History Of Hematopoietic Stem Cell Transplantation Research Articles

Rare Co-occurrence of Spinal Cord Hemorrhage from Radiation-induced Cavernous Hemangioma and Classical Hodgkin Lymphoma Post-transplant Lymphoproliferative Disorder.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoproliferative diseases that occur after solid organ transplantation or hematopoietic stem cell transplantation (HSCT). The development of PTLD is often associated with reactivation of Epstein-Barr virus (EBV). A 26-year-old woman with a history of HSCT and total-body irradiation developed spinal cord hemorrhage from a radiation-induced cavernous hemangioma (RICH) shortly after the development of classical Hodgkin lymphoma PTLD with EBV reactivation. Although little is known about the factors leading to hemorrhagic events from spinal cord RICH, we suspect that EBV reactivation may have been a factor contributing to the hemorrhage in the present case.

Patient Characteristics and Outcomes of Sinusoidal Obstruction Syndrome with and without Hematopoietic Stem Cell Transplant

Introduction Sinusoidal obstruction syndrome (SOS), also called hepatic veno-occlusive disease (VOD) is a condition causing damage of hepatic vascular endothelial cells, it can progress to multi-organ failure and is associated with high mortality ( >80%). It is known to occur mainly after high dose chemotherapy use in hematopoietic stem cell transplant (HSCT) but with recent advances in chemotherapy, there is an increase in its incidence in non-hematopoietic stem cell transplant patients (non-HSCT). Currently, there is limited literature comparing the patient characteristics and survival of SOS in HSCT vs non-HSCT patients. Therefore we conducted this retrospective analysis. Methods We performed a retrospective analysis using the 2016-2020 National inpatient sample (NIS) database, generated by the Health care cost and utilization project (HCUP). We gathered data on all patients who had SOS/VOD during this time period. They were divided into two cohorts, those who received hematopoietic stem cell transplant (HSCT group) vs those who did not receive hematopoietic stem cell transplant (non-HSCT group). Among the two cohorts we compared the patients characteristics, underlying malignancies, comorbidities and mortality. Results From the NIS database during the study period 1740 cases had documented SOS/VOD. Of those, 520(30%) had a history of HSCT and 1220(70%) did not have HSCT. Of the 520 cases with HSCT, 135 (26%) had Acute lymphoblastic leukemia (ALL), 105 (20.2%) had Acute myeloid leukemia (AML), 55 (10.6%) had Non-Hodgkin lymphoma (NHL), 20 (3.8%) had Chronic myeloid leukemia (CML), 15 (2.9%) had Hodgkin lymphoma (HL), the rest were other malignancies which were not included in the search. Of the 1220 cases without HSCT, 320 (26.2%) had ALL, 150 (12.3%) had AML, 90 (7.4%) had Solid tumors, 55 (4.5%) had NHL, 15 (1.2%) had CML, 15 (1.2%) had HL, the rest were likely malignancies not included in the search. ALL was the predominant cancer in both HSCT and non-HSCT groups (26% and 26.2% respectively), followed by AML, with more AMLs noted in the HSCT group (20%) versus the non-HSCT group (12.3%). The study population predominantly consisted of Whites followed by Hispanics and then African-Americans in both groups. The population also consisted predominantly of males across both cohorts. (Table 1). The solid tumors which were associated with SOS in the non-HSCT group included colorectal cancer, liver cancer, pancreatic cancer and Breast cancer in that order (Table 2). Preexisting liver disease was present in 215 (17.6%) of patients in non-HSCT cohort vs 60 (11.5%) patients in SCT cohort. Pre-existing lung disease was insignificant in both groups. Mortality was compared between the two groups after adjusting for primary cancer, age, sex, race and we found that SCT group had higher odds of mortality compared to non-SCT (14.4% vs 7.4%, aOR 1.866, 95% CI 1.29-2.68, p<0.01). Further multivariate analysis could not be carried out due to low sample size. Discussion Although traditionally, SOS/VOD has been thought to be a complication related to SCT, our study goes on to show that there is actually a higher incidence of SOS in the non-SCT patient population. ALL was the most common hematological malignancy encountered and had similar prevalence in both groups indicating that treatment regimens used in this cancer carry a high risk of SOS. Drugs like inotuzumab ozogamicin are the possible culprits although this information could not be obtained from our database. AML patients also exhibited high rates of SOS, more so in the SCT setting. Patients with preexisting liver disease and hematological malignancies could also benefit from close monitoring for symptoms of SOS with a high index of suspicion based on our results. Despite rising incidence in non-SCT patients, SCT patients with SOS continue to have a higher mortality possibly indicating the higher toxicity of chemotherapy regimens used in this setting. Thus, our study brings forth some important differences between HSCT and non-HSCT SOS and enables clinicians to identify the associated risk factors.

Mortality in pediatric oncology and stem cell transplant patients with bloodstream infections.

Bloodstream infections (BSI) continue to represent a significant source of morbidity for pediatric oncology patients, however less is known regarding this population's risk of death. We sought to evaluate the risk of BSI and death at a large pediatric cancer center. We retrospectively collected inpatient data from pediatric oncology and hematopoietic stem cell transplant (HSCT) patients over a 9-year period. We performed univariate and multivariable modeling to assess risk of BSI and mortality examining the following variables: demographics, underlying malignancy, history of HSCT, central line type, and febrile neutropenia (FN). During the study period, 6763 admissions from 952 patients met inclusion criteria. BSI occurred in 367 admissions (5.4%) from 231 unique individuals. Risk factors for BSI include younger age, diagnoses of hemophagocytic lymphohistiocytosis or acute myeloid leukemia, ethnicity, and history of HSCT. Mortality for those with BSI was 6.5%, compared to 0.7% without (OR 7.2, CI 4.1 - 12.7, p<0.0001). In patients with BSI, admissions with FN were associated with reduced mortality compared to admissions without FN (OR 0.21, CI 0.05 - 0.94, p=0.04). In both univariate and multivariable analysis, no other risk factor was significantly associated with mortality in patients with BSI. BSI is a significant source of mortality in pediatric oncology and HSCT patients. While demographic variables contribute to the risk of BSI, they did not influence mortality. These findings highlight the importance of BSI prevention to reduce the risk of death in pediatric oncology patients. Future studies should focus on comprehensive BSI prevention.

Real-World Treatment Patterns, Outcomes and Disease Burden of Japanese Patients with High-Risk Myelodysplastic Syndrome: A Claims Database Study

Introduction Inherent complex pathophysiology of myelodysplastic syndrome (MDS) along with its higher occurrences in elderly population often limits available treatment options. In Japan, azacitidine (AZA) is the only first-line (1L) treatment, which is not cytarabine-based, available for patients (pts) with high-risk MDS (HR-MDS) ineligible for hematopoietic stem cell transplantation (HSCT). Prior autoimmune diseases have been associated with susceptibility of MDS. However, durability of AZA treatment and data on MDS-specific comorbidities, especially immune-driven events are currently lacking in Japanese pts. This study aimed to answer clinical questions on AZA real-world treatment outcomes in Japan, the epidemiology of autoimmune diseases in this specific pt cohort, as well as treatment cost. Methods This was a retrospective, longitudinal study utilizing hospital-based administrative claims for MDS patients in the Medical Data Vision (MDV) database in Japan. Data on pt demographics, clinical characteristics, treatments, procedures and hospitalization records were collected. Adult pts with first a confirmed MDS diagnosis either as an inpatient or twice in outpatient setting during the identification period (1October 2008 - 30 September 2017), who had a bone marrow biopsy in ±3 months from index date and at least 1 MDS-related treatment post-index date, were included in this real-world study. Pts with confirmed acute myeloid leukemia (AML) diagnosis or who had any history of HSCT, graft-versus-host-disease or transplant-related disorder/complications were excluded. As IPSS/R scoring is unavailable in MDV, pts were classified as HR-MDS if they had either AZA treatment or HSCT within 6 months post-index date, or pancytopenia diagnosis within 6 months post-index date and initiated AZA within 12 months. Results Of 6204 pts who met the eligibility criteria (main cohort), 2138 pts were assigned as HR-MDS. The median age of pts in the main cohort was 74.0 years (range: 18.0 - 100.0 years, ≥60 years old: 87.8%) vs 73.0 years (range: 20.0 - 95.0 years; ≥60 years old: 88.6%) in the HR-MDS cohort. Mean Charlson Comorbidity Index was 1.7 (± 1.66) and 1.6 (± 1.47) for the main cohort and HR-MDS cohort respectively. The proportion of transfusion-dependent pts in the main cohort was 9.4% vs 7.1% of patients in the HR-MDS cohort. Among 2138 pts with HR-MDS, 251 pts reported having concomitant autoimmune disease with rheumatoid arthritis (32.3%), glomerulonephritis (26.7%) and seronegative arthritis (23.1%) being the most common. More pts in the main cohort (53.2%) compared to pts with HR-MDS (38.9%) received anti-anemic drugs, G-CSF and iron chelators as supportive therapy at 1L. Compared to 39.5% pts in main cohort, 88.3% pts with HR-MDS received antineoplastic agents at 1L therapy. In HR-MDS cohort, 2078 pts received AZA in different cycles (1-3 cycles: 40.5%, 4-6 cycles: 21.1%, 7-9 cycles: 11.5%, >9 cycles: 26.9%) but only 121 pts received intensive chemotherapy (1 cycle: 90.1%, 2 cycles: 9.1%, >2 cycles: 0.8%). Median duration of MDS-specific treatment for patients with HR-MDS was 9.8 months. Significantly higher median OS (P<0.001) was achieved in pts with HR-MDS who received more cycles of AZA (Fig. 1: 1-3 cycles: 14.6 months, 4-6 cycles: 21.4 months, 7-9 cycles: 22.8 months, >9 cycles 40.8 months). After controlling for death as a competing risk, the cumulative incidence function (CIF) of HSCT and AML transformation was not affected by the number of cycles of AZA received. Although more cycles of AZA treatment increased the total treatment cost, median cost per pt per month was inversely affected with the lowest cost for pts receiving >9 cycles (Fig. 2). Conclusion Our findings based on the real-world data analysis in Japanese pts follow the similar trend of elderly pts with HR-MDS mostly receiving AZA as 1L treatment. Despite higher median OS being associated with higher number of AZA cycles, only ~27% pts with HR-MDS received >9 cycles of AZA. Autoimmune disease was reported by 11.7% of pts with HR-MDS. Although treatment cost increased with number of cycles of AZA received, median cost per pt per month was lowest in patients receiving >9 cycles. The cost per pt per month for other MDS-related treatment as well as costs for blood transfusions and infection related treatments were lower as increasing cycles of AZA were given which contributed to lower cost per pt per month. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Global longitudinal strain assessment in long-term survivors of childhood acute lymphoblastic leukemia

Abstract Background The role of global longitudinal strain (GLS) in the long-term cardiac evaluation of childhood acute lymphoblastic leukemia (ALL) survivors is not clearly defined. Purpose To assess the prevalence of subclinical left ventricular systolic dysfunction (SLVD) in long-term survivors of ALL. We also aimed to compare echocardiographic measurements with a control group. Methods Patients &amp;lt;18 years of age diagnosed with ALL between 1985–2015 at our center were enrolled. Healthy siblings willing to participate were conformed the control group. GLS was measured with an automated software (AutoStrain, Tomtec). SLVD was defined as GLS&amp;lt;18.5% (absolute value) based on the lower limit of the 95% confidence interval in the control group. Group differences were accounted with nverse probability of treatment weighting. Results Of the 90 survivors included (37.8% female, time from diagnosis 18 [11–26] years), 24 (26.6%) had SLVD. Left ventricular systolic but not diastolic measurements were reduced compared to the control group (Table 1). Predictors of GLS in the survivors were smoking (p=0.004) and history of hematopoietic stem-cell transplantation (p=0.042) (Table 2). Conclusions Over ¼ of childhood ALL survivors had abnormal GLS values after a median follow-up of 18 years. Left-ventricular systolic parameters were reduced compared to a control group. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Sociedad Española de Cardiología. Sociedad Andaluza de Cardiología.

Clinical Outcomes of COVID-19 Infection Among Children with Cancer: A Single-Center Experience

▪BackgroundOutcomes of COVID-19 infection among children with underlying malignancy remain unclear, with limited data available to date. Here we report clinical characteristics and outcomes following COVID-19 infection among children with underlying malignancy or a history of hematopoietic stem cell transplant (HSCT) during the first year of the global COVID-19 pandemic, in Dallas, TX.Methods:We retrospectively reviewed children with a history of malignancy or prior HSCT and positive SARS-CoV-2 polymerase chain reaction (PCR) result between March 1, 2020 - March 31, 2021. Demographic, clinical, and outcome data were reviewed, and analyzed according to underlying condition and disease severity.Results:Forty-six patients with underlying malignancy or HSCT met inclusion criteria. Median age was 9 years, with twenty (43%) female, and twenty-seven (59%) of Hispanic ethnicity. Underlying conditions included Acute Lymphoblastic Leukemia (67%), Acute Myelogenous Leukemia (9%), HSCT (11%), sarcoma (9%), solid tumors (9%), and Hodgkin's lymphoma (2%). Fifteen subjects (33%) were asymptomatic, with twenty-four children (52%) classified as having mild, five (11%) with severe, and two (4%) with critical COVID-19 disease. The most common symptoms at presentation were fever (46%), cough (39%), and gastroenteritis (19%).Thirty-four children (74%) were hospitalized, with seven (15%) requiring intensive care unit (ICU) care. 17% of patients were admitted for treatment of COVID-19 alone, with other indications including neutropenic fever, relapse, and chemotherapy. Six (13%) patients required non-invasive ventilation, and two patients (4%) required invasive mechanical ventilation. Median length of stay was 9 days (IQR 4.5-24.5), with median ICU stay of 3.5 days (IQR 2-26.7).Seven children (15%) received COVID-19 targeted therapy including steroids, remdesivir or convalescent plasma. Among severe and critically ill children, six (86%) had underlying hematologic malignancies (5 HR ALL, 1 AML), and two (28%) a prior history of HSCT. Two children (4%) died.Thirty-six patients (78%) achieved documented clearance of SARS-CoV-2 by PCR, at median of 43.5 days (IQR 28.7-65.2).Conclusion:Among children with underlying malignancy or a history of HSCT, COVID-19 results in a spectrum of illness ranging from asymptomatic disease to death. Rates of hospitalization are high compared to the general pediatric population, and illness may be complicated by additional factors including co-infection, neutropenic fever, relapse of malignancy and need for chemotherapy. Children with hematologic malignancy or a history of HSCT may be at increased risk for severe disease. Additional studies are urgently needed to elucidate risk factors for severe/critical COVID-19 disease among children with underlying malignancy. DisclosuresNo relevant conflicts of interest to declare.

An Evidence Review of the Long-Term Consequences Associated with Components of the CHOP Chemotherapy Regimen in Transplant Recipients

Introduction: Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV + PTLD) can be an aggressive, often deadly disease without any approved treatments. Current available treatments for EBV + PTLD may include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). However, the long-term consequences of CHOP are poorly understood in immunocompromised transplant patients with cancer who may have different outcomes than immunocompetent cancer patients. This study reviewed and described the evidence for the long-term consequences associated with components of CHOP in transplant recipients.Methods: Potential long-term consequences of the components of CHOP were identified from the Children's Oncology Group Long-Term Follow-Up (COG LTFU) Guidelines. Abstracts were screened and eligibility was based on reporting data for the identified COG LTFU long-term consequences along with pre-specified criteria (English, systematic review, randomized controlled trial n>100, observation study n>100, case series n>20). Relevant studies that met the criteria were extracted and synthesized; of these, studies were selected if they evaluated patients who received any type of transplantation as part of their primary cancer treatment.Results: A total of 7 studies met the pre-specified selection criteria, all of which evaluated patients with hematopoietic stem cell transplantation (HCT) and none assessed solid organ transplant (SOT). None of the studies focused specifically on the CHOP regimen or EBV + PTLD. Long-term consequences of alkylating agents (eg, cyclophosphamide) and corticosteroids as primary treatment reported in these HCT studies included: hormone deficiencies and infertility (n=4 studies), osteonecrosis (n=2), and health status and quality of life (QoL; n=1).Results from three studies suggested that cancer survivors who received alkylating agents experienced hormone deficiencies and those with a HCT had a high risk. One quantified this by showing that, compared with cancer survivors without a history of HCT (CS), cancer survivors with a history of HCT (CS-HCT) and a history of total body irradiation had significantly impaired follicle stimulating hormone (40.42 vs 9.39 mIU/ml, P<0.001), Estradiol (15.09 vs 25.13 pg/ml, P=0.04), Inhibin B (10.61 vs 32.92 pg/ml, P=0.003), anti-Müllerian hormone (0.01 vs 1.28 ng/ml, P<0.001), antral follicle count (0.71 vs 17.78, P<0.001) and ovarian volume (1.82 vs 8.21 ml, P<0.001). In one study on the risk of osteonecrosis, the CS-HCT group had a significantly increased risk of developing osteonecrosis compared to the CS group treated with chemotherapy (6.8% vs 1.4%, respectively); cumulative incidence of osteonecrosis was 3.8% in the CS group for a steroid dose >5,835 mg/m 2 and 23.8% in the CS-HCT group for a post-transplant steroid dose >2,055 mg/m 2; and patients developed symptomatic osteonecrosis within a median of 2.4 years in the CS group with chemotherapy and 0.9 years after the first transplant in the CS-HCT group. A second study showed the rate ratio (RR) of osteonecrosis compared with a sibling comparison group was highest among the CS-HCT for acute lymphoblastic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively; P<0.001 for all). One study reported that childhood acute leukemia survivors treated with HCT with preparative regimen with either busulfan-cyclophosphamide or total body irradiation/cyclophosphamide had a significantly lower QoL short-form (SF)-36 mental and physical composite scores in both treatment groups compared with norms.Conclusions: Since only a small number of studies (7) of long-term consequences in transplant recipients were identified and none were seen in patients with EBV + PTLD or in SOT recipients, more research is needed to evaluate adverse consequences of CHOP or its components in EBV + PTLD, especially in SOT patients where no studies were found. Results from this review suggest that immunocompromised HCT recipients who were cancer survivors are significantly more impaired by long-term consequences (hormone deficiencies and infertility, osteonecrosis, and QoL) of alkylating agents (eg, cyclophosphamide) and corticosteroids as primary treatment compared with other cancer survivors without HCT. DisclosuresWatson: Atara Biotherapeutics: Current Employment, Current holder of individual stocks in a privately-held company. Gadikota: Maple Health Group: Current Employment. Barlev: Atara Biotherapeutics: Current Employment. Beckerman: Maple Health Group: Current Employment.

COVID-19 Among Patients with Hematological Malignancies: Experience from a Tertiary Center Showing Lower Than Expected Mortality and Establishing the Safety of in-Hospital Patient Care during the Pandemic

Previous studies and meta-analyses addressing COVID-19 in patients with hematological malignancies (HM) have reported dramatically high mortality rates of up to 34% [Vigenthira 2020, Garcia-Suarez 2020, Sharafeldin 2021]. These studies, however, were strongly biased towards hospitalized patients, and poorly represented patients who experienced a milder course of COVID-19, not requiring hospitalization. Jerusalem and its metropolitan area, comprising of over 1.3 million inhabitants, was the epicenter of Israel's COVID-19 crisis, with over 200,000 cases. Hadassah Medical Center, one of only two tertiary centers serving this multi-ethnic population, houses a Hematology Department that includes inpatient services, a hematopoietic stem cell transplant (HSCT) center, day care services and in-campus outpatient clinics. From February 20 th, 2020, we tracked patients with confirmed COVID-19 reporting to their treating hematologists while being hospitalized due to COVID-19, at routine visits to the hematology services, or remotely via phone or email communication. This assured the representation of COVID-19 cases of various clinical severities. Data were collected retrospectively and included demographics, comorbidities, hematological diagnoses and treatments, course of COVID-19 and, importantly, source of infection. Univariate and multivariate analyses were used to assess association between prognostic factors and outcomes including hospitalization, severe COVID-19 (per updated WHO criteria) and critical COVID-19, defined as a composite of ICU admission and mortality. Almost all the patients in this series were diagnosed prior to their vaccination. To the best of our knowledge, this is the largest single center series of HM patients with COVID-19 reported to date.Our series included 183 patients. Median age was 62.5 years, 57% were men, and 72% had at least one comorbidity. The most frequent hematological diagnoses were indolent lymphoma and CLL (40%), aggressive lymphoma (20%) and multiple myeloma (19%). At the time of COVID-19 diagnosis, 41% of the patients were receiving systemic anti-neoplastic treatment (excluding TKIs for CML and hydroxyurea for MPN), and 16% had undergone a previous allogeneic or autologous HSCT. Overall mortality, severe COVID-19, and hospitalization rates in the entire group were 9.8%, 14.2% and 32%, respectively, remarkably lower than in previous reports. Of the patients not receiving anti-neoplastic treatment, mortality and severe COVID-19 rates were comparable to those of the age-matched general population according to the Israeli Ministry of Health database [Table 1]. Consistent with previous studies, ischemic heart disease (IHD), dyslipidemia, chronic kidney disease, smoking and hypertension, as well as age and active anti-neoplastic treatment, each emerged as a risk factor significantly associated with hospitalization due to COVID-19 [Fig. 1, Table 2]. IHD, smoking, age and active treatment remained significant in multivariate analysis. Age and active treatment as well as ≥4 comorbidities were significantly associated with critical COVID-19. Interestingly, we observed a strong association between the number of prior anti-neoplastic treatment lines and critical COVID-19. Neither history of HSCT nor treatment with monoclonal antibodies were associated with COVID-19 outcomes. Notably, we did not detect any patient that contracted COVID-19 within the Hematology Department services, both inpatient and outpatient.Taken together, we present a different COVID-19 severity landscape in patients with HM as compared to previous observations. While active treatment was significantly associated with COVID-19 hospitalization and mortality, these rates were remarkably lower than previously reported. Despite harboring various degrees of immune suppression, patients with stable or indolent diseases not receiving active treatment appeared to be at a risk comparable to that of the age-matched general population, which depended largely on age and comorbidities. Routine preventive measures including symptom questioning, masks, and social distancing in both our inpatient and outpatient services provided a COVID-19-safe environment, obviating the need for changes in treatment schedules or assignment. These findings may have important consequences for future management of patients with HM in COVID-19 affected regions. [Display omitted] DisclosuresLavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures; Takeda: Consultancy. Goldschmidt: AbbVie: Consultancy, Research Funding.

The importance of central airway dilatation in patients with bronchiolitis obliterans.

BackgroundBronchiolitis obliterans (BO) is a clinical syndrome characterised by progressive small airway obstruction, causing significant morbidity and mortality. Central airway dilatation is one of its radiological characteristics, but little is known about the clinical and pathological associations between airway dilatation and BO.MethodsThis retrospective study consecutively included patients who underwent lung transplantation due to BO at Kyoto University Hospital from 2009 to 2019. Demographic and histopathological findings of the resected lungs were compared between patients with and without airway dilatation measured by chest computed tomography (CT) at registration for lung transplantation.ResultsOf a total of 38 included patients (median age, 30 years), 34 (89%) had a history of hematopoietic stem-cell transplantation, and 22 (58%) had airway dilatation based on CT. Patients with airway dilatation had a higher frequency of Pseudomonas aeruginosa isolation with greater residual volume than those without airway dilatation. Quantitative CT analysis revealed an increase in lung volume to predictive total lung capacity and a percentage of low attenuation volume <−950 HU at inspiration in association with the extent of airway dilatation. Airway dilatation on CT was associated with an increased number of bronchioles with concentric narrowing of the lumen and thickening of the subepithelium of the walls on histology.ConclusionsIn patients with BO, airway dilatation may reflect increased residual volume or air trapping and pathological extent of obstructive bronchioles, accompanied by a risk of Pseudomonas aeruginosa isolation. More attention should be paid to the development of airway dilatation in the management of BO.

Epstein\u2013Barr virus-positive lymphoproliferative disorder manifesting as pulmonary disease in a patient with acute myeloid leukemia: a case report

Background Patients with lymphoproliferative disorders following hematopoietic stem cell transplant (HSCT) most commonly present with fever and lymphadenopathy within the first 5 months of transplant. Pulmonary post-transplant lymphoproliferative disorder (PTLD) is a particularly aggressive and rapidly progressive disease, with high morbidity and mortality. There are a very limited number of reported pulmonary PTLD cases following HSCT in patients with acute myeloid leukemia (AML). Early diagnosis and detection of pulmonary PTLD is critical given its high lethality. However, variable clinical presentations and nonspecific radiographic findings make pulmonary PTLD difficult to distinguish from other more common causes of pulmonary disease in AML patients.Case presentationHere, we describe a 68-year-old Caucasian man who presented for salvage induction therapy following relapse of his AML after a haploidentical allogeneic HSCT 10 months earlier. He developed recurrent fevers, dry cough, and hypoxemia, with chest computed tomography (CT) showing bibasilar consolidations and increased nodularity without increased lymphadenopathy. His symptoms initially improved with antibiotic and antifungal therapy, but his follow-up chest CT showed progression of disease despite symptomatic improvement. Epstein–Barr virus (EBV) was detected in his blood by polymerase chain reaction (PCR), and a lung biopsy revealed monomorphic PTLD with B cells positive for EBV. Unfortunately, the patient’s condition rapidly deteriorated, and he passed away prior to treatment initiation.Conclusions To our knowledge, this is the first reported case of an AML patient developing pulmonary PTLD relatively late in his post-transplant course in the setting of relapsed disease and salvage therapy. Pulmonary PTLD, a rare but highly lethal disorder, can imitate the symptoms and radiographic findings of pneumonia, a common diagnosis in immunocompromised AML patients. This case illustrates the importance of considering pulmonary PTLD in the differential diagnosis for pulmonary disease in AML patients with a history of HSCT, especially in the setting of progressive radiographic findings despite broad antibacterial and antifungal therapy. Further, our case demonstrates the importance of biopsy and uninterrupted EBV DNA monitoring in the definitive diagnosis of PTLD, given nonspecific symptomatology and radiographic findings.

Hematopoietic stem cell transplantation in children and adolescents with nonremission acute lymphoblastic leukemia.

The appropriateness of allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents with leukemia in whom complete remission is not possible remains unclear. This retrospective analysis aimed to investigate the outcomes associated with HSCT, and the risks of HSCT in children and adolescents with nonremission acute lymphoblastic leukemia (ALL). Data from the Japan Society for Hematopoietic Cell Transplantation registry on 325 patients with nonremission ALL (aged <21years, with blasts in the peripheral blood and/or bone marrow) who had undergone HSCT between January 2001 and December 2015 were evaluated. To assess survival, we developed a scoring system using significant adverse pre-HSCT variables. Overall, 247 patients died. The median length of follow up among survivors was 1145days, and the 3-year overall survival was 22% (95% confidence interval [CI]: 18-27%). A low performance score, presence of >25% bone marrow blasts, T-cell phenotype, poor-risk or normal cytogenetics, and history of HSCT were predictors of a poor outcome. Patients scoring 0-1 (n=109), 2 (n=91), and 3-7 (n=125) had a 3-year overall survival of 41% (95% CI: 31-51%), 21% (95% CI: 13-31%), and 7% (95% CI: 3-12%), respectively. These results support HSCT in certain nonremission patients. Even in patients without complete remission, outcomes differed according to pre-HSCT factors. A scoring system could help determine the appropriateness of HSCT in children and adolescents with nonremission ALL.

MULTIPLE ORAL CARCINOMAS IN A PATIENT WITH FANCONI ANEMIA AND A HISTORY OF HEMATOPOIETIC STEM CELL TRANSPLANATION

Fanconi Anemia (FA) is a rare autosomal recessive genetic disorder that can cause bone marrow failure and increased risk for malignancies. Hematopoietic stem cell transplantation (HSCT) in patients with FA also increases the risk of tumors. The following reported case is of a male patient, diagnosed with AF, with a history of HSCT at 4 years of age. At 14 years old, he presented with a painless ulcerated lesion, irregular borders, 3 cm in size, on the right lateral border of the tongue with a 20-day course, associated with a submandibular lymphadenopathy. Incisional biopsy was performed, and a squamous cell carcinoma (SCC) was diagnosed. The patient underwent surgery and radiotherapy. In 2017, another ulcerated lesion was found on the left lateral border of the tongue, with hard, raised edges. After the incisional biopsy, a new SCC was reported. The patient underwent surgery and microsurgical reconstruction of the area. Due to the susceptibility to tumor development in patients with FA, periodic examinations of the oral cavity are mandatory.

Comparison of Outcomes in Hospitalizations for Sepsis in Patients with Hematopoietic Stem Cell Transplantation: A Nationwide Analysis

Background Sepsis with multiple organ failure is one of the frequent causes of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Patients with HSCT are at particular risk of developing sepsis due to their immunocompromised state. Studies have suggested that anywhere from 3.3% and 55% of such patients require Intensive Care admissions. Reports on outcomes of patients with sepsis with HSCT are limited. With our study we aim to study the demographics and outcomes of sepsis in adult patients with HSCT. Methods We analyzed hospitalizations for sepsis among adults in the Nationwide Inpatient Sample (NIS) available through Agency for Healthcare Research and Quality as a part of Healthcare Cost and Utilization Project. Patients were stratified into two groups based on the status of HSCT; using ICD-9 CM diagnostic codes. Descriptive statistics were represented as means/medians for continuous and as frequencies and percentages for categorical variables. A survey weighted multivariate regression analysis was used to adjust for confounders when calculating mortality. Results A total of 4501621 admissions with sepsis were identified from 2010-2014 and amongst these 4396 admissions also had underlying HSCT. Patients with history of HSCT admitted with sepsis was younger in age (55.96 years vs 67.06 years; p value=0.00), mostly males (60.56% vs 48.23%; p value=0.00) and increased comorbidities. They were more likely to be admitted to an urban teaching hospital. Patients with history of HSCT had increased mortality (17.82% patients vs 14.22% patients; p value=0.002) and increased costs per hospitalization ($ 83241 vs $65590; p value=0.0003). There was no significant difference in length of stay. When adjusted for confounders, patients admitted with sepsis with history of HSCT were found to have a 56% increased risk of mortality compared to general population. (Odds Ratio=1.565; 95% CI 1.283-1.911; p value=0.00). Conclusion Patients admitted with sepsis with history of HSCT are more likely to have poor outcome from sepsis than nontransplant patients. Clinicians should be vigilant about the screening and managing infections timely in patients with history of HSCT, to prevent poor outcomes from sepsis in patients with HSCT. Implementationof strategies that are known to improve outcomes in sepsis such as early administration of antibiotics and fluid resuscitation may be of particular importance in this high-risk population.

Impact of Hospital Teaching Status on Hospital Costs and Length of Stay for Heart Failure Patients with History of Hematopoietic Stem Cell Transplant: A National Inpatient Sample Analysis 2010-2014

Background As emphasis on optimization healthcare resources and costs is increasing, several studies have suggested higher healthcare costs associated with hematopoietic stem cell transplant (HSCT). Proposed guidelines are present to prevent treatment-related long-term complications. This allows for early intervention with resultant reduction in morbidity and mortality and reduction in healthcare costs. Cardiovascular morbidity and mortality have been associated with increased healthcare cost burden for patients in HSCT. Armenian et al have reported a cumulative incidence of congestive heart failure at 5 years after HSCT of 4.8 %, increasing to 9.1 % at 15 years. The influence of hospital teaching status on average health care costs for patients with history of HSCT developing heart failure (HF) is unknown. Methods NIS is the largest publicly available all-payer inpatient care database in the United States and is sponsored by the Agency for Healthcare Research and Quality as a part of Healthcare Cost and Utilization Project. We queried the Healthcare Cost and Utilization Project's (HCUP) Nationwide Inpatient Sample (NIS) between 2010 and 2014 to identify all adult (>18 years of age) hospitalizations for HF with history of HSCT using ICD-9 CM diagnostic codes and stratified these hospitalizations into two groups based on teaching status of the hospital. STATA version 15.0 (College Station, TX) was used for analysis to accommodate for the complex design of survey sample data. Results We identified 2095980 admissions in teaching hospitals and 2385912 admissions in non-teaching hospitals for HF from 2010 to 2014. Amongst these 1080 total admissions with HF had underlying diagnosis of HSCT, patients admitted to teaching hospitals were younger (average age 55.95 years in teaching vs 61.97 years in non-teaching; p value=0.001). No difference was noted in other baseline characteristics like gender, race, charlson comorbidity index. Patients admitted to teaching hospitals were noted to have a higher average cost per admission ($76555 vs $32440; p value=0.005) and increased length of stay (6.06 days vs 4.23 days; p value=0.0043). Conclusion Our study found increased mean hospital charges and length of stay in heart failure patients with a history of HSCT in teaching hospitals. Previous studies have reported similar results in general population. Opportunities that target cost reduction and length of stay may be leveraged. The use of preventive guidelines, close follow up with targeted services addressing specific conditions such as congestive heart failure in patients with HSCT can help reduce health care cost burden.

Cardiac and Vascular Events in Patients with History of Hematopoietic STEM CELL Transplant (HSCT) Are NOT Associated with Poor Outcomes: Analysis of National Inpatient Sample 2010-2014

Background Studies have suggested an increased risk of cardiovascular, cerebrovascular and peripheral vascular disease in patients with history of hematopoietic stem cell transplant (HSCT). (Tichelli et al, Blood 2007). This is attributed cumulative exposure to anthracyclines, total body or chest irradiation during treatment of the primary malignancy as well as the high prevalence of metabolic syndrome reported among HSCT survivors. Data on impact of HSCT on cardiovascular mortality are limited to single center studies. Our study aims to assess impact of HSCT on mortality associated with cardiovascular and cerebrovascular disease in a large national database. Methods We extracted data for all the adult admissions with cardiovascular or cerebrovascular events (myocardial infarction, angina, stroke and transient ischemic attack) from National Inpatient Sample (NIS) database from 2010-2014 and stratified it into two groups based on the status of HSCT; using ICD-9 CM diagnostic codes. The baseline characteristics, total charges per admission, length of stay and mortality were compared. Results A total of 6808386 admissions with primary diagnosis of either a cardiovascular or cerebrovascular event were identified, and amongst those 1254 admissions had underlying history of HSCT. Average age of patients was lower in patients with concomitant HSCT (59.57 yrs vs 69.01 yrs; p=0.00), with higher percentage of male patients (62.34% vs 53.8%, p=0.007). In-hospital mortality was noted in 44 (3.54%) patients in HSCT group, but it was not a clinically significant, when compared to the group without HSCT (in-hospital mortality in 3.84% patients). No significant difference was found in length of stay or average costs per admissions for patients with HSCT. Conclusion Annual cardiovascular risk factor evaluation for all HSCT recipients, with more frequent evaluations for high risk patients. Our study suggests that HSCT does not impact the mortality associated with cardiovascular events. These results support and validates strong efforts to promote healthy lifestyle behaviors and to treat cardiovascular risk factors aggressively in HCT survivors. Educating and reinforcing this published screening and preventive practice recommendations for Metabolic syndrome and cardiovascular disease amongst stakeholders like primary care physicians, oncologists, advanced practice providers may reduce future ischemic heart disease in this high-risk population.

Hematopoietic Stem Cell Transplantation in Children with Refractory Acute Lymphoblastic Leukemia

▪PurposeIt is difficult to decide whether children with leukemia who could not achieve complete remission (CR) after relapse or primary induction failure should undergo transplantation. Nonetheless, allogeneic hematopoietic stem cell transplantation (HSCT) is a possible approach for refractory acute leukemia including acute lymphoblastic leukemia (ALL). Even after refractory to conventional chemotherapy, a graft versus leukemia (GVL) effect could be expected to some extent. This approach is considered to be experimental because the mortality rate of HSCT is extremely high. A previously conducted large-scale study showed that age younger than 10 years was a factor of good prognosis; however, the details in children are unclear. The purpose of this retrospective analysis was to describe the outcomes and risk factors of HSCT for children with refractory ALL.Patients and MethodsThe data was collected through the Transplant Registry Unified Management Program (TRUMP) system, the registry of The Japan Society for Hematopoietic Cell Transplantation. In total, 325 patients with ALL younger than 21 years old when HSCT was performed between January 2001 and December 2015 and who harbored blasts in peripheral blood and/or bone marrow were analyzed. Both myeloablative regimens and reduced-intensity conditioning regimens were analyzed. Patients were classified as having poor-risk cytogenetics with either t(4;11), t(9;22), t(8;14), hypodiploidy or near triploidy, or more than 5 cytogenetic abnormalities. Other ALL cytogenetic findings were classified as other abnormalities or normal. Myeloablative conditioning was defined as total body irradiation (TBI) of >8 Gy and the administration of 8 mg/kg of busulfan (BU), >140 mg/m2 of melphalan, or >10 mg/kg of thiotepa. All other regimens were analyzed as reduced-intensity conditioning HSCT, including low-dose TBI (≤8 Gy) and low-dose BU (≤8 mg/kg). The graft included bone marrow, peripheral blood stem cells, or cord blood. Overall survival (OS) was used as a primary outcome because for HSCT during relapse, post-HSCT CR was not always achieved or reliably documented.ResultsThe median follow-up time of survivors was 1145 days (range 110-3710). The median age was 11 years. Thirty-five percent of patients had a pre-HSCT performance status (PS) of 0, which corresponds to a Karnofsky PS of ≥90. The rate of pre-HSCT fungal infection was 14%. Fifty-nine patients had more than 25% marrow blasts when HSCT was performed. When HSCT was performed, 10%, 60%, and 30% of patients exhibited primary induction failure, first relapse, and second or later relapse, respectively. Ninety-one percent of patients had neutrophils and 67% exhibited platelet recovery by day 100. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) on day 100 was 43%. The cumulative incidence of chronic GVHD (cGVHD) at 3 years after HSCT was 19%. Two hundred and forty-seven patients died. The causes of death were leukemia progression (57%), followed by graft failure (11%), GVHD (10%), hemorrhage (6%), and infection (5%). The 3-year OS rate in all the patients was 22% (95% confidence interval (CI), 18-27). Age, white blood cell count at diagnosis, prior history of central nervous disease, disease status, conditioning regimens, donor-recipient human leukocyte antigen match, graft type, or year in which HSCT was performed did not affect the OS. Grade ≥2 aGVHD did not affect OS. Whereas Patients with chronic GVHD had better 3-year OS (49%, 95% CI 35-61%) compared to that in patients without chronic GVHD (22%, 95% CI 16-29%) (p = 0.001) (Figure 1). Multivariate analysis showed that other than cGVHD, low PS (relative risk (RR): 2.53), blasts in bone marrow greater than 25% (RR: 1.43), T cell phenotype (RR: 1.86), high-risk or normal cytogenetics (RR: 1.42), and a history of HSCT (RR: 1.90) were significant adverse pre-HSCT variables (Table 1). Patients who had 0 or 1 (n = 113), 2 (n = 113), and 3-5 pre-HSCT variables (n = 99) had 42% (95% CI, 32-51), 17% (95% CI, 10-25), and 6% (95% CI, 2-13) 3-year OS, respectively (Figure 2).ConclusionSome patients with refractory pediatric ALL achieved relatively long survival following HSCT in the relapsed period, especially when a GVL effect was obtained. A scoring system using pre-HSCT variables should help decide whether HSCT should be performed or not. HSCT is worth considering for children who have undergone ≤2 pre-HSCTs. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Children Receiving Hematopoietic Stem Cell Transplantation are at Increased Risk of Onychocryptosis Requiring Surgical Management

At our institution, a high proportion of children with onychocryptosis (ingrown toenail) requiring surgical intervention were noted to have a history of hematopoietic stem cell transplantation (HSCT). We analyzed the characteristics of patients who underwent surgical intervention for onychocryptosis and examined our institutional HSCT database to determine if an association exists between onychocryptosis and HSCT. Surgical cases for onychocryptosis performed from 2000 to 2012 were identified. Nine demographic, clinical, and perioperative variables for both patients with and without prior HSCT were assessed. In a separate analysis, the institutional HSCT database was then queried to identify the prevalence and clinical characteristics associated with onychocryptosis after HSCT. We identified 17 children who had undergone surgical management of onychocryptosis, of which 8 (47.1%) had previous HSCT. Children who had undergone HSCT had an aggressive form of onychocryptosis with 50.0% having bilateral great toe and nail edge involvement and 37.5% having a recurrence. In HSCT cohort analysis of 1069 children, 91 (8.5%) had onychocryptosis. Male sex, non-black race, acute graft versus host disease, and increasing age at transplantation were independently associated with onychocryptosis. HSCT is strongly associated with onychocryptosis requiring surgical intervention. Children with a history of HSCT may also have more aggressive toenail disease, with higher rates of surgical intervention, bilateral ingrown toenails, recurrence, and need for return to the operating room. Clinicians should perform careful screening and early treatment in these patients.

Imaging of Abdominal and Pelvic Manifestations of Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplant.

Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplant (HSCT). GVHD predominantly affects the skin, gastrointestinal system and hepatobiliary systems. Imaging findings in the gastrointestinal tract include bowel wall thickening with mucosal enhancement, mesenteric edema, and vascular engorgement. In the hepatobiliary system, hepatosplenomegaly, periportal edema, bile duct dilatation, and gallbladder and biliary wall thickening are seen. Although the imaging findings of GVHD are nonspecific, with a known history of HSCT, GVHD should be considered. GVHD is a serious complication of HSCT, which involves multiple organ systems, with imaging manifestations most commonly seen in the gastrointestinal tract and hepatobiliary system. Knowledge of the imaging manifestations of GVHD, which alone may be relatively nonspecific, taken in conjunction with clinical history including the timing and type of HSCT, laboratory values, stool studies, and dermatologic findings can increase radiologist confidence in suggesting this diagnosis.

Platelet Transfusion Refractoriness among Patients with Hematological Malignancies in a Tertiary Center in Saudi Arabia

Patients with hematological malignancies (HMs) and that undergoing hematopoietic stem cell transplantation (HSCT) for HMs or other disorders require multiple blood product transfusions. Approximately 30% of these patients develop platelet transfusion refractoriness (PTR), which increases the risk of serious and potentially fatal bleeding complications. The incidence of PTR in the Saudi population is unknown. To determine the occurrence of PTR in adult HMs and HSCT patients at King Abdul-Aziz Medical City (KAMC), Riyadh, we performed a study of 29 HMs and HSCT patients. Platelet counts were determined prior to and one hour after each platelet transfusion event. Four (13.8%) patients qualified for PTR, as they had corrected count increment of less than 5000 following two consecutive platelet transfusions. PTR was detected following 17 of the 102 (16.7%) platelet transfusion events. Subgroup analysis showed a significant association between the patient’s diagnosis and the development of PTR (75.0% CML, 18.9% NHL, 16.7% AML, 7.1% ALL, 0.0% HL p=0.011). No significant correlations between the development of PTR and either age, history of HSCT or previous exposure to blood products were found. Our observed incidence of PTR in Saudi HM and HSCT patients is significantly lower than the reported worldwide incidence (24-34%), which might be attributable to consanguinity within the community. Patients with AML and NHL might be at a higher risk of developing PTR.

Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study.

We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9-62.2), which is 30-fold (95% CI 18-51; P<0.001) higher compared with persons without HSCT. Incidence was higher in allogeneic HSCT compared with autologous HSCT (70.0 vs 15.8 per 100 000 patients per year). Causative organisms were Streptococcus pneumoniae in 11 patients, Neisseria meningitidis in two and Streptococcus mitis in one patient. Mortality was 3 of 14 (21%) and 6 of 11 (55%) survivors had sequelae. Nine of 11 patients (82%) with pneumococcal meningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur.