Factors associated with survival in a contemporary adult sickle cell disease cohort: Factors Associated with Survival in Sickle Cell Disease

We examined the relationship of clinical differences among sickle cell disease (SCD) patients in order to understand the major contributors to early mortality in a contemporary cohort

Haploidentical donor hematopoietic cell transplantation for myelodysplastic/myeloproliferative overlap neoplasms: results from a North American collaboration

Haploidentical donors offer a potentially readily available donor, especially for non-White patients, for hematopoietic cell transplantation (HCT). In this North American collaboration, we retrospectively analyzed outcomes of first HCT using haploidentical donor and post-transplantation cyclophosphamide (PTCy) in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap neoplasms (MDS/MPN). We included 120 consecutive patients who underwent HCT using a haploidentical donor for MDS/MPN across 15 centers. Median age was 62.5 years and 38% were of non-White/Caucasian ethnicity. The median follow-up was 2.4 years. Graft failure was reported in seven of 120 (6%) patients. At 3 years, nonrelapse mortality (NRM) was 25% (95% confidence interval [CI]: 17-34), relapse 27% (95% CI: 18-36), grade 3-4 acute graftversus- host disease 12% (95% CI: 6-18), chronic graft-versus-host disease requiring systemic immunosuppression 14% (95% CI: 7-20), progression-free survival (PFS) 48% (95% CI: 39-59), and overall survival (OS) 56% (95% CI: 47-67). On multivariable analysis, NRM was statistically significantly associated with advancing age at HCT (per decade increment, subdistribution hazard ratio [sdHR] =3.28; 95% CI: 1.30-8.25); relapse with the presence of mutation in EZH2/RUNX1/SETBP1 (sdHR=2.61; 95% CI: 1.06-6.44); PFS with advancing age at HCT (per decade increment, HR=1.98, 95% CI: 1.13-3.45); and OS with advancing age at HCT (per decade increment, HR=2.01; 95% CI: 1.11-3.63) and splenomegaly at HCT/prior splenectomy (HR=2.20; 95% CI: 1.04-4.65). Haploidentical donors are a viable option for HCT in MDS/MPN, especially for those disproportionately represented in the unrelated donor registry. Hence, donor mismatch should not preclude HCT for patients with MDS/MPN, an otherwise incurable malignancy. In addition to patient age, disease-related factors including splenomegaly and high-risk mutations dominate outcomes following HCT

Donor Types and Outcomes of Transplantation in Myelofibrosis: a CIBMTR Study

We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P \u3c .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries

Immune Reconstitution after Haploidentical Donor and Umbilical Cord Blood Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for a variety of hematologic diseases. However, this therapeutic platform is limited by an initial period when patients are profoundly immunocompromised. There is gradual immune recovery over time, that varies by transplant platform. Here, we review immune reconstitution after allogeneic HCT with a specific focus on two alternative donor platforms that have dramatically improved access to allogeneic HCT for patients who lack an HLA-matched related or unrelated donor: haploidentical and umbilical cord blood HCT. Despite challenges, interventions are available to mitigate the risks during the immunocompromised period including antimicrobial prophylaxis, modified immune suppression strategies, graft manipulation, and emerging adoptive cell therapies. Such interventions can improve the potential for long-term overall survival after allogeneic HCT

Immune Reconstitution after Haploidentical Donor and Umbilical Cord Blood Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for a variety of hematologic diseases. However, this therapeutic platform is limited by an initial period when patients are profoundly immunocompromised. There is gradual immune recovery over time, that varies by transplant platform. Here, we review immune reconstitution after allogeneic HCT with a specific focus on two alternative donor platforms that have dramatically improved access to allogeneic HCT for patients who lack an HLA-matched related or unrelated donor: haploidentical and umbilical cord blood HCT. Despite challenges, interventions are available to mitigate the risks during the immunocompromised period including antimicrobial prophylaxis, modified immune suppression strategies, graft manipulation, and emerging adoptive cell therapies. Such interventions can improve the potential for long-term overall survival after allogeneic HCT

Trends and in-hospital cardiac complications in patients with atrial fibrillation undergoing allogeneic stem cell transplant: A National Inpatient Sample analysis (2002-2019)

BACKGROUND: Cardiovascular comorbidities increase the risk of transplant-associated complications. However, the impact of atrial fibrillation (AF) as an independent risk factor remains limited. METHODS: The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases codes to identify patients admitted for allogeneic stem cell transplant (ASCT). The patients were then subclassified into with and without AF. Subsequently, a multivariate logistic regression model was constructed to account for patient demographics, comorbidities, and hospital characteristics to evaluate the impact of AF on the primary outcome of interest: all-cause mortality, and secondary outcomes of interest that included common hospitalization complications. RESULTS: The data for 77 157 cases of ASCT were collected between 2002 and 2019. Among these 5086 (6.6%) cases had concurrent AF. Multivariate logistic regression revealed patients undergoing ASCT with AF had almost a three times higher risk of all-cause mortality (odds ratio = 2.99 [95% confidence interval: 2.73-3.28]; p \u3c .01). AF patients also had a higher risk for cardiac arrest, cardiogenic shock, acute kidney injury, and need for hemodialysis (all p \u3c .01). CONCLUSION: AF causes a higher risk of death and cardiovascular complications among patients undergoing ASCT. This signifies the importance of pretransplant consultation and optimization for cardiovascular comorbidities to improve hospitalization outcomes

Factors associated with survival in a contemporary adult sickle cell disease cohort

In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand the major contributors to early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who were enrolled since 2002 at three university hospitals in the southeast United States. Subjects were followed up for a median of 9.3 years. At enrollment, clinical parameters were collected, including hemoglobin (Hb) genotype, baseline laboratory values, comorbidities, and medication usage. Levels of soluble adhesion molecules were measured for a subset of 87 subjects. The relationship of clinical characteristics to survival was determined using regression analysis. Median age at enrollment was 32 years. Median survival was 61 years for all subjects. Median survival for Hb SS and Sb 0 was 58 years and for Hb SC and Sb 1 was 66 years. Elevated white blood count, lower estimated glomerular filtration rate, proteinuria, frequency of pain crises, pulmonary hypertension, cerebrovascular events, seizures, stroke, sVCAM-1, and short-acting narcotics use were significantly associated with decreased survival. Forty-two percent of subjects were on hydroxyurea therapy, which was not associated with survival. SCD continues to reduce life expectancy for affected individuals, particularly those with Hb Sb 0 and SS. Not only were comorbidities individually associated with decreased survival but also an additive effect was observed, thus, those with a greater number of negative endpoints had worse survival (P < 0.0001). The association of higher sVCAM-1 levels with decreased survival suggests that targeted therapies to reduce endothelial damage and inflammation may also be beneficial

Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients

Supplementary tables - baseline characteristics of CYP3A4, CYP3A5 and ABCB1 phenotypes</p