

1994 ◽  
Vol 12 (4) ◽  
pp. 650-652 ◽  
Author(s):  
S C Gulati
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation

scholarly journals Concentrations of Insulin-like Growth Factors and Insulin-like Growth Factor-Binding Proteins and Respective Gene Expressions in Children before and after Hematopoietic Stem Cell Transplantation

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4333
Author(s):  
Wojciech Strojny ◽  
Wojciech Czogała ◽  
Przemysław Tomasik ◽  
Mirosław Bik-Multanowski ◽  
Małgorzata Wójcik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Healthy Controls ◽  
Hematopoietic Stem ◽  
Before And After ◽  
Insulin Like Growth Factors

Insulin-like growth factors (IGF-1 and IGF-2) and insulin-like growth factor-binding proteins (IGFBP-1 to -7) are involved in the regulation of cell proliferation and differentiation and may be associated with various metabolic parameters. The aim of our study was to compare levels of IGFs and IGFBPs and the expressions of their genes in children before and after hematopoietic stem cell transplantation (HSCT) to assess their potential as markers of late metabolic complications of HSCT. We also conducted additional comparisons with healthy controls and of correlations of IGF and IGFBP levels with anthropometric and biochemical parameters. We analyzed 19 children treated with HSCT and 21 healthy controls. We found no significant differences in the levels of IGFs and IGFBPs and expressions of their genes before and after HSCT, while IGF and IGFBP levels were significantly lower in children treated with HSCT compared with controls. We conclude that our results did not reveal significant differences between the levels of IGFs and IGFBPs before and after HSCT, which would make them obvious candidates for markers of late complications of the procedure in children. However, due to the very low number of patients this conclusion must be taken with caution and may be altered by further research.

The Effect of Prophylactic Administration of Myeloid Growth Factors Following Autologous Stem Cell Transplantation for Patients with Hematological Malignancies: A Systematic Review.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2192-2192
Author(s):  
Graeme A.M. Fraser ◽  
Ahmed Al-Sagheir ◽  
Donald M. Arnold ◽  
C. Tom Kouroukis ◽  
Ronan Foley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Early Administration ◽  
Post Transplant ◽  
Significant Difference ◽  
Duration Of Hospitalization

Abstract BACKGROUND. Myeloid growth factors (G-CSF, GM-CSF) are often administered following autologous stem cell transplantation to reduce the duration of neutropenia and limit infection-related morbidity and mortality. OBJECTIVES. (1) To determine if prophylactic myeloid growth factors (GF) administered to adult patients undergoing autologous stem cell transplantation for a hematological malignancy improve clinical outcomes post-transplant, and (2) to determine the optimal dose and schedule for the administration of GF post-transplantation. METHODS. Computerized databases were searched for reports from 1966 to March 2004. Reference lists from published reports were hand searched and published abstracts were also considered. Randomized trials comparing different GF regimens were selected by two independent assessors based on explicit inclusion and exclusion criteria; disagreement was resolved by consensus. Two independent reviewers blinded to authors, institution, journal name, and results used a validated scale to assess study quality. When possible, study results were pooled using a random effects model to obtain a pooled relative risk. RESULTS. Of 985 citations identified, 27 studies evaluating 2268 patients were included. Studies were grouped and analyzed according to their control and experimental arms: (1) early administration of growth factor (< day +3 post-transplant) compared with placebo or no growth factor (N=18 studies), (2) early administration of growth factor compared with delayed growth factor (> day +3, N=8 studies), and (3) high doses of GF (> 5ug/kg/d) compared to standard/low doses of GF (<5ug/kg/d, N=5 studies). Compared to no GF support, early administration of GF resulted in a statistically significant reduction in the median days to neutrophil engraftment (>0.5x109/L) in 14 of 15 studies (range 2–13 days). The magnitude of this benefit was diminished when only studies of higher methodologic quality and optimal transplant conditions (peripheral blood stem cells) were considered (range 2–3 days). A significant decrease in duration of hospitalization was reported in 8 of 15 studies; however no consistent benefit was observed for median days of i.v. antibiotics (3 of 10 studies), median days of fever (1 of 10 studies), or in the rate of microbiologically documented infections (RR 0.94, 95% CI 0.69–1.29). Compared to delayed administration of GF, early administration of GF was not associated with a significant difference in median duration of neutropenia any of 5 studies. Only 1 study reported a significant difference in the median duration of hospitalization and median days of i.v. antibiotics and it was of lower methodological quality. No difference in the rate of microbiologically documented infections was detected (RR 1.29, 95% CI 0.83–2.03). Compared to standard doses of GF, no study evaluating high dose GF reported a statistically significant improvement in any reported outcome but treatment was more costly owing to an increase in total GF administered. CONCLUSION. The administration of GF post-autologous stem cell transplant reduces the time to neutrophil engraftment and may reduce length of hospital stay. The effectiveness of delayed administration of standard dose GF (5 ug/kg/d) appears similar to strategies that initiate GF support immediately post-transplant or utilize high doses.

Hematologic malignancies developing in previously healthy individuals who received hematopoietic growth factors: Implications for use of colony stimulating factors in healthy volunteers participating in early phase clinical studies and in healthy blood product donors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2559-2559
Author(s):  
A. E. Lyons ◽  
L. Balasubramanian ◽  
L. A. Andritsos ◽  
A. Evens ◽  
T. Kuzel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Healthy Volunteers ◽  
Cell Transplantation ◽  
Peripheral Blood Stem Cell ◽  
Hematologic Malignancies ◽  
Healthy Individuals ◽  
Hematopoietic Growth Factors

2559 Background: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHu-MGDF aka MGDF) and recombinant granulocyte colony stimulating factor (G-CSF) promote the maturation of hematopoietic progenitor cells. Healthy volunteers/donors have received MGDF in phase I/II clinical trials and G-CSF in allogeneic peripheral blood stem cell transplantation procedures. Herein, we review clinical findings for five previously healthy volunteers/donors who developed hematologic malignancies after the use of MGDF or G-CSF. Methods: Clinical information related to hematologic malignancies were reviewed for three volunteers who had participated in a phase I/II clinical trial with MGDF and two donors who underwent G-CSF mobilized peripheral blood stem cell harvesting procedures for sibling allogeneic stem cell transplantation for acute leukemia. Results: Mantle cell, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia were diagnosed three to five years after exposure among three volunteers who received MGDF. For one of these patients, autoimmune thrombocytopenia and antibodies to MGDF that cross-reacted with endogenous thrombopoietin had developed shortly after MGDF administration and persisted until lymphoma chemotherapy was administered. Following chemotherapy, all three achieved complete remission, although one patient subsequently relapsed. Acute myelogenous leukemia was diagnosed four to five years after exposure in two donors who underwent G-CSF primed stem cell harvests prior to their siblings’ allogeneic stem cell transplantation. Following intensive chemotherapy, one of these patients died from acute leukemia and the second is now in complete remission. Conclusion: Controversy exists over the appropriateness of administering hematopoietic growth factors to healthy individuals. While a causal relationship with hematologic malignancies is uncertain, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed. No significant financial relationships to disclose.

Preventing Infections in Cancer Patients: Antibiotics, Hematopoetic Growth Factors or Both? a Network Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1315-1315 ◽  
Author(s):  
Christine Herbst ◽  
Frauke Naumann ◽  
Olaf Herbst ◽  
Julia Bohlius ◽  
Peter Jüni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Network Analysis ◽  
Febrile Neutropenia ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cancer Patients ◽  
Cell Transplantation ◽  
Myelosuppressive Chemotherapy ◽  
Related Mortality

Abstract Background: Infectious complications such as febrile neutropenia belong to the most serious complications of chemotherapy including stem cell transplantation for cancer. The mortality rate associated with febrile neutropenia is approximately 10%. Meta-analyses have shown that both hematological growth factors (CSFs) and antibiotics prevent infections. A comparison of these two agents or their combination has not been examined in systematic reviews. We therefore conducted a network analysis to determine the role of antibiotics and CSFs for the prophylaxis of infections in cancer patients receiving myelosuppressive chemotherapy or hematopoetic stem cell transplantation (SCT). Methods: The network analysis included all randomized controlled trials that compared two or more of the following prophylaxis options: no prophylaxis, prophylaxis with antibiotics alone, prophylaxis using CSFs alone or prophylaxis using combinations of both, CSFs and antibiotics. Trails that did report overall survival, on study mortality, infection-related mortality, clinically documented infections, microbiologically documented infections or fever/febrile neutropenia were excluded. A Bayesian network analysis with four treatment options was performed; results are presented as odds ratios (OR) with 95% credibility intervals (CI). Results: The best prophylaxis in the network with regard to preventing infections and infection-related mortality is the combination of antibiotics and CSFs. Comparing antibiotics alone to CSFs alone yields an OR of 1.00 (95% CI 0.69–1.52) for clinically documented infections. For the combination of both antibiotics and CSFs compared to only antibiotics or only CSFs, the incidence of clinically documented infections was also reduced (OR=0.61, 95% CI (0.46–0.77)). This is also true for the subgroup of patients receiving SCT or patients with acute leukemia. Conclusions: For patients receiving myelosuppressive chemotherapy, antibiotics and CSFs are similarly efficient in reducing infections. The choice of agent can therefore be based on preferences of the treating physician and the adverse events expected. The best prophylactic regimen however is the prophylaxis using both, antibiotics and CSFs. The combination should be considered for patients at high risk of developing infections such as those receiving SCT or patients with acute leukemia.

scholarly journals Autologous stem cell transplantation: release of early and late acting growth factors relates with hematopoietic ablation and recovery

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3532-3539 ◽  
Author(s):  
U Testa ◽  
R Martucci ◽  
S Rutella ◽  
G Scambia ◽  
S Sica ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Base Line ◽  
Hematopoietic Growth Factors ◽  
Pronounced Increase

We have monitored the serum concentrations of hematopoietic growth factors (HGFs; ie, stem cell factor [SCF], leukemia inhibitory factor [LIF], interleukin-3 [IL-3], IL-6, IL-8, and granulocyte colony- stimulating factor [G-CSF]) in 15 lymphoma/leukemia and 6 ovarian cancer patients undergoing autologous bone marrow (BM) or peripheral blood (PB) stem cell transplantation (SCT). Thus, the analysis was performed during and after high-dose chemotherapy (from day -6 to day - 1), at the time of SCT (day 0), and thereafter (through day +17). Despite the heterogeneity of these patients and their conditioning regimens, a consistent kinetic pattern was observed for all analyzed cytokines. Particularly, (1) SCF serum concentration did not significantly fluctuate. (2) High levels of LIF (approximately 250 to 450 pg/mL) before chemotherapy rapidly declined to markedly lower concentrations (approximately 10 ng/mL) starting from day -1 through day +17; (3) conversely, IL-3 level was low before treatment, sharply increased during chemotherapy, and rapidly returned to base-line level after SCT. Hypothetically, the sharp LIF decrease and IL-3 increase during chemotherapy may underlie the induction of stem cell cycling and differentiation caused by hematopoietic ablation. Furthermore, (4) IL-6 concentration was low before and immediately after chemotherapy, but increased starting from day +5, peaked at day +6 through 9 and then declined to baseline level from day +10 onward; (5) a strictly similar pattern was consistently observed for both G-CSF and IL-8 levels, in agreement with our previous studies. It is relevant that peak IL-6, G- CSF, and IL-8 concentrations were directly correlated to peak neutrophil numbers in the recovery phase, thus suggesting an important role for these cytokines in granulocyte rescue; in line with this interpretation, hematologic patients undergoing PBSCT (10 of 15) exhibited higher peaks of IL-6, G-CSF, and IL-8 and a more pronounced increase of neutrophil/platelet number than did hematologic cases undergoing BMSCT (5 of 15). Altogether, these studies indicate a coordinate pattern of cytokine release during hematopoietic ablation/recovery after chemotherapy and autologous SCT, the fluctuations of LIF and IL-3 levels during chemotherapy are seemingly related to stem cell recruitment, whereas the post-SCT increase of IL- 6, G-CSF, and IL-8 may underlie the neutrophil recovery.

Feasibility of Hematopoietic Stem Cell Collection and Cryopreservation in Waldenstrom's Macroglobulinemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4128-4128
Author(s):  
Dilshad Khan ◽  
Krina Patel ◽  
Sheeba K. Thomas ◽  
Donna M. Weber ◽  
Kay B Delasalle ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Growth Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Cancer Center ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Cd34 Cells

Abstract Abstract 4128 Background: Although autologous stem-cell transplantation (auto-HCT) is sporadically used in patients with Waldenström macroglobulinemia (WM), hematopoietic stem cells (HSC) are routinely collected and cryopreserved at many transplant centers after initial cytoreduction, prior to the use of myelotoxic agents like cladribine. The aim of this study is to evaluate the number of patients who underwent HSC collection, the adequacy of collection and the number of patients who eventually received auto-HCT. Methods: We performed a retrospective chart review for 431 adult patients with WM who were seen at the University Of Texas-MD Anderson Cancer Center (MDACC). Fifty-five patients (12.8%) underwent HSC collection. Our analyses were focused on these 55 patients. Results: A total of 431 patients with WM were seen at our institution between 1978 and 2010. One-hundred and seven (24.8%) of these patients were referred to the Department of Stem cell Transplantation (SCT). Fifty-two patients either continued conventional therapy (31) or received plasmapheresis for hyperviscosity (21). Fifty-five (12.8%) patients underwent HSC collection either through peripheral blood (PB) HSC mobilization or bone marrow (BM) harvest. Characteristics of the 55 patients undergoing HSC collection are summarized Table 1. In 2 patients, HSC were collected by BM harvest only. Fifty-three patients underwent PB HSC mobilization with either growth factors only (34) that included filgrastim, pegfilgrastim or plerixafor; or with growth factors plus chemotherapy (19) that included cyclophosphamide alone or in combination with vincristine, doxorubicin and dexamethasone (CVAD). Out of 53 patients undergoing PBHSC mobilization, 2 patients failed to mobilize any HSC despite growth factors and chemotherapy, while 2 additional patients had inadequate HSC collection (< 2 × 10e6 CD34+ cells/kg). Forty-nine of the 53 patients undergoing PBHSC mobilization had adequate HSC collection (> 2 × 10e6 CD34 cells/kg). Overall, 51 patients (PBHSC: 49, BM harvest: 2, 93%) had an adequate (> 2 × 10e 6 CD34/kg) HSC collection. The median HSC dose collected from these patients was 6.9 × 10e6/kg ((0.5–24.1) after a median of 3 collections (1 to 7). Fifteen patients had received cladribine prior to HSC collection, and 14 (93%) of them had adequate HSC collection. However, 7/15 patients (47%) with prior cladribine required chemomobilization, in contrast to 11/39 (28%) without prior cladribine (p=0.21). In 34/51 patients with adequate collection, HSC were cryopreserved for use at the time of relapse. Thus far, 3/34 (8.8%) have gone on to receive auto-HCT after 12, 27.3 and 45.2 months, respectively. In 31/34 (91%) patients, HSC have been cryopreserved for a median duration of 24.6 months (3.1 to 187.6 months). In 17 patients, HSC were collected with the intention to immediately proceed to auto-HCT, and these patients proceeded to HDM and auto-HCT within 3 months of HSC collection (range being 0.1–2.7 months). Forty-four patients are alive after a median of 37.5 months (2.4 to 187.6) from HSC collection. Kaplan-Meier estimate of 5-year overall survival for all patients from HSC collection was 76%. Conclusions: Current frontline regimens for WM are associated with high overall response rates (66–94%); however, complete remission (CR) rates (4–7%) remain low. Given the feasibility of HSC collection in patients with WM, earlier incorporation of auto-HCT for younger patients could be studied as a means of improving CR rates, and perhaps thereby improving both remission duration and overall survival. Disclosures: No relevant conflicts of interest to declare.

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