Risk Factors and Options to Improve Engraftment in Unrelated Cord Blood Transplantation

Use of umbilical unrelated cord-blood (UCB) cells as an alternative source of hematopoietic cell transplantation has been widely used mainly for patients lacking an HLA-matched donor. UCB present many advantages over bone marrow or mobilized peripheral blood from volunteer donors, such as rapid availability, absence of risk for the donor, and decreased incidence of acute graft-versus-host disease. However, a significant clinical problem is delayed engraftment that is directly correlated with the number of hematopoietic stem cells in a cord-blood unit. The identification of prognostic factors associated with engraftment that can be easily modified (e.g., strategies for donor choice) and the development of new approaches including use of multiple donors, intrabone injection of UCB, ex vivo expansion, and cotransplantation with accessory cells are of crucial importance in order to circumvent the problem of delayed engraftment after UCB transplantation. Those approaches may increase the quality and availability of UCB for transplantation

Optimizing Unrelated Donor Cord Blood Transplantation

In contrast to the very high transplant-related mortality (TRM) associated with the early experience of cord blood (CB) transplantation (CBT), recent transplant series have been associated with comparable survival to that of human leucocyte antigen (HLA)-matched unrelated donor transplantation in children with similarly promising results in adults. Consequently, the use of CB as an alternative stem cell source and the global inventory of units in public banks are rapidly increasing although challenges remain. This review will address efforts to optimize CBT from 3 different perspectives: that of the transplant center, the CBT registry, and the CB bank

Competing Risks Regression for Stratified Data

For competing risks data, the Fine–Gray proportional hazards model for subdistribution has gained popularity for its convenience in directly assessing the effect of covariates on the cumulative incidence function. However, in many important applications, proportional hazards may not be satisfied, including multicenter clinical trials, where the baseline subdistribution hazards may not be common due to varying patient populations. In this article, we consider a stratified competing risks regression, to allow the baseline hazard to vary across levels of the stratification covariate. According to the relative size of the number of strata and strata sizes, two stratification regimes are considered. Using partial likelihood and weighting techniques, we obtain consistent estimators of regression parameters. The corresponding asymptotic properties and resulting inferences are provided for the two regimes separately. Data from a breast cancer clinical trial and from a bone marrow transplantation registry illustrate the potential utility of the stratified Fine–Gray model

Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT

Association of Human Development Index with rates and outcomes of hematopoietic stem cell transplantation for patients with acute leukemia

Abstract Human Development Index (HDI) is used by the United Nations Organization to measure socioeconomic achievements of countries. We evaluated the association of HDI with rates and outcomes of hematopoietic stem cell transplantation (HSCT) for patients with acute leukemia. For the analysis of HSCT rates, all adults with acute leukemia (n = 16 403) treated in 30 European countries, between 2001 and 2005, were included. Association of HDI with the outcome was analyzed for 2015 patients with acute myeloid leukemia treated with myeloablative allotransplantation. Countries were classified according to HDI quintiles. Highly significant correlation was found for HDI and the total number of HSCT per population (R = 0.78; P < .001), as well as separately for sibling HSCT (R = 0.84; P < .001), unrelated HSCT (R = 0.66; P < .001), and autologous HSCT (R = 0.43; P = .02). The probabilities of leukemia-free survival for 5 consecutive groups of countries with increasing HDI were: 56%, 59%, 63%, 58%, and 68% (P = .01). In a multivariate analysis, transplantations performed in countries belonging to the upper HDI category were associated with higher leukemia-free survival compared with the remaining ones (HR = 1.36, P = .008), which resulted mainly from reduced risk of relapse (HR = 0.72, P = .04). We conclude that, in Europe, the HDI is associated with both rates and results of HSCT for acute leukemia

Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience

OBJECTIVES: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used. METHODS: We conducted a retrospective comparison of ‘‘MEC’’ (mitoxantrone, etoposide, and cytarabine) and ‘‘FLAG-IDA’’ (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML. RESULTS: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) died before undergoing bone marrow assessment. No statiscally significant difference in CR rate was found between the two protocols (p=0.447). The median survival in the total cohort was 4 months, with a 3-year overall survival (OS) rate of 9.7%. In a multivariable model including age, fms-like tyrosine kinase 3 (FLT3) status, and stem-cell transplantation (SCT), only the last two indicators remained significant: FLT3-ITD mutation (hazard ratio [HR] =4.6, po0.001) and SCT (HR=0.43, p=0.01). CONCLUSION: In our analysis, there were no significant differences between the chosen regimens. High rates of early toxicity were found, emphasizing the role of supportive care and judicious selection of patients who are eligible for intensive salvage therapy in this setting. The FLT3-ITD mutation and SCT remained significant factors for survival in our study, in line with the results of previous studies

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P \u3c .001) and chronic (HR, 0.35; P \u3c .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up

Consolidative mediastinal radiotherapy for advanced-stage classical Hodgkin lymphoma with bulky disease in patients who achieve complete response after chemotherapy in PET-CT era

Background: The role of consolidation mediastinal radiotherapy (RT) for mediastinal bulky disease in advanced-stage classical Hodgkin lymphoma (cHL) is controversial in the positron emission tomography/computed tomography (PET-CT) era. Materials and methods: We reviewed the medical charts of patients with advanced-stage (clinical stage IIX–IVX) cHL and mediastinal bulky that achieved a complete response after first line chemotherapy treatment between August 2010 and December 2020 and compared the results of those who received with those who did not receive consolidation mediastinal RT. Inclusion criteria required PET-CT imaging for staging and response assessment. Results: We included 115 patients; 91 received mediastinal RT and 24 did not. Patient's characteristics were balanced between the two groups. The median age in patients that received and did not receive mediastinal RT was 28 years and 24.5 years, respectively. Median International Prognostic Score among patients that received and did not receive mediastinal RT was 2 and 2.5, respectively. Disease free survival (DFS) was statistically better in patients that received mediastinal RT (p = 0.013). Two-year DFS for patients that received and did not receive mediastinal RT was 95.2% [95% confidence interval (95% CI): 87.6–98.2%] and 76.4% (95% CI: 52.2–89.4%), respectively. Overall survival (OS) was not different between the two groups (p = 0.617). In multivariate analysis, not receiving mediastinal radiotherapy and only achieving partial response (vs. complete response) after 2 cycles of chemotherapy were factors predictive of lower DFS. Conclusion: DFS, but not OS, was superior in patients that received mediastinal RT