L Madero

Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results

Summary:Umbilical cord blood (CB) has been rapidly established as an alternative source of stem cells to bone marrow for allogeneic-related and unrelated hematopoietic transplantation. To date, almost 70 000 CB units are available for transplantation and more than 2000 CB transplants (CBT) have been performed, mostly in children, for the treatment of a variety of malignant and nonmalignant conditions. Considerable experience has been rapidly accumulated in this field and many aspects of CBT have been elucidated, while other questions remain unresolved. A concise review of the clinical results achieved after related and unrelated CBT is presented and discussed.

Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study

Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells (MSCs) may allow the use of MSCs as cellular vehicles for targeted delivery. In this work, we study the safety and the efficacy of infusing autologous MSCs infected with ICOVIR-5, a new oncolytic adenovirus, for treating metastatic neuroblastoma. Four children with metastatic neuroblastoma refractory to front-line therapies received several doses of autologous MSCs carrying ICOVIR-5, under an approved preliminary study. The tolerance to the treatment was excellent. A complete clinical response was documented in one case, and the child is in complete remission 3 years after this therapy. We postulate that MSCs can deliver oncolytic adenoviruses to metastatic tumors with very low systemic toxicity and with beneficial antitumor effects.

Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury

Mesenchymal cells recruited to damaged tissues must circulate through the bloodstream. The absolute numbers of circulating mesenchymal stem cells (cMSCs) in two different models of acute and chronic skeletal muscle injury were determined. cMSCs were present in significantly higher numbers in both models than in healthy controls. These results support the hypothesis that MSCs are mobilised into the bloodstream after skeletal muscle tissue damage. These two models (acute and chronic) would be of value in the search for molecular mediators of mobilisation of MSCs into the circulation.

Exercise Training and Cytokines in Breast Cancer Survivors

The purpose of this randomized controlled trial was to determine the effects of an 8-week (aerobic+strength) exercise training program (3 sessions/week) on the circulating cytokine levels of breast cancer survivors. We randomly allocated 16 female survivors of breast cancer (mean±SD age: 50±5 years) to an intervention or usual care (control) group (N=8 in each group). The intervention group followed an 8-week exercise program consisting of 3 sessions/week (session duration: 90 min). We measured the levels of the following cytokines before and after the intervention: beta-NGF, CTACK, eotaxin, FGF basic, G-CSF, gmCSFα, HGF, ICAM1, IFNα2, IFNγ, IL1α, IL1ß, IL1ra, IL2, IL2ra, IL3, IL4, IL6, IL7, IL8, IL9, IL10, IL12, IL13, IL15, IL16, IL17, IL18, IP10, LIF, MCS-F, MIP1α, MIP1β, MIF, MCP1, MCP3, MIG, PDGF bb, SCF, SCGFβ, SDF1α, TRAIL, TNFα, TNFβ, VCAM1, and VEGF. We only observed a significant interaction (group*time) effect for CTACK ( P=0.016), with mean values remaining stable in the intervention group but increasing over time in controls. The intervention program did not induce a significant decrease in the main breast cancer-related cytokines such as IL6 and IL8. A combined (aerobic+strength) 8-week exercise training intervention did not induce major changes in the basal cytokine levels of breast cancer survivors.

Granulocyte colony-stimulating factor alone at 12 μg/kg twice a day for 4 days for peripheral blood progenitor cell priming in pediatric patients

In children, the optimal mobilization schedule for harvesting peripheral blood progenitor cells (PBPC) is an issue of continuous research. We have studied a schedule based on high and daily divided doses of G-CSF (12 μg/kg body weight twice daily) for 4 days for PBPC priming. Toxicity related to G-CSF was observed in 13 patients (23%), mainly mild bone pain and myalgia. The median CD34+cell number collected was 4.4 (0.4–35 × 106/kg body weight), with 46 patients achieving 2 × 106/kg body weight (83.6%) after a single large volume leukapheresis. In conclusion, this mobilization schedule allows safe and efficient collection of the minimum target CD34+ cell dose in most pediatric patients by only one procedure.

Intrahospital supervised exercise training: a complementary tool in the therapeutic armamentarium against childhood leukemia.

Intrahospital supervised exercise training: a complementary tool in the therapeutic armamentarium against childhood leukemia

Cerebral toxoplasmosis following etanercept treatment for idiophatic pneumonia syndrome after autologous peripheral blood progenitor cell transplantation (PBPCT)

Idiophatic pneumonia syndrome (IPS) is a term used to describe lung injury following hematopoietic stem cell transplantation (HSCT) without an infectious etiology. Diagnostic criteria include multilobar infiltrates on chest X-ray, clinical symptoms consistent with pneumonia and evidence of abnormal pulmonary physiology. The incidence after autologous transplantation is low (6%) but it has a high mortality (70–80%). Treatment with high-dose steroids has been used but the results are discouraging. Etanercept is a recombinant human soluble TNF receptor fusion protein that inhibits tumor necrosis factor α (TNFα) function. Recently, promising results have been obtained with etanercept for the treatment of acute and chronic GVHD after HSCT, but there is a little information regarding adverse effects. We report a case of IPS after autologous peripheral blood progenitor cell transplantation (PBPCT) successfully treated with etanercept. The patient developed cerebral toxoplasmosis immediately after etanercept treatment with a good outcome.

Use of concurrent G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells in children with malignant disease.

There is limited experience in the mobilization of peripheral blood progenitor cells (PBPC) in children and the optimal method for PBPC mobilization is unknown. The present study was conducted to ascertain whether mobilization with G-CSF + GM-CSF (group I) provides some advantage over G-CSF alone (group II) in terms of collected CD34+ cells and hematopoietic recovery following myeloablative conditioning in children with malignancies. An economic analysis was also performed. Each group comprised 21 consecutive patients. The mean number of aphereses was 1.5 ± 0.5 in group I and 1.2 ± 0.46 in group II (NS). The mean number of CD34+ cells was 3.8 × 106 ± 4.03/kg in group I and 4.2 ± 5.4 in group II (NS). The mean number of total blood volumes (TBV) processed was 4.4 ± 1.5 in group I and 4.3 ± 1.5 in group II (NS). The mean duration of the procedure was 276 ± 74.1 min in group I and 286.7 ± 75.9 min in group II (NS), and the inlet flow was 45.1 ± 12 ml/min in group I and 39.5 ± 15.1 ml/min in group II (NS). No significant differences in the neutrophil and platelet engraftment probability were observed between the two groups. The mean overall cost of group II was not statistically significant from that of group I (US

Acute autoimmune hemolytic anemia following unrelated cord blood transplantation as an early manifestation of chronic graft-versus-host disease

9521 ± 330 vs US

Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH)

10201 ± 1028, P = NS). The cost of mobilization was significantly higher in group I than in group II, conditioning regimen costs were similar in both groups and the costs related to the post-transplant period were similar in both groups. We conclude that PBPC mobilization with G-CSF + GM-CSF in children does not enhance hematological recovery in comparison with mobilization using G-CSF alone. However, the combination of G-CSF + GM-CSF does not significantly increase the overall cost of transplantation. Bone Marrow Transplantation (2000) 26, 365–369.