Background: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. Results: The invasive cancer incidence decreased by 47.8% during 1995–2006. The carcinoma in situ incidence increased 1.7-fold during 1995–2000, and decreased by 19.6% during 2000–2006. Conclusion: The Taiwan national programme has significantly decreased invasive cervical cancer.
Background: While haploidentical transplantation has led to the near-universal availability of donors, several challenges for this form of transplant still exist. This study sought to investigate the rates of infection-related mortality and other complications following haploidentical vs nonhaploidentical transplant. Methods: We conducted a retrospective cohort study in adults with various malignant and benign hematological conditions who underwent allogeneic hematopoietic stem cell transplantation from 2011 to 2018. One hundred-day and 1-year overall survival were defined as survival from the time of transplant until 100 days or 1 year later. Results: A total of 187 patients were included in this study, with 45 (24.1%) receiving transplants from haploidentical donors and 142 (75.9%) from nonhaploidentical donors. There were similar rates of acute graft-versus-host disease (GVHD) (40% vs 38% in haploidentical vs nonhaploidentical recipients, P=0.86) and chronic GVHD (44.4% vs 43.7%, P=1). Rates of 100-day and 1-year infection-related mortality were significantly higher in the haploidentical group compared to the nonhaploidentical group (8.9% vs 1.4% at 100 days, P=0.03, and 15.9% vs 3.8% at 1 year, P=0.01). There were also higher rates of cytomegalovirus infections (59.1% vs 23.8%, P<0.01), BK virus-associated hemorrhagic cystitis (40.9% vs 8.4%, P<0.01), and BK viremia (15.9% vs 0.8%, P<0.01) in haploidentical recipients. Conclusions: Despite the use of identical antimicrobial prophylactic and treatment agents, haploidentical recipients were found to have significantly increased rates of 100-day and 1-year infection-related mortality as well as several other infectious complications.
Checkpoint inhibitors have become a widely used and available immunotherapy option for treating a variety of malignancies, including hematological malignancies. Patients receiving these therapies may go on to receive a curative allogeneic hematopoietic stem cell transplant (allo-HSCT). This presents a clinical challenge as the safety and efficacy of HSCT is not well reported in this subset of patients and residual programmed death-ligand 1 inhibition could potentially enhance allogeneic T-cell responses, improving the graft-versus-tumor effect, but also increasing the incidence and severity of immune complications such as graft-versus-host disease (GVHD). Here, this report includes a detailed literature review summarizing all available data on HSCT outcomes in the setting of using checkpoint inhibitor therapy pre-transplant. Moreover, we report a case of acute GVHD after allo-HSCT in a patient with high-risk myelodysplastic syndrome who received prior atezolizumab therapy, highlighting the importance of further research into this specific population in order to improve transplant-related outcomes.
Background: Haploidentical hematopoietic cell transplantation (haplo-HCT) has emerged as a popular alternative to traditional HLA-matched hematopoietic cell transplant. As the number of haplo-HCT's rises, investigating the factors that may affect outcomes is necessary in order to improve overall survival and reduce transplant-related mortality. The optimal dose of CD34+ cells used during haplo-HCT to ensure favorable outcomes using PTCy has not yet been reported though a range of 2 to 5.00x106 cells/kg is commonly used.Furthermore, the optimal dose of CD3+ cells is unknown however recent data has suggested less than 3.00x108 cells/kg may prevent the development of acute GVHD. The importance of studying the impact of CD34+/CD3+ cell dosing may help to improve outcomes in this setting. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 21) who received haplo-HCT from 2014 to 2019. The primary end-point assessed was 1-year GVHD-free/relapse-free survival (GRFS) defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. Secondary end-points included 1-, 2-, and 3-year relapse-related mortality (RRM) and overall survival (OS) in addition to 1-year transplant related mortality (TRM) and incidence of both acute and chronic GVHD. Results: A total of 67 adult haplo-HCT recipients were reviewed. Of the patients evaluated, approximately 50% (n = 33) were male and 49% (n = 32) were female. The age range was 21-71 years old (median = 44), and the most common underlying hematologic disorders included AML (40%), ALL (38%), aplastic anemia (7.7%), and others (MDS, lymphoma, myelofibrosis, and HLH) (13.8%). 67% of patients received myeloablative conditioning regimens while 33% received reduced intensity regimens. 70% (n = 47) of patients received peripheral blood as a stem cell source with 30% (n = 20) receiving bone marrow. The mean CD34+ dose infused was 6.07x106 cells/kg and the mean CD3+ dose was 2.94x108 cells/kg. The mean time to recovery of platelets, neutrophils, and lymphocytes was 25, 18, and 37 days respectively. CD34+ stem cells ≥5.00x106 cells/kg was significantly associated with shorter time to lymphocyte recovery (p = 0.0265) though recovery less than 30 days was not significantly associated with OS (p = 0.5268). Incidence of 1-year GRFS was 71% (n= 46) and 1-, 2-, and 3-year RRM were 4.6%, 6%, and 7.7% respectively. 1-year TRM was 15.3% with 50% of deaths from acute GVHD. 1-, 2-, and 3-year OS were 80%, 78%, and 77% respectively. Factors significantly associated with increased mortality included use of RIC regimen (p = 0.004) and disease status at time of transplant (p = 0.04). Cumulative incidence of GVHD was 63% (n = 42) with 33% (n = 22) and 30% of patients (n = 20) with acute and chronic GVHD respectively. Lack of mild chronic GVHD was associated with increased mortality (p = 0.0029) and use of a myeloablative regimen (p = 0.0029) was significantly associated with GVHD. Subgroup analysis of those who received CD34+ dose ≥7.00x106 cells/kg (n = 24) and ≥10x106 cells/kg (n = 7) were found to have 1-year OS of 87.5% and 85.7% compared with 77% and 80% in those that received lower doses (p= 0.2229 and p = 1.00) respectively however this was not found to be significantly associated with increased incidence of GVHD, relapse, or mortality. Discussion: Our results demonstrate improved outcomes specifically 71% survived 1 year without experiencing at least 1 GRFS event compared with 24-35% reported by CIBMTR, Holtan et al 2015, and Solh et al 2016 with 3-year OS of 77% when compared with a previously reported 48%. The mean CD34+ cell dose of our population is higher than the standard range which may account for the improved outcomes however the dosing of CD34+/CD3+ cells were not significantly associated with our primary and secondary end-points. It was significantly associated, however, with shorter time to lymphocyte recovery, a factor that has been reported to be associated with decreased RRM and therefore improved OS. Furthermore, subgroup analysis of higher CD34+ dose did show a better 1-year OS though this was not statistically significant. Limitations of this study include small sample size and short follow-up period. Further research with a prospective study identifying the optimal CD34+/CD3+ cell dose in addition to comprehensive evaluation of immune recovery is warranted in order to improve haplo-HCT outcomes. Figure Disclosures Yaghmour: Jazz Pharmaceutical company: Consultancy, Speakers Bureau; Astella company: Speakers Bureau; Takeda: Speakers Bureau.
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