Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation

ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey

ABSTRACT Introduction: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. Objective: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. Method: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. Results: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. Conclusion: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey.

INTRODUCTION: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. OBJECTIVE: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. METHOD: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. RESULTS: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. CONCLUSION: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation.

INTRODUCTION: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. OBJECTIVE: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. MATERIALS AND METHODS: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. RESULTS: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). CONCLUSION: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible.

PURPOSE: To evaluate the safety and efficacy of ocular cyclosporine in the prevention of the development of ocular graft versus host disease (oGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) in comparison with historic data. DESIGN: We developed a longitudinal, observational, prospective nonrandomized study. We evaluated the feasibility of prophylactic use of topical cyclosporine A (CsA) to prevent or decrease the incidence of oGVHD and compared this with historic data. METHODS: Patients undergoing AHSCT were treated with prophylactic topical CsA for 12 months after engraftment, followed by serial ophthalmic evaluations, including the Schirmer test. RESULTS: Twenty patients were included. No serious adverse effects were reported. Poor adherence was documented in 15% of patients. In spite of observing extra-ocular GVHD (acute and chronic GVHD incidence of 50 and 45%, respectively), only 1 in 20 patients developed oGVHD over the 20-month follow-up for the entire cohort. No statistically significant difference was observed in the incidence of oGVHD when compared to a historical cohort. CONCLUSIONS: Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial.

Efficacy of three filgrastim-intended copies for hematopoietic stem cell mobilization in healthy adult and pediatric donors in Mexico.

INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.

Erectile dysfunction treated with intracavernous stem cells: A promising new therapy?

In the past decades, great interest has been shown in the development of new therapies for erectile dysfunction. Stem cell therapy has generated promising results in numerous preclinical trials in animal models, which is why has led to the development of the first clinical trials in humans. The main cause involved in the pathophysiology of erectile dysfunction is vascular damage related to endothelial and neuronal injury. The interest in stem cell therapy is justified by their capability to differentiate into specific damaged tissues, including endothelium and nervous tissue, and induction of the host own cell proliferation. Despite the great effort of the many studies carried out to date, knowledge about biological effects, therapeutic efficacy and safety of stem cells therapy for erectile dysfunction is still very limited.

Erectile dysfunction treated with intracavernous stem cells: A promising new therapy? / Células madre vía intracavernosa para el tratamiento de la disfunción eréctil: ¿una nueva modalidad terapéutica?

In the past decades, great interest has been shown in the development of new therapies for erectile dysfunction. Stem cell therapy has generated promising results in numerous preclinical trials in animal models, which is why has led to the development of the first clinical trials in humans. The main cause involved in the pathophysiology of erectile dysfunction is vascular damage related to endothelial and neuronal injury. The interest in stem cell therapy is justified by their capability to differentiate into specific damaged tissues, including endothelium and nervous tissue, and induction of the host own cell proliferation. Despite the great effort of the many studies carried out to date, knowledge about biological effects, therapeutic efficacy and safety of stem cells therapy for erectile dysfunction is still very limited

En las últimas décadas, ha habido gran interés en el desarrollo de nuevos tratamientos para tratar la disfunción eréctil. El tratamiento con células madre ha arrojado prometedores resultados en numerosos estudios preclínicos en modelos animales, lo cual ha generado el desarrollo de los primeros ensayos clínicos en seres humanos. Puesto que la principal causa implicada en la fisiopatología de la disfunción eréctil es una lesión vascular asociada con lesión endotelial y neuronal, el interés por el tratamiento con células madre se justifica por la capacidad que tienen para diferenciarse en los distintos tejidos dañados, incluyendo endotelio y tejido neuronal, y en la inducción de la reparación de las propias células del huésped. A pesar del gran esfuerzo de los distintos estudios realizados hasta el momento actual, el conocimiento sobre los efectos biológicos, la eficacia terapéutica y la seguridad del tratamiento con células madre aún se encuentra muy limitado

The effect of intra-articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis.

AIM: Management of osteoarthritis (OA) is basically symptomatic. Recently, stem cells (SC) have been used in the search for an optimum treatment. We decided to conduct a controlled clinical trial to determine if a single intra-articular injection of in vivo stimulated bone marrow SC could lead to an improvement in pain management and quality of life in patients with knee OA. METHOD: This was a prospective, open-label, phase I/II clinical trial to assess the safety and efficacy of a single intra-articular injection of autologous stimulated bone marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders older than 30 years with confirmed diagnosis of OA who signed informed consent were included in two groups: SC group received in vivo BM stimulation with subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC were obtained by BM aspiration and administered in a single intra-articular injection. The control group received exclusively oral acetaminophen. Visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were performed at 1 week, 1 month and 6 months in both groups. This trial was registered in ClinialTrials.gov NCT01485198. RESULTS: A total of 61 patients were included. Socio-demographic characteristics, OA grades and initial scores were similar in both groups. The BM-SC group showed significant improvement in knee pain and quality of life during the 6-month follow-up. CONCLUSION: The study demonstrates feasibility and supports efficacy of a completely ambulatory procedure in treatment of knee OA.

Hospitalization rate and costs in acute lymphoblastic leukemia of childhood in a low-income group: Financial impact in Northeast Mexico.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the main and most expensive and prolonged causes of hospitalization for childhood cancer. We describe the hospitalization rate and its costs for an open population with ALL in a low-middle income country. PROCEDURE: We retrospectively analyzed 449 hospital admissions for 101 pediatric patients with ALL over 8 years. Clinical files and electronic databases were scrutinized to document causes, duration, readmission rate, costs, and outcome of each admission. Hospitalizations were divided into two categories: general pediatric ward and pediatric intensive care unit (PICU). Hospitalization rates and its costs per patient were estimated considering person-time at risk. RESULTS: Patients had an admission rate of 2.09 hospitalizations per patient-year and median length of stay per admission was 5 days. Most admissions occurred during the first 2 years from diagnosis. Mean cost per day was 239 US dollars (USD) and mean cost per stay was 2,246 USD versus 1,016 and 19,004 USD (P = 0.001) in the PICU, respectively. Total hospitalization cost per patient per year (PPPY) was 5,991 USD for high-risk patients and 3,038 USD for standard-risk patients. Patients between ages 1 and 9 years had a PPPY cost of $4,057; while for children younger than 1 year or older than 9 years, it was 7,463 USD. The popular medical insurance program covered 70% of hospitalizations and 63% of its total cost; patients contributed 2%, with the hospital absorbing 35%. CONCLUSIONS: Hospitalizations for children with ALL were less expensive than in high-income countries but had a significant cost to low-income families and to the healthcare system.

Comparative analysis of iron status and other hematological parameters in preeclampsia.

OBJECTIVE: To compare serum ferritin (SF) concentrations and other hematological parameters between patients with preeclampsia (PE) and normal pregnant women of the same gestational period who received supplemental iron during pregnancy. METHODS: Prospective, comparative, observational pilot study that included 31 women with PE and 30 healthy pregnant women, at 20 weeks' of gestation. Ferritin, iron and complete blood cell count were compared between groups. RESULTS: In comparison with controls, preeclamptic patients had a higher weight, body mass index, and arterial pressure. Serum ferritin and serum iron were higher in patients with PE (median: 36.5 µg/l vs. 20.9 µg/l and 103.9 µg/dl vs. 90.8 µg/dl) with a significant difference (P = 0.019 and P = 0.345). SF values >40 µg/l correlated with PE (r = 0.281; P = 0.032). A platelet count less than 100 × 109/l was higher in the PE group than in the control group (13% vs. 3%, P = 0.354). CONCLUSION: Higher SF levels, despite being within normal range, were associated with PE. The incidence of thrombocytopenia was higher in preeclamptic women, however, the remaining hematological parameters were similar in both groups.

[Comparison of the effectiveness of hematopoietic cell mobilization with chemotherapy and filgrastim versus filgrastim alone for autologous transplant in patients with lymphoma.] / Comparación de la efectividad de la movilización de células hematopoyéticas con quimioterapia y filgrastim, o con filgrastim solo, para autotrasplante en pacientes con linfoma.

INTRODUCTION: Autologous hematopoietic stem cell transplantation is the treatment of choice for high-risk Hodgkin's lymphoma and non-Hodgkin's lymphoma. OBJECTIVE: Compare the capacity to mobilize CD34+ cells for autologous hematopoietic stem cell transplantation using schemes with chemotherapy and without chemotherapy plus filgrastim in patients diagnosed with Hodgkin's lymphoma or non-Hodgkin's lymphoma. MATERIAL AND METHODS: The clinical records of patients with Hodgkin's lymphoma or non-Hodgkin's lymphoma who received an autologous hematopoietic stem cell transplant were analyzed retrospectively. Filgrastim alone or in combination with chemotherapy was used as mobilization scheme. Cell harvesting was classified as adequate when > 2 × 106 cells/kg were collected. RESULTS: Forty-seven patients (Hodgkin's lymphoma, 24; non-Hodgkin's lymphoma, 23) were included. Comparing groups of Hodgkin's lymphoma mobilized with chemotherapy (15 patients) and without chemotherapy (nine patients), one apheresis procedure was sufficient in 73 and 44% of patients, respectively (p = 0.04), the average of CD34 + cells/kg collected was 11 x 106 and 3 x 106, respectively (p = 0.017), and the collection was adequate in 100 and 55.6% of cases, respectively (p = 0.014). Comparing the groups of non-Hodgkin's lymphoma mobilized with chemotherapy (six patients) and without chemotherapy (17 patients), one apheresis procedure was sufficient in 33 and 65% of patients, respectively (p = 0.26), the average of CD34+ cells/kg was 3.56 x 106 and 3.41 x 106, respectively (p = 0.47), and collection was adequate in 66.6 and 59% of cases, respectively (p = 0.37). CONCLUSION: In Hodgkin's lymphoma patients, mobilization schemes with chemotherapy were more effective considering the number of cells collected, the number of apheresis required, and the percentage of successful cell collections. In non-Hodgkin's lymphoma patients, there were no significant differences between the two groups.

Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant.

CONTEXT: Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous hematopoietic stem cell transplantation (AHSCT). OBJECTIVE: The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management. DESIGN: We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25-56 mo). SETTING: Ambulatory care. INTERVENTIONS: We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting. PATIENTS: Patients were of both sexes, age 8-25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and <3 months since diagnosis. MAIN OUTCOME MEASURE(S): Insulin independence. RESULTS: Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of -2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8-17 years old). A mean of 11.5 × 10(6) CD34+ cells (SD ± 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%. CONCLUSIONS: Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.

Cost structure and clinical outcome of a stem cell transplantation program in a developing country: the experience in northeast Mexico.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) in developing countries is cost-limited. Our primary goal was to determine the cost structure for the HSCT program model developed over the last decade at our public university hospital and to assess its clinical outcomes. MATERIALS AND METHODS: Adults and children receiving an allogeneic hematopoietic stem cell transplant from January 2010 to February 2011 at our hematology regional reference center were included. Laboratory tests, medical procedures, chemotherapy drugs, other drugs, and hospitalization costs were scrutinized to calculate the total cost for each patient and the median cost for the procedure. Data regarding clinical evolution were incorporated into the analysis. Physician fees are not charged at the institution and therefore were not included. RESULTS: Fifty patients were evaluated over a 1-year period. The total estimated cost for an allogeneic HSCT was $12,504. The two most expensive diseases to allograft were non-Hodgkin lymphoma ($11,760 ± $2,236) for the malignant group and thalassemia ($12,915 ± $5,170) for the nonmalignant group. Acute lymphoblastic leukemia ($11,053 ± 2,817) and acute myeloblastic leukemia ($10,251 ± $1,538) were the most frequent indications for HSCT, with 11 cases each. Median out-of-pocket expenses were $1,605, and 1-year follow-up costs amounted to $1,640, adding up to a total cost of $15,749 for the first year. The most expensive components were drugs and laboratory tests. CONCLUSION: Applying the cost structure described, HSCT is an affordable option for hematological patients living in a developing country.

Cultural factors related to adherence to imatinib in CML: a Mexican perspective.

INTRODUCTION: The advent of imatinib as a therapeutic option of chronic myeloid leukemia (CML) has transformed this previously highly resistant disease into one that is susceptible to management with oral drugs that now offer high long-term survival rates. However, achieving an adequate adherence to treatment regimes is of critical importance. The characteristics of treatment compliance in Mexican patients have not been determined. METHODS: We evaluated 38 CML patients, members of the Glivec(®) International Patient Assistance Program (GIPAP). A bimonthly simplified medication adherence questionnaire was applied and the adherence rate was calculated by direct tablet counting. RESULTS: Two groups, one of local patients and another of out-of-town patients, were studied using an 85% adherence rate as a cut-off. The overall adherence rate was 85.9%. Fifteen patients were considered non-adherent (39.5%). The group of out-of-town patients presented a higher adherence rate of 92.8% in contrast with 76.3% in the local population (P = 0.021). The probability of achieving a complete cytogenetic response at some point of evolution after 8 years of follow-up was 93% in the adherent group vs. 58% in the group with an adherence rate <85% (P = 0.008). In patients with imatinib failure, the adherence rate was 75.8% compared to 95.5% (P = 0.008) in the optimal response group. CONCLUSIONS: In Mexican patients with CML, non-adherence to treatment is a cause of the failure to achieve remission or the subsequent loss of a complete cytogenetic and major molecular response.

Allogeneic peripheral blood stem cell transplantation using reduced-intensity conditioning in an outpatient setting in ABO-incompatible patients: are survival and graft-versus-host disease different?

BACKGROUND: Graft-versus-host disease (GVHD) is a major cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Minor ABO incompatibility has been associated with an increased risk of GVHD. We analyzed the impact of ABO matching on patient outcome after peripheral blood, reduced-intensity allo-HSCT in an outpatient setting, and its relationship with GVHD. STUDY DESIGN AND METHODS: Data of 121 patients were included. All patients received allo-HSCT from HLA-identical siblings as outpatients using a reduced-intensity conditioning regimen. Influence of ABO matching as a risk factor for the development of GVHD and survival was analyzed using logistic regression and Cox proportional hazards regression, respectively. RESULTS: Median age was 36 years (range, 1-71 years); 88 patients were ABO identical: 13 presented major mismatch and 20 minor mismatch, with an ABO incompatibility rate of 27.3%. The median follow-up period was 54 months (range, 0.3-120 months). Minor ABO incompatibility patients presented the highest rate of acute GVHD (aGVHD; 25%), in comparison with ABO-identical (20.5%) and major ABO incompatibility patients (15.4%; p = 0.79). The highest incidence of chronic GVHD (cGVHD) occurred in the context of minor ABO incompatibility (35%), in contrast to ABO-identical (30.8%) and major ABO incompatibility (15.4%). Survival was higher for patients in the minor ABO mismatch group; however, there was no significant correlation between ABO matching status and survival (p = 0.45). CONCLUSION: Using this type of peripheral blood stem cell transplantation, minor ABO-mismatched allo-HSCT was associated with a higher incidence of aGVHD and cGVHD and with increased survival, albeit with no significance.

Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial.

BACKGROUND AIMS: Cerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion. METHODS: In this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow-derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733). RESULTS: A median of 13.12 × 10(8) TNCs (range, 4.83-53.87) including 10.02 × 10(6) CD34+ cells (range, 1.02-29.9) in a volume of 7 mL (range, 4-10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10(8) TNCs (range, 1.36-17.85), with 3.39 × 10(6) cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found. CONCLUSIONS: Subarachnoid placement of autologous bone marrow-derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function.