High-risk Transplant Patients Research Articles

Asciminib Maintains Antibody-Dependent Cellular Cytotoxicity against Leukemic Blasts.

B cell acute lymphoblastic leukemia (B-ALL) is characterized by an accumulation of malignant precursor cells. Treatment consists of multiagent chemotherapy followed by allogeneic stem cell transplantation in high-risk patients. In addition, patients bearing the BCR-ABL1 fusion gene receive concomitant tyrosine kinase inhibitor (TKI) therapy. On the other hand, monoclonal antibody therapy is increasingly used in both clinical trials and real-world settings. The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839). The efficacy of monoclonal antibodies is based, at least in part, on their ability to induce antibody-dependent cellular cytotoxicity (ADCC). Combination treatments, e.g., chemotherapy and TKI, should therefore be screened for potential interference with ADCC. Here, we report on in vitro data using BCR-ABL1 positive and negative B-ALL cell lines treated with rituximab and TKI. NK cell activation, proliferation, degranulation, cytokine release and tumor cell lysis were analyzed. In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials.

Quantifying the Benefits of Increasing Decision-Making Frequency for Health Applications with Regular Decision Epochs

Sequential decision-making problems in the context of uncertainty naturally arise in healthcare settings. In general, the frequency at which decisions can be made or changed is determined by physical limitations, such as the frequency of doctor’s visits or transplantation offers. Quantifying the benefits of increasing the frequency of decision-making allows us to quantify the value of changing these physical constraints and thus improve the quality of care. In this paper, we study the value provided by having additional decision-making opportunities in each epoch. We model this problem using a Markov decision process (MDP) framework. We provide structural properties of the optimal policies and quantify the difference in optimal values between MDP problems of different decision-making frequencies. We analyze numerical examples using liver transplantation in high-risk patients and treatment initiation in chronic kidney disease to illustrate our findings.

310.4: Disparities in Low Respiratory Vaccination Among Solid Organ Transplant Recipients

Introduction: Influenza is the most common vaccine-preventable infection the first 5 years post-transplant. Despite the availability of safe and effective vaccines, vaccine uptake is low among high-risk transplant patients who are recommended to receive pneumococcal and annual influenza vaccines. While disparities in vaccination have been observed by race, with lower uptake among Blacks and Hispanics, little is known about the role of sociodemographic characteristics including an individual-level housing-based HOUSES index, education, marital status and geographic location (rural/urban classification) play in vaccine uptake. To improve health outcomes and vaccine coverage, we must identify and target populations with low uptake. Methods: We conducted a cross-sectional, population-based study using the Rochester Epidemiology Project (REP), a medical records linkage system, to assess sociodemographic factors associated with influenza and pneumococcal vaccination rates among adults aged 19-64 years old with solid organ transplants, living in four counties in southeastern Minnesota. Socioeconomic status (SES) was assessed via HOUSES, measure of SES. Vaccination data was obtained from the Minnesota Immunization Information Connection (MIIC) from June 1, 2010-June 30, 2020. Influenza vaccination rate was assessed with Poisson regression models, offset by number of vaccines eligible for; pneumococcal status was assessed with logistic regression models. Results: 468 solid organ transplant patients were identified (Table 1). Liver and lung transplant patients were least vaccinated for influenza. Influenza vaccination ranged from 52-58% over the past 10 years which was slightly higher than national averages and adults in our area who were recommended to receive pneumococcal vaccines (35-43%). Race was not significantly associated with influenza vaccine uptake when adjusted for geographic region or SES as assessed by HOUSES. If patients were up-to-date on pneumococcal vaccine they had a 26% higher influenza vaccination rate. Heart transplants recipients were least up-to-date on pneumococcal vaccines. 56% of patients were compliant with pneumococcal vaccines, with a median of 18 months under vaccinated. Those living in urban settings were significantly better vaccinated for both influenza and pneumococcus even when adjusted for all other variables (Table 2). Conclusions: Rates of vaccination were well below national goals, even though transplant recipients did better than other national estimates of this high-risk group. The transplant process includes rigorous review of vaccinations with close follow-up, and despite this many patients remained under vaccinated. Further investigation is needed to understand and address barriers to vaccination among transplant recipients. This is especially important among subgroups with particularly low rates of adoption, seen particularly in those outside urban areas.Funding received from Eradicating Racism, Mayo Clinic and Rochester Epidemiology Project, Mayo Clinic.

Precision Medicine in Myeloid Malignancies: Hype or Hope?

We review how understanding the fitness and comorbidity burden of patients, and molecular landscape of underlying acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the time of diagnosis is now integral to treatment. The upfront identification of patients' fitness and molecular profile facilitates selection of targeted and novel agents, enables risk stratification, allows consideration of allogeneic hematopoietic cell transplantation in high-risk patients, and provides treatment selection for older (age ≥ 75) or otherwise unfit patients who may not tolerate conventional treatment. The use of measurable residual disease (MRD) assessment improves outcome prediction and can also guide therapeutic strategies such as chemotherapy maintenance and transplant. In recent years, several novel drugs have received FDA approval for treating patients with AML with or without specific mutations. A doublet and triplet combination of molecular targeted and other novel treatments have resulted in high response rates in early trials. Following the initial success in AML, novel drugs are undergoing clinical trials in MDS. Unprecedented advances have been made in precision medicine approaches in AML and MDS. However, lack of durable responses and long-term disease control in many patients still present significant challenges, which can only be met, to some extent, with innovative combination strategies throughout the course of treatment from induction to consolidation and maintenance.

Clinical Analysis of Pediatric Acute Myeloid Leukemia with CCLG-AML 2015 Regimen

To analyze the clinical effects of CCLG-AML-2015 protocol on newly diagnosed children with acute myeloid leukemia (AML). The clinical data of 60 newly diagnosed AML children in the Department of Hematology and Oncology, Wuhan Children's Hospital from August 2015 to September 2019 were summarized, the effect of chemotherapy using the CCLG-AML-2015 regimen (hereinafter referred to as the 2015 regimen) were retrospectively analyzed. 42 children with AML treated by the AML-2006 regimen (hereinafter referred to as the 2006 regimen) from February 2010 to July 2015 were used as control group. There were no statistical differences between the 2015 regimen group and the 2006 regimen group in sex, age at first diagnosis, and risk stratification (P>0.05). The complete remission rate of bone marrow cytology after induction of 1 course of chemotherapy (84.7% vs 73.1%, P=0.155), and minimal residual disease detection (MRD) negative (42.3% vs 41.4%, P=0.928) in the 2015 regimen group were not statistically different than those in the 2006 regimen group. The bone marrow cytology CR (98.1% vs 80.6%, P=0.004) and MRD negative (83.3% vs 52.8%, P=0.002) in the 2015 regimen group after 2 courses of induction were higher than those in the 2006 regimen group. The 5-year overall survival (OS) rate in the 2015 regimen group (62.3%±6.4% vs 20.6%±6.4%, P=0.001), the 5-year disease-free survival (EFS) rate (61.0%±6.4% vs 21.0% ±6.4% , P=0.001) were better than those in the 2006 regimen group. The 5-year OS and EFS of high-risk transplant patients in the 2015 regimen group were significantly better than those of high-risk non-transplant patients (OS: 86.6%±9.0% vs 26.7%±11.4%, P=0.000; EFS: 86.6%±9% vs 26.7%±11.4%, P=0.000). The 2015 regimen can increase the CR rate after 2 courses of induction compared with the 2006 regimen. High-risk children receiving hematopoietic stem cell transplantation can significantly improve the prognosis.

POS-754 PERSISTENT HYPERPARATHYROIDISM AFTER KIDNEY TRANSPLANTATION, ITS PREVALENCE AND RISK FACTORS

Persistent hyperparathyroidism (pHPT) is common after successful kidney transplantation (KTx) and is related to pretransplant risk factors. pHPT is associated with increased graft loss, mortality and increased risk of fractures. This study aims to evaluate the prevalence and risk factors for pHPT after KTx. A retrospective study of kidney transplant recipients attending the transplant clinic between November 2018 and March 2020 was performed. The laboratory data of patients (Serum calcium, phosphorus, creatinine, intact parathyroid hormone (iPTH) and estimated glomerular filtration rate (eGFR)) were collected at 12 months posttransplantation and at pretransplantation. The persistency of HPT after transplant was defined as iPTH ≥ 130 pg/mL, and the term "tertiary hyperparathyroidism" (THPT) was used for patients with pHPT how needed parathyroidectomy (PTx). Risk factors for the development of pHPT were investigated by comparing THPT and non-pHPT groups. Data for 80 patients were analyzed. After one year of KTx, HPT persists in 18 patients (22.5%), of whom six patients underwent parathyroidectomy, and 12 patients were kept on conservative management. Compared with non-HPT group, patients with THPT had significantly longer dialysis duration (43 ± 32.6 mo vs 12.6 ± 13.9 mo. P = 0.013), higher pre-KTx iPTH (1138.7 ± 669.8 vs 365.5 ± 178.6 pg/ml, P = 0.001), and higher pre-KTx calcium (10.1 ± 0.61 vs 8.6 ± 0.60 mg/dl, P < 0.0001). Based on our study results, the most important risk factors for post-KT pHPT are long dialysis duration and high pre-KTx iPTH and Ca levels. Therefore, parathyroidectomy must be considered before kidney transplantation in high-risk patients.

Newly Diagnosed Childhood AML Patients Treated with Bortezomib Show Superior Survival If CD74 Is Expressed: A Report of 991 Patients from the Children's Oncology Group AAML1031 Protocol

Introduction: CD74 is a type II transmembrane protein expressed on antigen-presenting cells and an MHC class II chaperone. It has been associated with tumor progression and metastasis in solid tumors, and its expression has been suggested to serve as a prognostic factor in many cancers, with higher relative expression associated with oncogenesis. As the expression of CD74 has been associated with response to bortezomib in multiple myeloma, we inquired whether such correlation might be seen in pediatric AML. We prospectively evaluated CD74 expression by difference from normal (ΔN) flow cytometry and correlated expression with clinical characteristics and outcome as part of Children's Oncology Group protocol AAML1031 that randomized patients younger than 30 years of age with de novo AML to standard treatment with (Arm B) or without (Arm A) bortezomib. The addition of bortezomib to standard chemotherapy increased toxicity but did not improve survival. Given the association of CD74 with B-lymphoid neoplasms and bortezomib's known efficacy in B-cell neoplasms and multiple myeloma, we hypothesized that within Arm B, the patients with CD74 expression would have a more favorable outcome. Methods: In total, 1,139 newly diagnosed pediatric patients with de novo AML were randomized to standard chemotherapy (n=561, Arm A) or standard chemotherapy with bortezomib (n=578, Arm B). All patients received the identical chemotherapy backbone with either four intensive chemotherapy courses or three courses followed by allogeneic hematopoietic stem cell transplantation for high-risk patients. To qualify for this correlative study, 991 patients satisfied 2 criteria: (1) submitting a bone marrow aspirate for ΔN at diagnosis and (2) providing consent for correlative biology studies. All diagnostic specimens were centrally and prospectively evaluated for the expression of CD74 by ΔN. AML was considered to be CD74-positive if the MFI was more than two times above background autofluorescence and more than 40% of the leukemia was above background autofluorescence. Results: Among 991 patients, 263 were CD74-positive (26.5%) by ΔN, with similar prevalence in Arm A (27.9%) and Arm B (25.2%). Correlation of CD74 expression with clinical characteristics showed that those with CD74 expression had higher median age (p&amp;lt;0.001), lower median WBC (p&amp;lt;0.001), higher prevalence of low risk protocol status (p=0.039), lower frequency of CEBPA mutation (p=0.039), inv(16) (p=0.001), and KMT2A rearrangements (p=0.002), and were enriched for t(8;21) (p&amp;lt;0.001) and t(6;9) (p=0.014) fusions. All these features retained significance when patients were sub analyzed by respective treatment arms. CD74-positive patients had a higher morphologic CR rate (p=0.016), however, measurable residual disease by flow cytometry was not significant in the entire cohort or in the sub analysis of treatment arms (p=0.155). CD74-positive patients showed superior 5-year OS (70.6% vs 61.8%, p=0.003) and EFS survival (51.2% vs 43.1%, p=0.007) compared to those who were CD74-negative. For patients in Arm A (no bortezomib), the differences in OS (66.1% vs 61.0%, p=0.138) and EFS (48.9% vs 41.7% p=0.088) were not significant between those that were CD74-positive and those that were CD74-negative (Figure 1). However, patients in Arm B receiving bortezomib that were CD74-positive showed a significant improvement in OS (75.3% vs 62.5%, p=0.006) and EFS (53.6% vs 44.3%, p=0.028) compared to those who were CD74-negative (Figure 1). Comparison of the outcomes for CD74-positive patients with and without bortezomib exposure showed a difference in OS of 66.1% vs. 75.3% for those in Arm A vs. Arm B but did not reach significance (p=0.155). Multivariable analysis for OS yielded a hazard ratio of 0.67 (95% CI: 0.44 - 1.02) and p=0.061, approaching, but not reaching, statistical significance. Conclusions: These data demonstrate that CD74 expression is associated with more favorable disease characteristics and survival. Patients receiving bortezomib that were CD74-positive showed a superior response to therapy compared to patients who did not express CD74, by both OS and EFS, suggesting that CD74-positive childhood AML patients stand to benefit from bortezomib therapy. Bortezomib may induce a mechanistic response in CD74-positive AMLs similar to that in bortezomib-treated B-cell neoplasms and/or multiple myeloma, where bortezomib has proven to be beneficial. Disclosures Cooper: Celgene: Other: Spouse was an employee of Celgene (through August 2019). Pollard:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Short-term Interim Results of Clinical Outcomes and Complications After Implantation of Boston Keratoprosthesis in Japanese Patients.

Keratoprosthesis is used for corneal transplantation in high-risk patients who require penetrating keratoplasty (PKP). Boston keratoprosthesis (BKpro) is a representative type of keratoprosthesis used worldwide. In Japan, the first BKpro was implanted in an eye after multiple corneal graft failures in 2008, but its use remains limited. A recent patient survey revealed that among the Japanese patients who had previously undergone multiple PKPs, the retention rate of BKpro was significantly higher than that of PKP at 5 years postoperatively (100% vs. 26%; P < 0.01). Patients with implanted BKpro also had better best corrected visual acuity of 20/200 or higher than those with PKP at 5 years postoperatively (80.0% vs. 17.6%; P = 0.03). Regarding the postoperative complications, retroprosthetic membrane formation was observed in 88.9%, infectious keratitis in 33.3%, and glaucoma progression in 11.1% of cases. Another retrospective analysis showed that fungal keratitis occurred in 0.09 patients per year and severely affected visual acuity. Furthermore, because it is difficult to accurately examine intraocular pressure after BKpro implantation, the intraocular pressure of patients with implanted BKpro was prospectively estimated using a transpalpebral tonometer (Diaton). In conclusion, BKpro implantation is effective and safe for Japanese patients, given the reported improvements in visual acuity and low rates of complications.

Decitabine induction with myeloablative conditioning and allogeneic hematopoietic stem cell transplantation in high-risk patients with myeloid malignancies is associated with a high rate of infectious complications

Patients with high-risk myelodysplastic syndrome or acute myeloid leukemia have an increased risk of death following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases, and post-transplant cyclophosphamide (PTCy) has reduced rates of graft-versus-host-disease (GVHD). We hypothesized that decitabine induction with allo-HSCT and PTCy would improve outcomes in a high-risk myeloid disease population. We performed a phase-II trial of decitabine at 20 mg/m2 for 10 days followed by allo-HSCT using a myeloablative regimen of fludarabine, IV busulfan and 4 Gy total body irradiation with PTCy for GVHD prophylaxis. Twenty patients underwent decitabine induction and 17 patients proceeded to transplant per protocol. Median overall survival from decitabine induction was 210 days (95 % CI 122-not reached). All patients developed grade 4 neutropenia after decitabine, eleven patients (55 %) developed grade 3−4 infections, and 5 cases were fatal. There were 5/20 (25 %) long-term survivors with a median follow-up of 3.6 years. Decitabine induction followed by myeloablative allo-HSCT in a high-risk population was associated with a high risk of infection and mortality related to enhanced immunosuppression. Further exploration of decitabine conditioning on reduced intensity platforms and improved infectious prophylaxis and screening may better mitigate toxicity (ClinicalTrials.gov (NCT01707004)).

Extracorporeal Photopheresis Immediately after Heart Transplantation in High Risk Patients

Extracorporeal photopheresis (ECP) is an established therapy for treatment of heart transplant rejection. We started a protocol with avoidance of antibody induction therapy and calcineurin inhibitor (CNI) delay in high risk patients after HTX incorporating ECP as rejection prophylaxis. We report our first experience on 16 patients that were treated according to this protocol. Inclusion criteria were: history of cancer (n=4), bridge to transplant via extracorporeal membrane oxygenation (ECMO) (n=4) and eight patients had infections within one month before HTX. None of the patients received antithymocyte globuline (ATG) as induction therapy. Immunosuppression consisted of low dose tacrolimus with a delayed start (2 to 7 days post HTX) mycophenolate mofetil, and steroids. ECP was applied according to the protocol published by M. Barr (NEJM 1998) on days 2+3, 5+6, 10+11, 17+18, 27+28, 2 times every other week for month 2 and 3, and 2 times every 4 weeks month 4 - 6 after HTX. Routine biopsy protocol was performed in weeks 2,3,4, Months 2,3,6 and 12. Fifteen of 16 (82%) patients are alive with excellent graft function after a median follow-up of 8.3 (range, 0.25 - 33) months after HTX. Two patients showed biopsy proven signs of cellular rejection. One patient (2R rejection according to histology) was treated with steroids and in another patient with (1R) immunosuppression was switched from MMF to Ev. No signs of antibody-mediated rejection (ABMR) with C4d or C3d positivity were found in regular biopsies. Two patients developed severe pneumonia and one fever of unknown origin. One patient experienced candida septicemia but had candida positive skin swabs at the ECMO cannula insertion region pre-transplant. The latter patient died one week after HTX due to multi organ failure. One patient with history of cancer showed recurrence of disease and died 12 months after transplantation due to disease progression. This is the first report on prophylactic ECP with avoidance of induction therapy and CNI delay in HTX patients. Infectious complications remain a problem in this high risk group and occur in approximately 24%. However, ECP is a safe and effective strategy for patients at risk for cancer recurrence or sepsis to avoid organ rejection.

Right Ventricular Assist Devices After Heart Transplantation

BackgroundSevere right ventricular failure (RVF) has a significant incidence among cardiac transplant patients. It is a serious complication and an independent risk factor for postoperative mortality. In this setting, ventricular assist devices (VADs) must be considered if conservative medical management fails. This study sought to examine our series of patients with early RVF after heart transplantation requiring VAD support. MethodWe analyzed consecutive, adult heart transplant recipients at a third level intensive care unit who underwent transplantation from January 2011 to March 2019 requiring post-transplant mechanical circulatory support for RVF. Demographic characteristics, clinical data, complications, and survival rates were collected. ResultsTen patients were included. Median age was 50 years (range, 31.7-57). Eight patients (80%) were male. The most frequent indication for heart transplantation was ischemic heart disease (4 patients) followed by dilated cardiomyopathy and congenital heart disease (2 patients). Preoperative pulmonary hypertension was present in 6 patients. Three patients required a VAD before transplant. Whole survival rate was 60%. After heart transplantation, 7 patients required renal replacement therapy, 2 patients suffered a hemorrhagic stroke, and 5 patients needed a tracheostomy for long-term ventilation. ConclusionPatients who develop RVF after transplantation have an increased incidence of complications and high mortality after surgery. VADs could be implanted immediately after heart transplantation in high-risk patients.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplantpatients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Tandem autologous stem cell transplantation in high-risk patients with newly diagnosed multiple myeloma: Feasibility and preliminary results.

Tandem autologous stem cell transplantation in high-risk patients with newly diagnosed multiple myeloma: Feasibility and preliminary results.

Molecular profiling refines minimal residual disease-based prognostic assessment in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia.

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high-risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome-negative B-cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD-negative after induction therapy.

Induction, Bridging, or Straight Ahead: The Ongoing Dilemma of Allografting in Advanced Myelodysplastic Syndrome

Induction, Bridging, or Straight Ahead: The Ongoing Dilemma of Allografting in Advanced Myelodysplastic Syndrome

Low platelet counts after liver transplantation: validation of the 60-5 criterion

Background: Platelets play a critical role in hepatic ischemia-reperfusion injury and regeneration. In a single-centre cohort of liver transplanted patients (derivation cohort), platelet counts <60x109/L at postoperative day 5 (POD5) (the 60-5 criterion) were shown to be an independent predicting factor for severe postoperative complications and early graft and patient survival. The aim of this study was to validate those findings using a validation cohort containing prospective data. Methods: The validation cohort comprised prospectively collected data on donors, recipients, perioperative laboratory values, graft function, complications and survival from 285 liver transplantations between 2008 and 2014. The primary outcome was grade IIIb/IV complications, secondary outcomes were graft and patient survival. Results: Mean patient and donor ages were 57 ±11.6 and 51 ±18.3 years respectively. The average MELD score was 18 ± 10.6. Patients with POD5 platelet counts <60 x109/L had higher rates of severe (grade IIIb/IV) complications [27.8% versus 16.8%, odds ratio (OR) 1.9 (95% CI 1.1-3.5), p<0.05] and worse 90-day mortality [6.1% versus 1.3%, OR 5.0 (95% CI 1.0-24.6), p<0.05]. The 1-, 3-, and 5-year graft and overall survival rates were similar in both groups. Conclusion: This study validates the 60-5 criterion as a predictor of severe complications and 90-day mortality after liver transplantation. These findings may help in developing protective strategies or interventions early after liver transplantation in high-risk patients.

Cutaneous Ewing's sarcoma of scalp with lung metastases in an elderly female: A rare case report

Ewing's sarcoma (ES) is a primitive neuroectodermal tumor. It is usually a primary bone tumor but rarely occurs in the skin and subcutaneous tissues (primary cutaneous ES [PCES]). It usually involves the deep subcutaneous tissue or muscles and rarely occurs as primary skin cancer. Most patients are white, women, and in the second decade of life. The diagnosis is made by aspiration cytology, histochemical stains, immunohistochemistry, electron microscopy, cytogenetics, and molecular genetics of translocations. Due to their rarity and morphological similarity to other cutaneous tumors, ESs are subject to being clinically and pathologically underdiagnosed. Cutaneous ES has a better prognosis than primary bone or soft-tissue ES, with a survival rate of 91% in 10 years and the presence of metastasis being rare. At present, no specific treatment guidelines inform the management of cutaneous Ewing tumor. The treatment modalities are extrapolated based on the management of bone ES while includes neoadjuvant chemotherapy, surgery, adjuvant chemotherapy (±radiotherapy), and autologous bone marrow transplantation in high-risk patients. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin®), and cyclophosphamide, alternating with ifosfamide and etoposide. We report a rare case in a 60-year-old female diagnosed as PCES with lung metastases, treated by palliative chemotherapy.

Low Platelet Counts After Liver Transplantation: Validation of the 60-5 Criterion

Background: Platelets play a critical role in hepatic ischemia-reperfusion injury and regeneration. In a single-centre cohort of liver transplanted patients (derivation cohort), platelet counts <60x109/L at postoperative day 5 (POD5) (the 60-5 criterion) were shown to be an independent predicting factor for severe postoperative complications and early graft and patient survival. The aim of this study was to validate those findings using a validation cohort containing prospective data. Methods: The validation cohort comprised prospectively collected data on donors, recipients, perioperative laboratory values, graft function, complications and survival from 285 liver transplantations between 2008 and 2014. The primary outcome was grade IIIb/IV complications, secondary outcomes were graft and patient survival. Results: Mean patient and donor ages were 57 ±11.6 and 51 ±18.3 years respectively. The average MELD score was 18 ± 10.6. Patients with POD5 platelet counts <60 x109/L had higher rates of severe (grade IIIb/IV) complications [27.8% versus 16.8%, odds ratio (OR) 1.9 (95% CI 1.1-3.5), p<0.05] and worse 90-day mortality [6.1% versus 1.3%, OR 5.0 (95% CI 1.0-24.6), p<0.05]. The 1-, 3-, and 5-year graft and overall survival rates were similar in both groups. Conclusion: This study validates the 60-5 criterion as a predictor of severe complications and 90-day mortality after liver transplantation. These findings may help in developing protective strategies or interventions early after liver transplantation in high-risk patients.

A Phase II Study of Decitabine Followed By Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Patients with Myeloid Malignancies

Introduction:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for myelodysplastic syndrome (MDS) and high-risk acute myeloid leukemia (AML). Patients with high-risk disease have a markedly increased risk of relapse and death following transplant (Armand et al, Blood, 2014). Those who remain disease-free are at risk of severe morbidity from graft-versus- host-disease (GvHD). These issues highlight the importance of improved allo-HSCT platforms designed to reduce relapse rate without increasing risk of GvHD. Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases (Blum et al, PNAS, 2010). Use of post-transplant cyclophosphamide has demonstrated improved rates of GvHD following allo-HSCT using haplo-identical donors (Bashey et al, JCO, 2013). No studies have reported on outcomes in patients undergoing decitabine immediately prior to transplantation followed by post-transplant cyclophosphamide (PTCy). We hypothesized that the combination of decitabine induction prior to transplant and PTCy would be safe and result in improved disease control with low rates of GVHD, translating into improved survival in a high-risk transplant cohort.MethodsIn this single-arm, single institution trial, eligible patients received 10 days of IV decitabine at 20mg/m2 no sooner than 24 days and no later than 17 days prior to conditioning. Myeloablative conditioning included fludarabine (50mg/m2 day-5-2), busulfan (IV 3.2mg/kg/day -5-2), and 4 Gy total body irradiation on day -1. Patients above age 65 received a 25% busulfan dose reduction. Patients received a fully or partially matched related bone marrow graft on day 0. GvHD prophylaxis included 50mg/kg of IV cyclophosphamide on day +3-4. Patients with fully matched donors received only PTCy while those with partially matched donors also received mycophenolate mofetil through day +35 and tacrolimus through day +180.ResultsWe enrolled 20 patients, fifteen patients with AML and 5 with MDS. The cohort had a median age of 64 (29-73) and was predominantly male (14/20, 70%). Eight (40%) patients scored as high risk by the HSCT comorbidity index. Eighteen patients (90%) had a high or very high-risk score by the refined disease risk index.All patients received decitabine and 18/20 (90%) underwent transplantation; 2 patients did not receive a transplant due to infectious complications. The majority of patients received a haplo-identical graft (13/18, 72%), and the remaining 5 received a matched related graft.Outcomes are reported in table 2 and figure 1. There were no engraftment failures. Five patients, 3 MDS and 2 AML, are long-term survivors with median follow-up over 3 years. One patient developed donor derived MDS and required a second transplant. Most transplanted patients (13/18, 72%) survived to day 100 with a median post-transplant survival of 138 days. There were 15 deaths on study with the majority due to underlying disease. Six patients (6/20, 30%) died of infectious complications or did not receive a transplant due to infection. Incidence of grade 3-4 acute GvHD was low among those surviving at least 40 days from transplant (3/17, 17%). There were also low rates of chronic GvHD among the 12 patients alive without ongoing GvHD at day 100 (2/12, 17%).ConclusionsDecitabine induction followed by myeloablative conditioning in this high-risk population resulted in a high treatment related mortality of 40%. Still, outcomes fell into an expected range for high-risk myeloid disease in an elderly and comorbid population. Based on expected outcomes for high-risk patients from the literature (Armand et al, Blood, 2014), decitabine did not markedly improve overall survival outcomes, recognizing that no direct comparisons are available in our limited study population. Decitabine may increase the risk of peri-transplant infections by contributing to a cumulative immunologic insult combined with disease-related immunosuppression and transplant-related toxicity, highlighting the importance of strict vigilance for infections within this setting. Diligent monitoring may improve infectious outcomes as shown in the second half of the cohort; only two out of the latter 10 patients on protocol died of treatment related complications. There were no cases of engraftment failure. Rates of acute and chronic GvHD using a PTCy platform were low and support other studies reporting this benefit. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparison between Cadaveric Whole Liver and Live Donor Partial Liver Transplantation in High Risk Patients with MELD Score more than 40

Comparison between Cadaveric Whole Liver and Live Donor Partial Liver Transplantation in High Risk Patients with MELD Score more than 40