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Abstract Background Catheter-related bloodstream infection (CRBSI), caused by rapidly growing mycobacteria (RGM), is a rare infectious complication in hematopoietic stem cell transplant (HSCT) recipients and can often be misdiagnosed as Gram-positive rod (GPR) bacteremia. Case presentation We present a case of CRBSI caused by Mycobacterium wolinskyi, a rare RGM, in a 44-year-old female patient who received an umbilical cord blood transplant. Conclusions Rapidly growing mycobacteria can stain as GPRs and may grow in routine blood culture media after 3–4 days of incubation. These features are not widely known to clinicians, and acid-fast staining is therefore recommended when unidentifiable GPRs are detected in blood cultures, especially in immunocompromised patients, such as those with hematologic malignancies or intravascular devices.

Background: Catheter-related bloodstream infection (CRBSI), caused by rapidly growing mycobacteria (RGM), is a rare infectious complication in hematopoietic stem cell transplant (HSCT) recipients and can often be misdiagnosed as Gram-positive rod (GPR) bacteremia.Case Presentation: We present a case of CRBSI caused by Mycobacterium wolinskyi, a rare RGM, in a 44-year-old female patient who received an umbilical cord blood transplant.Conclusions: Rapidly growing mycobacteria can stain as GPRs and may grow in routine blood culture media after 3-4 days of incubation. These features are not widely known to clinicians, and acid-fast staining is therefore recommended when unidentifiable GPRs are detected in blood cultures, especially in immunocompromised patients, such as those with hematologic malignancies or intravascular devices. [ABSTRACT FROM AUTHOR]

Background: Juvenile myelomonocytic leukemia (JMML) is a rare hematological malignancy in young children and can only be cured through the allogeneic stem cell transplantation. Procedure: We have retrospectively analyzed the outcomes of nine children with JMML after unrelated cord blood transplantation (UCBT). Results: Eight patients who have received a myeloablative conditioning regimen of fludarabine (FLU), busulfan (BU), and cyclophosphamide (CY) have gotten engraftment. None of the nine patients has relapsed following initial UCBT. Six patients are still alive and in complete remission after UCBT with a median observation time of 43 months (range: 10–80 months). Conclusions: This study shows that UCBT with FLU‐BU‐CY conditioning regimen can represent a suitable option for children with JMML. [ABSTRACT FROM AUTHOR]

Abstract Background Deficiency in the enzyme β‐mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood‐onset β‐mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available. Methods We report 2‐year outcomes following the first umbilical cord blood transplant in a 4‐year‐old boy with early childhood‐onset disease. Results We show restoration of leukocyte β‐mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β‐mannosidase activity and dramatic decrease in urine‐free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers. Conclusion Our findings suggest that hematopoietic cell transplant can correct the biochemical defect in β‐mannosidosis, although preservation of the neurocognitive trajectory may be a challenge.

• HSCT is currently the preferred treatment for patients with certain early leukodystrophies. • Indications, donor selection, conditioning, and the unique supportive care needs are reviewed. • This report highlights the importance of multidisciplinary care for these patients. The leukodystrophies are a heterogeneous group of inherited diseases characterized by progressive demyelination of the central nervous system leading to devastating neurologic symptoms and premature death. Hematopoietic stem cell transplantation (HSCT) has been successfully used to treat certain leukodystrophies, including adrenoleukodystrophy, globoid leukodystrophy (Krabbe disease), and metachromatic leukodystrophy, over the past 30 years. To date, these complex patients have primarily been transplanted at a limited number of pediatric centers. As the number of cases identified through pregnancy and newborn screening is increasing, additional centers will be required to treat these children. Hunter's Hope created the Leukodystrophy Care Network in part to create and standardize high-quality clinical practice guidelines to guide the care of affected patients. In this report the clinical guidelines for the care of pediatric patients with leukodystrophies undergoing treatment with HSCT are presented. The initial transplant evaluation, determination of patient eligibility, donor selection, conditioning, supportive care, and post-transplant follow-up are discussed. Throughout these guidelines the need for early detection and treatment and the role of the partnership between families and multidisciplinary providers are emphasized. [ABSTRACT FROM AUTHOR]

Patients treated with allogeneic hematopoietic stem cell transplantation (SCT) have high rates of readmission, but the incidence after umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence and risk factors for readmission after UCBT and the impact of readmission on overall survival (OS). A retrospective review of patients receiving a UCBT at Dana-Farber/Brigham and Women's Hospital between January 1, 2004 and December 31, 2013 was performed. The readmission rates 30 days after discharge from the UCBT admission and at day +100 after the UCBT were examined. Reasons for readmission, as well as sociodemographic, disease-, and SCT-related variables were evaluated. Predictors of readmission and the impact of readmission on OS were identified using multivariate regression analysis. Of patients who received a UCBT, 42 of 126 patients (33.3%) were readmitted within 30 days of discharge and 57 of 123 patients (46.3%) were readmitted by day +100 after transplantation. The most common causes for readmission were infection (38.3%), fever without a source (14.8%), and graft-versus-host disease (8.6%). Infection during the index admission was the only significant risk factor for readmission at both time points in a univariate and multivariate regression analysis (OR, 11.66; 95% CI, 2.77 to 49.13; P  < .01 and OR, 5.4; 96% CI, 1.87 to 15.58; P  < .01). Prior radiation therapy was also associated with an increased risk of readmission at both time points in the multivariate regression model (OR, 20.6; 95% CI, 3.53 to 120.04; P  ≤ .01 and OR, 5; 95% CI, 1.21 to 20.71; P  = .03). The multivariate regression model also showed that black race and a median income of <60,000 in the patient's home zip code increased the risk of readmission by day +100 (OR, 30.17; 95% CI, 1.33 to 684.48; P  = .03 and OR, 2.88; 95% CI, 1.04 to 7.8; P  = .04, respectively). After adjusting for age, disease type, and the disease status at transplant, OS was reduced for the patients who were readmitted by day +100 (HR, 2.44; 95% CI, 1.46 to 4.06; P  < .01). There was also a trend toward decreased survival in patients readmitted 30 days after discharge (HR, 1.58; 95% CI, .96 to 2.6; P  = .07). Readmissions are common after UCBT. Infections and fever without a source are the most common causes of readmission. Being readmitted by day +100 resulted in a lower 5-year OS rate as compared with patients who were not readmitted. Prior radiation and infection during the transplant admission resulted in increased risk of readmission by 30 days and day +100. Similarly, race and socioeconomic status predicted readmission by day +100. Further understanding of the mechanisms leading to readmissions in these groups may allow for identification of interventions that could reduce readmissions and thus improve mortality. [ABSTRACT FROM AUTHOR]

Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4;p = 0.004). [ABSTRACT FROM PUBLISHER]

Existing literature shows mixed conclusions regarding the impact of ABO incompatibility on outcomes after hematopoietic stem cell transplantation. Because the future for umbilical cord blood (UCB) expansion technologies is bright, we assessed whether this typically overlooked graft characteristic impacted various outcomes after UCB transplantation (UCBT) for nonmalignant disorders (NMDs). A prospectively maintained institutional blood and marrow transplant program database was queried for all patients undergoing first UCBT for NMDs. UCB and recipient ABO compatibility was considered as matched, major mismatched, minor mismatched, or bidirectional mismatched. The impact of ABO incompatibility was assessed on overall survival, graft failure, acute and chronic graft-versus-host disease (GVHD), time to neutrophil and platelet recovery, day 0 to day 100 RBC transfusion burden, and donor hematopoietic chimerism. Through December 2014, 270 patients have undergone first UCBT for various NMDs. In both univariable and multivariable analyses, ABO compatibility status did not appear to impact any outcomes assessed, although a trend toward increased grades III to IV acute GVHD was seen in recipients of major mismatched units. When considering UCBT for treatment of NMDs, ABO compatibility between the donor unit and intended recipient does not appear to be an important consideration in the UCB unit choice. [ABSTRACT FROM AUTHOR]

Long-term neurocognitive deficits after human herpesvirus-6 (HHV-6) infection are common in stem-cell transplant recipients, but SIADH (Syndrome of inappropriate antidiuretic hormone secretion) with persistent hyponatremia is rare. A 51-year-old woman presented with somnolence, hyponatremia (121 mmol/L) and HHV-6 viremia (80,330 copies/ml) on day +22 post umbilical cord blood transplant (UCBT). With waterrestriction, tolvaptan and combination of foscarnet and ganciclovir, patient's hyponatremia and HHV-6 viremia improved. On day +94 UCBT, hyponatremia and HHV-6 viremia recurred. Foscarnet was restarted and continued until day +269 UCBT due to multiple HHV-6 recurrences with persistent hyponatremia. At day +712, patient remains on water-restriction, tolvaptan for continuous hyponatremia from SIADH., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the past decade, haplo-cord stem cell transplantation (SCT) using myeloablative or reduced intensive conditioning regimens has been shown to result in reliable and fast engraftment of neutrophils and platelets comparable to HLA-matched donors and much faster than after cord stem cell transplant. Haplo-cord SCT also has a low incidence of early non-relapse mortality, low incidences of acute and chronic graft-vs-host disease (GVHD), and excellent graft-vs-leukemia (GVL) effects. Favorable long-term outcomes for high-risk patients with hematologic malignancies have been reported, including older patients. Haplo-cord SCT will likely overcome the limitations of cell dose during cord stem cell selection and might significantly expand the use of cord stem cell transplant in the adult population. The comparable survival outcomes of matched related donor (MRD), matched unrelated donor (MUD), and haplo-cord stem cell transplant strongly argue that haplo-cord SCT should be considered as effective alternative stem cell transplant for high-risk patients lacking standard donors. Further improvement in supportive care and incorporation of a better understanding of the human fetal immune development into the haplo-cord SCT are required to further improve this strategy. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplant (HSCT) is the only established cure for sickle cell disease (SCD), a hemolytic disorder that arises due to a point mutation in the hemoglobin A gene. The result is an abnormal sickle hemoglobin (HbS) replacing hemoglobin A. Of the spectrum of sickle hemoglobinoapthies, homozygous (HbSS) and HbSβ0 thalassemia manifest severe forms of disease characterized by chronic endothelial injury/vasculopathy, ischemic pain, and vital organ damage that commence in childhood and escalate with age resulting in impaired quality of life, increased healthcare burden, and early mortality. HSCT has demonstrated durable disease control and regression of symptoms. Human leukocyte antigen (HLA) matched sibling donor (MSD) transplantation can achieve disease-free survival of > 90%. However, < 18% of SCD patients in the United States have a MSD. Familial mismatched and unrelated donors from registries provide alternate stem cell sources. Umbilical cord blood (UCB) from family or cord blood banks expand donor sources and are attractive due to donor-independent ease of use and availability. These naïve cells tolerate greater degrees of HLA-mismatch. The primary challenge with UCB is optimizing cell dose toward successful engraftment and timely immune reconstitution while minimizing graft-versus-host disease (GVHD). This review summarizes evidence that UCB remains a promising stem cell source where modern methods of graft expansion, conditioning, GVHD prophylaxis, and infection control can overcome these challenges and retain the value of this intervention. • Stem cell transplantation can eradicate disease symptoms in sickle cell disease. • Cord blood can be mismatched and hence expands donor availability for transplant. • Advantages include availability for ethnic minorities and low risk of chronic GVHD. • Advances targeting engraftment/infection challenges continue to improve outcomes. [ABSTRACT FROM AUTHOR]

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal condition that can be primary or secondary. Secondary HLH due to Mycobacterium tuberculosis (TB) is uncommon. We report a case of tuberculosis-associated HLH in an umbilical cord blood transplant (UCBT) recipient and discuss its clinical characteristics and challenges. Methods Hematologic investigations, bone marrow aspirates, Xpert MTB/RIF test of TB with peripheral blood were performed. Immune modulation with anti-TB therapy was initiated. Results Subsequent treatment with anti-TB treatment resulted rapid clinical response and disease remission. Conclusion It is important to consider TB as one of the underlying cause of HLH in high-risk patients, particularly those in immunodeficient states. Early diagnosis and treatment can improve the survival rates of patients with tuberculosis-associated HLH. [ABSTRACT FROM AUTHOR]

Abstract: Low incidence of graft-versus-host disease provides the major rational for pursuing umbilical cord blood (UCB) stem cell transplantation (SCT). Considerable evidence also suggests a lower rate of recurrence after UCB SCT than after transplantation from adult donors. Recent advances in understanding of the human fetal immune development provide a rational underpinning for these clinical outcomes. The fetal immune system is geared toward maintaining tolerance to foreign antigens, particularly to the maternal antigens to which it is exposed throughout gestation. To this purpose it is dominated by a unique population of peripheral T regulatory cells that actively maintain tolerance. This and other features of the UCB lymphoid system explains the low incidence of graft-versus-host disease and superior outcomes of UCB SCT with noninherited maternal antigen–matched grafts. At the same time, highly sensitized maternal microchimeric cells are frequently detected in UCB and likely contribute to superior graft-versus-leukemia effects and low rates of disease recurrence in inherited paternal antigen–matched UCB recipients. However, historically erratic and slow hematopoietic recovery after UCB SCT leads to increased early morbidity and mortality, excessive hospitalization, and increased costs. This has held up the widespread utilization of UCB SCT in adults. Here we summarize recent data on UCB SCT with an emphasis on studies of co-infusion of adult CD34 selected hematopoietic stem cells with UCB SCT. This procedure, through transient engraftment of adult hematopoietic stem cells, largely overcomes the problem of delayed engraftment. It also results in predictable engraftment of a UCB with the desired characteristics. We also briefly discuss unresolved issues and possible future applications of this technology. [Copyright &y& Elsevier]

Shibata M, Kato T, Awaya T, Adachi S, Heike T. Chronic immune-mediated axonal polyneuropathy following umbilical cord blood transplant for childhood-onset cerebral adrenoleukodystrophy. Abstract: Peripheral polyneuropathy is an unusual complication after organ transplantation and HSCT. The present study describes the case of an eight-yr-old boy diagnosed with ALD who underwent HLA-matched UCBT under a reduced-intensity conditioning regimen and developed progressive walking difficulty and hand clumsiness 11 months after transplantation. These symptoms were associated with cGVHD, identified as immune-mediated axonopathy by electrophysiological examination and sural nerve biopsy. Peripheral polyneuropathy should be kept in mind as a complication of GVHD. [ABSTRACT FROM AUTHOR]

Data on pretransplantation minimal residual disease (MRD) and outcomes of umbilical cord blood transplantation (UCBT) are limited. Out of the 143 patients with acute lymphoblastic leukemia (ALL) who underwent UCBT at the University of Minnesota between 2004 and 2010, we evaluated 86 patients with available MRD assessment data by 4- and 8-color flow cytometry analysis immediately before transplantation. Ten patients (11.6%) were MRD-positive, and 76 were MRD-negative (88.4%). Most of the patients (82%) received myeloablative conditioning. GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. In multivariate analysis, age, disease status (complete remission [CR] 1 versus CR2/CR3), disease group (precursor B cell ALL versus Philadelphia chromosome–positive ALL versus T cell ALL), and time to transplantation had no impact on relapse. Patients with MRD before UCBT had a greater incidence of relapse at 2 years (relapse rate, 30%; 95% confidence interval [CI], 4%-56%) and lower 3-year disease-free survival (30%; 95% CI, 7%-58%) compared with those without MRD (relapse rate, 16%; 95% CI, 8%-25%; P = .05; disease-free survival, 55%; 95% CI, 43%-66%; P = .02). Our data suggest that in patients with ALL, achieving an MRD-negative state before UCBT improves outcomes. [Copyright &y& Elsevier]

Umbilical cord blood (UCB) is used increasingly as a source of hematopoietic cells because of a lower risk of graft-versus-host disease (GVHD). Myeloablative conditioning before allogeneic umbilical cord blood transplant (allo-UCBT) results in thymic epithelial cell injury and T-cell immune deficiency. Full-term fetal blood cells were used as hematopoietic cells in a previous murine allo-UCBT model with a limited number of mice surviving the myeloablative conditioning. We designed a viable murine allo-UCBT protocol with platelet concentrate support. Keratinocyte growth factor (KGF) is a mitogen of thymic epithelial cells that promotes recovery of thymic epithelium when given before total body irradiation (TBI)-containing conditioning in experimental murine models. We hypothesized that KGF pre-administration would improve post-allo-UCBT thymopoiesis. To test this hypothesis, allo-UCBT recipient mice were given KGF or control saline prior to UCBT. Platelet concentrate support significantly improved the survival rate of murine allo-UCBT recipients. KGF administration significantly increased donor-derived T and natural killer T (NKT) cells at day  ++35 in spleens of allo-UCBT recipients. KGF administration also improved thymic function after allo-UCBT, resulting in higher copies of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in splenocytes. Finally, we found that KGF pre-administration could enhance the graft-versus-leukemia effect. In conclusion, KGF can be administered safely to recipients of allo-UCBT to enhance T-cell immune reconstitution. [ABSTRACT FROM AUTHOR]

Umbilical cord blood (UCB) has become an important source of hematopoietic stem cell transplant (HSCT) for hematologic malignancies in adults. Its ready availability, allowance of higher HLA disparity and lower incidence of graft-versus-host disease (GVHD) makes it a very attractive source especially for minority populations. The major limitation to a wider use of this source of HSCT is the relative low number of progenitor cells in the graft. For this reason, adult UCB transplants are usually associated with delayed engraftment and increased rates of infectious complications. CB ex vivo expansion holds the promise of delivering higher cell doses and improved outcomes. Here we discuss different methods of expansion, their shortcomings and future directions. [Copyright &y& Elsevier]

Umbilical cord blood transplant is an important alternative stem cell source for both children and adults with haematologic malignancies. Umbilical cord blood units are rapidly available and have less stringent human leucocyte antigen (HLA) matching requirements. Mismatch at two antigens actually improves the risk of relapse for umbilical cord blood transplant recipients with relatively low risk of severe acute or chronic graft-versus-host disease. However, umbilical cord blood transplant is associated with an inferior neutrophil recovery rate when compared with other stem cell sources. Therefore, we have explored double-unit umbilical cord blood transplants, not only as a platform for evaluating the safety and effectiveness of new methods of ex vivo expansion or methods of enhanced homing, but also as an approach in itself to remedy the problem of limited cell dose, particularly for adults. [Copyright &y& Elsevier]

Objectives: 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. Data Sources: Research studies, articles, and personal experiences. Conclusion: 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. [Copyright &y& Elsevier]

Delayed hematologic recovery is common after unrelated donor umbilical cord blood transplants (UCBT). Clinically it is important to quickly differentiate slow engraftment from graft failure (GF). We report the engraftment data on 110 pediatric UCBT recipients. By day 28, 71 patients achieved an ANC >0.5 × 109 per liter, and 6 others died early without recovery. Of the remaining 33 patients who were still neutropenic, 20 eventually attained donor myeloid recovery, 3 died of transplant-related complications or recurrent leukemia and 10 survived without donor-derived hematopoiesis. These patients received a second UCBT 33–95 days after the first transplant, after additional immunosuppression. One patient died early, the remaining nine patients were engrafted; eight demonstrated complete, and one mixed, donor chimerism (with subsequent graft loss). Acute GVHD developed in three, and chronic GVHD in six of the eight engrafted patients. Two patients developed EBV-lymphoproliferative disorder. Infections, especially viral, were common and protracted. Six of 10 patients are alive, 165–1375 (median 1147) days after second UCBT. Chimerism studies correlated with subsequent engraftment course. Any result showing <5% donor cells was associated with irreversible graft loss. In conclusion, early second UCBT after primary GF is a feasible treatment option. Chronic GVHD and viral reactivation are common post transplant.Bone Marrow Transplantation (2008) 42, 35–41; doi:10.1038/bmt.2008.40; published online 10 March 2008 [ABSTRACT FROM AUTHOR]

Umbilical cord blood, which offers a rich source hematopoietic stem cells, is now accepted as a valuable alternative to marrow for transplantation in a variety of hematologic, oncologic, and genetic disorders. Studies in both children and adults have shown the clinical utility of unrelated cord blood transplant. Additional clinical and logistic advantages of cord blood include collection at no risk to the donor, lower risks of infection, a reduced risk of both acute and chronic graft-vs-host disease (GVHD), and ready availability. The reduced risk of GVHD is attributed to the immaturity of T cells in donor cord blood, thereby diminishing the response to antigens in the recipient. Theoretically, this immunologic immaturity should allow for greater flexibility in HLA matching, thus expanding the potential pool of donors available for transplantation. Cord blood banking programs have now been established in both Europe and the United States for the storage and supply of hematopoietic stem and progenitor cells derived from cord blood for autologus, related and unrelated allogenic transplantation. More than 3500 cord blood transplant procedures have been performed worldwide, the majority of which involved units that were collected and stored in cord blood banking facilities. [ABSTRACT FROM AUTHOR]

Abstract: We present a comparative analysis of clinical presentation and response to treatment in 170 patients with chronic graft versus host disease (cGVHD) (123 following transplant from an unrelated donor [URD] and 47 from umbilical cord blood [UCB]). URD transplant recipients were significantly younger (median age 25 versus 39 years, P = .002; and the donor grafts were mostly HLA matched (67% versus 10%, P < .0001). UCB recipients had more frequent responses (complete remission [CR] + partial remission [PR]) to treatment (URD 48% versus UCB 74% at 2 months [P = .005]; 49% versus 78% at 6 months [P = .001] and 51% versus 72% at 1 year [P = .03] in the URD and UCB groups, respectively). Nonrelapse mortality (NRM) after diagnosis of cGVHD was worse after URD grafts. (1 year NRM 27% [19%-35%] URD versus 11% [2%-20%] UCB, P = .055). Separate multivariate analyses were performed in each cohort. In both, thrombocytopenia and no CR or PR at 2 months were independently associated with increased mortality. In addition, progressive onset of cGVHD was a significant predictor of increased mortality in URD cohort. These data suggest that cGVHD following UCB transplant may be more responsive to therapy and also lead to a lower NRM. [Copyright &y& Elsevier]

The article presents a case study of a 59-year-old woma who underwent long term lympho-haematopoietic reconstitution by umbilical cord blood stem cells following primary graft failure and autologous rescue. The patient undergone the allogeneic haematopoietic stem cell transplantation by using double UCB units. After the failure of the transplant, the patient showed improvement over the next two years.

Abstract: Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a 5-year period with serial neurological examinations, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first 2years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease. [ABSTRACT FROM AUTHOR]

While umbilical cord blood is increasingly utilized as a stem cell source, immune complications associated with the procedure have been recognized. These complications result from significant immune system dysregulation and defective reconstitution following transplant causing an imbalance between T-cell subsets, aberrant B cells, and abnormal antibody production. This may occur up to 12 months after transplant coinciding with thymic regeneration in adults. The aim of our review is to describe the incidence, pathophysiology, clinical features, and prognosis of autoimmune cytopenias following umbilical cord blood transplant. Furthermore, we review the treatment strategies reported in the existing literature, describe the authors' experience with the complication, and highlight novel treatment options being studied. The knowledge of the occurrence and timing of autoimmune complications of umbilical cord blood transplantation is essential for detection and treatment of the disease. Emerging therapeutic options include interleukin-2 (IL-2), which is also being studied for the treatment of acute and chronic graft-versus-host disease. IL-2 has favorable effects on growth, differentiation, and function of regulatory T cells. Monoclonal antibody treatments, such as daratumumab, are also on the forefront and more experience with them will guide further treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Background: Deficiency in the enzyme β‐mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood‐onset β‐mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available. Methods: We report 2‐year outcomes following the first umbilical cord blood transplant in a 4‐year‐old boy with early childhood‐onset disease. Results: We show restoration of leukocyte β‐mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β‐mannosidase activity and dramatic decrease in urine‐free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers. Conclusion: Our findings suggest that hematopoietic cell transplant can correct the biochemical defect in β‐mannosidosis, although preservation of the neurocognitive trajectory may be a challenge. [ABSTRACT FROM AUTHOR]

Background Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. Methods All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. Results Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. Conclusions Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT. [ABSTRACT FROM AUTHOR]

Objectives: Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis., Methods: We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups., Results: We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57-0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02-1.95, I2=56.8%, and 1.77, 95% CI 1.1-2.87, I2=82.5%, respectively., Conclusion: Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective/background: Cytomegalovirus (CMV) causes significant morbidity and mortality in CMV seropositive patients undergoing umbilical cord blood transplants (UCBT). Our study aimed to describe the incidence of CMV reactivation and burden of disease, as well as the tolerability of an intensive prevention strategy as compared to historical prevention., Methods: This was a retrospective chart review of 33 CMV seropositive patients that underwent UCBT. The intensive prevention strategy in UCBT consisted of ganciclovir 5mg/kg/d intravenously or valganciclovir 900mg by mouth daily initiated at the beginning of the conditioning regimen until Day -2. Then from Day -1 to Day +100, patients received valacyclovir 2g by mouth three times daily, and from Day +101 to Day +365, acyclovir 800mg by mouth twice daily. Historical standard prevention was acyclovir 800mg by mouth twice daily initiated at the beginning of the conditioning regimen until Day +365., Results: Thirty-three patients were included from 2008 to 2014. There were no differences in the adverse effects experienced between the two regimens (p=.4). CMV reactivation occurred significantly later with intensive prevention (p=.003). The median CMV viral titer at reactivation was lower in the intensive versus the historic prevention (1,800copies/mL and 2,700copies/mL, respectively), but was not significantly different. CMV disease occurred significantly less often in the intensive group (p=.039)., Conclusion: The results from this study indicate that the intensive prevention strategy was well tolerated, significantly delayed CMV reactivation, and patients had less CMV disease., (Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Moraxella catarrhalis is a gram negative diplococcus that causes a variety of upper and lower respiratory tract infections. Patients with malignant, hematological disorders treated with intensive cytotoxic chemotherapy, and recipients of various forms of haematopoietic stem cell transplant receiving immunosuppressive agents are at high risk of developing severe infections and septic complications. Early detection of the organism and prompt treatment with appropriate antibiotics provide both resolution of the infection and prevention of further consequences. Two patients with haematopoietic stem cell transplant who developed pneumonia caused by M. catarrhalis at King Faisal Specialist Hospital and Research Centre in Riyadh are reported and the literature is reviewed. To our knowledge, these are the first case reports of M. catarrhalis pneumonia in haematopoietic stem cell transplant patients.