Impact of Disease and Mobilizing Agents on Initial and Remobilization Failure.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5222-5222
Author(s):  
John F. DiPersio ◽  
Angela Smith ◽  
Dianne Sempek ◽  
Albert Baker ◽  
Steven Jiang ◽  
...  
Keyword(s):  
Failure Rate ◽  
Surrogate Marker ◽  
High Dose Chemotherapy ◽  
Disease State ◽  
High Dose ◽  
Failure Rates ◽  
Gm Csf ◽  
Scheffe Test ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Background: High-dose chemotherapy with autologous stem cell transplantation (ASCT) is a widely used treatment strategy in lymphoma and myeloma; however, no standard approach for the mobilization of peripheral hematologic stem and progenitor cells (HSPCs) has been established. Levels of circulating CD34+ cells, a surrogate marker for mobilization efficiency, vary widely between pts, and may be influenced by disease state, prior therapy, and/or mobilization regimen. Methods: The Washington University (St. Louis, MO) transplantation database includes clinical parameters from 407 multiple myeloma (MM), 562 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 (1133 pts) population was conducted to determine factors associated with mobilization efficiency. Mobilization failure was defined as collection of < 2 × 10^6 CD34+ cells/kg within 5 apheresis days. Statistical analysis included analysis of variance (ANOVA) with Scheffe Test to determine differences in mobilization between the various mobilization regimens (G-CSF, G-CSF/chemotherapy, G-/GM-CSF, G-CSF/AMD3100). Results: All pts were included in the analysis; 87% received G-CSF alone as the initial mobilization regimen. Mobilization failure rates are summarized in Table 1. NHL and HD pts had an approx. 4-fold higher failure rate than MM pts. The combination of G-CSF with chemotherapy increased the median CD34+ yield compared to G-CSF alone, although no obvious impact on the failure rate was noted in this relatively small group of pts. Remobilization was associated with high failure rates in NHL (79.2%), HD (77.1%), and MM (73.3%). Pooled collections were <2 × 10^6 CD34+/kg in 33.6%, 37.1%, and 36.7% of failed mobilizers, respectively. ANOVA analysis indicated a significant difference in outcome based on remobilization regimen. A post hoc comparison using the Scheffe Test determined that G-CSF mobilization failures remobilized with G-CSF plus AMD3100 collected significantly more CD34+ cells than G-CSF-failures remobilized with either G-CSF, G/GM-CSF or G-CSF/chemo (1-way ANOVA: F(3, 233) = 27.878, F0.5(3, 233).05 = 2.643, p < .0001). The compared groups did not significantly differ in initial mobilization efficiency with G-CSF (as determined by ANOVA and Scheffe Test). Conclusions: The mobilization failure rate is substantially higher in NHL and HD pts than MM pts. Pts who fail initial mobilization are highly likely to fail a 2nd mobilization, regardless of disease state. As the combination of chemotherapy to G-CSF may not be sufficient to reduce failure rates, alternative mobilization strategies are needed to improve HSPC collection, particularly in NHL/HD pts and failed mobilizers. First mobilization failure rates (< 2×10^6 CD34+/kg) Mobilization regimen N Failures Median yield (×10^6) 95% C.I (×10^6) * Incl. pts mobilized w. alternative regimens NHL G-CSF 471 26.5% 2.89 2.76–3.04 G-CSF/Chemo 35 22.9% 4.68 2.8–8.53 All* 564 28.7% HD G-CSF 130 26.2% 3.01 2.75–3.37 G-CSF/Chemo 12 16.7% 5.38 2.35–9.52 All* 165 24.8% MM G-CSF 386 6.5% 4.62 4.16–4.98 G-CSF/Chemo 17 5.9% 8.52 4.46–16.3 All* 409 6.6%

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

Expansion and Multipotencial Differentiation of Mesenchymal Stem Cells Isolated from Patients after High Dose Chemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4259-4259
Author(s):  
Karen L. Prata ◽  
Maristela D. Orellana ◽  
Aparecida M. Fontes ◽  
Karina R. Solano ◽  
Simone Kashima ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Cell Cycle Status ◽  
Supportive Function

Abstract Background. High dose chemotherapy (HDCT) followed by autologous PBSC rescue has been increasingly used for the treatment of several human diseases. However, little is known on the extent of this therapy on the marrow mesenchymal stem cells (MSCs). Aims. To evaluate the feasibility of expansion and multipotencial differentiation of MSCs isolated from patients after HDCT. Patients and Methods. Twelve lymphoma’s patients (LP) free of disease in bone marrow (BM) were enrolled in the study. They were submitted to BEAM’s protocol with autologous PBSC rescue 28 to 1836 days before the sample collection. Six normal bone marrow donors (ND) were used as controls. The LP and ND median age were 37.5 (range 22–49) and 31.5 years old (range 23–42), respectively. MSCs were isolated by plastic adherence and expanded ex vivo by cultivation in flasks with α-MEM with 15% fetal bovine serum. Media was changed every 3–4 days. At 90% confluence, the cells were re-plated and expanded. The isolation efficiency, colony-forming unit-fibroblast (CFU-F) frequency, growth kinetics, phenotypic characteristics, cell cycle status, multi-lineage differentiation capacity as well as hematopoiesis-supportive function were determined and compared with those of ND-MSCs. This study protocol and the consent form were approved by the institution ethics committees. Results. The results were analyzed by Mann-Whitney test and are expressed as median (range) to LP and ND, respectively. MSCs were successful isolated from all BM samples collected for this study. The cell population showed typical fibroblast-like morphology, appearing as an adherent, spindle shaped cell layer and growing to confluence after a few weeks of culture. The number of CFU-F found at 14 days of culture were 0.94 (0.00–3.75) and 1.25 (0.13–9.25) x10−5 nucleated cells (p = 0.4421). The doubling time between the 1st and 2nd passages was 80.66 (34.08–195.35) and 46.30 (36.36–270.59) hours (p = 0.1025). The cell clones proliferated extensively until 8.17 (1.81–28.27) and 18.11 (11.85–27.48) population doublings (p = 0.0668) in 71.50 (46–88) and 81 (57–103) cultivation days (p = 0.1505). Immunophenotypically, these cells were positive for the CD73, CD105, CD90, CD29, CD13, CD44, CD49e, CD54, HLA-class 1 and Stro-1 markers and negative for CD34, CD45, CD14, CD51/61, HLA-DR and KDR. Regarding the cell cycle status, 85.63 (63.19–92.17) and 82.41 (82.19–87.02) % were in GO-G1 phase (p = 1,000), while only 12.17 (3.33–36.81) and 10.67 (6.59–12.05) % were in S phase (p = 0,6828). All samples tested were capable of differentiating along adipogenic, osteogenic and chondrogenic lineages in vitro, demonstrated by morphology, cyto- and imunohistochemistry or RT-PCR reaction (PPARg and osteopontin genes expression). After co-culture with CD34+ cord blood cells for 1 and 4 weeks, no significant difference CD34+ expansion or colony-forming cells (BFU-E or CFU-GM) were observed between the CD34+ cells/LP-MSCs and CD34+ cells/ND-MSCs co-cultures with cytokines or not. Interpretation and Conclusions. Our results demonstrate that is possible to cultivate and expand MSCs with multipotential differentiation capabilities and hematopoiesis-supportive function from patients after HDCT. Despite there were no significant differences in the median values between LP and ND, the comparative study indicates a possible damage in MSCs by HDCT.

scholarly journals Peripheral Blood Progenitor Cell Mobilization of CD34+ Cells with Combine G-CSF and GM-CSF in Pediatric Patient Outcome and Economic Advantage

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Heidy lyz Garcia
Keyword(s):  
Conflicts Of Interest ◽  
Cost Effective ◽  
High Dose Chemotherapy ◽  
Economic Advantage ◽  
Hematological Toxicity ◽  
High Dose ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Stems Cells ◽  
Cell Mobilization

Background: Clinical trials to mobilize PBPC for autologous and allogeneic harvesting prior to high dose chemotherapy/radiotherapy include chemotherapy, cytokines, or chemotherapy combine with cytokines. PBPC mobilized by G-CSF or GM-CSF reduces the hematological toxicity and supportive care requirements in recipients of autologous and allogeneic transplants, in our study we combined G-CSF and GM-CSF to mobilize PBPC for transplantation. Methods: We selected 63 patients with different cancers to participate in the study and 7 healthy donors. We utilize to mobilize in all the patient the combination of G-CSF and GM-CSF (10μg/Kg/day each) administered for 5 consecutive days. Then we proceed it to harvest the PBPC until we obtain a threshold of 2.0 x 10^6/Kg CD34+ cells. A total of 31 PBPC transplants were performed (27 autologous and 8 allogeneic). Neutrophil engraftment was defined as ANC&gt; 500/mm³ and, platelet engraftment was defined as a platelet count &gt; 30,000/mm³ (transfusion independent) for more than 48 hours. Results: Data on PBC 24, 48, 72, and 96hrs. For the 31 PBPC autologous transplant patients, the median days to ANC&gt;500 was 10.6 days; 11 days for the allogeneic. None of the subject's experience bone pain, headache, flu like side effects or a documented or proven infection. Median days to platelet engraftment following infusion CD34+ cells, was 13.2 for the autologous PBPC; 13 days for the allogeneic. Conclusions: The combination the G-CSF and GM-CSF (10μg/kg/day x 5 days) was well tolerated. We can appreciate that there is a reduction in the duration and severity of neutropenia as well of thrombocytopenia in both types of transplant (autologous/allogeneic). The GVHD incidence were not increase by the use of G-CSF and GM-CSF. We conclude that this procedure is cost effective and a suitable way to mobilize an average number of PBPC (from 1-3 apheresis) in a shorter amount of time indicating an economic advantage. It is proven to be less expensive than other agent used to mobilize stems cells for transplant. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-1 beta (IL-1 beta), IL-6, IL-3, interferon-gamma, and erythropoietin

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2579-2584 ◽  
Author(s):  
W Brugger ◽  
W Mocklin ◽  
S Heimfeld ◽  
RJ Berenson ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Interferon Gamma ◽  
Large Scale ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Factor Combination

Abstract To provide sufficient numbers of peripheral blood progenitor cells (PBPCs) for repetitive use after high-dose chemotherapy, we investigated the ability of hematopoietic growth factor combinations to expand the number of clonogenic PBPCs ex vivo. Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) mobilized CD34+ cells from 18 patients with metastatic solid tumors or refractory lymphomas were cultured for up to 28 days in a liquid culture system. The effects of interleukin-1 beta (IL-1), IL-3, IL-6, granulocyte-macrophage-CSF (GM-CSF), G-CSF, macrophage-CSF (M-CSF), stem cell factor (SCF), erythropoietin (EPO), leukemia inhibitory factor (LIF), and interferon- gamma, as well as 36 combinations of these factors were tested. A combination of five hematopoietic growth factors, including SCF, EPO, IL-1, IL-3, and IL-6, was identified as the optimal combination of growth factors for both the expansion of total nucleated cells as well as the expansion of clonogenic progenitor cells. Proliferation peaked at days 12 to 14, with a median 190-fold increase (range, 46- to 930- fold) of total clonogenic progenitor cells. Expanded progenitor cells generated myeloid (colony-forming unit-granulocyte-macrophage), erythroid (burst-forming unit-erythroid), as well as multilineage (colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte) colony-forming units. The number of multilineage colonies increased 250- fold (range, 33- to 589-fold) as compared with pre-expansion values. Moreover, the absolute number of early hematopoietic progenitor cells (CD34+/HLA-DR-; CD34+/CD38-), as well as the number of 4-HC-resistant progenitors within expanded cells increased significantly. Interferon- gamma was shown to synergize with the 5-factor combination, whereas the addition of GM-CSF significantly decreased the number of total clonogenic progenitor cells. Large-scale expansion of PB CD34+ cells (starting cell number, 1.5 x 10(6) CD34+ cells) in autologous plasma supplemented with the same 5-factor combination resulted in an equivalent expansion of progenitor cells as compared with the microculture system. In summary, our data indicate that chemotherapy plus G-CSF-mobilized PBPCs from cancer patients can be effectively expanded ex vivo. Moreover, our data suggest the feasibility of large- scale expansion of PBPCs, starting from small numbers of PB CD34+ cells. The number of cells expanded ex vivo might be sufficient for repetitive use after high-dose chemotherapy and might be candidate cells for therapeutic gene transfer.

scholarly journals Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-1 beta (IL-1 beta), IL-6, IL-3, interferon-gamma, and erythropoietin

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2579-2584 ◽  
Author(s):  
W Brugger ◽  
W Mocklin ◽  
S Heimfeld ◽  
RJ Berenson ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Interferon Gamma ◽  
Large Scale ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Factor Combination

To provide sufficient numbers of peripheral blood progenitor cells (PBPCs) for repetitive use after high-dose chemotherapy, we investigated the ability of hematopoietic growth factor combinations to expand the number of clonogenic PBPCs ex vivo. Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) mobilized CD34+ cells from 18 patients with metastatic solid tumors or refractory lymphomas were cultured for up to 28 days in a liquid culture system. The effects of interleukin-1 beta (IL-1), IL-3, IL-6, granulocyte-macrophage-CSF (GM-CSF), G-CSF, macrophage-CSF (M-CSF), stem cell factor (SCF), erythropoietin (EPO), leukemia inhibitory factor (LIF), and interferon- gamma, as well as 36 combinations of these factors were tested. A combination of five hematopoietic growth factors, including SCF, EPO, IL-1, IL-3, and IL-6, was identified as the optimal combination of growth factors for both the expansion of total nucleated cells as well as the expansion of clonogenic progenitor cells. Proliferation peaked at days 12 to 14, with a median 190-fold increase (range, 46- to 930- fold) of total clonogenic progenitor cells. Expanded progenitor cells generated myeloid (colony-forming unit-granulocyte-macrophage), erythroid (burst-forming unit-erythroid), as well as multilineage (colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte) colony-forming units. The number of multilineage colonies increased 250- fold (range, 33- to 589-fold) as compared with pre-expansion values. Moreover, the absolute number of early hematopoietic progenitor cells (CD34+/HLA-DR-; CD34+/CD38-), as well as the number of 4-HC-resistant progenitors within expanded cells increased significantly. Interferon- gamma was shown to synergize with the 5-factor combination, whereas the addition of GM-CSF significantly decreased the number of total clonogenic progenitor cells. Large-scale expansion of PB CD34+ cells (starting cell number, 1.5 x 10(6) CD34+ cells) in autologous plasma supplemented with the same 5-factor combination resulted in an equivalent expansion of progenitor cells as compared with the microculture system. In summary, our data indicate that chemotherapy plus G-CSF-mobilized PBPCs from cancer patients can be effectively expanded ex vivo. Moreover, our data suggest the feasibility of large- scale expansion of PBPCs, starting from small numbers of PB CD34+ cells. The number of cells expanded ex vivo might be sufficient for repetitive use after high-dose chemotherapy and might be candidate cells for therapeutic gene transfer.

Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

2021 ◽  
Vol 39 (2) ◽  
pp. 107-115
Author(s):  
Paul J. Bröckelmann ◽  
Horst Müller ◽  
Teresa Guhl ◽  
Karolin Behringer ◽  
Michael Fuchs ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
High Dose Chemotherapy ◽  
Sensitivity Analyses ◽  
High Dose ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
First Diagnosis

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

scholarly journals Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2096
Author(s):  
Celina L. Szanto ◽  
Annelisa M. Cornel ◽  
Sara M. Tamminga ◽  
Eveline M. Delemarre ◽  
Coco C. H. de Koning ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Nk Cells ◽  
Immune Cell ◽  
High Dose Chemotherapy ◽  
Immune Monitoring ◽  
High Dose ◽  
Effector Cells ◽  
Gm Csf ◽  
Immune Cell Subsets

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.

Outcomes of Inside-out Meniscal Repair in the Setting of Multiligament Reconstruction in the Knee

2017 ◽  
Vol 45 (9) ◽  
pp. 2098-2104 ◽  
Author(s):  
Jorge Chahla ◽  
Chase S. Dean ◽  
Lauren M. Matheny ◽  
Justin J. Mitchell ◽  
Mark E. Cinque ◽  
...  
Keyword(s):  
Failure Rate ◽  
Meniscal Repair ◽  
Postoperative Outcome ◽  
Control Group ◽  
Failure Rates ◽  
Significant Difference ◽  
Outcome Scores ◽  
Inside Out ◽  
Repair Group

Background: Limited evidence exists for meniscal repair outcomes in a multiligament reconstruction setting. Purpose/Hypothesis: The purpose of this study was to assess outcomes and failure rates of meniscal repair in patients who underwent multiligament reconstruction compared with patients who underwent multiligament reconstruction but lacked meniscal tears. The authors hypothesized that the outcomes of meniscal repair associated with concomitant multiligament reconstruction would significantly improve from preoperatively to postoperatively at a minimum of 2 years after the index surgery. Secondarily, they hypothesized that this cohort would demonstrate similar outcomes and failure rates compared with the cohort that did not have meniscal lesions at the time of multiligament reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Inclusion criteria for the study included radiographically confirmed skeletally mature patients of at least 16 years of age who underwent multiligamentous reconstruction of the knee without previous ipsilateral osteotomy, intra-articular infections, or intra-articular fractures. Patients were included in the experimental group if they underwent inside-out meniscal suture repair with concurrent multiligament reconstruction. Those included in the control group (multiligament reconstruction without a meniscal tear) underwent multiligament reconstruction but did not undergo any type of meniscal surgery. Lysholm, Western Ontario and McMaster Universities Osteoarthritis Index, Short Form–12 physical component summary and mental component summary, Tegner activity scale, and patient satisfaction scores were recorded preoperatively and postoperatively. The failure of meniscal repair was defined as a retear of the meniscus that was confirmed arthroscopically. Results: There were 43 patients (16 female, 27 male) in the meniscal repair group and 62 patients (25 female, 37 male) in the control group. Follow-up was obtained in 93% of patients with a mean of 3.0 years (range, 2.0-4.7 years). There was a significant improvement between all preoperative and postoperative outcome scores ( P < .05) for both groups. The meniscal repair group had significantly lower preoperative Lysholm and Tegner scores ( P = .009 and P = .02, respectively). There were no significant differences between any other outcome scores preoperatively. The failure rate of the meniscal repair group was 2.7%, consisting of 1 symptomatic meniscal retear. There was no significant difference in any postoperative outcome score at a minimum 2-year follow-up between the 2 groups. Conclusion: Good to excellent patient-reported outcomes were reported for both groups with no significant differences in outcomes between the cohorts. Additionally, the failure rate for inside-out meniscal repair with concomitant multiligament reconstruction was low, regardless of meniscus laterality and tear characteristics. The use of multiple vertical mattress sutures and the biological augmentation resulting from intra-articular cruciate ligament reconstruction tunnel reaming may be partially responsible for the stability of the meniscal repair construct and thereby contribute to the overall improved outcomes and the low failure rate of meniscal repair, despite lower preoperative Lysholm and Tegner scores in the meniscal repair group.

scholarly journals Clinical Evaluation of Bracket Bonding Using Two Different Polymerization Sources

2008 ◽  
Vol 78 (5) ◽  
pp. 922-925 ◽  
Author(s):  
Nikolaos S. Koupis ◽  
Theodore Eliades ◽  
Athanasios E. Athanasiou
Keyword(s):  
Failure Rate ◽  
Orthodontic Treatment ◽  
Light Emitting Diode ◽  
Rank Test ◽  
Dental Arch ◽  
Halogen Lamp ◽  
Failure Rates ◽  
Bond Failure ◽  
Significant Difference ◽  
The Right

Abstract Objective: To comparatively assess clinical failure rate of brackets cured with two different photopolymerization sources after nine months of orthodontic treatment. Materials and Methods: The sample of this study comprised 30 patients who received comprehensive orthodontic treatment by means of fixed appliances. Using the same adhesive, 600 stainless steel brackets were directly bonded and light cured for 10 seconds with the light-emitting diode (LED) lamp or for 20 seconds with the conventional halogen lamp. A split-mouth design randomly alternated from patient to patient was applied. Failure rates were recorded for nine months and analyzed with Pearson χ2 test, and log-rank test at α = .05 level of significance. Results: The overall failure rate recorded with the halogen unit (3.33%) was not significantly different from the failure rate for the LED lamp (5.00%). Significantly more failures were found in boys compared with girls, in the mandibular dental arch compared with the maxillary arch, and in posterior segments compared with anterior segments. However, no significant difference was found between the right and left segments. Conclusion: Both light-curing units showed sufficiently low bond failure rates. LED curing units are an advantageous alternative to conventional halogen sources in orthodontics because they enable a reduced chair-time bonding procedure without significantly affecting bond failure rate.

scholarly journals Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3808-3814
Author(s):  
HJ Sutherland ◽  
CJ Eaves ◽  
PM Lansdorp ◽  
GL Phillips ◽  
DE Hogge
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Time Course ◽  
Recovery Phase ◽  
High Dose ◽  
Gm Csf ◽  
Cell Counts ◽  
Cd34 Cells

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.

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