Umbilical Cord Stem Cell Transplantation Research Articles

Effect of fetal distress on viability and yield of umbilical cord blood stem cells–a prospective comparative study

IntroductionDifferent factors affect the quality and viability of cord blood stem cells, and therefore the efficacy of umbilical cord stem cell transplantation. Fetal distress is one factor affecting the quantity of CD34+ cells in cord blood. This study was designed to compare the viability and yield of the umbilical cord blood stem cells of women who have undergone emergency lower segment caesarean section for fetal distress or for other causes. Materials and methodsThis cross-sectional analytical study was performed at a tertiary care hospital facility with a total sample size of 68: 34 participants had undergone emergency C-section for fetal distress, and 34 had undergone emergency C-section for other causes. Umbilical cord blood was collected ex-utero in a 350 mL bag with citrate-phosphate-dextrose solution with adenine. Three milliliter of blood were transferred to an ethylenediaminetetraacetic acid (EDTA) tube for cell counts and flow cytometry testing for CD34+. The chi-square test was used to compare the total mononuclear cell, CD34+, and viability between the groups. ResultsThe CD34+ count [mean 4.9 versus 1.1 (× 106 cells/unit)] and total nucleated cell count [mean 14.2 versus 7.5 (× 108/unit)] were significantly higher in cord blood units collected from women who delivered by C-section for fetal distress (p-value <0.05). However, the volume of umbilical cord stem cells and viability of stem cells did not vary significantly based on the presence or absence of fetal distress (p-value >0.05). ConclusionThe current study shows that umbilical cord blood collected during fetal distress has a significantly higher content of stem cells and total nucleated cells than the non-fetal distress group

Umbilical Cord Stem Cell Stem Cell Therapy For Rare Genetic Disease Prader-Willi Syndrome

This abstract summarises the studies on the use of umbilical cord stem cells to treat Prader-Willi syn- drome. Among the various stem cells found in the umbilical cord, hematopoietic and mesenchymal stem cells may create bioactive molecules that aid in tissue repair and regeneration, control immunological responses, and give birth to a variety of cell types. Because of this, they present a feasible option for treating the multidisciplinary character of PWS. Preclinical research on PWS animal models has shown promising outcomes, with umbilical cord stem cell transplantation improving metabolic disorders, hy- hypothalamic function, and general behavior. It has been investigated if immunological regulation, trophic support, and paracrine signaling are among the factors that promote stem cell therapeutic potential. Several clinical studies employing umbilical cord stem cells to treat PWS are now underway, and the findings should aid in assessing the advantages and disadvantages of using this approach on patients. The preliminary evidence is encouraging, since some trial participants improved in hyperphagia, mus- cular tone, and cognitive ability. Although the use of umbilical cord stem cells as a PWS treatment has shown some promise, further study is required to determine its long-term safety, optimal dose, and ongoing effectiveness. A variety of key elements, such as ethical issues, regulatory frameworks, and the availability of standardized stem cell products, will have a considerable impact on the future development of this treatment technique. SD is a disease known as a neurodevelopmental problem represented through problems with social communication, sensor sensitivity, and repetitive behaviors. Despite years of study, therapy options for autism spectrum disorder (ASD) remain relatively limited. As regenerative medicine has improved, stem cell treatment has been investigated as a novel therapeutic option for the underlying neurological disorders that underpin ASD. The development, possible methods, and potential uses of stem cell treatment for autistic children are discussed in this article.

Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.

A study to assess the knowledge and attitude regarding uses of umbilical cord blood storage among antenatal mothers in selected rural areas at Tumkur district with a view to develop an information booklet

A study to assess the knowledge and attitude regarding uses of umbilical cord blood storage among antenatal mothers in selected rural areas at Tumkur district with a view to develop an information booklet

High Dose Valaciclovir As CMV Prophylaxis in Allogeneic Hematopoietic Stem Cell Recipients at High Risk of CMV Reactivation

Background Cytomegalovirus (CMV) is a common, potentially devastating complication of allogeneic haematopoietic stem cell transplantation (alloHSCT). Universal antiviral prophylaxis strategies including letermovir are effective, but unsubsidised in Australia. Prophylactic ganciclovir or valganciclovir are challenging due to myelotoxicity. Valaciclovir demonstrates anti-CMV activity in high doses, but little current data explore prophylaxis in the alloHSCT setting, particularly in haploidentical transplantation. We aimed to evaluate the clinical efficacy and tolerability of high dose valaciclovir (high dose VALA) as CMV prophylaxis in high risk patients undergoing alloHSCT. Methods This study was completed at the Royal Melbourne Hospital, Melbourne Australia. We performed a retrospective analysis of alloHSCT recipients at high risk of CMV reactivation (defined as recipient and/or donor CMV seropositivity, and undergoing T-cell depletion, haploidentical or umbilical cord stem cell transplantation). Patients transplanted between July 2018 - June 2019, treated with high dose VALA (2g TDS) from day +7 to +100 and beyond were compared to a historical cohort (transplanted between July 2017 - June 2018) on standard dose valaciclovir (std dose VALA) (500mg BD until engraftment then 500mg daily). We compared the rates and time to reach a CMV threshold of 400 IU/ml, at which point pre-emptive CMV therapy was commenced. Tolerability was also evaluated. Results Patient demographics are described in Table 1. Of the standard dose VALA cohort, (median follow-up 259 days), 23/31 (74%) developed a viral load &amp;gt;400 IU/mL, requiring pre-emptive CMV therapy. None had CMV disease. Median time to viral load &amp;gt;400 IU/mL was 39 days (range 13 - 68). Of the high dose VALA cohort (median follow-up 209 days), 11/25 (44%) developed a viral load &amp;gt;400 IU/mL, requiring pre-emptive CMV therapy. Of these 11 cases, 7 patients had viral load &amp;gt;400 IU/mL while on high dose VALA prior to D+100, 3 patients had ceased high dose VALA prior to D+100 due to intolerance and in 1 patient this occurred post D+100 while on high dose VALA. One patient developed CMV (gut) disease following early cessation of high dose VALA, whilst on standard dose VALA. Median time to reactivation &amp;gt;400 IU/mL was 64 days (range 26-170). Time to reactivation &amp;gt;400 IU/ml was significantly different between the standard vs high dose VALA cohorts (mean ± SEM; 37.9 ± 2.7 vs 67.8 ± 11.3 days, **p=0.0015). Median duration of high dose VALA prophylaxis was 50 days (range 11-288). Seven (28%) patients continued high dose VALA to day +100 and beyond. Intolerance led to early cessation in 10 (40%) patients (acute kidney injury, n=6; cytopenia, n=3; both, n=1). Other patients ceased due to requirement for definitive CMV therapy (n=6) and unclear reasons (n=2). Conclusions In high risk alloHSCT recipients, high dose VALA is an effective CMV prophylactic strategy resulting in lower CMV reactivation rates, and delays CMV reactivation. This may reduce requirements for myelotoxic CMV treatment during the early post-engraftment period and need for inpatient admission. CMV infection following high dose VALA cessation remains a risk, particularly when dose reductions have occurred due to toxicity, and intolerance and ongoing monitoring is required. Treatment tolerability remains a limitation. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Valaciclovir, for CMV prophylaxis

Impact of maternal and neonatal factors on umbilical cord CD34+ cells.

The achievement of optimal number of CD34+ umbilical cord stem cells is essential for successful umbilical cord stem cell transplantation. So the aim of this study was to assess the potential effect of both maternal and neonatal factors on the umbilical cord blood CD34+ cell count. The study was done on umbilical cord blood samples obtained from 20 mothers during labor. Their ages ranged from 22 to 34 years and were subjected to history taking, physical examination of the baby and assessment of the CD34+ cells count in umbilical cord blood. Number of previous live births and weight of the baby had a significant effect on CD34+ cells count while the sex of the baby, delivery route, maternal age and gestation period had no significant effect on CD34+ cells count. Umbilical cord blood-derived CD34+ cell count is better with good weight and first babies and decreased with subsequent babies.

Liposomal Daunorubicin/Cytarabine As a Bridge to Donor Lymphocyte Infusion or Allogeneic Stem Cell Transplantation for High-Risk Acute Myelogenous Leukemia

Introduction: Liposomal daunorubicin/cytarabine (Vyxeos®) is a dual drug liposomal encapsulation of cytarabine and daunorubicin, delivering drugs at a fixed 5:1 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, liposomal cytarabine/daunorubicin (lipo-cytara/dauno) patients had improved survival and remission rates in a pivotal phase III study of elder adults with high-risk acute myelogenous leukemia (AML). Furthermore, more lipo-cytara/dauno patients went to allogeneic stem cell transplantation (HCT), with lower mortality and improved survival compared to those induced with 7+3. With its enhanced pharmacokinetics, lipo-cytara/dauno may provide a potent bridge to transplant. We report our experience using lipo-cytara/dauno as a bridge to same donor lymphocyte infusion (DLI) or different donor HCT in high-risk AML. Methods: We retrospectively reviewed all patients who received lipo-cytara/dauno at our institution since the FDA approval in August 2017. Of the 21 patients who have been treated, 9 received it as a bridge to cell therapy. All patients received the drug by usual means under the FDA label. Results: The median age of the 9 patients who received lipo-cytara/dauno as a bridge to cell therapy was 59 years. Seven were male, and two were female. Patients had had 1-4 prior lines of chemotherapy (median 2) with 7 of 9 patients having received prior standard 7+3 induction (cytarabine 100-200 mg/m2 x 7 days infusion and daunorubicin 60-90 mg/m2 x 3 days). Most had adverse cytogenetics, and all 9 patients received full lipo-cytara/dauno induction (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy [Table]. Of the 9 patients, 6 had AML with very early relapse after HCT, with median time to relapse of 4 months (range 3 to 7 months). All 6 successfully proceeded to their planned cell infusion: 5 received same donor DLI after melphalan at 140 mg/m2, and 1 underwent second HCT from a different donor with busulfan/fludarabine conditioning at Days 15-40 after lipo-cytara/dauno. Of the remaining 3, two had relapsed AML after an initial remission (one was in first complete remission (CR1) for 3 months after 7+3/midostaurin induction and the other was in CR1 for 7 months after 7+3 induction/high dose cytarabine consolidation) and one had primary refractory disease (PREF) after 7+3 and azacitidine/venetoclax induction regimens. All 3 successfully underwent first HCT at Days 15-100 days after lipo-cytara/dauno bridge. The PREF patient received fludarabine/cyclophosphamide/TBI conditioning followed by matched unrelated donor transplant. Of the 2 with relapsed AML after initial remission, one received busulfan/fludarabine/thiotepa conditioning followed by umbilical cord stem cell transplantation and the other patient received fludarabine/cyclophosphamide/TBI conditioning prior to matched related donor transplant. Six of 9 had Day 14 bone marrow biopsies after lipo-cytara/dauno: 2 were in CR, 2 had &gt;80% cytoreduction, and 2 had similar blast count. Three with persistent disease underwent reinduction with lipo-cytara/dauno (Days 1 and 3) and proceeded straight to cell therapy after. Median days to hospitalization after outpatient lipo-cytara/dauno was 6 days (range 3 to 14 days). Four out of 9 patients remain alive. Two were very early post HCT relapses (relapsed at 3 and 6 months post-HCT), both of which are remarkably in CR at 14 and 17 months after second cell therapy. Interestingly, both had CNS relapse, which were successfully treated, and both remain alive and in remission today. The other two had relapsed AML and PREF AML and underwent first HCT after lipo-cytara/dauno bridge. They remain alive and in remission at 1 and 8 months. Conclusion: In this retrospective study, outpatient lipo-cytara/dauno as a bridge to cell therapy is feasible and effective in very high-risk AML with no other viable options. While preliminary, survival appears favorable to that reported elsewhere at 14-23% at 1 year in this poor risk group, including those with adverse cytogenetic and/or very early post-HCT relapse. Prospective multi-center trials are planned to further evaluate lipo-cytara/dauno as a bridge to DLI/HCT in those with early relapse post-HCT and in those with refractory disease, with therapy to include CNS prophylaxis. Disclosures Stiff: Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Tsai:Jazz pharmaceuticals: Speakers Bureau; Jazz pharmaceuticals: Consultancy.

Myelin repair by transplantation of myelin-forming cells in globoid cell leukodystrophy.

Globoid cell leukodystrophy (GLD), or Krabbe disease, is a devastating demyelinating disease that affects both the central and peripheral nervous systems. It is caused by genetic deficiency in the activity of a lysosomal enzyme, galactocerebrosidase (GALC), which is necessary for the maintenance of myelin. Hematopoietic stem cell transplantation (HSCT) including umbilical cord stem cell transplantation is the only effective therapy available to date. HSCT significantly prolongs the life span of patients with GLD when performed before disease onset, although it is not curative. In HSCT, infiltrating donor-derived macrophages are thought to indirectly supply the enzyme (called "cross-correction") to the host's myelinating cells. Given the limitation in treating GLD, it is hypothesized that remyelinating demyelinated axons with GALC-competent myelinating cells by transplantation will result in more stable myelination than endogenous myelin repair supported by GALC cross-correction. Transplantation of myelin-forming cells in a variety of animal models of dysmyelinating and demyelinating disorders suggests that this approach is promising in restoring saltatory conduction and protecting neurons by providing new healthy myelin. However, GLD is one of the most challenging diseases in terms of the aggressiveness of the disease and widespread pathology. Experimental transplantation of myelin-forming cells in the brain of a mouse model of GLD has been only modestly effective to date. Thus, a practical strategy for myelin repair in GLD would be to combine the rapid and widespread cross-correction of GALC by HSCT with the robust, stable myelination provided by transplanted GALC-producing myelin-forming cells. This short review will discuss such possibilities. © 2016 Wiley Periodicals, Inc.

Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin.

Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone.

Serum-Negative, Site Specific HHV-6 Infection Causes Nausea and Vomiting Following Double Umbilical Cord Stem Cell Transplantation

Purpose: Current literature describes similar clinical manifestations between human herpes virus 6 (HHV-6) infection and graft versus host disease (GvHD) in post-hematopoietic stem cell transplant (HSCT) recipients. Therefore, it is essential to consider HHV-6 infection in patients with gastrointestinal (GI) symptoms suggestive of GvHD. We present a case that highlights the importance of testing gastroduodenal tissue as an adjunct to serological testing of HHV-6 in this patient population. A 30-year old woman (HHV-6 IgG +) with acute lymphocytic leukemia (ALL) presented for a double umbilical cord stem cell transplant with myeloablative conditioning. Her post-transplant course was complicated by late engraftment, Klebsiella pneumoniae sepsis, BK cystitis, HHV-6 viremia and biopsy-proven stage 4 GvHD of the upper and lower GI tract associated with fever, abdominal pain, diarrhea and vomiting. She was treated with 3 months of high dose steroids for GvHD and one month of a combination of IV foscarnet and oral valganciclovir for HHV-6 reactivation (viral load 66,292 cpy/ml). Her symptoms improved (viral load undectable), but she then returned to the hospital day + 150 post transplant for dehydration secondary to persistent nausea and vomiting. Serum PCR testing for HHV-6 and gastroduodenal biopsies for GvHD were negative. However, PCR of gastroduodenal tissue biopsies for HHV-6 was positive (viral load 5,912 viral copies/1,000 cell equivalent). She was restarted on valgancyclovir for 4 weeks and had total resolution of her symptoms at the end of this time. HHV-6 is a lymphotrophic virus which belongs to the β-herpesviridae family. It typically remains latent in certain host cells but can reactivate in immunocompromised patients. In HSCT recipients, gastrointestinal complications of HHV-6 may include abdominal pain, nausea, vomiting, diarrhea, cholestasis and hepatitis which mimics and can worsen the grade of GvHD. Cord blood transplant recipients and previous episodes of GvHD are found to be predictors of HHV-6 reactivation, as was seen in our patient. This case highlights that HHV-6 viremia need not be synchronous with a site-specific infection in HSCT patients with upper GI symptoms. Given the prevalence and correlation between GI manifestations of HHV-6 and GvHD, isolated local infection should be considered in the differential diagnosis of persistent GI symptoms despite serumnegative HHV-6 testing. The clinical benefit of treating biopsy-proven HHV-6 of the GI tract should be further studied in patients with and without GvHD post-HSCT.

Umbilical cord stem cell transplantation – two decades of clinical experience

Umbilical cord blood (UCB) is an abundant source of haematopoietic stem cells (HSC) for allogeneic HSC transplant. Since the first UCB transplant in 1988, many scientific data have been collected. Many umbilical cord blood banks have been established worldwide for the collection and cryopreservation as well as for the international exchange with more than 400,000 UC units available. There is probably a twofold figure of UCB units collected for the private UCB banks. More than 20,000 UCB units have been used for treating malignant and non-malignant diseases both in adults and children. Unrelated UCB HSCs became an alternative to bone-marrow derived HSCs based on their advantages, including a prompt availability, decrease of graftversus- host disease (GVHD) and better longterm immune recovery, resulting in a similar long-term survival. UCB stem cells can be transplanted to an allogeneic patient in spite of the high degree of HLA mismatches, which is highly important for the patients who cannot find a HLA-identical allogeneic donor. Since the low number of cells in the UCB units still represents the main cause of failure of engraftment, new strategies, such as double-unit UCB transplantation, intra-bone injection of UCB cells, simultaneous transplantation of accessory cells and the reduced intensity conditioning regimen, were developed to increase the success of UCB transplantation. Several clinical studies using UCB stem cells that have been previously expanded in vitro are underway. These procedures and the future development of regenerative medicine will further broaden possible indications for the use of UCB derived stem cells in adults.

Stem Cell Course in the Middle East: Science Diplomacy and International Collaborations During the Arab Spring

In April 2011, an international advanced course and workshop entitled “Frontiers in Human Pluripotent Stem Cells” and an International Congress on Fertility and Genetics (http://www.fertigen.com.jo/ConferenceDetails.aspx) was held in Amman Jordan hosted by the Jordanian Society of Fertility and Genetics under the auspices of the International Cell Research Organization (ICRO), a UNESCO associated NGO. The Congress President Dr. Zaid Kilani, with Dr. Abdel Latif Abu Khadra, President of the Jordanian society for Fertility and Genetics, Dr. Rana Dajani of the Hashemite University of Jordan, and their Organizing Committee proved to be an excellent organizers and dedicated physician-scientists and, focusing on fertility, genetics and stem cells in a wide range of advanced therapeutic applications. Brilliant course participants included trainees, scientists and clinicians from the Greater Middle East. The lectures and practical sessions, presented by internationally acknowledged scientists, included overviews of recent achievements in pluripotent stem cell research, emphasizing the role of both the embryonic (ES) and induced pluripotent stem (iPS) cells. A major emphasis was placed on the clinical achievements in germ cell and umbilical cord stem cell transplantation issues, and on the potential of fast and successful prenatal and pre-implantation molecular genetics diagnostics. The organization of the stem cell course in the Holy Land especially emphasized that issues of “eternal life” and “rejuvenation” are already at hand—at least in the pluripotent stem cell research field. In the lively atmosphere of the course about 60 participants had heated discussions on the possibility and ethics of advanced prenatal diagnostics, and on regulatory issues reflecting the need of separation of clinically effective versus unapproved, unwarranted stem cell treatments. An open discussion of many ethical issues, reflecting profound differences in religion and medical tradition in the different countries, made this course exceptionally interesting for both teachers and trainees.

Delayed Platelet Recovery After Allogeneic Peripheral Blood, Marrow and Umbilical Cord Stem Cell Transplantation: Risk Factors and Clinical Outcomes.

Abstract 867 Introduction:Several reports have shown that despite prompt neutrophil engraftment after allogeneic stem cell transplantation, there can be delayed platelet recovery, especially in umbilical cord blood (UCB) stem cell transplant recipients. This dichotomy in platelets and neutrophils engraftment is poorly explained. In addition, the risk factors and complications associated with delayed platelet recovery are not clearly identified. Methods:We conducted a retrospective analysis to characterize the frequency of delayed platelet recovery and its associated risk factors and related complications. All allografts at the University of Minnesota between 2000 and 2005 were included. Results:875 patients with hematologic malignancies or benign disorders were included. Myeloablative conditioning was used in 576 (66%) patients and non-myeloablative conditioning in 299 (34%) patients. 343 (39%) patients received related donor and 532 (61%) unrelated grafts. The source of the graft was bone marrow in 226 (26%) patients, peripheral blood in 255 (29%) patients and UCB in 394 (45%) patients. 150 (17%) patients were excluded due to early death (n=87, 10%), graft failure (n=62, 7%) and second transplant without engraftment (n=1). The 60 day cumulative incidence of platelet recovery by donor type was UCB single cord 39% (n=180, CI 31-47%), UCB double cord 40% (n=206, CI 32-48%), URD mismatched 57% (n=28, CI 39-75%), URD matched 56% (n=117, 48-64%) and sibling 74% (n=319, 65-85%). Overall, 232 (32%) had delayed platelet recovery (platelets<50K by day 60) and 475 (67%) had successful recovery (platelets>50K by day 60). Cox regression analysis showed that variables significantly associated with delayed platelet recovery were donor type (UCB RR 0.3 [CI 0.2-0.35], p<0.01 vs sibling RR 1.0), ABO match (major mismatch RR 0.8 [CI 0.6-1.0], p<0.01 vs matched RR 1.0), CMV status (positive RR 0.8 [CI 0.6-1.0], p=0.04 vs negative RR 1.0) and the vs negative RR 1.0). Transplant related mortality (TRM) at 12 months was also higher in patients with delayed platelet recovery compared to patients with successful platelet recovery (30% vs 11%) (p<0.01). Risk factors for TRM by proportional hazard regression were delayed platelet engraftment (RR 3.9 [2.6-6.0], p=<0.01 vs early RR 1.0), HLA mismatched unrelated donor (RR 3.7 [CI 2.5-7.1], p=0.01 vs sibling RR 1.0), severe aGVHD (RR 1.8 [CI 1.2-2.8], p=0.02 vs no severe RR 1.0) and age > 35 (RR 1.6 [CI 1.0-2.5], p=0.03 vs age < 35 RR 1.0). Successful platelet recovery was associated with a 77% 1 year survival versus only 59% in patients with delayed platelet recovery (p<0.01). Conclusions:These results suggest that delayed platelet recovery and poor graft function are common complications of allogeneic stem cell transplantation, especially after UCB grafts. Further study is needed to determine if modification of these associated risk factors will reduce the risks of severe complications and improve survival. Disclosures:No relevant conflicts of interest to declare.

Cardiac potential of stem cells from whole human umbilical cord tissue

We investigated the role of stem cells from human umbilical cord tissue in cardiomyocyte regeneration. The umbilical cord stem cells were initially characterized and differentiated in a myocardial differentiation medium containing 5-azacytidine for 24 h. Differentiation into cardiomyocytes was determined by expression of cardiac specific markers, like cardiac alpha-actin, connexin43, myosin, Troponin T, and ultrastructural analysis. In vivo, the transplanted umbilical cord stem cells were sprouting from local injection and differentiated into cardiomyocyte-like cells in a rat myocardial infarction model. Echocardiography revealed increasing left ventricular function after umbilical cord stem cell transplantation. These results demonstrate that umbilical cord stem cells can differentiate into cardiomyocyte-like cells both in vitro and in vivo. Therefore, human umbilical cord might represent a source of stem cells useful for cellular therapy and myocardial tissue engineering. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

Umbilical Cord Stem Cell Transplantation

To discuss the history, current state, and future directions of umbilical cord blood (UCB) transplantation as it relates to the emerging field of cellular therapies. Research studies, articles, and personal experiences. Transplantation using hematopoietic stem cells from UCB is a life-saving option for patients with select oncologic and immunologic diseases, bone marrow failure, hemoglobinopathies, and inborn errors of metabolism.

Invasive Pulmonary Aspergillosis with Hematological Malignancy Caused by Aspergillus terreus and in vitro Susceptibility of A. terreus Isolate to Micafungin

A 35-year-old man developed invasive pulmonary aspergillosis (IPA) with severe neutropenia after umbilical cord stem cell transplantation for chronic myelogenous leukemia. Filamentous fungus isolated from his sputum was identified as Aspergillus terreus. Despite systemic amphotericin B (AMPH) administration, IPA progressed. However, intravenous administration of micafungin (MCFG) and oral itraconazole improved clinical data and symptoms, although he later died of massive hemoptysis. Examination of the in vitro susceptibility of this A. terreus isolate to MCFG revealed a good minimum inhibitory concentration and good time-kill assay results compared to AMPH. Thus, MCFG might be useful for IPA caused by A. terreus.

Correction of Immunodeficiency Associated with NEMO Mutation by Umbilical Cord Stem Cell Transplantation Using a Reduced-Intensity Conditioning Regimen.

X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is a developmental and immunologic disorder caused by hypomorphic mutations in the nuclear factor-κB essential modulator (NEMO) gene. NEMO is the regulatory subunit of the IκB kinase (IKK) complex, which phosphorylates and degrades NF-κB inhibitor α (IκBα), causing NF-κB activation. Following the identification of amorphic NEMO mutations causing familial incontinentia pigmenti (IP), hypomorphic mutations in NEMO have been identified in XL-EDA-ID patients. Affected boys are susceptible to infections with various microorganisms, mostly pyogenic bacteria and mycobacteria. Stem cell transplantation (SCT) is thought to be the only curative treatment, but successful SCT has not yet been reported. We here report the first successful treatment of the disorder by SCT. The patient was a 3-year-old boy. His mother and maternal grandmother had been diagnosed with IP. He had frequent episodes of enterocolitis, and Enterobacter aerogenes sepsis. Mutation analysis revealed NEMO mutation (1167 insC) in both the patient and his mother. Flow cytometry analysis showed lower NEMO expression in each PBMC lineage, and CD40L induced less up-regulation of CD23, CD54, CD86, and CD95 in the patient's cells. The patient did not have an HLA-matched related or unrelated bone marrow donor. At 3 years of age, an unrelated UCSCT was performed after written consent was obtained from his parents. Pretransplant conditioning consisted of fludarabin (30 mg/m2/d) from day -7 to day -3, melpharan (70 mg/m2/d) from day -6 to day -5, and rabbit anti-T-lymphocyte globulin (ATG) (2.5 mg/kg/d) from day -5 to day -1. The patient received 4.6 × 107 total nucleated cells/kg from a male donor. The recipient and donor were one antigen mismatched by serology and four loci mismatched by DNA typing. Following uneventful engraftment, NEMO protein expression was normalized and cytokine response was significantly improved. Lineage-specific genetic analysis confirmed full donor chimerism. Six months after UCSCT, the patient is in perfect performance status. This outcome shows that correction of immunodeficiency associated with NEMO mutation is possible by SCT, and UCSCT with a reduced-intensity regimen can be a suitable therapy for affected patients.

Umbilical cord stem cell transplantation for primary immunodeficiencies

Primary immunodeficiencies (PIDs) are a rare but important cause of mortality and morbidity in childhood: the most severe – known as severe combined immunodeficiency (SCID) – are fatal within the first year of life; other PIDs are less immediately life-threatening, but have a poor long-term outlook. Haematopoietic stem cell transplantation (HSCT) is the best treatment for SCID and is increasingly offered for other PIDs. The best results are achieved with an HLA-matched family donor. Umbilical cord stem cells (UCSCs) are an alternative stem cell source. Results using UCSCs in the treatment of haematological disorders and malignancy are as good as those for which marrow is the stem cell source. Although PIDs make up a small proportion of disorders amenable to treatment by HSCT, UCSCs are an ideal source of haematopoietic stem cells for many of these patients. Of the 52 patients with SCID or other PIDs for whom detailed information on outcome is available, results of engraftment, immune reconstitution, incidence of graft-versus-host disease and survival are comparable with other stem cell sources. Small stem cell dose and prolonged time to viral immunity limit the patients for whom UCSCs can be used. Newer methods of achieving better engraftment, ex vivo expansion of stem cells and generation of antigen-specific cytotoxic T cells are being developed at present, and will widen the application of UCSCs as a viable source for more patients.

Single centre experience of umbilical cord stem cell transplantation for primary immunodeficiency

Primary immunodeficiencies (PID) are an important cause of childhood mortality. Haematopoietic stem cell transplantation (HSCT) is the best treatment for many PID. Umbilical cord stem cells are an alternative source of HSC. There is little data regarding outcome of umbilical cord stem cell transplantation (UCSCT) for PID. Our single centre experience is reported. A retrospective study of 14 of 148 patients transplanted for PID, who have received 15 UCSCT was performed, with specific regard to graft-versus-host disease (GvHD) and immune reconstitution. Eight patients with severe combined immunodeficiency (SCID), and six with other combined immunodeficiencies were treated. Of the patients, 12 received unrelated cords, and two had sibling transplants. Median age at transplant was 3.5 months, median nucleated cell dose was 0.8 x 10(8)/kg. All engrafted. Median time to neutrophil engraftment was 22 days, median time to platelet engraftment was 51 days. One developed significant grade III GvHD post transplantation. In total, 11 patients had full donor T and six full donor B-cell chimerism, six of nine patients >1 year post-BMT had normal IgG levels and specific antibody responses to tetanus and Hib vaccines; two are being assessed. Two patients died of multi-organ failure related to pre-existing infection and inflammatory complications respectively. UCSCT should be considered for patients requiring stem cell therapy for PID.

Extremely low frequency magnetic fields originating from equipment used for assisted reproduction, umbilical cord and peripheral blood stem cell transplantation, transfusion, and hemodialysis

The extremely low-frequency (ELF) magnetic fields (MFs) originating from equipment used for assisted reproduction, umbilical cord-blood and peripheral-blood stem cell transplantation, transfusion, and hemodialysis were measured. The ELF-MF values were 0.1-1.2 microT on clean benches, <0.1-8.0 microT on inverted microscopes, <0.1-13.6 mmicroT in CO2 incubators, 4.3-11.5 microT in centrifuges, 0.4-18.8 microT in programmed freezers, <0.1-0.3 microT in deep freezers, 0.3-3.1 microT on cell separators, and 0.2-0.9 microT in hemodialysers. Frequencies of MFs were nominally 60 Hz, but some devices showed non-sinusoidal 120 Hz. Such MFs can be reduced by shielding the sources or altering the protocols employed.