Worldwide network for blood and marrow transplantation recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources, part II: Clinical, technical, and socioeconomic considerations

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings

Outcomes of subsequent neoplasms after umbilical cord blood transplantation in Europe

Subsequent neoplasms (SNs) compromise long-term survivors after hematopoietic cell transplantation. We performed a retrospective analysis of SNs in 10 358 recipients of umbilical cord blood transplantation (UCBT) from 1988 to 2018. SNs developed in 233 patients and 84 were of pediatric age. Indications for UCBT were malignant hematological diseases in 199 patients (85%). Three groups of SNs were observed. Posttransplant lymphoproliferative disorders (PTLD) were reported in 145 patients in a median of 4 months after UCBT. Of these, 9 patients died from relapse, 83 from PTLD, and 24 from transplant-related causes. At last follow-up, 29 were alive; 5-year overall survival (OS) after PTLD diagnosis was 21%. Acute leukemia/myelodysplasia (AL/MDS) was diagnosed in 23 patients in a median of 28 months after UCBT and included 3 donor-cell AL. Four of 23 patients died from relapse of primary disease, 8 from progression of SNs, and 4 from TRM. Seven patients remain alive; the 5-year OS after AL/MDS diagnosis was 36%. Solid tumors (ST) were reported in 65 patients in a median of 54 months after UCBT. Most common tumor sites were lung, thyroid, bone, and soft tissue. A total of 33 patients died (26 owing to ST, 6 to relapse of primary disease, and 1 cause missing). At last follow-up, 32 of 65 patients were alive; the 5-year OS after the diagnosis of ST was 51%. In conclusion, despite their poor outcomes, SNs that occur after UCBT are extremely rare. Identification of risk factors and early detection may help to improve OS

Low Body Mass Index Is Associated with Increased Risk of Acute GVHD after Umbilical Cord Blood Transplantation in Children and Young Adults with Acute Leukemia: A Study on Behalf of Eurocord and the EBMT Pediatric Disease Working Party

Abstract Body mass index (BMI) may influence outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients age 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (fifth to 85th percentile), underweight (less than fifth percentile), overweight (85th to 95th percentile), and obese (>95th percentile) using growth charts for age and sex. All patients received single-unit UCBT after a myeloablative conditioning regimen. Diagnosis was acute lymphoblastic leukemia in 68% of the patients. Sixty-one percent of patients (n = 523) were in the normal BMI category, 11% (n = 96) were underweight, 16% (n = 137) overweight, and 12% (n = 99) obese. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was 35% (32% to 38%). According to pretransplantation BMI, aGVHD was 46% (33% to 59%) for underweight, 34% (31% to 42%) for normal, 36% (18% to 38%) for overweight, and 27% (15% to 37%) for obese ( P  = .04). In multivariate analysis, a BMI less than the fifth percentile was associated with higher incidence of acute grade II to IV GVHD compared with normal-BMI patients (hazard ratio,  1.61; 95% confidence interval, 1.15 to 2.26; P  = .006). Our results show that being underweight at the time of transplantation is associated with an increased risk of aGVHD, highlighting the importance of nutritional status before UCBT

Early and late outcomes after cord blood transplantation for pediatric patients with inherited leukodystrophies

Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013. Factors associated with higher overall survival (OS) included presymptomatic status (77% vs 49%; P = .006), well-matched (80 preCBT, 50% remained stable, 20% declined to 60 to 80, and 30% to, 60. Overall, an encouraging OS was found for LD patients after CBT, especially for those who are presymptomatic before CBT and received adequately dosed grafts. Early identification and fast referral to a specialized center may lead to earlier treatment and, subsequently, to improved outcomes

Salvage use of allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning from unrelated donors in multiple myeloma. A study by the Plasma Cell Disorders subcommittee of the European Group for Blood and Marrow Transplant Chronic Malignancies Working Party

Non peer reviewe

Risk Factor Analysis of Outcomes after Unrelated Cord Blood Transplantation in Patients with Hurler Syndrome

AbstractAllogeneic stem cell transplantation (SCT) is considered effective in preventing disease progression in patients with Hurler syndrome (HS). Unrelated umbilical cord blood (UCB) grafts are suggested as an alternative to bone marrow (BM) or peripheral blood stem cells (PBSC). We studied 93 HS patients receiving an UCB graft to analyze risk factors for outcomes. The median time from diagnosis to transplant was 4.6 months, median follow-up was 29 months, and median number of nucleated CB cells infused was 7.6 × 107/kg. Most of the patients received 1 or 2 HLA disparate grafts, and the most frequently used conditioning regimen was cyclophosphamide + busulfan (Bu/Cy). All patients received anti-T cell antibody. At post transplant day +60, the cumulative incidence of neutrophil engraftment was 85%. A younger age at transplant and a higher CD34+ dose at infusion were favorably associated with engraftment. With the exception of 2 patients, all engrafted patients achieved full and sustained donor chimerism. The 3-year event-free survival (EFS) and 3-year overall survival (OS) rates were 70% and 77%, respectively. In a multivariate analyses, use of Bu/Cy and a shorter interval from diagnosis to transplant were predictors for improved EFS rate (82% for patients transplanted within 4.6 months after diagnosis compared to 57% for the rest). Improved outcomes from early transplantation and immediate availability of CB unit lead us to conclude that CB transplantation is a beneficial option, which should be considered expediently for children with HS

Outcomes of Advanced Hodgkin Lymphoma after Umbilical Cord Blood Transplantation: A Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party Study

Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL), but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in European Society for Blood and Marrow Transplantation centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 patients (47%), and almost all patients had received a previous autologous stem cell transplantation. The 4-year progression-free survival (PFS) and overall survival (OS) were 26% (95% confidence interval [CI], 19% to 34%) and 46% (95% CI, 37% to 55%), respectively. Relapse incidence was 44% (95% CI, 36% to 54%), and nonrelapse mortality (NRM) was 31% (95% CI, 23% to 40%) at 4 years. In multivariate analysis refractory/relapsed disease status at UCBT was associated with increased relapse incidence (hazard ratio [HR], 3.14 [95% CI, 1.41 to 7.00], P = .005) and NRM (HR, 3.61 [95% CI, 1.58 to 8.27], P = .002) and lower PFS (HR, 3.45 [95% CI, 1.95 to 6.10], P < .001) and OS (HR, 3.10 [95% CI, 1.60 to 5.99], P = .001). Conditioning regimen with cyclophosphamide + fludarabine + 2 Gy total body irradiation (Cy+Flu+2GyTBI) was associated with decreased risk of NRM (HR, .26 [95% CI, .10 to .64], P = .004). Moreover, Cy+Flu+2GyTBI conditioning regimen was associated with a better OS (HR, .25 [95% CI, .12 to .50], P < .001) and PFS (HR, .51 [95% CI, .27 to .96], P = .04). UCBT is feasible in heavily pretreated patients with HL. The reduced-intensity conditioning regimen with Cy+Flu+2GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT

Effect of HLA-matching recipients to donor non-inherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy

peer reviewe