Autologous Bone Marrow Cell Transplantation Research Articles

Efficacy of Activated Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

To compare the efficacy of activated autologous bone marrow and peripheral blood hematopoietic stem cell transplantation (Auto-HSCT) and matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for the first complete remission of adult acute myeloid leukemia (AML-CR1). For 86 adult patients with first complete remission of AML who underwent auto-HSCT (41 cases) and MSD-HSCT (45 cases) in our hospital from June 2012 to June 2020, the patients were treated with modified MAC ［Malflane 160 mg/(m2·d), -3 days, Ara-C 2 g/(m2·2), -3 days 21∶00, -2 days 9∶00, CTX 60 mg/(kg·d),-3 d, -2 d］, the stem cells were activated by IL-2 (1 000 U/ mL), IFN-α (100 U/ mL) and IFN-γ (100 U/ml). The overall survival (OS), leukemia free survival (LFS), cumulative incidence of recurrence (CIR) and non-recurrence mortality (NRM) of patients with different types of transplantation were compared. The 3-year OS rates of Auto-HSCT group and MSD-HSCT group were 75% and 69.5%, and the 3-year LFS rates were 70.6% and 82.4%, respectively. There was no statisticaly significant difference in the 3-year OS rates of low risk, medium risk and high risk patients in the Auto-HSCT and MSD-HSCT group (90.2% vs 87.5%, 68.4% vs 68.8%, 28.6% vs 53.3%), the LFS rates of low risk, medium risk and high risk patients in the auto-HSCT and MSD-HSCT group were 90.2% and 87.5%(P=0.838), 71.8% and 91.7%(P=0.184), 0 and 67.5%(P=0.027), respectively. The NRM of Auto-HSCT and MSD-HSCT group were 4.9% and 20% (P=0.036), and CIR were 24.4% and 13.3% (P=0.188). Univariate analysis showed that the survival time of patients was significantly correlated with the number of CR courses and disease risk stratification (P=0.005, P=0.000). Cox multivariate analysis showed that disease risk stratification was an independent risk factor affecting OS (P=0.001). For adult patients with primary AML-CR1, Auto-HSCT is safe and effective. In the absence of sibling donor, Auto-HSCT can be regarded as an effective post-remission treatment for patients with intermediate risk AML-CR1.

Analysis of curative effect of percutaneous autologous bone marrow cell transplantation for treating nonunion under laser positioning and navigation guidance

Fracture end cleaning, local bone grafting, and fixation are the classic treatment methods for fracture nonunion, but patients normally need to wait for a long time to ensure that there are signs of further healing. The purpose of this research is to verify whether precision injection improvement can be developed as treatment associated with autologous bone marrow cell injection to promoting fracture healing. The curative effect of traditional autologous bone marrow injection for the treatment of poor fracture healing is affected by injection accuracy and locally available cell retention the clinical. The curative effect of autologous bone marrow injection can be effectively improved through autologous bone marrow centrifugation and bone grinding at fracture end when combined with preoperative three-dimensional computed tomography (CT) planning. This minimally invasive treatment method is especially suitable for patients with delayed fracture healing within six months of presentation. Patients with nonunion over six months can be treated with improved autologous bone marrow injection. The convenient and minimally invasive method itself will not be difficult for patients, physically and mentally, and the most reliable treatment method for nonunion is to cut and clean hardened bone and implant autologous bone fixation.

One-year results of the treatment of critical lower limb ischemia with indirect revascularization methods

The OBJECTIVEwas to compare the efficiency of autologous bone marrow cell implantation and lumbar sympathectomy in the treatment of chronic critical lower limb ischemia.MATERIAL AND METHODS. The complex examination and treatment of 66 patients with critical lower limb ischemia, divided into 2 statistically homogeneous groups, was analyzed. The first group underwent sympathectomy, and the second – autologous bone marrow cell transplantation.RESULTS. After 1 year, in patients of the second group, compared with the first, the clinical status increased by 51.5 %, the number of amputations decreased by 3 %, the physical component of health increased by 7.9 %, the psychological component – by 17.7 %.CONCLUSION. The autologous bone marrow cell transplantation was pathogenetically substantiated and effective.

Multiple Autologous Bone Marrow-Derived CD271+ Mesenchymal Stem Cell Transplantation Overcomes Drug-Resistant Epilepsy in Children.

There is a need among patients suffering from drug‐resistant epilepsy (DRE) for more efficient and less toxic treatments. The objective of the present study was to assess the safety, feasibility, and potential efficacy of autologous bone marrow cell transplantation in pediatric patients with DRE. Two females and two males (11 months to 6 years) were enrolled and underwent a combined therapy consisting of autologous bone marrow nucleated cells (BMNCs) transplantation (intrathecal: 0.5 × 109; intravenous: 0.38 × 109–1.72 × 109) followed by four rounds of intrathecal bone marrow mesenchymal stem cells (BMMSCs) transplantation (18.5 × 106–40 × 106) every 3 months. The BMMSCs used were a unique population derived from CD271‐positive cells. The neurological evaluation included magnetic resonance imaging, electroencephalography (EEG), and cognitive development assessment. The characteristics of BMMSCs were evaluated. Four intravenous and 20 intrathecal transplantations into the cerebrospinal fluid were performed. There were no adverse events, and the therapy was safe and feasible over 2 years of follow‐up. The therapy resulted in neurological and cognitive improvement in all patients, including a reduction in the number of epileptic seizures (from 10 per day to 1 per week) and an absence of status epilepticus episodes (from 4 per week to 0 per week). The number of discharges on the EEG evaluation was decreased, and cognitive improvement was noted with respect to reactions to light and sound, emotions, and motor function. An analysis of the BMMSCs' characteristics revealed the expression of neurotrophic, proangiogenic, and tissue remodeling factors, and the immunomodulatory potential. Our results demonstrate the safety and feasibility of BMNCs and BMMSCs transplantations and the considerable neurological and cognitive improvement in children with DRE. stem cells translational medicine 2018;7:20–33

Combined Therapy with Shock Wave and Retrograde Bone Marrow-Derived Cell Transplantation for Osteochondral Lesions of the Talus

Multiple treatment strategies have been developed for osteochondral lesions (OCLs) of the talus. The purpose of this retrospective study was to assess retrograde autologous bone marrow cell (BMC) transplantation via core drilling (CD) combined with focused extracorporeal shock wave treatment (ESWT) in undisplaced OCL of the talus. A total of 69 patients with unilateral osteochondral lesions of the talus (Hepple grade I–III) were divided into two groups: 41 patients received combined therapy of ESWT and BMC transplantation (group A), while 28 were administered BMC transplantation alone (group B). The patients were followed up clinically and radiographically for a minimum of 2 years. Mean follow-up was 4.1 ± 2.8 years. AOFAS scores increased more significantly while pain intensity levels decreased in group A after treatment, compared with group B values (P < 0.001). In MRI follow-up, a more remarkable improvement of OCLs of the talus was observed in group A compared with group B (P = 0.040). Therefore, the combined technique reported here is a highly effective therapeutic option in OCLs of the talus with intact cartilage. It promotes patient recovery with pain control, and improves clinical outcome for more than 2 years after surgery.

High-dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the woman is both donor and recipient) has been considered a promising technique because it permits use of much higher doses of chemotherapy. To compare the effectiveness and safety of high-dose chemotherapy and autograft (either autologous bone marrow or stem cell transplantation) with conventional chemotherapy for women with early poor prognosis breast cancer. We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE (1966 to October 2015), EMBASE (1980 to October 2015), the World Health Organization's International Clinical Trials Registry Search Platform, and ClinicalTrials.gov on the 21 October 2015. Randomised controlled trials (RCTs) comparing high-dose chemotherapy and autograft (bone marrow transplant or stem cell rescue) versus chemotherapy without autograft for women with early poor prognosis breast cancer. Two review authors selected RCTs, independently extracted data and assessed risks of bias. We combined data using a Mantel-Haenszel fixed-effect model to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed the quality of the evidence using GRADE methods. Outcomes were survival rates, toxicity and quality of life. We included 14 RCTs of 5600 women randomised to receive high-dose chemotherapy and autograft (bone marrow transplant or stem cell rescue) versus chemotherapy without autograft for women with early poor prognosis breast cancer. The studies were at low risk of bias in most areas.There is high-quality evidence that high-dose chemotherapy does not increase the likelihood of overall survival at any stage of follow-up (at three years: RR 1.02, 95% CI 0.95 to 1.10, 3 RCTs, 795 women, I² = 56%; at five years: RR 1.00, 95% CI 0.96 to 1.04, 9 RCTs, 3948 women, I² = 0%; at six years: RR 0.94, 95% CI 0.81 to 1.08, 1 RCT, 511 women; at eight years: RR1.17, 95% CI 0.95 to 1.43, 1 RCT, 344 women; at 12 years: RR 1.18, 95% CI 0.99 to 1.42, 1 RCT, 382 women).There is high-quality evidence that high-dose chemotherapy improves the likelihood of event-free survival at three years (RR 1.19, 95% CI 1.06 to 1.34, 3 RCTs, 795 women, I² = 56%) but this effect was no longer apparent at longer duration of follow-up (at five years: RR 1.04, 95% CI 0.99 to 1.09, 9 RCTs, 3948 women, I² = 14%; at six years RR 1.04, 95% CI 0.87 to 1.24, 1 RCT, 511 women; at eight years: RR 1.27, 95% CI 0.99 to 1.64, 1 RCT, 344 women; at 12 years: RR 1.18, 95% CI 0.95 to 1.45, 1 RCT, 382 women).Treatment-related deaths were much more frequent in the high-dose arm (RR 7.97, 95% CI 3.99 to 15.92, 14 RCTs, 5600 women, I² = 12%, high-quality evidence) and non-fatal morbidity was also more common and more severe in the high-dose group. There was little or no difference between the groups in the incidence of second cancers at four to nine years' median follow-up (RR 1.25, 95% CI 0.90 to 1.73, 7 RCTs, 3423 women, I² = 0%, high-quality evidence). Women in the high-dose group reported significantly worse quality-of-life scores immediately after treatment, but there were few statistically significant differences between the groups by one year.The primary studies were at low risk of bias in most areas, and the evidence was assessed using GRADE methods and rated as high quality for all comparisons. There is high-quality evidence of increased treatment-related mortality and little or no increase in survival by using high-dose chemotherapy with autograft for women with early poor prognosis breast cancer.

Joint-preserving regenerative therapy for patients with early-stage osteonecrosis of the femoral head.

Osteonecrosis of the femoral head is an intractable disease often occurring in patients aged 30–40 years that can cause femoral head collapse, pain, and gait disturbance. Background factors, including corticosteroid use, alcohol intake, and idiopathic causes, have been indicated. It is estimated that 70–80 % of osteonecrosis patients experience femoral head collapse, for which total hip arthroplasty is considered the most effective treatment, even in young patients. Thus, there is a crucial need for developing a minimally invasive regenerative therapy as a preventive surgery for femoral head collapse: this has been an important area of research in the past decades. Core decompression, the most popular minimally invasive surgery for osteonecrosis of the femoral head, has been used for a long time; however, it has been insufficient to prevent femoral head collapse. For further improvement in therapeutic efficacy, cell transplantation and the use of artificial bone and growth factors have been proposed in addition to core decompression. Since 2000, newer therapies such as autologous bone marrow cell transplantation and the embedding of metal implant rods have been developed in Europe and the USA; however, these approaches have yet to become a global standard. This practical review summarizes applied state-of-the-art regenerative therapy-based core decompression. We introduce the clinical application of recombinant human fibroblast growth factor (rhFGF)-2-impregnated gelatin hydrogel for patients with precollapse osteonecrosis of the femoral head. Radiography and computed tomography have confirmed bone regeneration inside the femoral heads around the region of rhFGF-2 gelatin hydrogel administration. With further development, the minimally invasive method, which can be expected to promote bone regeneration in necrotic areas, could become a useful early-stage treatment for osteonecrosis of the femoral head. Patients can resume their daily routine soon after surgery, and the procedure is inexpensive. As such, it is a promising regenerative therapy that can be actively employed in osteonecrosis of the femoral head before femoral head collapse.

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion.

To determine the safety and effects on insulin secretion of umbilical cord (UC) mesenchymal stromal cells (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D). Between January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 × 10(6)/kg UC-MSC, 106.8 × 10(6)/kg aBM-MNC through supraselective pancreatic artery cannulation) or standard care (control). Patients were followed for 1 year at 3-month intervals. The primary end point was C-peptide area under the curve (AUC(C-Pep)) during an oral glucose tolerance test at 1 year. Additional end points were safety and tolerability of the procedure, metabolic control, and quality of life. The treatment was well tolerated. At 1 year, metabolic measures improved in treated patients: AUCC-Pep increased 105.7% (6.6 ± 6.1 to 13.6 ± 8.1 pmol/mL/180 min, P = 0.00012) in 20 of 21 responders, whereas it decreased 7.7% in control subjects (8.4 ± 6.8 to 7.7 ± 4.5 pmol/mL/180 min, P = 0.013 vs. SCT); insulin area under the curve increased 49.3% (1,477.8 ± 1,012.8 to 2,205.5 ± 1,194.0 mmol/mL/180 min, P = 0.01), whereas it decreased 5.7% in control subjects (1,517.7 ± 630.2 to 1,431.7 ± 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6% (8.6 ± 0.81% [70.0 ± 7.1 mmol/mol] to 7.5 ± 1.0% [58.0 ± 8.6 mmol/mol], P < 0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 ± 0.9% [72.0 ± 7.5 mmol/mol] to 8.8 ± 0.9% [73 ± 7.5 mmol/mol], P < 0.01 vs. SCT). Fasting glycemia decreased 24.4% (200.0 ± 51.1 to 151.2 ± 22.1 mg/dL, P < 0.002) and 4.3% in control subjects (192.4 ± 35.3 to 184.2 ± 34.3 mg/dL, P < 0.042). Daily insulin requirements decreased 29.2% in only the treated group (0.9 ± 0.2 to 0.6 ± 0.2 IU/day/kg, P = 0.001), with no change found in control subjects (0.9 ± 0.2 to 0.9 ± 0.2 IU/day/kg, P < 0.01 vs. SCT). Transplantation of UC-MSC and aBM-MNC was safe and associated with moderate improvement of metabolic measures in patients with established T1D.

In women with metastatic breast cancer, how does high dose chemotherapy and autologous bone marrow or stem cell transplantation compare with conventional chemotherapy at improving outcomes?

In women with metastatic breast cancer, how does high dose chemotherapy and autologous bone marrow or stem cell transplantation compare with conventional chemotherapy at improving outcomes?

Effect of Autologous Bone Marrow Cell Transplantation Combined with Off-Pump Coronary Artery Bypass Grafting on Cardiac Function in Patients with Chronic Myocardial Infarction

Objectives: This study aimed to investigate the feasibility and effects of intramuscular injections of autologous bone marrow cells (BMC) combined with off-pump coronary artery bypass grafts (OPCAB) on improving cardiac function in chronic myocardial infarction patients. Methods: Ninety patients with chronic myocardial infarction were prospectively enrolled and randomized to an OPCAB with saline or an OPCAB with BMC-treatment group. After finishing CABG, patients received injections of BMC or saline into the marginal area of the infarct. The primary endpoint was incidence of emergent adverse events within 6 months. Results: There were no differences between the control and BMC-treated groups in baseline ejection fractions (EF) or wall motion score indices (WMSI) in the affected segments. At the 6-month follow-up, the ejection fraction was significantly increased in the BMC-treated group compared to controls (47.58 w 6.34 vs. 40.11 w 7.42; p < 0.05), whereas the WMSI were significantly decreased (1.25 w 0.32 vs. 1.54 w 0.53; p < 0.05), with no occurrences of life-threatening arrhythmias or death. The addition of BMC injections to OPCAB treatment increased regional perfusion to the marginal infarct area. Conclusion: These results demonstrate that BMC transplant is beneficial to the cardiac function with no adverse effects, and therefore a safe and feasible adjunct therapy providing beneficial effects in clinical practice. i 2014 S. Karger AG, Basel

C-peptide increase in chronic type 1 diabetic patients treated with autologous bone marrow cell transplantation through pancreatic artery catheterization: Three years follow-up

Background: Recent extensive clinical evidence demonstrated that autologous adult stem cell therapy was safe and effective as a treatment strategy for type 1 diabetes. Our initial work was designed to examine the safety and efficacy of the implantation technique on 20 subjects with six months of evolution. This new report analyzes the results from three years follow up. Methods: With the authorization from the Ministry of Health of Argentina, 20 subjects with type 1 diabetes were treated with single autologous bone marrow cell transplantation into pancreatic blood flow through pancreatic artery catheterization immediately after bone marrow aspiration. The primary endpoint was defined as normalization of C-peptide and glycated hemoglobin (HbA1c) with insulin independence at 3 years posttreatment. Results: 15 subjects (75%) achieved clinical improvements. 7 subjects (33%) reached the primary endpoint, in which 4 subjets with decreased C-peptide levels required insulin administration again at 3 years post-treatment. Other 8 subjects (34%) showed partial function at 3 years post-treatment. There were no serious adverse events observed. No increases of islet cell antibody (ICA) and glutamic acid decarboxylase (GAD) antibody. Conclusion: This procedure may be a safe and effective treatment for chronic type 1 diabetes. The follow-up results showed a significant increase of the pancreatic secretion of C-peptide and a decrease in the daily dose of exogenous insulin. This effect partially disappears by the three years follow-up without an increase of the level of the ICA and GAD antibodies.

The Editor's Roundtable: Advances in Stem Cell Therapy for Treatment of Cardiovascular Disease

The first clinical trials of stem cell (SC) treatment for cardiac disease in humans, using autologous bone marrow cell transplantation in patients with severe chronic heart failure (HF), were reported in 2002 (using the intracoronary injection route) and in 2003 (using the intramyocardial injection route). Since those initial reports, numerous additional clinical SC trials have been conducted in the treatment of cardiac disease, with approximately 30 trials under way in the United States in 2012. In addition to bone marrow–derived hematopoietic SCs, subsequent clinical trials have used mesenchymal SCs, endothelial progenitor cells, skeletal myoblasts, induced pluripotent SCs (and derivatives), and cardiac-resident SCs. Currently, the 3 main indications for SC treatment in patients with heart disease are chronic ischemic HF, acute myocardial infarction, and idiopathic dilated cardiomyopathy. On the basis of trials over the past decade, “cell herapy may transform the treatment of acute and chronic eart disease, with an anticipated impact rivaling the results

Enhanced mobilization of the bone marrow–derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow–derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45+- and CD133/45+-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45+: P < 0.001, CD133/45+: P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45+ and CD133/45+ BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM-CPCs in PB and this might increase the regenerative potency after AMI.

Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients

BackgroundIn recent years, some studies were conducted to evaluate the effects of stem cells from different sources on patients with spinal cord injury (SCI). This study was carried out to evaluate the feasibility and therapeutic potential of autologous bone marrow cell (BMC) transplantation in 11 complete spinal cord injured patients at thoracic level. Methods and materialsThis nonrandomized clinical trial compared the results of autologous BMC transplantation into cerebrospinal fluid (CSF) via lumbar puncture (LP) in 11 patients having complete SCI, with 20 patients as control group who received conventional treatment without BMC transplantation. The patients underwent preoperative and follow-up neurological assessments using the American Spinal Injury Association (ASIA) impairment scale. Then, the participants were followed for 12–33 months. ResultsEleven patients with the mean age of 33.2±8.9 years and 20 patients with the mean age of 33.5±7.2 years were enrolled in the study and in the control group, respectively. None of the patients in the study and control group experienced any adverse reaction and complications, neither after routine treatment nor after cell transplantation. Five patients out of 11 (45.5%) in the study group and three patients in the control group (15%) showed marked recovery, but the result was statistically borderline (P=0.095). ConclusionWe conclude that transplantation of autologous BMC via LP is a feasible and safe technique, but at the moment, no clear answer can be given regarding the clinical potential, despite a potential tendency to treat SCI patients, observed through statistics.

Intraarterial Versus Intramuscular Delivery of Autologous Bone Marrow Blood to Patients with Critical Limb Ischemia

Abstract 2999 Introduction:Autologous bone marrow cell application has been proposed as an alternative therapy in patients (pts) with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization, but the way of their administration is currently unresolved. The aim of our study is to compare intramuscular (i.m.) and intraarterial (i.a.) bone marrow blood (BMB) delivery. Methods:Fifty nine patients (median age 67 years, range 38 – 89; gender M :F = 50 :9) with advanced CLI (Rutherford category 5, 6) not eligible for revascularization underwent analgosedation with profolol and total of 240 ml of BMB from both posterior iliac crests were harvested and stabilized with heparin. Bone marrow aspirate was processed with SmartPreP2 Bone Marrow Aspirate Concentrate System (Harvest, Plymouth, MA) – gradient density centrifugation to provide 40 ml of BMB concentrate (BMBc) within 15–20 minutes. Patients were randomized to treatment with 40 ml of BMBc either using local i.m. or i.a. infusion. Primary end points were limb salvage and wound healing. Secondary end points included changes in transcutaneous oxygen pressure (tcpO2), quality of life questionnaire (EQ 5D), ankle-brachial index (ABI), and pain scale (0–10 scale). Patients with limb salvage and wound healing were considered as responders to BMBc therapy. Results:Fifty nine collected BMB contained median mononucleated cell number 35, 8 × 109/l (range 12, 5 – 79, 8) and CD34+ cells 237, 25 × 106/l (range 57, 2 – 694, 3). Processing of BMB reduced to volume from 240 ml to 40 ml (e.g. 6x) and increased concentration of mononucleated cells and CD34+ cells (2, 9x). According to the randomization BMBc was administered i.m. (24 patients) into the ischemic limb or by means of i.a. infusion (800ml/hour) through the catheter positioned into the popliteal artery (25 patients).Since procedure 41 patients could reach 180 days follow up, 4 patients died from unrelated reason to study and 37 patients were evaluable for response. Twenty seven of 37 had limb salvage (73%). There was significant improvement in tcpO2 (15±10 to 29±13mmHg, p<0.001), in pain scale (4.4±2.6 to 0.9±1.4, p<0.001) and EQ 5D (51±15 to 70±13, p<0.001), and significant decrease in Rutherford category of CLI (5.0±0.2 to 4.3±1.6, p<0.01). There were no differences among functional parameters in patients undergoing i.m. versus i.a. delivery. Responders (n=27) vs. nonresponders (n=10) received higher CD34+ cells amounts in the bone marrow concentrate (29±15×10^6 vs 17±12×10^6, p<0.05), but similar number of total nucleated cells (4.3±1.4×10^9 vs 4.1±1.2×10^9, p=0.66). Responders had significantly lower C-reactive protein level (CRP 18±28 vs 100±96 mg/l, p<0.05) and white blood cell counts (8.3±2.1×10^9/l vs 12.3×4.5×10^9/l, p<0.05) at the time of study procedure. Conclusions:Autologous bone marrow blood harvest and administration is safe. There is no difference in i.m. versus i.a. application, both methods of autologous BMB delivery are effective in pts with CLI. Higher CD34+ cell content in BMBc and lower degree of inflammation are associated with good response to BMB application.Funding of project “Transplantation of autologous bone-marrow stem cells in patients with critical limb ischemia” ITMS code 26240220023 is supported by Operational programme Research and Innovation from European Regional Development Fund. Disclosures:No relevant conflicts of interest to declare.

Targeting the Right Treatments for Neuroblastoma

L ike most childhood cancers, neuroblastoma is relatively rare. But it is the most commonly diagnosed cancer in the first year of life, and more than half of children diagnosed develop aggressive forms of the disease that are difficult to cure. “Not only are there a lot of deaths in the high-risk population, but high-risk patients require very, very intensive therapy to cure them,” said Darrell Yamashiro, M.D., Ph.D., professor of pediatrics and pathology at the Columbia University Medical Center in New York. “These treatments include autologous bone marrow and stem cell transplant, so the morbidity associated with these is signifi cant as well.” Most of today ’ s research focuses on improving the survival of these high-risk children. With more than 100 trials actively recruiting patients, most for relapsed or unresponsive patients, researchers are testing a broad range of treatments. Among them are various kinase inhibitors, vaccines, and methods of stimulating the immune system, as well as new combinations of standard chemotherapies and radiation. “It ’ s an exciting time for clinical scientists but also a challenging time for physicians and parents,” said Peter Zage, M.D., Ph.D., assistant professor in the department of pediatrics at Baylor College of Medicine in Houston. “There is a wide range of new drugs and treatment strategies available for children with neuroblastoma.”

Preliminary evaluation of radioimmunotherapy with Tenarad, a I-131 labeled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin lymphoma.

8063 Background: The extra-domain A1 (ED-A1) of tenascin-C is a highly expressed component of the tumor extracellular matrix and constitutes a valuable target for radionuclide therapy. Tenarad is a human antibody which is capable of recognizing ED-A1, has been labeled with I-131 and is expressed as small immunoprotein (SIP) for improving its biodistribution properties. Previous phase I/II studies with a similar compound (131I-L19SIP) have shown efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad is administered to patients with progressive Hodgkin lymphoma refractory to conventional treatment. Methods: Eight patients (4 M, 4 F, 19-41 yo) have been enrolled between April and December 2010. All patients had undergone at least three lines of chemotherapy; seven pts had prior external beam radiation therapy and six had prior autologous bone marrow or stem cell transplantation. All patients presented with nodal disease and some had involvement of the bone (n=3), lung (n=2) or liver...

Beneficial Effects of VEGF Secreted from Stromal Cells in Supporting Endothelial Cell Functions: Therapeutic Implications for Critical Limb Ischemia

Critical limb ischemia (CLI) is the end stage of peripheral vascular disease (PVD). One third of CLI patients progresses to leg amputation with high associated morbidity and mortality. In no-option patients with end-stage critical limb ischemia, bone marrow cell transplantation has shown promising results, improving leg perfusion to the level of reducing major amputations and allowing limb salvage. We recently reported the successful application of an innovative protocol based on repeated autologous bone marrow cell transplantation, which resulted in an effective and feasible strategy for achieving long-term revascularization in patients with severe CLI. In an effort to understand the clinical benefit provided by stem cells therapy in patients with CLI, we characterized the marrow-derived stromal cells of CLI patients and we provided a correlation between the in vitro features of these cells and the clinical follow up at 12 months. We showed that cells derived from CLI patients had a reduced capacity to proliferate, adhere, and migrate, but that they stimulated proliferation and migration of endothelial cells through the release of VEGF-A, supporting the idea that the paracrine mechanisms underpinned the biological effects of long-term angiogenesis in CLI patients.

Cell treatment after acute myocardial infarction prevents early decline in circulating IGF-1

Objectives. To examine the influence of intracoronary autologous bone marrow cell transplantation after acute myocardial infarction on circulating growth factors and their relationship to left ventricular function. Methods. Circulating insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), stromal derived factor-1-alpha (SDF-1α), and transforming growth factor beta (TGF-β) were measured in patients randomized to cell treatment or control, in the ASTAMI study. Autologous cells were injected intracoronary on day 6; blood was sampled on days 5, 9, and at three months. Left ventricular ejection fraction was recorded by electrocardiogram-gated single photon emission computed tomography at six months. Results. Only change in IGF-1 from baseline to three months differed between groups (p=0.024). A weak but significant correlation was found between left ventricular ejection fraction and the averaged IGF-1 concentrations of all patients (r=0.24, p=0.02). Patients with IGF-1 above or below median (102 ng/ml) had a left ventricular ejection fraction of 52.3% (±11.4) versus 46.4% (±12.2) respectively (p=0.017). Conclusions. Intracoronary bone marrow cell treatment after myocardial infarction attenuates a reduction in circulating IGF-1. IGF-1 levels over time were weakly, but significantly correlated to left ventricular ejection fraction.

Long-term results of high-dose chemotherapy with autologous bone marrow or peripheral stem cell transplant as first salvage treatment for relapsed or refractory Hodgkin lymphoma: a single institution experience

The introduction of high-dose (HD) chemotherapy (CT) and autologous stem cell (ASCT) or bone marrow transplant (ABMT) in the last two decades has improved the prognosis of patients with refractory or relapsed Hodgkin lymphoma (HL) over conventional-dose salvage CT. To evaluate the outcome of adult patients with HL treated with HD CT and ASCT or ABMT after failure or relapse from first-line treatment with CT ± radiotherapy, we report the results of a retrospective analysis in 82 consecutive patients given HD CT and autologous transplant as second-line therapy between October 1984 and December 2006. Thirty-two patients were given sequential high-dose cytoreductive therapy while 50 received other conventional induction regimens. Seventy-three patients with chemoresponsive disease underwent the myeloablative phase, while eight patients had progressive disease during cytoreductive CT. After a median follow-up of 73 months, the 10-year progression-free survival (PFS) and overall survival (OS) were 57% and 51%, respectively. According to response to first-line treatment, PFS and OS were, respectively, 54% and 82% for patients with complete remission (CR) lasting 12 months or more; 49% and 51% for patients with CR less than 12 months; and 47% and 50% for patients who never achieved CR or progressed during first-line CT (induction failure). Response to cytoreductive CT significantly influenced outcome, with PFS and OS being, respectively, 56% and 68% vs. 44% and 47% (p = 0.009) in patients in CR versus patients not in CR after induction therapy. Treatment was well tolerated, and therapy related mortality was only 3.7%. These long-term results confirm that HD CT and ASCT or ABMT was feasible, safe, and very effective. Therefore, this therapeutic strategy may represent an active salvage approach even in the unfavorable group of patients with induction failure.