Citations

As cellular therapies gradually become the mainstay of treatment for several nonmalignant diseases, there appears to be varied accessibility to these therapies globally. Despite considerable burden of nonmalignant conditions, such as sickle cell disease, thalassemia, and aplastic anemia in populations of low–middle-income countries, the utilization of cellular therapies remain sparse because of lack of resources. Globally, the frequency of hematopoietic stem cell transplant (HSCT) has increased disproportionately in countries with higher gross national income (GNI) per capita, governmental healthcare expenditures, and a high human development index. This leads to a large subset of international patients seeking care in the United States. This review summarizes the unique set of challenges that often arise when offering sophisticated therapies such as HSCT to international patients constituting of cross-cultural, logistical, financial, and medical challenges and the opportunities that are available to bridge the gap.

AbstractThe number of non‐Hodgkin lymphoma (NHL) survivors is increasing. With the advancement of NHL therapies, it is crucial to focus on the challenges these survivors may face. Three main categories are to be considered in NHL survivorship, including quality of life and uncertainty about the future, possible physical health complications (including cardiovascular disease, infertility, and subsequent neoplasms), and the impact of novel NHL treatments and their potential complications. The latter includes CAR T‐cell therapy, monoclonal antibodies, checkpoint inhibitors, and hematopoietic stem cell transplantation. In this report, we aim to shed the light on these aspects and to discuss survivorship care plan for NHL.

Abstract Background There has been an increase in overall utilization as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for most hematologic disorders over time. It is not known if these changes have impacted racial/ethnic minorities equally. In this study, we describe changes in the volume and rate of autologous (auto) and allogeneic (allo) HCT and examine trends in survival in different racial/ethnic groups from 2009 to 2018. Methods Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) which collects patient data on most autologous and allogeneic HCT recipients in the US. We compared the number of auto and allo transplants in 4 different racial/ethnic groups: Non-Hispanic Whites (NHWs), African Americans (AAs), Hispanics and 'Others' across five 2-year cohorts from 2009 to 2018. 'Others' included Asians, Pacific Islanders and Native Americans as well as non-US residents. Since numbers in individual categories were too low to be meaningful, they were grouped together as 'Others'. Multi race individuals and those with either race or ethnicity missing were excluded. Cox proportional hazards models were used to examine trends in overall mortality after auto HCT in adult patients (for NHL, HD, and MM), and allo HCT among adult and pediatric patients (for AML, ALL, lymphoma including chronic lymphocytic leukemia, and MDS/MPD) in the 4 different racial ethnic groups over 5 study time periods. These models were adjusted for sociodemographic and clinical variables (age, sex, Karnofsky/Lansky score, HCT-comorbidity index, disease, disease status, geographic region, insurance, marital status, education, distance to the transplant center, median income derived from patient's ZIP code). Graft type, donor, conditioning, GVHD prophylaxis, donor-recipient CMV match and donor-recipient sex match were included for allo HCT models. Results A total of 80,080 (59,666 NHWs, 10,683 AAs, 7,110 Hispanics) patients received an auto HCT and 60,412 (44,272 NHWs, 4,964 AAs, 7,826 Hispanics) received an allo HCTs from 2009 to 2018. The volume of auto and allo transplants increased overall, as well as within each race/ethnicity group, over the study periods. In addition, there was a significant change in the proportion of patients in each racial/ethnic group undergoing an auto HCT, with a lower proportion of NHWs and increased proportion of minorities over time (from 78%, 12% and 8% in 2009 -2010 to 71%, 15% and 10% in 2017-2018 for NHWs, AAs and Hispanics respectively; p<0.001). Similar trends were observed for allo HCT: from 76%, 8% and 12% in 2009-2010 to 71%, 9% and 14% in 2017-2018 of all allo HCTs for NHWs, AAs and Hispanics respectively; p<0.001. While there was an increase in the rate of transplants over the years across all racial/ethnic groups, the rate was higher in AAs and Hispanics as compared to NHWs (Table 1). There was no significant difference in overall mortality amongst the three main racial ethnic groups, though there was decrease in mortality over time for auto HCT and adult allo HCT patients. In the allo HCT pediatric group, AAs had higher overall mortality as compared to NHWs across all time periods. (Table 2) Figure 1 shows temporal trends in two-year survival by race and ethnicity. Conclusions This large population-based study shows an improvement in the rates and survival of auto and allo HCT in adults over time. Changes in the proportion of different racial/ethnic groups undergoing HCT are higher than rate of change of population growth (3% decline for NHWs, no change in AAs and 2% increase in Hispanics from 2010 to 2019 per William H. Frey analysis of census population estimates released June 25, 2020). Progress is reflected in higher rates of increase in racial/ ethnic minority groups and comparable survival across the racial ethnic groups in our cohort as compared to two prior registry studies (Baker et al. JCO 2005 and Baker et al. BBMT 2009) for most HCT patients. However, in pediatric patients undergoing allo HCT, the gap in survival between NHWs and AAs has continued to persist over the years. With increasing diversity of the US population, we need to strengthen our efforts for improving access to, and outcomes of HCT to narrow the gap for all patients requiring HCT, irrespective of their sociodemographic characteristics. Figure 1 Figure 1. Disclosures Wood: Koneksa Health: Consultancy, Current equity holder in publicly-traded company; Teladoc: Consultancy; Pfizer: Research Funding. Ailawadhi: Karyopharm: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Takeda: Consultancy; GSK: Consultancy, Research Funding; Xencor: Research Funding; Cellectar: Research Funding; Medimmune: Research Funding; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; BeiGene, Ltd.: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy. Saber: Govt. COI: Other.

Abstract Introduction: In recent years, there has been an expanding focus on interplay between intestinal microbiotal diversity and outcome of acute graft versus host disease(GVHD) in hematopoietic stem cell transplantation (HCT) recipients. One of the compelling intervention to maintain healthy gut microbiota for better outcome of GVHD in HCT recipients is Fecal microbial transplantation(FMT). Several non randomized small clinical studies and case reports on the efficacy and safety of FMT were reported so far. However, the ultimate role of FMT as a therapeutic option to treat GVHD is yet to be determined due to lack of randomised, large scale, statistically significant studies. Here in, we report a systemic review of literature available so far in an effort to establish a definite role of FMT. Methodology: A systemic literature search was conducted using various electronic databases. The case reports, case series and clinical studies related to FMT were used as a therapeutic or preventative modality specifically for GVHD are included. Results: Upon pooling of data, 87 patients from 6 studies and 5 case reports were included in the study in which complete remission(CR) occured in 43.7% and partial remission(PR) occured in 20.7% patients which is equivalent to 64.4% overall response rate in treating GVHD. Furthermore, out of all the species in fecal matter, clostridium was found to be the most valuable species in decreasing the rates of GVHD re-occurrence. Only a limited number of patients had treatment-related mortality (TRM) from GVHD while few showed mild GI-related (abdominal pain/distention, nausea, regurgitation) and non-GI adverse reactions including infections, anemia, thrombocytopenia, paroxysmal, and atrial fibrillation. We emphasize that the most of the patients did not have any major complications after FMT. Conclusion: We conclude that the FMT is a safe and effective strategy for the management of GVHD based on our study. The establishment of gut diversity along with the patient's intrinsic factors like fucosyltransferase 2 (FUT2) secretor status and baseline gut microbial diversity play a major role in the success of FMT. Given the restricted size and absence of randomized data, one cannot portray FMT as a standard of care yet, however, the low or absent toxicity along with improvement in survival justifies this modality to be tested in a randomized fashion. We strongly encourage the transplant community to enroll patients in innovative trials utilizing FMT, as this may be a one of the safest strategies for both prevention and treatment of GVHD Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: It has been shown that racial/ethnic minorities have worse survival after matched unrelated donor allogeneic hematopoietic cell transplantation(allo-HCT) compared to Whites. Whether the racial disparity in allo-HCT outcomes persists in long-term survivors, and possibly may even be exacerbated in this population that frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study we sought to compare long-term outcomes among one-year survivors, by race/ethnicity and socioeconomic status (SES), after allo-HCT reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods: The CIBMTR database was used to identify 5,473 patients with Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myeloid Leukemia (CML), or Myelodysplastic Syndrome (MDS) who received HCT between 2007-2017, who were alive and in remission for at least 1 year after allo-HCT. Study was restricted to patients transplanted in the United States. Cox regression model was used to determine association of ethnicity/race and SES with overall survival (OS), relapse, and treatment related mortality (TRM). Standardized mortality ratio (SMR) was calculated to compare mortality rates of the study patients to their general population peers matched on race/ethnicity, age and sex. Results: Patients were reported to be Non-Hispanic White (W) (n=4385), Non-Hispanic Black (B) (n=338), Hispanic (H) (n=516), and Asian (A) (n=234). Median follow up after 1 year allo-HCT (months): 69 W, 50 B, 59 H and 57 A (Table 1). Patient neighborhood poverty level was estimated from residential ZIP code at the time of allo-HCT. A ZIP code with ≥20% of persons below the federal poverty level was considered high poverty area. In multivariable analysis, we observed no significant differences in OS, relapse or TRM based on race or poverty level when adjusted for patient-, disease- and transplant-related covariates (Table 2). Conclusions: Our study highlights that among those who survived at least 1-year in remission after allo-HCT, previously reported disparities in post HCT outcomes based on racial/ethnic factors, are not evident in contemporary practice. This might suggest that previously recognized disparity in outcomes could be due to factors that mostly affect patients in their first year post HCT. Future studies are needed to identify these early adverse factors and implement strategies to mitigate them. Figure 1 Figure 1. Disclosures Blue: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; WebMD: Consultancy. Wood: Pfizer: Research Funding; Teladoc: Consultancy; Koneksa Health: Consultancy, Current equity holder in publicly-traded company. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Saber: Govt. COI: Other.