ALBERT

Description: Introduction: Haploidentical hematopoietic stem cell transplantation (HSCT) is a potentially curative intervention for various malignant and non-malignant hematological conditions. Its use has led to the near universal availability of donors, but major challenges compared to HLA-matched related donor (MRD) and HLA-matched unrelated donor (MUD) transplants still exist. Although the most frequently discussed complication of haploidentical HSCT is graft rejection or severe/fatal graft-versus-host disease (GVHD), infection remains a significant cause of morbidity and mortality compared to other forms of transplant. Methods: This was a retrospective, single institution study that analyzed the outcomes of 187 patients with various hematological diseases who received allogeneic HSCT with haplo donor transplants, MRD transplants, or MUD transplants from 2011-2018. Conditioning regimens included combinations of fludarabine, busulfan, cyclophosphamide, melphalan, antithymocyte globulin, and total body irradiation. GVHD prophylaxis included either the combination of cyclosporine, tacrolimus, and mycophenolate mofetil (MMF) or tacrolimus and methotrexate (MTX). All patients received anti-viral prophylaxis with acyclovir, anti-fungal prophylaxis with either an azole or echinocandin, and anti-bacterial prophylaxis with trimethoprim-sulfamethoxazole or levofloxacin if the absolute neutrophil count (ANC) was 0.05). Rates of chronic GVHD were also similar between the two groups at 45% in haplo patients and 48% in non-haplo patients (p 〉0.05). The 100-day infection-related mortality rate following transplant was significantly higher in the haploidentical group at 9% compared to 1% in the non-haploidentical group (p = 0.03, Figure 1). In addition, the 1-year rate of infection-related mortality after transplant was also significantly increased at 16% vs. 4% in the haplo vs. non-haplo groups, respectively (p = 0.01, Figure 2). The proportion of patients who experienced bacterial and fungal infections over this time period was comparable between the two groups (41% vs. 42% for bacterial infections and 18% vs. 12% for fungal infections in haploidentical patients vs. non-haploidentical patients, p 〉0.05 for both) while the incidence rate of viral infections was significantly higher in the haplo group at 72% vs. 38% in the non-haplo group (p 〈 0.001). However, all cases of infection-related mortality were due to bacterial and fungal infections rather than viral with 27% of bacterial or fungal infections leading to patient death in haploidentical patients compared to 7% in non-haploidentical patients (p = 0.02, Figure 3). Conclusion: The results of our study showed that compared to non-haplo transplant recipients, patients who underwent haplo transplants had significantly increased risks of 100-day and 1-year mortality secondary to infections. This finding is supported by prior data demonstrating that there is a longer time to immune reconstitution, specifically of the T-cell subset and dendritic cell subgroup, in the haploidentical population (Chang et. al. Journal of Clinical Immunology 2011). Furthermore, our results showed that the increased risk of infection-related mortality is not due to higher rates of acute or chronic GVHD, implying that the risk may be due to haploidentical transplantation itself as opposed to increased amounts of immunosuppressive therapy. While there was a greater incidence rate of viral infections amongst haploidentical patients, no viral infections led to mortality in either transplant group. In contrast, despite similar rates of bacterial and fungal infections between haploidentical and non-haploidentical patients, these infections led to death more often in the haplo population. These findings are important in considering future approaches to infection prophylaxis and treatment in haploidentical transplant recipients. Disclosures No relevant conflicts of interest to declare.

Description: Background: High dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective choice of treatment for relapsed/refractory non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Historically, carmustine, etoposide, cytarabine, and melphalan (BEAM) has been the most widely used conditioning regimen, shown to significantly improve progression free survival (PFS) and overall survival (OS) with relatively low toxicity. However, high doses of carmustine and etoposide combined with melphalan (BEM), despite increased risks of pulmonary toxicity and severe mucositis, has also demonstrated efficacy as a more intensive preparative regimen with acceptable tolerability in younger populations. We performed a single institution descriptive study in order to compare the outcomes of patients with both NHL and HL treated with either consolidative BEAM or BEM preparative regimens and auto-HSCT. Methods: We identified 65 patients who were treated at USC Norris Comprehensive Cancer Center for relapsed/refractory NHL or HL with HDT and auto-HSCT between 2013 and 2018. 14 patients were excluded from statistical analysis due to insufficient data. The primary outcome was 1-year OS and the secondary outcomes were 100-day mortality and 1-year relapse rate (RR). BEAM consisted of carmustine 150mg/m2, etoposide 200mg/m2, cytarabine 200mg/m2, and melphalan 140mg/m2, while BEM was carmustine 12mg/kg, etoposide 60mg/kg, and melphalan 140mg/m2. Patient baseline characteristics, including age, sex, and diagnosis, were identified to describe the population. The T-test was used to describe groups with continuous outcomes and the Fisher's exact test was used to describe groups with categorical outcomes. A p-value of 〈 0.05 was considered statistically significant. Results: 22 patients who received BEM and 29 patients who received BEAM were included for statistical analysis. The patient's baseline characteristics are shown in Table 1. There was an insignificant trend towards increased 1-year OS (100% vs. 93.10%; p = 0.4996) but a higher 1-year RR (35.29% vs. 33.33%; p = 0.77) in BEM than BEAM. All patients were alive at 100 days; so, no difference was observed between BEAM and BEM with regards to 100-day mortality. Notable differences in demographics between the patients treated with BEAM versus BEM were observed primarily in age and diagnosis. Compared to BEAM, BEM was utilized significantly more in younger patients (mean age at transplant 41.7 vs. 58.6 years old; p 〈 0.0001) with a significantly larger percentage of HL diagnosis (48.28% vs. 5.56%; p = 0.0001). There was no significant difference in the 1-year OS, 100-day mortality or 1-year RR between HL and NHL (p = 0.5333, p = 1, and p = 0.7287, respectively) or between age 〈 50 and age ≥ 50 (p = 0.5271, p = 1, and p = 1, respectively). Conclusions: Both BEAM and BEM HDT for auto-HSCT to treat relapsed/refractory NHL or HL resulted in similar outcomes with no difference observed in 100-day mortality and only minor differences in 1-year OS and 1-year RR. However, significant differences in age and diagnoses of patients treated with these conditioning regimens serve as obstacles for more direct and applicable comparisons. Further analyses including tighter-matched patient cohorts, induction and salvage therapy prior to auto-HSCT, maintenance therapy, as well as treatment-related toxicities are necessary to better differentiate these two preparative regimens and provide additional utility in the clinical setting. Nonetheless, despite the much wider usage of BEAM as a preparative regimen for auto-HSCT in patients with relapsed/refractory lymphomas, BEM appears to be an efficacious alternative, and, therefore, warrants further consideration for future studies. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: The presence of the Philadelphia chromosome has historically been associated with a poor prognosis in patients with acute lymphoblastic leukemia (ALL). Prior studies had demonstrated that the 5-year overall survival (OS) rate among adult patients with Philadelphia-chromosome positive (Ph+) ALL was 25% compared to 41% in Philadelphia-chromosome negative (Ph-) ALL (Moorman et. al. Blood 2007). While hematopoietic stem cell transplantation (HSCT) has long been regarded as the standard of care for adult Ph+ ALL patients despite its significant transplant-related morbidity and mortality, its benefit is less clear in the era of newer-generation tyrosine kinase inhibitors (TKI) such as dasatinib. Methods: We conducted a retrospective study at a single urban transplant center with academic affiliation to analyze the outcomes of adult patients diagnosed with Ph+ ALL between 2005-2018. Patients were treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib and allogeneic HSCT. Chemotherapy regimens included hyper-CVAD, Berlin-Frankfurt-Munster-like (BFM-like) protocol, and a regimen developed at the University of Southern California (USC ALL regimen) using pegaspargase (Douer et. al. Journal of Clinical Oncology 2014). All patients in both the transplant group and the non-transplant group received TKI therapy with dasatinib throughout their treatment courses; in the former, patients received dasatinib both prior to and following their transplants. Statistical analysis was performed using the Fisher Exact Probability Test with p-values 30 x 109/L at the time of diagnosis. When comparing rates of OS and RFS between transplant vs. non-transplant patients in this group, there was also no significant difference. Conclusion: This study showed that in the management of adult Ph+ ALL patients, there was no significant difference in OS or RFS between patients who underwent allogeneic HSCT compared to those who received only combination chemotherapy with dasatinib. In addition, prior studies of Ph+ ALL patients treated with either chemotherapy alone or chemotherapy followed by HSCT concluded that the OS rates were approximately 50%, 35%, and 30% at the 1-year, 2-year, and 3-year marks, respectively (Rowe et. al. Blood 2005). Our analysis, however, demonstrated improved rates of survival at all time points for this patient population with the addition of dasatinib. Subgroup analysis of patients with a WBC 〉30 x 109/L at the time of diagnosis also showed no significant difference in OS between transplant and non-transplant patients despite previous reports showing a survival benefit from HSCT (Huang et. al. Blood 2016). This may be attributed to the fact that our patients received the newer and more potent agent dasatinib compared to imatinib in these prior studies. Since allogeneic HSCT demonstrated no survival benefit in our study and can also introduce risks of serious infectious complications, venoocculsive disease (VOD), and graft-versus-host disease (GVHD) that contribute to patient morbidity and mortality, it may serve a less beneficial role for the Ph+ ALL population in the era of newer-generation TKIs. Disclosures No relevant conflicts of interest to declare.