Systematic review of controlled clinical studies using umbilical cord blood for regenerative therapy: Identifying barriers to assessing efficacy.

Clinical use of umbilical cord blood (UCB) for novel indications in regenerative therapy continues to rise, however, whether new indications are proven is less clear. An updated systematic search of the literature, focusing only on controlled clinical studies, is needed to properly assess potential efficacy. After updating our systematic search to April 1, 2018 (PROSPERO protocol CRD42016040157), a total of 16 studies were identified that addressed the treatment of cerebral palsy (four studies), type 1 diabetes (three studies), and nine other novel potential indications where only a single controlled study was identified. In the four controlled studies of patients with cerebral palsy, three used allogeneic cells and reported greater improvement in motor-related scores at 1, 3 and 6 months compared with controls. The results were mixed for other scores at other time points, including additional measures of mental and motor function. One study of autologous UCB treatment reported an improvement in motor function scores at 12 months compared with controls. In the three controlled studies of type 1 diabetes, two studies used autologous cells whereas one used allogeneic cord blood cells to "educate" autologous lymphocytes. Taken together, there was no clear difference in HbA1c levels or daily insulin requirements between treated patients and controls. For the nine published reports with a single controlled study, eight used allogeneic UCB cells and seven infused mesenchymal stromal cells derived from UCB. All but one study reported benefit. Many other published reports that lack a control group were not included in our analysis. More controlled studies are needed that use similar approaches regarding cell source and outcome measures at similar time points. Pooled estimates of results from multiple studies will be essential as published studies remain modest in size. Patients should continue to be enrolled in clinical trials because there are no novel potential indications remain unproven.

The incidence, risk factors and outcomes of early bloodstream infection in patients with malignant hematologic disease after unrelated cord blood transplantation: a retrospective study.

BACKGROUND: Bloodstream infection (BSI) is one of the major causes of morbidity and mortality for patients undergoing hematopoietic stem cell transplantation (HSCT). The unrelated cord blood transplantation (UCBT) can provided opportunities for patients without suitable donors for bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT), while few studies have addressed BSI after UCBT. The aim of this study was to analyse the incidence and risk factors of BSI, causative organisms, microbial resistance, and its impact on the clinical outcomes and survival of patients. METHODS: There are 336 patients, were divided into two groups depending on whether developing BSI. Demographic characteristics, laboratory data, and clinical outcome were compared between different groups. The risk factors of BSI was examined using logistic regression and the survival was examined using the Kaplan-Meier method and log-rank test. RESULTS: Ninety-two patients (27.4%) developed early BSI with 101 pathogenic bacteria isolated, and the median day of developing initial BSI was 4.5 d. Gram-negative bacteria were the most common isolate (60, 59.4%), followed by Gram-positive bacteria (40, 39.6%) and fungi (1, 1.0%). Thirty-seven (36.6%) isolates were documented as having multiple drug resistance (MDR). Myeloid malignancies, conditioning regimens including total body irradiation (TBI), and prolonged neutropenia were identified as the independent risk factors for early BSI. The 3-year OS was 59.9% versus 69.2% in the BSI group and no-BSI group (P = 0.0574), respectively. The 3-year OS of the MDR group was significantly lower than that of the non-BSI group (51.1% versus 69.2%, p = 0.013). CONCLUSIONS: Our data indicate that the incidence of early BSI after UCBT was high, especially in patients with myeloid disease and a conditioning regimen including TBI and prolonged neutropenia. Early BSI with MDR after UCBT had a negative impact on long-term survival.

Factors Determining the Outcome of Hematopoietic Stem Cell Transplantation in Patients With Acute Lymphoblastic Leukemia at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Medical records of 82 patients with acute lymphoblastic leukemia (ALL) who underwent hematopoietic cell transplantation (HCT) at our institution from 2005 to 2011 were reviewed. Forty-five patients were male (54.8%). The median age at HCT was 7.46 years (range, 0.98 to 14.31 y), the median time to HCT after diagnosis was 12.56 months. Ten patients were below the age of 1 year (12%). All patients were in complete remission at the time of HCT. In 83 transplants, 64 patients received HCT from human leukocyte antigen-identical-related donors and 19 from other donors. Stem cell source was bone marrow in 65 (78%) and cord blood in 18 (22%). Five-year overall survival was 58.8% and event-free survival was 54.3%. The cumulative incidence of acute graft versus host disease was 4.8%±2.3% and of chronic graft versus host disease was 8.9%±3.2%. The median time to absolute neutrophil count and platelet recovery was 17 days (range, 12 to 43 d) and 28 days (range, 15 to 98 d), respectively. One patient acquired CMV infection after transplant. No one developed venoocclusive disease, hemorrhagic cystitis, or other complication. Patient's age at diagnosis, sex, donor's human leukocyte antigen status and sex, source of transplant and complete remission status at HCT did not affect overall survival and event-free survival. Our results show a favorable outcome to HCT for acute lymphoblastic leukemia patients comparable to published data, and no single factor was associated with superior outcome.

Prevalence of Medical Conditions Potentially Amenable to Cellular Therapy among Families Privately Storing Umbilical Cord Blood.

Introduction Little is known about the prevalence of conditions potentially amenable to cellular therapy among families storing umbilical cord blood in private cord blood banks. Methods A cross-sectional study of families with at least one child who stored umbilical cord blood in the largest private cord blood bank in the United States was performed. Respondent families completed a questionnaire to determine whether children with stored cord blood or a first-degree relative had one or more of 16 conditions amenable primarily to allogeneic stem cell transplant ("transplant indications") or 16 conditions under investigation for autologous stem cell infusion ("regenerative indications"), regardless of whether they received a transplant or infusion. Results 94,803 families responded, representing 33.3 % of those surveyed. Of respondent families, 16.01 % indicated at least one specified condition. 1.64 % reported at least one first-degree member with a transplant indication potentially treatable with an allogeneic stem cell transplant. The most common transplant indications reported among first-degree family members were Non-Hodgkin's Lymphoma (0.33 %), Hodgkin's Lymphoma (0.30 %), and Acute Lymphoblastic Leukemia (0.28 %). 4.23 % reported at least one child with a regenerative indication potentially treatable with an autologous stem cell infusion. The most common regenerative indications among children with stored umbilical cord blood were Autism/Autism Spectrum Disorder/Apraxia (1.93 %), Other Developmental Delay (1.36 %), and Congenital Heart Defect (0.87 %). Discussion Among families storing umbilical cord blood in private cord blood banks, conditions for which stem cell transplant or infusion may be indicated, or are under investigation, appear to be prevalent, especially for regenerative medicine indications.

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.

Cord blood transplantation in Japan.

Cord blood transplantation (CBT) has increasingly been used in Japan and the annual number of CBT now exceeds 1,200. The cumulative number of CBT reached 12,853 in 2015, accounting for almost 1/3 of total CBT performed worldwide. It is true that smaller body size and lower costs, as compared to western countries, have been advantages for Japanese people in using CB as graft alternative. In addition, several novel findings regarding serious issues following CBT have been obtained, which further enhanced the use of CB. First, several mechanisms of engraftment failure following CBT other than cell dose have been reported, such as the presence of donor-specific anti-HLA antibodies or the development of hemophagocytic syndrome. Second, unique profiles of infectious complications following CBT have been reported, such as higher incidences of early bacterial infections and HHV-6 encephalitis, as compared to those following bone marrow (BM)/peripheral blood (PB) transplants. Third, the incidence of disease relapse was comparable to those following BM/PB transplants. Novel pre-transplant conditioning regimens using intravenous busulfan have been investigated with promising results being obtained to date. A recent analysis of Japanese transplant registry data revealed similar survival following CBT to HLA-matched unrelated BM/PB transplants.

Impact of long-term cryopreservation on single umbilical cord blood transplantation outcomes.

Umbilical cord blood (UCB) may be collected and cryopreserved for years before use. In vitro and murine models suggest that the duration of storage does not affect UCB progenitor cell performance; however, the impact of UCB age on clinical outcomes has not been definitely defined. This study sought to determine the effect of UCB unit cryopreservation time on hematopoietic potency. We analyzed 288 single UCB units used for transplantation from 1992 to 2013, with unit cryopreservation time ranging from .08 to 11.07 years. UCB unit post-thaw characteristics were examined, including percent recovery of total nucleated cells (TNC). The number of years the UCB unit spent in cryopreservation had no impact on TNC recovery nor UCB unit post-thaw viability. Duration of cryopreservation also had no impact on neutrophil or platelet engraftment in single UCB transplantations. These results show that UCB units can undergo cryopreservation for at least 10 years with no impact on clinical outcomes.

Cord Blood Banking in the Arab World: Current Status and Future Developments.

Umbilical cord blood transplants are now used to treat numerous types of immune- and blood-related disorders and genetic diseases. Cord blood (CB) banks play an important role in these transplants by processing and storing CB units. In addition to their therapeutic potential, these banks raise ethical and regulatory questions, especially in emerging markets in the Arab world. In this article, the authors review CB banking in five countries in the region, Jordan, Saudi Arabia, Egypt, Qatar, and the United Arab Emirates, selected for their different CB banking policies and initiatives. In assessing these case studies, the authors present regional trends and issues, including religious perspectives, policies, and demographic risk factors. This research suggests strong incentives for increasing the number of CB units that are collected from and available to Arab populations. In addition, the deficit in knowledge concerning public opinion and awareness in the region should be addressed to ensure educated decision-making.

Allogeneic haematopoietic stem cell transplantation for infant acute lymphoblastic leukaemia with KMT2A (MLL) rearrangements: a retrospective study from the paediatric acute lymphoblastic leukaemia working group of the Japan Society for Haematopoietic Cell Transplantation.

Allogeneic haematopoietic stem cell transplantation (HSCT) is still considered to play an important role as a consolidation therapy for high-risk infants with acute lymphoblastic leukaemia (ALL). Here, we retrospectively analysed outcomes of HSCT in infants with ALL based on nationwide registry data of the Japan Society for Haematopoietic Cell Transplantation. A total of 132 allogeneic HSCT for infant ALL with KMT2A (MLL) gene rearrangements, which were performed in first complete remission (CR1), were analysed. The 5-year overall survival rate after transplantation was 67·4 ± 4·5%). Although recent HSCT (after 2004) had a trend toward better survival, no statistical correlation was observed between outcomes and each factor, including age at diagnosis, initial leucocyte count, cytogenetics, donor types or conditioning of HSCT. Myeloablative conditioning with total body irradiation did not provide a better survival (60·7 ± 9·2%) over that with busulfan (BU; 67·8 ± 5·7%). Two of the 28 patients treated with irradiation, but none of the 90 BU-treated patients, developed a secondary malignant neoplasm. In conclusion, allogeneic HSCT using BU was a valuable option for infant ALL with KMT2A rearrangements in CR1.

Cytomegalovirus infection in seropositive unrelated cord blood recipients: a study of 349 Korean patients.

To gain insight into the natural history of cytomegalovirus (CMV) infection following unrelated cord blood transplantation (UCBT) in seropositive patients, we analyzed the data of 349 seropositive patients who received UCBT in Korea between 2000 and 2011. CMV reactivation occurred in 49 % (171/349) of the CMV-seropositive transplant recipients at a median of 31 days post UCBT. One hundred sixty-four out of 171 patients (96 %) received preemptive therapy. The median duration of CMV reactivation was 29 days. In multivariate analysis, weight >22 kg, use of total body irradiation, use of pre-transplant antithymocyte globulin, graft-versus-host disease (GVHD) prophylaxis with mycophenolate mofetil, and presence of grade II-IV acute GVHD were independent predictors of CMV reactivation. CMV reactivation did not impact transplantation-related mortality (TRM), leukemia relapse, or survival. CMV disease was diagnosed in 62 patients (17.8 %) at a median 55 days after UCBT. Longer duration of CMV reactivation was the only risk factor for progression to CMV disease (p = 0.01). CMV disease resulted in higher TRM (56.0 vs. 31.4 %, p < 0.01) and lower survival (36.1 vs. 55.1 %, p = 0.02).

Impact of Ethnicity on Donor Search Results for Children Requiring Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) can be curative for children with various malignant and nonmalignant conditions. Access to suitable unrelated living donors (ULDs) or unrelated cord blood (UCB) may be limited for certain ethnic backgrounds. We therefore determined the impact of ethnicity upon donor availability in a pediatric cohort referred for allogeneic HSCT to a single Canadian transplant center. Among 252 eligible patients, 58 (23.0%) had suitable family donors. Of 161 patients with combined ULD and UCB searches, 78 (48.4%) had a suitable ULD, whereas 143 (88.8%) had suitable UCB. The probability of finding a suitable ULD differed significantly by ethnicity (P=0.007). Non-white patients were significantly less likely to have suitable ULDs (odds ratio [OR] 0.35; 95% confidence interval [CI], 0.17-0.69; P=0.003) compared with white patients but were equally likely to have suitable UCB (OR 1.02; 95% CI, 0.36-2.89; P=0.97). Although ethnic disparities exist in pediatric patients' access to ULD for HSCT, they are narrowed by the availability of international UCB registries. These findings, however, also highlight the importance of continued recruitment of individuals of non-white ethnicities to donor registries.

Transplantation of umbilical cord blood-derived cells for novel indications in regenerative therapy or immune modulation: a scoping review of clinical studies.

Although used mainly for transplantation of hematopoietic stem cells in the treatment of blood disorders, umbilical cord blood (UCB)-based therapies are now being used increasingly for novel applications in nonhematopoietic diseases and as a form of cellular regenerative therapy or immune modulation. We performed a systematic scoping review by searching Medline, EMBASE, and the Cochrane Library for published articles, and we searched www.clinicaltrials.com and the World Health Organization International Clinical Trials Registry Platform to describe the breadth of published studies and ongoing clinical activity in umbilical cord-based cellular therapy for regenerative therapy and immune modulation. The most commonly published area of expertise in the use of UCB-derived cellular transplantation for novel indications is for neurological disorders and this remains the most active area of study in ongoing registered trials. An increasingly broad range of disorders, however, are reflected in ongoing registered trials, which suggests greater activity, interest, and investment in UCB-derived cellular therapy. Interestingly, adult patients compose the majority of patients reported in published reports and registered ongoing clinical studies continue to enroll predominantly adult subjects. Geographically, Asian countries appear most active in UCB-derived cellular therapy and our analysis of ongoing studies suggests this trend will likely continue. Regular assessment of published and ongoing activity in UCB transplantation for emerging novel indications will be critical for informing UCB banking establishments and funding agencies to guide changes in banking practices related to emerging trends in cell therapy.

Efficacy and safety of human umbilical cord derived mesenchymal stem cell therapy in children with severe aplastic anemia following allogeneic hematopoietic stem cell transplantation: a retrospective case series of 37 patients.

The treatment of pediatric severe aplastic anemia (SAA) with allogeneic hematopoietic stem cell transplantation (allo-HSCT), presents major challenges including the risks of graft failure, septic complications, and graft-versus-host disease (GVHD). Additive infusions of human umbilical cord derived mesenchymal stem cell (hUC-MSC) may be administered to improve patient survival. We retrospectively examined 37 pediatric patients with SAA who received allo-HSCT and subsequent infusions of hUC-MSC suspension at a dose of 1.0 × 10(6 )/kg. The times and doses of hUC-MSC infusions were increased in patients with severe GVHD. All patients received hUC-MSC infusions. The median time to post-transplantation neutrophil count of greater than 0.5 × 10(9 )/L was 14 days (range, 11-20 days) and time to post-transplantation platelet count of greater than 20 × 10(9 )/L was 19 days (14-29 days). The overall frequency of acute GVHD (aGVHD) was 45.9% (17/37). These aGVHD episodes occurred at a median time of post-transplantation 47 days (15-83 days). The frequency of chronic GVHD (cGVHD) was 18.9% (7/37); cGVHD developed from aGVHD in 10.8% (4/37) of patients. The GVHD-associated mortality rate was 18.9% (7/37) and aGVHD-specific mortality rate was 8.1% (3/37). The median overall survival time was 35 months (9-67 months) and the three-year overall survival rate was 74.2% (28/37). Seven patients died of GVHD, one patient died of a severe invasive fungal infection, and one patient died of renal failure. In conclusion, post-transplantation hUC-MSC infusions seemed to be safely infused in children with SAA who have previously received allo-HSCT.

Analysis of 120 pediatric patients with nonmalignant disorders transplanted using unrelated plasma-depleted or -reduced cord blood.

BACKGROUND: Unrelated cord blood (CB) is an important stem cell source for unrelated hematopoietic cell transplantation (HCT) of patients with nonmalignant disorders. Processing methods to prepare red blood cell-reduced CB units incur significant nucleated cell loss. In contrast, plasma depletion or reduction (PDR) processing of CB units entails the removal of only a portion of the plasma with minimal nucleated cell loss. However, there are relatively limited data regarding outcomes of CB transplants using units processed by PDR. STUDY DESIGN AND METHODS: A Center for International Blood and Marrow Transplant Research (CIBMTR)-audited analysis was performed on 120 pediatric patients with nonmalignant disorders transplanted between November 2001 and January 2008 at 29 US and 17 international centers using PDR CB units from two CB banks. RESULTS: Transplant characteristics were as follows: median age, 3.5 years (range, 0.1-14 years); median patient weight, 15 kg (range, 4-61 kg); 58% male; HLA matches (intermediate-resolution HLA-A and HLA-B and high-resolution HLA-DRB1) of the units used in these patients six of six in 26, five of six in 48, four of six in 47, and three of six or two of six in 6; median prefreeze total nucleated cell dose, 10.5×10(7)/kg; median prefreeze CD34+ dose, 3.7×10(5)/kg; and nonmyeloablative regimen in 24%. The median times to myeloid and platelet engraftment were 21 and 49 days, respectively. The cumulative incidence of reported Grade II to IV acute graft-versus-host disease (aGVHD) was 38±5%, and 19±4% had Grade III to IV aGVHD. The Kaplan-Meier estimates of 3-year transplant-related mortality, overall survival, and disease-free survival were 20±4, 79±4, and 70±6%, respectively. CONCLUSION: These data demonstrate the effectiveness of PDR CB units for HCT.

Cord blood banking activities at a university hospital in northeast Mexico: an 8-year experience.

BACKGROUND: Umbilical cord blood (UCB) represents an alternative source of stem cells for transplantation for the treatment of hematologic malignancies and genetic disorders. There is scarce information detailing cord blood bank (CBB) collection and transplantation activities from developing countries. We documented our experience at a public university hospital in northeast Mexico. STUDY DESIGN AND METHODS: We carried out a retrospective and descriptive analysis of our CBB activity during an 8-year period from May 2002 to September 2010. Collection, processing, and cryopreservation of CB were carried out following standard operating procedures. The minimum volume and total nucleated cell (TNC) content for cryopreservation were 80 mL and 8.0 × 10(8) , respectively. RESULTS: A total of 1256 UCB units were collected; 428 (34%) were banked and 828 (66%) were discarded. The main reason for exclusion was biologic: low volume and/or low number of TNC accounted for 84% of the total discarded units. Cryopreserved cord blood units (CBUs) had a median volume of 113.8 mL (range, 80-213.2 mL) and 13.0 × 10(8) (range, 8 × 10(8) -36.6 × 10(8) ) TNCs. Cell viability was 99.3% (88-100%). The median CD34+ cell content was 4.0 × 10(6) (0.46 × 10(6) -19.38 × 10(6) ). Sixteen units have been released for transplantation, leading to a utilization rate of 3.7%. CONCLUSION: CBB demands considerable human and financial resources; it is then essential for centers at developing countries to share their experience, results, and databases to increase the probability of finding matching units for their patients. Efforts to create and maintain CBBs allow to offer this therapeutic option at an affordable cost.

Bayesian continual reassessment method for dose-finding trials infusing T cells with limited sample size.

We consider the design of dose-finding trials for patients with malignancies when only a limited sample size is available. The small sample size may be necessary because (1) the modality of treatment is very expensive, and/or (2) the disease under investigation is rare, requiring a lengthy period to enroll a target patient population. Both of these are common in the field of adoptive immunotherapy, in which T cells are infused to prevent and treat infections and malignancies. The clinical trial described in this paper investigates a novel therapy to adoptively transfer genetically modified T cells in small pilot protocols enrolling patients with B-lineage malignancies. Due to the constraints of cost and infrastructure, the maximum sample size for this trial is fixed at 12 patients distributed among four doses of T cells. Given these limitations, an innovative statistical design has been developed to efficiently evaluate the safety, feasibility, persistence, and toxicity profiles of the trial doses. The proposed statistical design is specifically tailored for trials with small sample sizes in that it uses the toxicity outcomes from patients treated at different doses to make dose-finding decisions. Supplementary materials including an R function and a movie demo can be downloaded in the websites mentioned in the paper.

Cord blood transplantation in Western Australia.

BACKGROUND/AIMS: Thirty-one umbilical cord blood transplants performed in Western Australia were retrospectively examined in order to document local experience and relevant prognostic factors. Three cord units were from human leucocyte antigen-matched siblings and the remainder were unrelated single (n= 22) or double (n= 6) cord blood transplants. METHODS: Twenty patients were transplanted for malignant conditions and 11 for non-malignant conditions. Cord units contained a median of 5.6 × 107 total nucleated cells/kg and 1.4 × 105 CD34+ cells/kg. Cumulative incidence of neutrophil engraftment was 76% at day 60. RESULTS: Of those who did not engraft, two patients remain alive following subsequent allogeneic bone marrow transplant. There were no deaths caused by graft-versus-host disease. Overall survival at median follow up of 28 months was 62%. Two year overall survival was influenced by type of disease (non-malignant = 91 ± 9% vs malignant = 41 ± 13%, P= 0.005), total nucleated cell dose (>3.5 × 107/kg = 87 ± 9% vs <3.5 × 107/kg = 34 ± 15%, P= 0.01) and CD34 dose (>1.7 × 105/kg = 92% vs <1.7 × 105/kg = 46%, P= 0.04). Age and human leucocyte antigen match did not influence survival. Four relapses occurred, all of which were fatal. CONCLUSION: Cord blood transplantation for malignant and non-malignant disease is practised in Western Australia and outcomes are satisfactory. Trends and techniques in cord blood transplantation in this state are comparable with those observed nationally and overseas. Although numbers are small, cell dose appears to be predictive of overall survival

Cord blood unit access and selection: 2010 and beyond: best practices and emerging trends in cord blood unit selection.

One-fifth, more than 1000, of all transplants facilitated in 2010 by the National Marrow Donor Program (NMDP) have employed 1 or 2 umbilical cord blood units as the graft source. As the use of umbilical cord blood for unrelated allogeneic hematopoietic cell transplantation increases, several issues emerge that require additional attention and refinement. The U.S. Food and Drug Administration is now far along in its implementation of regulatory controls for umbilical cord blood. After October 20, 2011, every unrelated-donor cord blood unit transplanted in the United States must be either licensed or covered under an FDA-accepted IND. It is incumbent upon transplant physicians to review and understand the implications of the FDA's new regulations. In addition, as more transplant programs adopt umbilical cord blood for transplantation, it is important to stay current with the best practices surrounding identification and selection of the best available units. Cell dose, HLA matching, location of mismatched loci, and the role of noninherited maternal alleles are all important considerations for unit selection. This complexity in selection of appropriate units raises issues about the desired inventory of umbilical cord blood units. How many units are needed to meet the needs of all patients who might benefit from cord blood transplantation? Newly developed simulation models are being utilized by NMDP to answer this question.

Umbilical cord blood transplantation for children with thalassemia and sickle cell disease.

We examined the efficacy of unrelated cord blood (CB) transplantation in children with thalassemia (n = 35) and sickle cell disease (n = 16), using data reported to 3 registries. Donor-recipient pairs were matched at HLA-A and -B (antigen level) and DRB1 (allele level) in 7 or HLA mismatched at 1 (n = 18), 2 (n = 25), or 3 loci (n = 1). Transplant conditioning was myeloablative (n = 39) or reduced intensity (n = 12). Neutrophil recovery with donor chimerism was documented in 24 patients; 11 patients developed grade II-IV acute graft-versus-host disease (aGVHD) and 10 patients, chronic GVHD (cGVHD). Overall survival (OS) and disease-free survival (DFS) were 62% and 21% for thalassemia and 94% and 50% for sickle cell disease (SCD), respectively. In multivariate analysis, engraftment rate (hazard ratio [HR] 2.2, P = .05) and DFS (HR 0.4, P = .01) were higher with cell dose >5 × 10(7)/kg. The 2-year probability of DFS was 45% in patients who received grafts with cell dose >5 × 10(7)/kg and 13% with lower cell dose. Primary graft failure was the predominant cause of treatment failure occurring in 20 patients with thalassemia and 7 patients with SCD. Primary graft failure was fatal in 5 patients with thalassemia. These results suggest that only CB units containing an expected infused cell dose >5 × 10(7)/kg should be considered for transplantation for hemoglobinopathy.