Outcome Of Hematopoietic Cell Transplantation Research Articles

Development of a Prototype Clinical Decision Support Tool for a Machine Learning Based Individualized Prediction of Outcomes of Hematopoietic Cell Transplantation for Sickle Cell Disease

Development of a Prototype Clinical Decision Support Tool for a Machine Learning Based Individualized Prediction of Outcomes of Hematopoietic Cell Transplantation for Sickle Cell Disease

Comparison of Outcomes of Hematopoietic Cell Transplantation (HCT) for Asymptomatic Patients with Sickle Cell Disease (SCD) and That of Propensity Matched Symptomatic Patients Undergoing HCT

Comparison of Outcomes of Hematopoietic Cell Transplantation (HCT) for Asymptomatic Patients with Sickle Cell Disease (SCD) and That of Propensity Matched Symptomatic Patients Undergoing HCT

The Prevalence and Impact of Pre-Transplant Frailty and Mental Distress on Outcomes in Hematopoietic Cell Transplantation

The Prevalence and Impact of Pre-Transplant Frailty and Mental Distress on Outcomes in Hematopoietic Cell Transplantation

Long-Term Follow-up of Outcomes of Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia: A Single Center Retrospective Review Spanning More Than 25 Years.

Long-Term Follow-up of Outcomes of Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia: A Single Center Retrospective Review Spanning More Than 25 Years.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Vexas Syndrome: A Systematic Review and Meta-Analysis

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Vexas Syndrome: A Systematic Review and Meta-Analysis

Long-Term Follow-up of Outcomes of Hematopoietic Stem Cell Transplantation for Patients with Fanconi Anemia: A Single Center Retrospective Review

Long-Term Follow-up of Outcomes of Hematopoietic Stem Cell Transplantation for Patients with Fanconi Anemia: A Single Center Retrospective Review

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Aged 70 Years and Older.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Aged 70 Years and Older.

Limited Impact of Donor-Recipient Weight Difference on Outcomes of Allogeneic Hematopoietic Cell Transplantation

Limited Impact of Donor-Recipient Weight Difference on Outcomes of Allogeneic Hematopoietic Cell Transplantation

Neurodevelopmental outcomes of hematopoietic stem cell transplantation for infantile Krabbe disease diagnosed through newborn screening

Neurodevelopmental outcomes of hematopoietic stem cell transplantation for infantile Krabbe disease diagnosed through newborn screening

Chemotherapy for a secondary malignancy nearly restores complete chimerism in an SCID-patient after HSCT

For patients with inborn errors of immunity (IEI) and other inborn diseases, mixed donor chimerism is a well-accepted outcome of hematopoietic stem cell transplantation (HSCT). Cytoreductive chemotherapy for a secondary malignancy is a potential challenge for the stability of the graft function after HSCT. We report on a boy with X-SCID who developed Ewing sarcoma ten years after HSCT which was successfully treated with cytoreductive chemotherapy, surgery and local radiation. Surprisingly, this treatment had a positive impact on mixed chimerism with an increase of donor-cell proportions from 40% for neutrophils and 75% for non-T-mononuclear cells (MNCs) to >90% for both. T-cell counts remained stable with 100% of donor origin. This is -to our knowledge- the first report on the impact of cytoreductive chemotherapy on post-HSCT mixed chimerism and provides an important first impression for future patients.

Comparison of long-term outcomes after first HLA-mismatched unrelated donor transplantation with single unrelated cord blood transplantation using reduced-intensity or reduced-toxicity conditioning

BackgroundNo comparative data have shown significant survival differences between HLA-mismatched unrelated donor (MMUD) transplantation and cord blood (CB) transplantation, each with reduced-intensity/reduced-toxicity conditioning (RIC/RTC). However, advances in graft-versus-host disease (GVHD) prophylaxis might help update current strategies. MethodsWe retrospectively compared the outcomes of first allogeneic hematopoietic cell transplantation from MMUDs (n = 15) or single unrelated CB (n = 35) after RIC/RTC. ResultsThe median age was 60 years. The MMUD group had a numerically lower 100-day incidence of grade III–IV acute GVHD (7% vs. 29%, P = 0.079) and non-relapse mortality (0% vs. 40%, P = 0.12). Eight MMUD recipients received anti-thymocyte globulin, bortezomib, or posttransplant cyclophosphamide for GVHD prophylaxis. They did not develop grade III–IV acute GVHD. The MMUD group had significantly better 5-year overall survival than the CB group (62% vs. 31%, P = 0.021), although relapse rates were similar. A multivariable analysis and sensitivity analysis also showed trends toward higher overall survival in the MMUD group. ConclusionMMUD with better GVHD prophylaxis might be preferred over CB in patients with older age and comorbidities.

Association of individual comorbidities with outcomes in allogeneic hematopoietic cell transplantation from unrelated adult donors versus unrelated cord blood: A study on behalf of the Donor/Source and Transplant Complications Working Groups of the Japanese Society for Transplantation and Cellular Therapy.

We retrospectively evaluated the effect of 17 individual comorbidities, defined by the hematopoietic cell transplantation (HCT)-specific comorbidity index, on non-relapse mortality (NRM) and overall survival (OS) in 9531 patients aged between 16 and 70 years who underwent their first allogeneic HCT from 8/8 and 7/8 allele-matched unrelated donors (8/8 and 7/8 MUDs) or single-unit unrelated cord blood (UCB) between 2011 and 2020 using data from a Japanese registry database. In the multivariate analysis, infection (adjusted hazard ratio [HR], 1.62, 95% confidence interval [CI], 1.33-1.99 for 8/8 and 7/8 MUDs; adjusted HR, 1.33, 95%CI, 1.12-1.58 for UCB) and moderate/severe hepatic comorbidity (adjusted HR, 1.57, 95%CI, 1.04-2.38 for 8/8 and 7/8 MUDs; adjusted HR, 1.53, 95%CI, 1.09-2.15 for UCB) had a significant impact on NRM in both donor groups. Cardiac comorbidity (adjusted HR, 1.40, 95%CI, 1.08-1.80), mild hepatic comorbidity (adjusted HR, 1.22, 95%CI, 1.01-1.48), rheumatologic comorbidity (adjusted HR, 1.67, 95%CI, 1.11-2.51), renal comorbidity (adjusted HR, 2.44, 95%CI, 1.46-4.09), and severe pulmonary comorbidity (adjusted HR, 1.40, 95%CI, 1.11-1.77) were significantly associated with an increased risk of NRM but only in UCB recipients. Renal comorbidity had the strongest impact on poor OS in both donor groups (adjusted HR, 1.73, 95%CI, 1.10-2.72 for 8/8 and 7/8 MUDs; adjusted HR, 2.24, 95%CI, 1.54-3.24 for UCB). Therefore, unrelated donor selection should be taken into consideration along with the presence of specific comorbidities, such as cardiac, rheumatologic, renal, mild hepatic, and severe pulmonary comorbidities.

A comparison of haploidentical versus HLA-identical sibling outpatient hematopoietic cell transplantation using reduced intensity conditioning in patients with acute leukemia.

Hematopoietic cell transplantation (HCT) increases survival for acute leukemia. Outpatient allogeneic HCT reduces costs and increases transplant rates in developing countries. We report outcomes of outpatient HLA-identical and haploidentical HCT in acute leukemia. This single-center retrospective cohort study analyzed 121 adult patients with acute myeloblastic (AML) and acute lymphoblastic leukemia (ALL) receiving an outpatient allogeneic HCT with peripheral blood allografts after reduced-intensity conditioning (RIC) from 2012-2022. There were 81 (67%) haploidentical and 40 (33%) HLA-identical transplants. Complete chimerism (CC) at day +100 was not different in HLA-identical compared to haploidentical HCT (32.5% and 38.2%, P=0.054). Post-HCT complications, including neutropenic fever (59.3% vs. 40%), acute graft-versus-host-disease (aGVHD) (46.9% vs. 25%), cytokine release syndrome (CRS) (18.5% vs. 2.5%), and hospitalization (71.6% vs 42.5%) were significantly more frequent in haploidentical HCT. Two-year overall survival (OS) was 60.6% vs. 46.9%, (P=0.464) for HLA-identical and haplo-HCT, respectively. There was no difference in the 2-year disease-free-survival (DFS) (33.3% vs. 35%, P=0.924) between transplant types. In multivariate analysis, positive measurable residual disease (MRD) at 30 days (HR 8.8, P=0.018) and 100 days (HR 28.5, P=0.022) was associated with lower OS, but not with non-relapse mortality (NRM) (P=0.252 and P=0.123, univariate). In univariate analysis, both 30-day and 100-day MRD were associated with lower DFS rates (P=0.026 and P=0.006), but only day 30 MRD was significant in multivariate analysis (P=0.050). In the case of relapse, only MRD at day 100 was associated with increased risk in the univariate and multivariate analyses (HR 4.48, P=0.003 and HR 4.67, P=0.008). Chronic graft-versus-host-disease (cGVHD) was protective for NRM (HR 0.38, P=0.015). There was no difference in cumulative incidence of relapse (CIR) between transplant types (P=0.126). Forty-four (36.4%) patients died, with no difference between HCT type (P=0.307). Septic shock was the most frequent cause of death with 17 cases, with no difference between transplant types. Outpatient peripheral blood allogenic HCT after RIC is a valid and effective alternative for adult patients suffering acute myeloblastic or lymphoblastic leukemia in low-income populations.

Immunological outcomes of autologous hematopoietic stem cell transplantation for multiple sclerosis: a systematic review.

Autologous hematopoietic stem cell transplantation (AHSCT) is an extensive procedure that allows for the depletion of the immune system and its restoration from hemopoietic stem cells. The approach has been modified for the treatment of severe immune-mediated illnesses, including multiple sclerosis (MS), after being initially devised for the treatment of hematological malignancies. This systematic review aims to determine and consolidate the information on the short-term and long-term immunological effects of AHSCT on the cellular level in MS patients. The PubMed, Scopus, and Web of Science servers were used to conduct a systematic search in compliance with the PRISMA guidelines. The results were tabulated and analyzed. A total of 17 studies (10 clinical trials, 6 cohort studies, and 1 case-control study) were included in the final analysis, and 383 MS patients were analyzed. A significant decline in the cell count of CD4 T cells was reported when compared to the CD8 T cells, B cells, and NK cells. B cell count returned to baseline in 71.4% of the studies at the end of 6 months. The NK cell count was found to be above the baseline in 62.5% of studies. AHSCT has been proven to be one of the most effective treatment modalities for MS in recent studies. However, debilitating complications due to immunological outcomes of the procedure have led to increased morbidity. Further research into this domain will help boost the success rate and efficacy of AHSCT.

Graph-Based Imputation Methods and Their Applications to Single Donors and Families.

The outcome of Hematopoietic Stem Cell (HSCT) and organ transplant is strongly affected by the matching of the HLA alleles of the donor and the recipient. However, donors and sometimes recipients are often typed at low resolution, with some alleles either missing or ambiguous. Thus, imputation methods are required to detect the most probably high-resolution HLA haplotypes consistent with a typing. Such imputation algorithms require predefined haplotype frequencies. As such, the phasing of the typing is required for both imputation and frequency generation.We have developed a new approach to HLA haplotype and genotype imputation, where first all candidate phases of a typing are explicated, and then the ambiguity within each phase is solved. This ambiguity is solved through a graph structure of all partial haplotypes and the haplotypes consistent with them.This phasing approach was used to produce an imputation algorithm (GRIMM-Graph Imputation and Matching). GRIMM was then combined with the possibility of combining information from multiple races to produce MR-GRIMM (Multi-Race GRIMM). When family information is available, the phasing of each family member can be restricted by the others. We propose GRAMM (GRaph-bAsed faMily iMputation) to phase alleles in family pedigree HLA typing data and in mother-cord blood unit pairs. Finally, we combined MR-GRIMM with an expectation-maximization (EM) algorithm to estimate haplotype frequencies sharing information between races to produce MR-GRIMME (MR-GRIMM EM).We have shown that these algorithms naturally combine information between races and family members. The accuracy of each of these algorithms is significantly better than its current parallel methods. MR-GRIMM leads to high accuracy in matching predictions. GRAMM better imputes family members than either MR-GRIMM or any existing algorithm and has practically no phasing errors. MR-GRIMME obtains a higher likelihood than existing algorithms.MR-GRIMM, MR-GRIMME, and GRAMM are available as servers or through stand-alone versions in GITHUB and PyPi, as detailed in the appropriate sections.

Early Allogeneic Transplantation Favorably Influences the Outcome of Pediatric Acute Myeloid Leukemia—A Retrospective Study in a Single Center Over 2 Decades

Transplantation advancements offer the potential for improving the prognosis of patients with acute myeloid leukemia (AML). Controversies surrounding indications and timing persist. We focused on identifying prognostic factors and exploring the advantages of early transplantation. We studied 102 pediatric patients with AML (February 1999-August 2022), using Cox regression to analyze survival and hematopoietic cell transplantation (HCT) outcomes and Kaplan-Meier curves to assess HCT timing's impact on prognosis. "Treatment in First Complete Remission [CR1]: Chemotherapy" showed increased risk in multivariate and univariate Cox regression analyses, whereas "HCT during the study period" displayed divergent outcomes. Focusing on transplanted patients, "Treatment in CR1: Chemotherapy" still correlated with higher mortality risk. These findings emphasize the pivotal role of the treatment strategy adopted in CR1 on overall survival rather than HCT alone. Donor cytomegalovirus (CMV) positivity is also related to reduced mortality risk. Kaplan-Meier analysis supported superior 5-year survival rates with "HCT" compared with "chemotherapy" in CR1. In the 3-arm analysis, "HCT in CR1" demonstrated better 5-year overall survival (OS) and 5-year disease-free survival (DFS) compared with "Never HCT," whereas "HCT in CR2" had the least favorable prognosis (5-year OS: 79.2% vs 57.1% vs 50%, P = .056; 5-year DFS: 73.6% vs 55.2% vs 0%, P = .000). Our study highlights the benefits of transplantation during CR1 on prognosis. However, when contemplating CR1 transplantation recommendations, evaluation of various factors, such as the patient's clinical state, relapse risk, transplant-related mortality, CMV status, and other pertinent considerations, is vital. Comprehensive case discussions with patients and families are demanded in optimizing treatment.

Altered Serum Alpha1-Antitrypsin Protease Inhibition before and after Clinical Hematopoietic Stem Cell Transplantation: Association with Risk for Non-Relapse Mortality.

α1-Antitrypsin (AAT), an acute-phase reactant not unsimilar to C-reactive protein (CRP), is a serine protease inhibitor that harbors tissue-protective and immunomodulatory attributes. Its concentrations appropriately increase during conditions of extensive tissue injury, and it induces immune tolerance, in part, by inhibiting the enzymatic activity of the inflammatory serine protease, proteinase 3 (PR3). Typically administered to patients with genetic AAT deficiency, AAT treatment was recently shown to improve outcomes in patients with steroid-refractory graft-versus-host disease (GVHD). GVHD represents a grave outcome of allogeneic hematopoietic stem cell transplantation (HSCT), a potentially curative intervention for hematological diseases. The procedure requires radio/chemotherapy conditioning of the prospective marrow recipient, a cytotoxic process that causes vast tissue injury and, in some formats, interferes with liver production of AAT. To date, changes in the functional profile of AAT during allogeneic HSCT, and during the cytotoxic intervention that precedes HSCT, are unknown. The present study followed 53 patients scheduled for allogeneic HSCT (trial registration NCT03188601). Serum samples were tested before and after HSCT for AAT and CRP levels and for intrinsic anti-proteolytic activity. The ex vivo response to clinical-grade AAT was tested on circulating patient leukocytes and on a human epithelial cell line treated with patient sera in a gap closure assay. According to the ex vivo experiments, circulating leukocytes responded to AAT with a favorable immune-regulated profile, and epithelial gap closure was enhanced by AAT in sera from GVHD-free patients but not in sera from patients who developed GVHD. According to serum collected prior to HSCT, non-relapse mortality was reliably predicted by combining three components: AAT and CRP levels and serum anti-proteolytic activity. Taken together, HSCT outcomes are significantly affected by the anti-proteolytic function of circulating AAT, supporting early AAT augmentation therapy for allogeneic HSCT patients.

Analysis of risk factors for fatal renal complications after allogeneic hematopoietic cell transplantation.

Various complications can influence hematopoietic cell transplantation (HCT) outcomes. Renal complications can occur during the early to late phases of HCT along with various factors. However, studies focusing on fatal renal complications (FRCs) are scarce. Herein, we analyzed 36,596 first allogeneic HCT recipients retrospectively. Overall, 782 patients died of FRCs at a median of 108 (range, 0-3,440) days after HCT. The cumulative incidence of FRCs was 1.7% and 2.2% at one and five years, respectively. FRCs were associated with older age, male sex, non-complete remission (non-CR), lower performance status (PS), and HCT comorbidity index (HCT-CI) associated with renal comorbidity in multivariate analysis. The risk factors within 100 days included older age, multiple myeloma, PS, and HCT-CI comorbidities (psychiatric disturbance, hepatic disease, obesity, and renal disease). Older age and male sex were risk factors between 100 days and one year. After one year, HCT-CI was associated with the presence of diabetes and prior solid tumor; total body irradiation was identified as a risk factor. Non-CR was a common risk factor in all three phases. Furthermore, acute and chronic graft-versus-host disease, reactivation of cytomegalovirus, and relapse of underlying disease also affected FRCs. Systematic follow-up may be necessary based on the patients' risk factors and post-HCT events.

Outcomes of allogeneic hematopoietic stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a currative treatment modality for diffuse large B-cell lymphoma (DLBCL) because of the intrinsic graft-versus-lymphoma effect. However, limited information is available regarding which patients with relapsed or refractory DLBCL are likely to benefit from allo-HSCT. We retrospectively analyzed data from 1268 DLBCL patients who received allo-HSCT. The overall survival and progression-free survival (PFS) rates were 30.3% and 21.6% at 3 years, respectively. Multivariate analysis revealed that stable or progressive disease at transplantation, male patient, poorer performance status at transplantation, and shorter intervals from previous transplantation were associated independently with a lower PFS. Four prognostic factors were used to construct a prognostic index for PFS, predicting 3-year PFS of 55.4%, 43.7%, 20.4% and 6.6%, respectively. The prognostic model predicted relapse rates following allo-HSCT accordingly (P < 0.0001), whereas did not predict transplantation-related mortality (P = 0.249). The prognostic index can identify a subgroup of DLBCL patients who benefit from allo-HSCT and it is worthwhile to evaluate whether this model is also applicable to patients undergoing allo-HSCT in cases of relapse after chimeric antigen receptor engineered T-cell therapy, although the application of allo-HSCT has been declining with the increase of novel immunotherapies.

The Significance of Major Histocompatibility Complex Class I Chain-related Molecule A in Solid Organ and Hematopoietic Stem Cell Transplantation: A Comprehensive Overview.

Improving long-term allograft survival and minimizing recipient morbidity is of key importance in all of transplantation. Improved matching of classical HLA molecules and avoiding HLA donor-specific antibody has been a major focus; however, emerging data suggest the relevance of nonclassical HLA molecules, major histocompatibility complex class I chain-related gene A (MICA) and B, in transplant outcomes. The purpose of this review is to discuss the structure, function, polymorphisms, and genetics of the MICA molecule and relates this to clinical outcomes in solid organ and hematopoietic stem cell transplantation. The tools available for genotyping and antibody detection will be reviewed combined with a discussion of their shortcomings. Although data supporting the relevance of MICA molecules have accumulated, key knowledge gaps exist and should be addressed before widespread implementation of MICA testing for recipients pre- or posttransplantation.