Single Cord Research Articles

Single Lead Epidural Spinal Cord Stimulation Targeted Trunk Control and Standing in Complete Paraplegia.

A 25-year-old male with T3 complete AIS A was implanted with percutaneous spinal cord epidural stimulation (scES; eight contacts each) leads and a Medtronic Prime advance internal pulse generator. The two leads were placed at the midline level to cover the region of the T11–T12 vertebrae. Five days after implantation, X-ray showed complete migration of the left lead outside the epidural space. Two weeks after implantation, reprogramming of the single right lead (20 Hz and 240 µs) after setting the cathode at 0 and the anode at 3 resulted in target activation of the abdominal muscles and allowed for the immediate restoration of trunk control during a seated position, even with upper extremity perturbation. This was followed by achieving immediate standing after setting the single lead at −3 for the cathode and +6 for the anode using stimulation configurations of 20 Hz and 240 µs. The results were confirmed with electromyography (EMG) of the rectus abdominus and lower extremity muscles. Targeted stimulation of the lumbosacral segment using a single lead with a midline approach immediately restored the trunk control and standing in a person with complete paraplegia.

Unrelated Cord Blood Transplantation in Children, Adolescents, and Young Adults with Acute Leukemia or Myelodysplastic Syndrome: A Retrospective Comparative Study from the French Society for Bone Marrow Transplantation and Cellular Therapy Between Real-World Data and Previously Reported Results of a Randomized Clinical Trial

We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality [TRM], engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We compared the characteristics and outcomes of RCT participants (n=137) to a Francophone population-based registry of patients (real-world [RW] group) fulfilling the eligibility criteria used in our RCT and transplanted with 1 or 2 UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n=141). The primary endpoint was the 2-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The 2 groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, P< .001) and to receive a radiation-free regimen (39.0% versus 60.6%, P< .001). The 2-year CI of transplantation strategy failure, TRM, and the 2-year probability of OS were similar between the 2 groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% versus 20.4% ± 6.8%, P= .01), resulting in a significantly lower disease-free survival (DFS) (59.2% ± 8.4% versus 69.3% ± 8.0%, P= .047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used.

Infiltration in Pilocytic Astrocytoma: A Diagnostic Pitfall.

Glioma can be classified according to its infiltrative capacity into circumscribed and "diffuse"/infiltrative glioma. Pilocytic astrocytoma is typically grouped under the circumscribed astrocytic glioma in the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. The distinction of pilocytic astrocytoma from diffuse glioma is fundamental as it could be the difference between CNS WHO grade 1 and grade 4 glioma. This study aims to determine the infiltrative nature of pilocytic astrocytoma in different brain locations. All cases diagnosed as "pilocytic astrocytoma" were retrieved from 2008 to 2021. The clinical information (age, sex, location of the tumor), pathological description, and performed immunostaining were obtained from the pathological reports. The available pathological slides were retrieved and examined for the following features: diagnosis, infiltrative vs. circumscribed tumor, and immunostaining characteristics. There were 20 males and 19 females aged 17 months to 31 years. The diagnosis of pilocytic astrocytoma was confirmed in 38/39 cases, and in one case, the diagnosis changed to a dysembryoplastic neuroepithelial tumor. Histological infiltration is defined as the presence of neoplastic cells among the nonneoplastic brain parenchyma. Twenty cases were well-circumscribed with no evidence of infiltration histologically, while 18/38 cases showed apparent infiltration into adjacent brain tissue. The infiltration was not restricted to cerebellar pilocytic astrocytoma (12/24, 50%) but was also present in 3/7 supratentorial, single brainstem, and single spinal cord cases. In conclusion, cases with typical morphological features of pilocytic astrocytoma could show areas of brain infiltration, which should not affect the certainty of the diagnosis.

Review: Havoc and Reform: Workplace Disasters in Modern America, by James P. Kraft

Book Review| August 01 2022 Review: Havoc and Reform: Workplace Disasters in Modern America, by James P. Kraft James P. Kraft. Havoc and Reform: Workplace Disasters in Modern America. Baltimore: Johns Hopkins University Press, 2021. 256 pp. Hardcover $54.95. Mark Aldrich Mark Aldrich MARK ALDRICH is Marilyn Carlson Nelson Professor of Economics Emeritus at Smith College. He has written widely on the economics of safety, including Safety First: Technology, Labor and Business in the Building of American Work Safety, 1870–1939 (1997); Death Rode the Rails: American Railroad Accidents and Safety: 1828–1965 (2006); and Back on Track: American Railroad Accidents and Safety: 1965–2015 (2018). He is currently writing a book on American energy transitions, 1800–1940. Search for other works by this author on: This Site PubMed Google Scholar California History (2022) 99 (3): 64–65. https://doi.org/10.1525/ch.2022.99.3.64 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Mark Aldrich; Review: Havoc and Reform: Workplace Disasters in Modern America, by James P. Kraft. California History 1 August 2022; 99 (3): 64–65. doi: https://doi.org/10.1525/ch.2022.99.3.64 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentCalifornia History Search The core of James Kraft’s Havoc and Reform consists of five single-chapter studies of post–World War II disasters. There is also an introduction, an initial background chapter, and a conclusion. The disasters Kraft discusses are the Texas City explosion of 1946; the United Airlines–TWA midair collision over the Grand Canyon in 1956; the San Fernando earthquake of 1956 that leveled, among other buildings, two local hospitals; the MGM Grand fire in Las Vegas in 1980; and the bombing of the Murrah Federal Building in Oklahoma City in 1995. In the introduction and first chapter, Kraft introduces commonalities that link these tragedies. In the author’s view, all were workplace disasters; all occurred in modern times and in the South or Southwest, far from the older industrial regions. Finally, all had important policy consequences, because “havoc and reform…look like two strands of a single cord” (14). These claims are surely hard to... You do not currently have access to this content.

Organ-at-risk sparing with dynamic trajectory radiotherapy for head and neck cancer: comparison with volumetric arc therapy on a publicly available library of cases

BackgroundDynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation during beam-on. The aim of the study is to establish DTRT path-finding strategies, demonstrate deliverability and dosimetric accuracy and compare DTRT to state-of-the-art VMAT for common head and neck (HN) cancer cases.MethodsA publicly available library of seven HN cases was created on an anthropomorphic phantom with all relevant organs-at-risk (OARs) delineated. DTRT plans were generated with beam incidences minimizing fractional target/OAR volume overlap and compared to VMAT. Deliverability and dosimetric validation was carried out on the phantom.ResultsDTRT and VMAT had similar target coverage. For three locoregionally advanced oropharyngeal carcinomas and one adenoid cystic carcinoma, mean dose to the contralateral salivary glands, pharynx and oral cavity was reduced by 2.5, 1.7 and 3.1 Gy respectively on average with DTRT compared to VMAT. For a locally recurrent nasopharyngeal carcinoma, D0.03 cc to the ipsilateral optic nerve was above tolerance (54.0 Gy) for VMAT (54.8 Gy) but within tolerance for DTRT (53.3 Gy). For a laryngeal carcinoma, DTRT resulted in higher dose than VMAT to the pharynx and brachial plexus but lower dose to the upper oesophagus, thyroid gland and contralateral carotid artery. For a single vocal cord irradiation case, DTRT spared most OARs better than VMAT. All plans were delivered successfully on the phantom and dosimetric validation resulted in gamma passing rates of 93.9% and 95.8% (2%/2 mm criteria, 10% dose threshold).ConclusionsThis study provides a proof of principle of DTRT for common HN cases with plans that were deliverable on a C-arm linac with high accuracy. The comparison with VMAT indicates substantial OAR sparing could be achieved.

Predictors of cord blood unit cell content in a volume unrestricted large series collections: a chance for a fast and cheap multiparameter selection model

BackgroundCord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content.MethodsMaternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content.ResultsOur univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie’s gender and birth weight have a positive correlation with CB TNC content. The babie’s birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie’s, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 108 (group A) have a significant higher CD34+ content than group B (female babie’s, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 106, while no CBUs with high concentration of CD34+ were detect in group B.ConclusionThis study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries.

Bladder management in individuals with spinal cord injury or disease during and after primary rehabilitation: a retrospective cohort study.

The purpose of this study was to investigate the course of bladder evacuation and the predictors of intermittent self-catheterization (ISC) in individuals with neurogenic lower urinary tract dysfunction (NLUTD) during and after primary rehabilitation. The patient database of a single spinal cord injury rehabilitation center was screened for patients with NLUTD admitted for primary rehabilitation. Patient characteristics and bladder evacuation details were collected during and after rehabilitation. Binary logistic regression analysis was used to evaluate predictors of ISC: sex, age > 65years, injury severity, and bladder capacity ≥ 400ml. Data of 255 men (74.3%) and 88 women (25.7%) with a mean age of 54 ± 19years were analyzed. Early in rehabilitation, 21.6% of the evaluated individuals used ISC. In 17.8%, the bladder was evacuated by transurethral catheterization (TUC). The proportion of TUC decreased during rehabilitation and dropped below 2% at the last follow-up. In contrast, the proportion of ISC and suprapubic catheterization (SPC) increased to 28% and 12.8%, respectively, during rehabilitation. These proportions increased further thereafter and reached 37.7% and 18.6% for ISC and SPC, respectively. Age and injury severity were significant (p ≤ 0.041) negative predictors, whereas male sex and above-average bladder capacity were positive predictors of ISC. There is a shift toward bladder evacuation by ISC and SPC during and after primary rehabilitation. Bladder evacuation by ISC, regarded as the gold standard, is less common in individuals > 65years or with high-level tetraplegia. The optimal bladder evacuation method needs to be established individually, considering all medical and psychosocial factors rather than simply following a guideline.

Investigating the production of platelet lysate obtained from low volume Cord Blood Units: Focus on growth factor content and regenerative potential

BackgroundThe regenerative potential of platelet lysate (PL) and platelet gel (PG) is mediated by the release of platelets (PLTs) growth factors. The aim of this study was the evaluation of the PL production utilizing low volume single Cord Blood Units (CBUs) and the comparison of the biomolecule content between PLs obtained from intermediate and high volume CBUs. MethodsCBUs (n = 90) with volumes greater than 50 ml and initial platelet count > 150 × 109/L were used. CBUs were classified into the following groups: group A (50–80 ml), group B (81–110 ml) and group C (111–150 ml). The CBUs were centrifuged twice for the production of the platelet concentrate (PC), which was stored at − 80 °C for at least 48 h. Then, rapidly thawed and the biomolecule content was determined using commercial ELISA kits. The regenerative potential of PLs was evaluated using the scratch wound and in vitro angiogenesis assay. ResultsCBPL was produced from low volume single CBUs and contained 3.4 ± 0.3 ×109 PLTs. PL obtained from intermediate and high volume CBUs consisted of 10.2 ± 0.3 and 16.1 ± 0.4 × 109 PLTs. All PL groups were characterized by high biomolecule content. Gap closure was observed within 72 h after the wound assay initiation and the capillary tubes were formed in all study groups. ConclusionThis study provided significant evidence regarding the utilization of the low volume CBUs for the production of CB derivatives, thus can serve as healing mediators in regenerative medicine approaches.

Effect of Multiple HLA Locus Mismatches on Outcomes after Single Cord Blood Transplantation

The effect of single or multiple mismatches at each HLA locus on outcomes after cord blood transplantation (CBT) is controversial. We analyzed the effects of single or multiple HLA locus mismatches on the outcomes after single CBT using Japanese registry data from the Japan Society for Hematopoietic Cell Transplantation. Patients age ≥16 years with acute leukemia and myelodysplastic syndromes who underwent their first CBT between 2003 and 2017 (n=4074) were included. The effect of the number of HLA locus mismatches (0, 1, or 2 for the HLA-A, -B, -C, and -DRB1 loci) on outcomes was analyzed after adjusting for other significant variables. The patient cohort had a median age of 54 years. The median total nucleated and CD34 cell doses were 2.6×107/kg and .8×105/kg, respectively. The number of CBTs with single or double mismatches were 2099 and 292, respectively, for the HLA-A locus, 2699 and 341 for the HLA-B locus, 2555 and 609 for the HLA-C locus, and 2593 and 571 for the HLA-DRB1 locus. Single and double HLA-DRB1 mismatches were associated with a higher risk of grade II-IV acute graft-versus-host disease (GVHD; single: hazard ratio [HR], 1.29, P < .001; double: HR, 1.49, P < .001; P for trend <.001). Single and double mismatches at HLA-DRB1 as well as single mismatches at HLA-A and HLA-B also were associated with grade III-IV acute GVHD. Single and double HLA-B mismatches and double HLA-DRB1 mismatches were associated with a high risk of nonrelapse mortality (NRM). On the other hand, double mismatches at HLA-A or HLA-DRB1 and single mismatches at HLA-B were associated with a lower risk of relapse. HLA-DRB1 double mismatch was associated with high risk of grade II-IV and grade III-IV acute GVHD and NRM but lower risk of relapse. Not only the locus mismatch, but also the number of mismatches, should be considered in cord blood unit selection.

Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia

Unrelated cord blood transplantation (CBT) is an alternative curative option for adult patients with acute myeloid leukemia (AML) who need allogeneic hematopoietic cell transplantation (HCT) but lack an HLA-matched related or unrelated donor. However, large-scale data are lacking on CBT outcomes for unselected adult AML. To investigate the trends of survival and engraftment after CBT over the past 22 years, we retrospectively evaluated the data of patients with AML in Japan according to the time period of CBT (1998–2007 vs 2008–2013 vs 2014–2019). A total of 5504 patients who received single-unit CBT as first allogeneic HCT for AML were included. Overall survival (OS) at 2 years significantly improved over time. The improved OS among patients in ≥ complete remission (CR)3 and active disease at CBT was mainly due to a reduction of relapse-related mortality, whereas among patients in first or second CR at CBT, this was due mainly to a reduction of non-relapse mortality. The trends of neutrophil engraftment also improved over time. This experience demonstrated that the survival and engraftment rate after CBT for this group has improved over the past 22 years.

Single vocal cord irradiation for early-stage glottic cancer: Excellent local control and favorable toxicity profile

ObjectiveTo validate the earlier reported promising oncologic outcomes and favorable toxicity profile following single vocal cord irradiation (SVCI) in an expanded cohort of patients with early-stage glottic cancer treated at our institute with longer follow-up time. Materials and methodsBetween February 2011 and January 2020, 111 consecutive patients with early-stage glottic cancer were treated with SVCI to the whole involved vocal cord (58.08 Gy, given in 16 fractions of 3.63 Gy). Setup verification was done using cone-beam CT, prior to each fraction. The endpoints were local control (LC), overall survival (OS), grade ≥ 3 toxicity and voice quality assessment using voice-handicap index (VHI) questionnaires. ResultsMedian follow-up was 41 months (range; 8–84). Two patients developed in-field local failure (LF). The 3- and 5-year LC rates were 99.1% and 97.1%, respectively. As both patients with LF were successfully salvaged with total laryngectomy, the 5-year ultimate LC-rates was 99%. The 5-years OS was 80.6%. All patients finished treatment without any interruption. No patients developed acute grade ≥ 3 toxicity. Late grade 3 toxicity was reported in 7 patients (6.5%) out of 108 patients evaluable for late toxicity; 2 because of severe hoarseness and 5 because of laryngeal radionecrosis (4.5%). The 5-years laryngectomy-free survival was 98.1%. The VHI-scores improved over time, only 22% of patients had VHI > 30 at 3-years post-radiotherapy, compared to 38% at baseline. ConclusionsLocal control rate and laryngectomy-free survival of SVCI are excellent with favorable toxicity profile and good VHI-score. These results validate our early results.

Comparable Outcomes and Health-Related Quality of Life for Severe Aplastic Anemia: Haploidentical Combined With a Single Cord Blood Unit vs Matched Related Transplants.

We retrospectively compared the outcomes and health-related quality of life (HRQoL) of severe aplastic anemia (SAA) patients who received haploidentical hematopoietic stem cell transplantation with a single unrelated cord blood unit (Haplo-cord HSCT) (n = 180) or matched related donor (MRD)-HSCT (n = 128). After propensity score matching, we were able to match 88 patients in each group and to compare the outcomes between the two matched-pair groups. Haplo-cord recipients exhibited a longer median days for neutrophil engraftment (12 vs 11, P = 0.001) and for platelet engraftment (15 vs 13, P = 0.003). Haplo-cord recipients a high cumulative incidence of grades II–IV acute graft-versus-host disease (GVHD) (29.8 vs 14.0%, P = 0.006), while similar III–IV acute GVHD, total chronic GVHD, and moderate to severe chronic GVHD at four-year (all P < 0.05). Among the Haplo-cord HSCT and MRD-HSCT groups, the four-year GVHD-free/failure-free survival rates were 73.5% and 66.9% (P = 0.388) respectively, and the overall survival rates were 81.5% and 77.2% (P = 0.484), respectively. Similar comparable results also were observed between the corresponding first-line, older or younger than 40 years old subgroups. The Haplo-cord HSCT group exhibited higher scores in the physical component summary, physical functioning, general health and social functioning than the MRD-HSCT group (all P < 0.05). In the multivariate analysis, young age and Haplo-cord HSCT were favorable factors for HRQoL, while moderate to severe cGVHD was associated with lower HRQoL. These results suggest that for SAA patients, Haplo-cord HSCT could achieve at least comparable efficacy and HRQoL to MRD-HSCT.

Discordant umbilical arteries in the umbilical cord entanglement: a light microscope study

Objective The present study aimed to examine the histopathological diagnosis of the umbilical artery discordance in cases with single or multiple umbilical cord entanglement and pregnancy outcomes. Methods The vascular structure of the umbilical cord, histopathological findings of the placenta and obstetric outcomes were retrospectively examined in 50 cases. The cases were divided into two groups by the number of cord entanglement (single-multiple) and their histopathological findings and neonatal Apgar scores were assessed. Results Out of 50 cases, 38 (76%) had single and 12 (24%) had multiple cord entanglement. In 50 cases, the mean gestational age was 39.16±1.06 weeks, neonatal Apgar scores were 8.7±0.58 at 1 minute and 9.64±0.56 at 5 minute. No statistically significant difference was detected between single and multiple groups in terms of gestational age (p=0.79), 1-minute Apgar score (p=0.832) and 5-minute Apgar score (p=0.656). In histopathological examination, the diameters of umbilical arteries 1 and 2 were found to be 0.11±0.12, 0.09±0.05 µm, respectively in the single group (p=0.756) and 0.13±0.14, 0.06±0.02 µm, respectively in the multiple group (p=0.131). When the umbilical arterial diameters were compared by group, the diameter of the umbilical artery 2 was detected 0.09±0.05 µm in the single and 0.06±0.02 µm in the multiple group and statistically significant difference was detected (p=0.037). Out of 50 cases, placental hypoxia finding was detected as chorangiosis only in 10 cases (2 multiple, 8 single). Conclusion Umbilical artery discordance was detected in cases with multiple umbilical cord entanglement. However, poor pregnancy outcome was not observed in any of the cases. When multiple cord entanglement is seen during obstetric examination, umbilical artery discordance must be remembered and investigated, and also maternal-fetal condition should be considered.

Patterns of Nerve Injury and Recovery Rates of Infraclavicular Brachial Plexus Lesions Following Anterior Shoulder Dislocation

We reviewed our cases of infraclavicular brachial plexus injuries associated with anterior shoulder dislocation to determine patterns of injury, recovery rates, and factors associated with a poor motor outcome. This was a retrospective review of patients who had sustained a concomitant nerve injury following dislocation of the glenohumeral joint treated with closed manipulation. The data collected included patient demographics, injury factors, and patterns of neurological deficits. The Medical Research Council (MRC) grade for motor power was the primary outcome measure, where a grade of 4 or 5 was regarded as achieving good motor recovery. Univariate and multivariable analyses were used to identify factors associated with persistent motor weakness (MRC grades 0-3) at the final follow-up. Between 2015 and 2019, 61 patients were assessed. There were 36 males and 25 females, with a median age of 64 years (interquartile range [IQR], 53-73 years). Four patterns of injury were identified: (1) isolated axillary nerve lesions; (2) single cord lesions; (3) combined lesions involving the medial and posterior cords; and (4) diffuse lesions affecting all 3 cords. Of 28 patients with isolated axillary nerve injuries, 22 recovered. All lateral cord injuries (11/11) and 20 of 24 posterior cord injuries recovered spontaneously. Recovery of hand intrinsic function from medial cord injuries had the worst outcome, with 14 of 27 patients not recovering beyond MRC grades 0 to 3. The median duration of dislocation before reduction was 6 hours (IQR, 3-12 hours). A multivariate analysis showed an association between the duration of shoulder dislocation and the likelihood of persistent motor weakness. Shoulder dislocations with motor deficits should be regarded as orthopedic emergencies and reduced expediently. Persistent motor weakness may be associated with a prolonged duration of dislocation prior to glenohumeral relocation. Prognostic IV.

Umbilical Cord Blood Microtransplantation in Newly Diagnosed, Elderly Patients with Acute Myeloid Leukemia

Objective: We observed the efficacy and safety of umbilical cord blood microtransplantation (UCBMT) in the treatment of newly diagnosed with acute myeloid leukemia (AML) in the elderly.Methods: Prospective one-arm phase I clinical study. The patients should meet the following criteria: 60-80-year-old; newly diagnosed AML; receive the treatment of chemotherapy combined with UCBMT.Result: In total, 11 patients newly diagnosed with AML received chemotherapy in combination with UCBMT, from November, 2019 to January, 2021, including 7 males and 4 females. The average age was 71 (60-80). For the patients, 7 cases with normal chromosome karyotype, and 2 cases with +8 chromosome, 1 case with 7q- chromosome, and 1 case with karyotype of monomer. In the 7 patients with normal chromosome karyotype, 3 cases were FMS-liketyrosine kinease 3 (FLT3) positive (2 of them in combination with nucleophosmin 1 (NPM1) mutation); in addition, in 4 patients of the 7, one showed double mutation of CEBPA, one showed NPM1 mutation, one showed IDH1 mutation, and one showed IDH2 mutation. In 4 patients with chromosomal abnormalities, one patient showed no special gene, one patient showed ASXL1 mutation, one patient was IDH1 mutation, and one patient was TP53 mutation. All of the patients were treated with IA (IDA 8-10 mg/ m 2/day x 3 days, cytarabine 100 mg/ m 2/day x 7 days) for inducing chemotherapy. For the patients with 60-70-year-old, they were treated with IDA (8 mg/ m 2/day); and for the patients with 70-80-year-old, they were treated with darubicin (10 mg/ m 2/day). In the consolidation phase, the patients were treated with cytarabine (1 g/ m 2, q12h) for 3 consecutive days. There were 3 courses of consolidation chemotherapy. Next, patients received single unrelated cord blood transplantation (UCBT) from China's public umbilical cord blood bank, HLA matching was performed for all patients before treatment. A total of 4 units of UCB with HLA 0-3/6（HLA-A,-B,-DR）matching and the ABO blood type matched with the patient were transfused after induction and consolidation chemotherapy for 24-48 hours, then with follow-up. At the same time, the immunological characteristics of these patients were fully analyzed. We demonstrated that, 8 of 11 patients received one course of induction chemotherapy, and achieved a complete response. The complete response rate was 72.7%. What's more, the median time for neutrophils ≥ 0.5 x 10 9/L and platelete ≥ 20 x 10 9/L was 12 days. There were no treatment-related deaths during induction therapy. The median follow-up was 14 (7-31) months. 1 patient showed monomer karyotype with P53 gene mutation, and got complete remission after one course of induction chemotherapy with IA. However, the patient died for AML recurred. For the other 10 patients, they were alive, and the OS of 1 year was 89.8%. Moreover, we found the expression of PD-1 on CD8 +T cells decreased, while the expression of CD38 increased after therapy. Besides, the proportion of NKp30 +NK cells, as well as the IFN-γ +TFN-α +NK cells increased significantly.Conclusion: UCBMT therapy for newly diagnosed elderly AML patients could accelerate the recovery of hematopoietic function and improve the safety of chemotherapy. This method is effective and worthy of further promotion. DisclosuresNo relevant conflicts of interest to declare.

Comparing Single Cord Blood Transplantation and Matched Related Donor Transplantation in Non-Remission Acute Myeloid Leukemia

IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for refractory and relapsed acute myeloid leukemia (R/R AML) in non-remission status. Although human leukocyte antigen (HLA)-matched relatives are the preferred donors for R/R AML patients in non-remission status, their 2-year overall survival following HLA-matched related donor transplantation (MRDT) has only been reported to be 25% due to a high relapse rate of over 50%. Alternatively, cord blood transplantation (CBT) is a donor transplantation procedure that has similar advantages to MRDT in terms of rapid availability, making it possible for urgent HSCT. Moreover, CBT can induce a more potent graft-versus-leukemia (GVL) effect in AML patients under various conditions as compared to other donors. Therefore, this study aimed to investigate the impact of CBT as compared to MRDT using the Transplant Registry Unified Management Program 2 in Japan.MethodThis study included 2451 adult patients with non-remission AML who received CBT (1738 patients) or MRDT (713 patients), including bone marrow transplantation and peripheral blood transplantation, for their first HSCT between January 2009 and December 2018. The primary endpoint was set as 5-year progression-free survival (PFS), and secondary endpoints were set as 5-year overall survival (OS), 5-year cumulative incidence of relapse, 5-year cumulative incidence of non-relapse mortality (NRM), 100-day cumulative incidence of neutrophil engraftment, 1-year cumulative incidence of platelet engraftment, 1-year cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD), and 5-year cumulative incidence of extensive chronic GVHD. The impact of CBT compared to MRDT was then evaluated using propensity score (PS)-matching analysis. In PS calculation, covariates that may influence the selection of the donor and outcomes were selected clinically, and they included the following: age, sex, karyotype risk, disease status, presence of blasts in the peripheral blood, HCT-CI, intensity of conditioning regimen, acute graft versus host disease (GVHD) prophylaxis, and years of HSCT.ResultA total of 2451 patients, comprising 1738 who received CBT and 713 who received MRDT, were enrolled and analyzed. The median age was 55 years (interquartile range, 43-63 years), and 1484 patients (61%) were male. Differences in the clinical characteristics between the two groups were noted. Specifically, the CBT group had older patients, more patients with relapse, blasts in peripheral blood, a higher hematopoietic cell transplant comorbidity index, and had more patients who received reduced-intensity conditioning regimen, tacrolimus-based acute graft-versus-host disease prophylaxis, and transplanted recently. After PS matching, we selected 918 patients among the 2451 patients receiving CBT or MRD, and the patient characteristics were well balanced between the groups.Regarding the primary endpoint, the 5-year PFS was 25.2% (95% CI: 21.1%-25.5%) in the CBT group vs. 18.1% (95% CI: 14.5%-22.0%) in the MRDT group (P=0.009) in the PS-matched cohort (Figure 1). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69-1.00, P=0.045).Regarding secondary endpoints, CBT group compared to MRDT group had similar 5-year OS (28.4% in CBT group vs 21.7% in MRDT group, P=0.152), lower 5-year cumulative incidence of relapse (49.3% s 62.8%, P<0.001), higher cumulative incidence of 5-year NRM (25.5% vs 19.1% P=0.0158), lower 100 days neutrophil engraftment (49.5% vs 93.5%, P<0.001), lower one-year platelet engraftment (62.6% vs 79.1%, P<0.001), similar one-year cumulative incidence of grade II-IV acute GVHD (35.5% vs 30.5%, P=0.092), and lower 5-year cumulative incidence of extensive chronic GVHD (8.6% vs 18.5%, P<0.001) in the PS-matched cohort.ConclusionIn this population, CBT was associated with a better 5-year PFS as compared to MRDT after allogeneic HSCT. [Display omitted] DisclosuresKondo: MSD Pharmaceutical: Honoraria; Asahi Kasei Pharmaceutical: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Chugai Pharma: Honoraria; Sumitomo Dainippon Pharma: Honoraria. Kanda: NextGeM Inc: Patents & Royalties; Ono Pharma Inc.: Honoraria; Novartis Pharma K.K.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company Limited: Honoraria, Membership on an entity's Board of Directors or advisory committees; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; Bristol-Myers Squibb Co: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; Amgen Astellas BioPharma: Honoraria; TEIJIN PHARMA LIMITED.: Honoraria. Uchida: Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Novartis Pharma Inc.: Honoraria. Atsuta: Astellas Pharma Inc.: Speakers Bureau; Mochida Pharmaceutical Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Kyowa Kirin Co., Ltd: Honoraria; Meiji Seika Pharma Co, Ltd.: Honoraria.

Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Pediatric Patients With Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

<h3>Purpose/Objective(s)</h3> To evaluate the relationship between total body irradiation (TBI) and other factors in the development of idiopathic pneumonia syndrome (IPS) in pediatric patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute leukemia. <h3>Materials/Methods</h3> Between 2006-2019, 121 pediatric patients with acute leukemia (84 lymphoblastic, 37 myeloid), ranging in age from 1 to 21 years (median 12), underwent allogeneic HCT at a single institution with matched sibling (n = 33), single unrelated cord blood (sUCB; n = 57), or double unrelated cord blood (dUCB; n = 31) donor. Pretransplantation conditioning included cyclophosphamide (100-120 mg/kg) with (n = 89) or without fludarabine (75 mg/m²) (n = 32). TBI was delivered in 8 b.i.d. fractions of 1.65 Gy over 4 days via opposed lateral beams of 6, 18, or 25 MV prescribed to midplane at umbilicus, with the patient in a semi-recumbent position, and without lung shielding. Aluminum lung compensator was utilized if predicted mid-lung point dose was ≥3% higher than prescription dose (n = 28). Dose rate was specified at 9-20 cGy/min and depended on linear accelerator availability. Patients were stratified by receipt of high-dose-rate (HDR; > 15 cGy/min; 36%) or low-dose-rate (LDR; ≤15 cGy/min; 64%) delivery. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. The association between treatment factors and IPS was examined. <h3>Results</h3> Overall, IPS developed in 22 (18%) patients from day 6 to 83 (median 20) after HCT. On univariate analysis, factors associated with IPS included donor type (matched sibling 12%, sUCB 12%, dUCB 35%, <i>P</i> < 0.01), HDR TBI (35% vs 9% for LDR, <i>P</i> < 0.01), and lower beam energy (35% for 6 MV and 15% for 18/25 MV, <i>P</i> = 0.04). The finding of beam energy significance is likely the result of the 6 MV cohort having a greater dose rate (median 16 cGy/min) than the 18/25 MV cohort (11 cGy/min). On competing risk regression analysis, the pre-specified factors of dose rate, beam energy, lung compensator, age, HCT comorbidity index, and donor type were included in the model. All factors except age (hazard ratio [HR] 1.09, <i>P</i> = 0.20) and lung compensator (HR 1.8, <i>P</i> = 0.17) showed an independent statistically significant association with IPS. Kaplan-Meier estimated 1-year survival was 73% for the entire cohort. Time-dependent effect of IPS did not show an association with overall survival (HR 1.2, <i>P</i> = 0.76). <h3>Conclusion</h3> TBI dose rate is an important variable in the risk of pulmonary toxicity in children treated with allogeneic HCT. TBI dose rates ≤15 cGy/min reduced the risk of posttransplantation IPS and should be strongly considered as an easily implemented parameter in pre-transplantation TBI-based conditioning.

The impact of GVHD on outcomes after adult single cord blood transplantation in European and Japanese populations.

The impact of GVHD and graft-versus-leukemia effect in unrelated cord blood transplantation (UCBT) is controversial. In the Eurocord/ALWP EBMT and JSTCT/JDCHCT collaborative study, we evaluated the impact of GVHD on UCBT outcomes in Japanese and European registries. A total of 3,690 adult patients with acute leukemia who received their first single UCBT were included. A multivariate analysis of overall survival (OS) revealed a positive impact of grade II acute GVHD compared with grade 0-I GVHD, in the Japanese cohort (hazard ratio (HR), 0.81; P = 0.001), and an adverse impact in the European cohort (HR, 1.37; P = 0.007). A negative impact of grade III-IV acute GVHD on OS was observed regardless of registries. In the analysis of relapse, a positive impact of grade II acutes GVHD compared with grade 0-I GVHD was observed only in the Japanese cohort, regardless of disease risk. The positive impact of limited chronic GVHD on OS was observed only in the Japanese cohort. In conclusion, a positive impact of mild GVHD after a single UCBT was observed only in the Japanese cohort. This could explain the ethnic difference in UCBT outcomes and might contribute to the preference usage of UCBT in Japan.

Clinical, tomographic, and postmortem aspects of a rare congenital Dicephalus Monauchenos Iniodymus in a Nelore calf produced in vitro from Brazil - case report

ABSTRACT The aim of this work was to report the occurrence of dicephalus iniodymus monauchenos in a Nellore newborn. A three-days old calf, from in vitro production, with duplication of the head and a history of cesarean birth was attended. On physical examination, the dicephalus, iniodymus and monauchenos, which were almost the same size and shape, had four eyes and four ears. Computed tomography showed the presence of two skulls fused with a common occipital foramen, two nasopharynxes, oropharynxes with the presence of a cleft lip and a cleft palate in the right head, which continued in a single esophagus and a single trachea. At necropsy, the presence of duplication of the cerebrum and cerebellum was observed, with union of the parts in the region of the trapezoid body of the brainstem and continued as a single spinal cord. This study characterizes the clinical, tomographic, and necropsy findings of a dicephalus Nelore neonate.

Comparison of clinical outcomes between unrelated single umbilical cord blood and "ex-vivo" T-cell depleted haploidentical transplantation in children with hematological malignancies.

Over the last two decades, umbilical cord blood (UCB) and haploidentical transplantation (HaploHSCT) have emerged as alternative sources of hematopoietic stem cell for allogeneic transplantation. There are few retrospective studies and no prospective studies comparing both types of alternative transplantation in pediatric patients. We analyzed the data of 134 children with hematological malignancies who received a hematopoietic stem cell transplantation from a single umbilical cord blood (UCB) (n = 42) or an "ex-vivo" T-cell depleted transplant from a haploidentical-related donor (HaploHSCT) (n = 92) between 1996 and 2014. Hematological recovery was faster after HaploHSCT than the UCB transplant group (median times to neutrophil and platelet recovery: 13 vs. 16days, 10 vs. 57days, respectively) (P < 0.001). The HaploHSCT group had a significantly early immune reconstitution based on NK and CD8 + T cells compared with the UCB group. However, after thefirst year post-transplantation, HaploHSCT had a lower number of CD4 + T and B lymphocytes compared with the UCB transplant recipients. The cumulative incidence of TRM was 29±8% in the HaploHSCT group versus 40±5% in the UCB group. Relapse incidence was 21±7% in the HaploHSCT group and 19±8% in the UCB group. Probability of DFS was 58±8% in the HaploHSCT group versus 40±9% in the UCB group (P = 0.051). TCD haploidentical transplant is associated with advantages in terms of engraftment and early immune reconstitution kinetics. TCD haploidentical transplant was associated with lower incidence of infectious and non-infectious complications, especially in the early phases of the transplant compared with UCB transplant recipients. However, there are no advantages in transplant outcomes compared with UCB transplant.