Bone Marrow Transplant Patients Research Articles

Association of Thrombocytopenia and C-reactive protein in COVID-19 Patients Attending a Tertiary Care Hospital

OBJECTIVE: This study evaluates the frequency and relationship between Thrombocytopenia and CRP levels in Covid-19 patients. METHODOLOGY: The cross-sectional retrospective study was conducted at Dr. Ishrat ul Ebad Khan's Institute of Blood Diseases from October 2021 to September 2022. Data was collected from existing data from the blood bank and hematology laboratory. C reactive protein (CRP) and complete blood count (CBC) levels were observed in Covid-19 patients. Both genders, all age groups, COVID-19 patients and patients having Thrombocytopenia and raised levels of CRP were included in this study. At the same time, other bone marrow transplant patients and other infectious diseases such as Hepatitis B, Hepatitis C, Dengue, and Malaria were excluded from this study. Statistical analysis was done by using the SPSS 20.0 version. RESULTS: Out of 844 patients, the mean age was 50 years, and the male proportion was high at 70% (n=590). Most patients, 95% (n=803) had grade 1 thrombocytopenia. The mean age was found to be higher (>50 years) in Grades 1 and 2 as compared to Grades 3 and 4, where we found (<40 years). A significant (p=0.002) mean age difference among grades was found. No significant (p=0.749) median difference in CRP among Grades were found. CONCLUSION: The current study shows that COVID-19 significantly increases C-reactive protein levels. While treating and managing the patients of COVID-19, it is essential to detect the biomarkers that can predict the severity and prognosis of this disease. KEYWORDS: Thrombocytopenia, Bleeding, C-reactive Protein, COVID-19

Oncology Care at Home: A Patient-Centered Approach to Managing Care for Bone Marrow Transplant and CAR-T Cell Therapy Patients

Introduction. More than half of patients with cancer who receive cytotoxic chemotherapy and/or immunotherapies experience deleterious side effects such as febrile neutropenia, infection, neurotoxicity, and cytokine release syndrome. Early intervention and treatment for these side effects can help avoid complications and improve outcomes, but delays in treatment administration are common as most outpatient management approaches depend on patient self-assessment and patient-initiated pursuit of follow-up care. Remote patient monitoring through digital health technologies offers the opportunity to bridge this gap without imposing undue burden on either patients or healthcare providers. This feasibility study assessed the results of a technology-assisted in-home oncology care program to remotely monitor bone marrow transplant and CAR T-cell therapy patients and provide early intervention for symptomatic episodes needing clinical management. The program also offered support for patients to obtain routine lab draws, hydration, antiemetics, intravenous antibiotics, and a provider assessment at home. Technical and operational feasibility were evaluated together with perceived user experience among patients, caregivers, and providers. Methods. Ten patients between 18-89 years old participated in the study for up to 90 days following allogeneic bone marrow transplant and up to 30 days following CAR T-cell therapy or autologous bone marrow transplant. Patients used continuous-wear biometric sensors for passive vital sign monitoring around the clock seven days per week and engaged with a chatbot by SMS text for health status checks and symptom reporting. Scheduled home care was administered by licensed home health providers. Virtual care center personnel evaluated patient status based on wearable data and patient messaging and followed up directly with patients or engaged patients' treating clinicians for notification and management of urgent issues as needed. Patients and caregivers were asked to complete surveys about their experience with and perceptions of the program at midpoint and study completion, while providers were asked to complete end-of-study surveys to capture their perspectives across all patients. Patients were also asked to participate in brief interviews at study midpoint and at the end of the study. Interim Results. Eighty percent of patients participated in the program as intended through wearing devices and responding to engagement prompts. Wearable sensors detected a total of 184 outpatient alerts from patients between April and July 2023, of which 57 led to follow up with patients, 12 required further follow up with the clinical care team, and 5 required follow up care in a clinical setting due to elevated temperature or respiratory rate. Sixty percent of patients responded more than 50% of the time to requested health assessment surveys. Patient engagement with the chatbot and symptom reporting system led to 48 events needing virtual care team follow up, of which 20 were to answer patient questions and 28 were in response to reports of concerning symptoms. A total of 11 events were further referred by the virtual care team to the clinical care team, of which 5 required follow up care in a clinical setting. Study data collection will complete in August 2023. Initial Conclusions. Technology-assisted remote patient monitoring is feasible for use with bone marrow transplant and CAR T-cell therapy patients at home. Successful integration with clinical practice settings requires tailoring to existing workflows. Further assessment of patient acceptance for short-term versus long-term monitoring is recommended.

Efficacy of Sinopharm Vaccine Among Stem Cell Transplant Recipients During Two Peaks of Delta and Omicron variants of COVID-19.

Considering the dearth of research on the complications of Sinopharm coronavirus disease 2019 (COVID-19) vaccine in immunocompromised individuals and the lack of available data on COVID-19 vaccination from Iran. This study aimed to investigate the efficacy of vaccine of Sinopharm COVID-19 vaccine and its complications in bone marrow transplant (BMT) recipients. This was a retrospective cross-sectional study conducted on 250 patients with BMT who were referred to Montaserieh Hospital, Mashhad, Iran. Among them, 53 cases who received at least two doses of Sinopharm COVID-19 vaccine from March to January 2021 were entered in this study. The data were extracted from a student dissertation (Code:4000370). Sinopharm vaccine side effects were reported only in 7.7% of the patients, and shingles was the only serious side effect of the Sinopharm vaccine, which was observed only in one case. The results also revealed that Sinopharm COVID-19 vaccine side effects were not related to age or gender. Infection with the Delta variant of COVID-19 was reported in 7.5% (n=4) and no mortality was reported among them. Vaccine failure was reported in 39.6% of the cases; however, no mortality was reported among patients infected with the Omicron variant of COVID-19. In summary, it seems that Sinopharm COVID-19 vaccine adverse effects were not serious among stem cell transplant recipients. However, it may lead to some severe complications in the population. Vaccine failure against the Delta and Omicron variants of COVID-19 has been reported among more than one-third of BMT patients; however, no mortality was observed among BMT patients infected with the new variants of COVID-19.

Comparative analysis of Respiratory Syncytial Virus frequency rates and viral load in different patient cohorts in a University Hospital in São Paulo, Brazil, over an eight-year period (2005–2013)

Respiratory Syncytial Virus (RSV) poses a global health concern, particularly affecting young children, the elderly, and immunosuppressed individuals. RSV viral load is essential for understanding transmission, disease severity, prevention, and treatment. This retrospective study aimed to analyze the frequency rates and viral loads of RSV infections in different patient cohorts and age groups over an eight-year period in a university hospital in São Paulo, Brazil. This study analyzed 1380 Immunocompetent (IC) and Immunosuppressed (IS) patients with acute respiratory tract infections. IC included patients with chronic Heart Disease (HD), Primary Care service recipients (PC), and a subgroup suspected of having Severe Acute Respiratory Syndrome caused by Influenza A (H1N1)pdm09 virus (SARS H1N1). IS comprised transplant patients and those with HIV infection. Respiratory samples were collected between February 2005 and October 2013, with RSV detection and viral load quantification (Log10 copies of RNA/mL) using RT-qPCR. Overall RSV infection rate was 17.3 %, with higher rates in children (23.9 %) than in adults (12.9 %), particularly in children under two years of age (28.2 %). Children in the SARS H1N1 and PC subgroups had higher infection rates (16.4 % and 34.9 %, respectively), with the highest rate in PC children aged 1 to < 2 years (45.45 %). Adults with HD had a significantly higher frequency rate (27.83 %) than those in the SARS H1N1 (2.65 %) and IS (15.16 %) subgroups and higher hospitalization rate among adults under 65 years. RSV viral load ranged from 2.43 to 10.15 Log10 RNA copies/mL (mean ± SD 5.82 ± 2.19), with hospitalized patients exhibiting significantly higher viral loads (7.34 ± 1.9) than outpatients (4.38 ± 1.89). Elderly bone marrow transplant patients also had significantly higher viral loads (7.57 ± 2.41) than younger adults (5.12 ± 1.87). This study provides insights into the RSV infection patterns in different patient cohorts in Brazil. Further investigations are needed to understand susceptibility and risk factors associated with RSV infection. In conclusion, high RSV viral load among hospitalized patients could serve as a surrogate marker of disease severity. Additionally, patients with chronic heart disease deserve greater attention regarding complications associated with RSV infection.

Cytokine release syndrome after bronchoalveolar lavage

BackgroundImmunosuppressed bone marrow transplant patients with pulmonary infiltrates routinely undergo bronchoscopy with bronchoalveolar lavage (BAL) to investigate potential etiologies. Cytokine release syndrome after BAL is unreported in the literature in general and in this patient population.Case presentationWe report on an allogeneic bone marrow transplant patient with non-infectious organizing pneumonia of the lungs who developed delayed and rapidly progressive shock and hypoxia post-procedure over the course of 12 h resulting in intensive care unit admission for supportive care. BAL was characterized by a marked lymphocytic, cytotoxic T cell infiltrate on pathology and flow cytometry without clear evidence of infection. The patient’s clinical status improved quickly only after the initiation of high dose intravenous steroids and returned to baseline as an outpatient.ConclusionThe patient’s clinical data and course suggest a cytotoxic T cell response from the lung and BAL as the etiology. With an increasing number of cellular therapies for cancer entering the clinic, the potential for unusual but morbid complications from routine bronchoscopy should be considered.

Assignment of the antibacterial potential of Ag2O/ZnO nanocomposite against MDR bacteria Proteus mirabilis and Salmonella typhi isolated from bone marrow transplant patients

The rate of infectious diseases started to be one of the major mortality agents in the healthcare sector. Exposed to increased bacterial infection by antibiotic-resistant bacteria became one of the complications that occurred for bone marrow transplant patients. Nanotechnology may provide clinicians and patients with the key to overcoming multidrug-resistant bacteria. Therefore, this study was conducted to clarify the prevalence of MDR bacteria in bone marrow transplant recipients and the use of Ag2O/ZnO nanocomposites to treat participants of diarrhea brought on by MDR bacteria following bone marrow transplantation (BMT). Present results show that pathogenic bacteria were present in 100 of 195 stool samples from individuals who had diarrhea. Phenotypic, biochemical, and molecular analysis clarify that Proteus mirabilis and Salmonella typhi were detected in 21 and 25 samples, respectively. Successful synthesis of Ag2O/ZnO nanocomposites with a particle enables to inhibition of both pathogens. The maximum inhibitory impact was seen on Salmonella typhi. At low doses (10−5 g/l), it prevented the growth by 53.4%, while at higher concentrations (10−1 g/l), Salmonella typhi was inhibited by 95.5%. Regarding Proteus mirabilis, at (10−5 g/l) Ag2O/ZnO, it was inhabited by 78.7%, but at higher concentrations (10−1 g/l), it was inhibited the growth by 94.6%. Ag2O/ZnO nanocomposite was therefore found to be the most effective therapy for MDR-isolated bacteria and offered promise for the treatment of MDR bacterial infections that cause diarrhea.

Exploring the association between alpha hemolytic streptococcal infection and intensive treatment outcomes in acute myeloid leukemia.

Objective: To assess the prevalence of alpha hemolytic streptococcal (AHS) infections and related risk factors in patients with newly diagnosed acute myeloid leukemia (AML) undergoing consistent treatment. Study Design: Prospective study. Setting: Jinnah Teaching Hospital and DHQ Charsadda undergoing treatment from Hayatabad Medical Complex Peshawar. Period: June 2022 to February 2023. Material &amp; Methods: AML patients were recruited and algorithmically followed for AHS infections. Core symptoms, diagnostic workups, differential diagnoses, and relevant treatments were assessed in this manner. Results: AHS caused 22% of bacteremic infections in 22% of patients, mostly by blood transmission (87%). After treatment, 32% recurred. AHS had a 60% mortality rate (P &lt; 0.002). Age, precise induction timing, and high-dose cytarabine significantly enhanced AHS incidence (OR 2.0, 1.8–1.9, and 3.8, respectively). AHS infections increased hospital stays (P &lt; 0.0002) and decreased long-term survival (OR 2.8; P &lt; 0.001) and disease-free survival (OR 2.1; P 0.008) in bone marrow transplant patients. Conclusion: The first prospective study investigating AHS frequency in consistently treated individuals revealed increased rates with intensified AML therapy. AHS bacteremia is particularly likely in adults with prior cases and high-dose cytarabine usage.

The Role of Pre-bone Marrow Transplantation Pulmonary Function Test in Predicting Post-transplant Noninfectious Pulmonary Complications

Background: Pulmonary function test (PFT) is used as a tool for pre-transplant risk assessment and as a predictor of post-transplant outcomes. As there are currently few studies that discuss the role of PFT in bone marrow transplantation (BMT) patients in Saudi settings, and as the number of transplant patients with benign and malignant conditions continues to increase, this study was conducted with the aim of assessing the local practice. Methods: This retrospective cohort study included all adult patients who underwent BMT at Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, between 2014 and 2020. The association between established patient-related risk factors and the incidence of pulmonary complications among autologous and allogeneic groups was assessed. Results: A total of 186 patients were included (autologous = 143; allogenic = 43), of which 115 (61.8%) were male. At the pre-BMT phase, about 30% of the patients had comorbidities and 51% had received two rounds of salvage chemotherapy, while 16.1% had received radiation therapy. In the autologous group, the only PFT parameter that was a significant predictor of post-BMT pulmonary complications was forced vital capacity &lt;80% (P = 0.012), while in the allogenic group, no parameter was significantly associated with pulmonary complications. The patient-related factors that were associated with respiratory distress in the autologous group were lung involvement (P = 0.03) and pre-transplant radiation (P = 0.044). Conclusion: The findings of this study indicated that forced vital capacity &lt;80% was a significant factor in predicting non-infectious complications in the autologous group. Furthermore, lung involvement and pre-transplant radiation were the patient-related factors associated with pulmonary complications.

Quality of life in parents of Turkish and Syrian pediatric bone marrow transplant and oncology patients.

The success of the treatment depends on the well-being of the parents in pediatric cancer patients. In addition, migrants need to deal with the consequences of war. Our purpose was to compare the HRQoL of parents of Syrian and Turkish children followed in our bone marrow transplant and oncology units. One hundred SF 36 questionnaires, fifty from each group were collected between October 2019 and March 2020 in this cross-sectional study. Demographic characteristics of the patients (sex, age, cancer type, presence of relapse, duration of follow-up) and education level of parents were recorded. Analyses were performed using IBM SPSS Statistics version 20.0. Turkish parents reported better results in physical functioning, emotional well-being, physical pain, general health, and physical health composite score (P < 0.05). There were more fathers in the Syrian group and education status was significant between the two groups (P = 0.01, P = 0.001, respectively). There was no correlation between QoL and education levels in the Turkish group. In Syrian parents, pain score was high in middle school graduates (P = 0.043). In the presence of relapse, although the physical function score decreased, the physical role function score increased in Turkish parents (P = 0.0035, P = 0.005, respectively). Syrian parents' emotional role function and energy/fatigue score were both increased when children had relapses (P = 0.027for both). Migration is a complex issue. Turkish parents were better in physical functioning, emotional well-being, physical pain, general health, and physical health composite score. Screening for parental burden, assisting them to find appropriate support services is essential in improving the health and QoL of both our patients and their parents.

A-330 Trending Treatment of Transplant-associated Thrombotic Microangiopathy (TA-TMA): Validation and Performance of Soluble C5b-9 on the Dynex DS2 Platform

Abstract Background The complement system membrane attack complex is comprised of the C5b fragment along with C6, C7, C8 and C9 polymers that form a pore to disrupt a membrane during complement activation. Inactive complexes that are not membrane-bound combine with Protein S to form soluble C5b-9 (sC5b-9). Elevated concentrations of sC5b-9 are associated with risk of development of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), which can be treated by eculizumab therapy. TA-TMA is a complex syndrome of abnormal cell activation, microvascular hemolytic anemia, and complement dysregulation which can lead to multiple organ dysfunction and death. Therefore, recognition of this syndrome is critical in the context of not only preventing poor outcomes in patients but also promoting stewardship of an expensive, yet effective therapy. Our laboratory evaluated the performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay on the Dynex-DS2 platform for clinical use. Methods EDTA plasma samples were collected from remnant CBC samples ordered for bone marrow transplant (BMT) patients and other patients not at risk for TA-TMA. Validation studies included method correlation, inter- and intraday precision, assay linearity, hemolysis interference, and other experiments. Clinical accuracy was assessed by performing a retrospective review of sC5b-9 results from BMT pediatric patients at risk for TA-TMA. Results Intraday precision was 6.7%, 7.1% for the manufacturer low- and high-quality control materials, respectively and 9.9% for an in-house prepared plasma pool. Inter-day precision was 9.8% and 5.3% for manufacturer low- and high-quality control material, and 12.8% for an in-house plasma pool over a period of at least five days. The linearity of the assay was verified with a lower limit of quantification of 80 ng/mL and upper limit of qualification of 1600 ng/mL. Our method comparison indicated good correlation with send-out results, with an average percent bias of -10% and Pearson's r2 value of 0.986. The assay showed no interference up to 100 mg/dL of hemolysis. Retrospective analysis of a few patient results demonstrated that weekly monitoring of sC5b-9 concentrations detected rapid increases in patients at risk of TA-TMA, which prompted treatment with eculizumab therapy. Given the analytical performance, at least 2- to 3-fold changes in sC5b-9 concentrations are clinically meaningful when tracking trends in patients at risk for TA-TMA. Conclusion Our results indicate the Quidel Microvue sC5b-9 Plus enzyme immunoassay on the Dynex-DS2 platform had acceptable analytical and clinical performance for monitoring trends in patients at risk for TA-TMA.

Epidemiology of cytomegalovirus antiviral resistance testing for solid organ and bone marrow transplant patients from 2011 - 2019.

CMV reactivation post-transplantation is common, with need for prompt identification of patients most at-risk for CMV antiviral drug resistance (AVDR). This study describes CMV AVDR frequencies, antiviral prescribing practices, and AVDR risk factors in patients from 2011 to 2019 in British Columbia, Canada. Retrospective review of demographics, transplant type, viral loads, antiviral exposure duration, and 12-month mortality was conducted for all patients with samples submitted for CMV AVDR testing from 2011 to 2019. Genotyping of AVDR mutations occurred at the national reference laboratory. Mann-Whitney U, T-test or Fisher's exact tests examined differences between patients with and without AVDR. Fifty-three plasma and three tissue/fluid specimens successfully underwent CMV AVDR testing; of these samples, 27/56 (48%) had AVDR mutations detected. The commonest AVDR mutations were at UL97 loci A594 (20%), H596 (12%) and L595 (12%). Mutations occurred more frequently in requests from solid organ than hematopoietic stem cell transplant patients (58% vs. 27%, p=0.05). Previous resistance testing was a significant risk factor for AVDR (p<0.001). Patients with AVDR had approximately 51 more days of antiviral therapy (p=0.007) and took 9 days longer to clear viremia (p=0.23). The median turnaround time from sample send-out to reporting was nine days. However, empiric use of second-line antivirals occurred in most cases (39/53, 74%) before results were available. Laboratories should strive to provide timely CMV AVDR testing for transplant patients, to minimize unnecessary exposure to second-line antiviral agents. The findings of this study may help guide clinicians when selecting empiric antiviral therapy.

Tremor Induced by Cyclosporine, Tacrolimus, Sirolimus, or Everolimus: A Review of the Literature.

Calcineurin inhibitors such as cyclosporine and tacrolimus are immunosuppressant drugs that are known to induce tremors. Non-calcineurin inhibitors such as sirolimus and everolimus have also reportedly been accompanied by tremors, albeit less likely. However, the prevalence rates reported in the literature are notably wide, and the risk profiles for these drug-induced tremors are less understood. We searched PubMed to extract data on the risk of tremors with these drugs when prescribed for various transplant and non-transplant indications. We ascertained whether the risk of drug-induced tremor is influenced by the underlying diagnosis, dosing formulations, drug concentrations, and blood monitoring. We extracted data on treatment strategies and outcomes for tremors. Articles were primarily screened based on English language publications, abstracts, and studies with n ≥ 5, which included case series, retrospective studies, case-controlled studies, and prospective studies. We found 81 eligible studies comprising 33 cyclosporine, 43 tacrolimus, 6 sirolimus, and 1 everolimus that discussed tremor as an adverse event. In the pooled analysis of studies with n > 100, the incidence of tremor was 17% with cyclosporine, 21.5% with tacrolimus, and 7.8% with sirolimus and everolimus together. Regarding the underlying diagnosis, tremor was more frequently reported in kidney transplant (cyclosporine 28%, tacrolimus 30.1%) and bone marrow transplant (cyclosporine 40%, tacrolimus 41.9%) patients compared with liver transplant (cyclosporine 9%, tacrolimus 11.5%) and nontransplant indications (cyclosporine 21.5%, tacrolimus 11.3%). Most studies did not report whether the risk of tremors correlated with drug concentrations in the blood. The prevalence of tremors when using the twice-daily formulation of tacrolimus was nearly the same as the once-daily formulation (17% vs 18%). Data on individual-level risk factors for tremors were lacking. Except for three studies that found some benefit to maintaining magnesium levels, there were minimal data on treatments and outcomes. A large body of data supports a substantive and wide prevalence of tremor resulting from tacrolimus use followed by cyclosporine, especially in patients receiving a kidney transplant. However, there is little reporting on the patient-related risk factors for tremor, risk relationship with drug concentrations, treatment strategies, and outcomes.

Transfusion-Transmitted Disorders 2023 with Special Attention to Bone Marrow Transplant Patients.

Transfusion medicine is traditionally a strong/fundamental part of clinical practice, saving hundreds of millions of lives. However, blood-borne or transmitted infections are a well-known and feared possibility, a risk we relentlessly mitigate. Pathogens are continuously and rather quickly changing, so during the last decade, many, sometimes exotic, new pathogens and diseases were recorded and analyzed, and some of them were proved to be transmitted with transfusions. Blood or blood component transfusions are carried out after cautious preparative screening and inactivation maneuvers, but in some instances, newly recognized agents might escape from standard screening and inactivation procedures. Here, we try to focus on some of these proven or potentially pathogenic transfusion-transmitted agents, especially in immunocompromised patients or bone marrow transplantation settings. These pathogens are sometimes new challenges for preparative procedures, and there is a need for more recent, occasionally advanced, screening and inactivation methods to recognize and eliminate the threat a new or well-known pathogen can pose. Pathogen transmission is probably even more critical in hemophiliacs or bone marrow transplant recipients, who receive plasma-derived factor preparations or blood component transfusions regularly and in large quantities, sometimes in severely immunosuppressed conditions. Moreover, it may not be emphasized enough that transfusions and plasma-derived product administrations are essential to medical care. Therefore, blood-borne transmission needs continued alertness and efforts to attain optimal benefits with minimized hazards.

Investigation of KIR/HLA relationship and other clinical variables after T-cell-replete haploidentical bone marrow transplantation in patients with acute myeloid leukemia (AML)

BackgroundKIR/HLA mismatch in hematopoietic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia (AML), was related to decreased recurrence rates, improved engraftment, and a reduction in graft-versus-host disease, according to recent research (GVHD). Uncertainty exists about the impact of KIR/HLA mismatch on haploidentical-HSCTs treated with post-transplant cyclophosphamide (PTCy). We attempted to analyze the effects of KIR/HLA mismatch on clinical outcomes on transplant outcomes using the cohort of 54 AML patients who received a haplo-HSCT with PTCy.ResultsIn contrast to KIR/HLA match, our findings showed that donor KIR/HLA mismatch was substantially associated with superior OS (HR, 2.92; (P = 0.04)). Moreover, donor KIR/HLA mismatch (KIR2DS1D/C2+R and KIR2DS2D/C1+R mismatch versus KIR2DL1D/C2−R mm, KIR2DL2/3D/C1−R mm and KIR3DL1D/Bw4− mm) was correlated with the improvements in OS (HR, 0.74; P = 0.085) and activating. KIR/HLA mismatch versus KIR/HLA match was significantly correlated with improvements in OS (HR, .46; P = 0.03) and inhibitory. KIR/HLA mismatch versus KIR/HLA match was enhancement in the OS (HR, .93; P = 0.06). Despite a higher rate of aGvHD (grade I-IV) in the patients with KIR/HLA mismatch compared to KIR/HLA matched (57% vs. 33% (p = 0.04). However, the KIR/HLA mismatch group saw a decreased relapse rate (3.2% vs. 23%, p = 0.04).ConclusionThis analysis shows the significance of KIR/HLA Incompatibility, other clinical variables like CMV, the relationship between donor/recipient and donor age, and the relationship between donor/recipient and donor age in the haplo-donor selection process. It also suggests that KIR and HLA mismatching between donor and recipient could be routinely performed for haplo-donor selection and may improve clinical outcomes after haplo-HSCTs with PTCy.

Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract Funding Acknowledgements Type of funding sources: None. Background and Aims Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with sacubitril/valsartan (s/v) or enalapril (ena) might prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF Simpson’s Method). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (−19.8±2.8 vs −19.3±4.1%, p = 0.403 for s/v, −20.3±2.8 vs −20.0±3.6%, p = 0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (−20.9±2.1% vs −18.5±2.2, p = 0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p = 0.826 for s/v, 58.8±5.4 vs 60.7±7.1%, p = 0.419, for ena), while a borderline deterioration was noticed after treatment with placebo for six months (60.6±5.4 vs 57.7±6.7%, p = 0,045). We did not notice any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril. On the other hand, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p = 0.030) and GWW was diminished (111.5±75.7 vs 86.4±43.1 mmHg%, p = 0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p = 0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p = 0.045), GWE was diminished (95.9±2.1 vs 94.1±3.9 %, p = 0.039) and GCW did not change. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.

Cardiac iron overload in pediatric oncology and bone marrow transplant survivors.

e22022 Background: Cardiovascular late effects are a leading cause of mortality and morbidity in childhood cancer and Bone Marrow Transplant (BMT) survivors. In patients receiving chronic red blood cell transfusions, excess iron may be deposited in the liver, heart, and pituitary gland. Iron overload cardiomyopathy is characterized as a restrictive physiology with early diastolic dysfunction ultimately progressing to end-stage dilated cardiomyopathy. Iron loading in the heart can also lead to arrhythmias and increase myocardial ischemia reperfusion injury due to increased formation of reactive oxygen species. It is not yet known whether high transfused packed red blood cell (PRBC) volumes in cancer and BMT patients leads to cardiac iron deposition, and whether iron-induced cardiac injury contributes to the known cardiovascular late effects in these patients. Methods: 83 childhood cancer and BMT survivors with elevated serum ferritin levels and subsequent liver Magnetic Resonance (MR) imaging were identified. 18 patients (21.7%) who had liver iron content of &gt; 12mg/g (mean 16.0 ± 7.36 mg/g) also underwent Cardiac MRI (CMR) to determine cardiac iron content. Results: Median transfused blood volume was 393 ml/kg [95% Confidence Interval (CI) 170-780 ml/kg]. All 18 patients had at least one echocardiogram showing normal ventricular ejection fractions [mean 65.1 ± Standard Deviation (SD) 3.53%] and normal shortening fractions (mean 35.4 ± 3.67%). All patients had myocardial iron content within normal ranges (T2* relaxation time mean 35.1 msec ± 7.1 [normal &gt;20 msec], mean ± SD iron content 0.63± 0.2 mg/g dry weight, range 0.5-1.1). There was no association of cardiac iron content with transfused blood volume, anthracycline dose (mg/m2) or liver iron content (Pearson Correlation Coefficients 0.27, 0.29 and 0.89 respectively). Conclusions: Childhood cancer and BMT patients receive multiple PRBC transfusions to treat symptomatic anemia. It is currently unknown whether excess iron deposition in the heart contributes to the cardiac effects of impaired diastolic function and ultimately systolic dysfunction. In this study, 11 of 18 patients (61.1%) with high levels of liver iron had at least 1 other risk factor for the development of future cardiac dysfunction (either anthracycline exposure, radiation to the chest or total body irradiation or both). Larger studies are needed to determine whether oncology patients with high levels of iron deposition in their liver are also at risk for clinically significant cardiac iron loading, and what risk factors may exist for elevated myocardial iron content.

The role of plerixafor in conditioning regimens before unmanipulated bone marrow transplantation in patients with Wiscott–Aldrich syndrome

Our previous experience of using plerixafor and granulocyte colony stimulating factor (G-CSF) in addition to treosulfan-based conditioning in patients with Wiscott–Aldrich syndrome (WAS) demonstrated efficacy and a decreased risk of severe graft failure after hematopoietic stem cell transplantation (HSCT) with TCRab + /CD19 + graft depletion. Because of the remaining risk of graft failure in WAS patients following HSCT with unmanipulated grafts reported in a number of large-scale retrospective studies, we used plerixafor and G-CSF in conditioning regimens in 6 WAS patients who received native bone marrow as a graft source. None of the patients developed severe organ toxicity in the early post-transplantation period. All of them had long-term full donor chimerism in whole blood and the CD3 + line and a good graft function. At the last follow-up, 5 patients are alive at 3.7 to 74.7 months after HSCT (median follow-up time: 24.0 months). One patient died of chronic lung graft-versus-host-disease at 18 months after the transplantation. Despite limited experience, we believe that additional hematopoietic stem cell mobilization with plerixafor and G-CSF in treosulfan-based conditioning regimens may be effective in WAS patients undergoing HSCT with an unmanipulated graft. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Key words: plerixafor, conditioning regimen, hematopoietic stem cell transplantation, Wiscott–Aldrich syndrome, unmanipulated graft

The antimicrobial efficacy of copper, cobalt, zinc and silver nanoparticles: alone and in combination

With the advent of nanotechnology, there has been an extensive interest in the antimicrobial potential of metals. The rapid and widespread development of antimicrobial-resistant and multidrug-resistant bacteria has prompted recent research into developing novel or alternative antimicrobial agents. In this study, the antimicrobial efficacy of metallic copper, cobalt, silver and zinc nanoparticles was assessed against Escherichia coli (NCTC 10538), S. aureus (ATCC 6538) along with three clinical isolates of Staphylococcus epidermidis (A37, A57 and A91) and three clinical isolates of E. coli (Strains 1, 2 and 3) recovered from bone marrow transplant patients and patients with cystitis respectively. Antimicrobial sensitivity assays, including agar diffusion and broth macro-dilution to determine minimum inhibitory and bactericidal concentrations (MIC/MBC) and time-kill/synergy assays, were used to assess the antimicrobial efficacy of the agents. The panel of test microorganisms, including antibiotic-resistant strains, demonstrated a broad range of sensitivity to the metals investigated. MICs of the type culture strains were in the range of 0.625–5.0 mg ml−1. While copper and cobalt exhibited no difference in sensitivity between Gram-positive and Gram-negative microorganisms, silver and zinc showed strain specificity. A significant decrease (p < 0.001) in the bacterial density of E. coli and S. aureus was demonstrated by silver, copper and zinc in as little as two hours. Furthermore, combining metal nanoparticles reduced the time required to achieve a complete kill.

The effect of viral hepatitis B and C on the outcome of allogenic bone marrow transplantation of patients with adult acute myeloid leukemia (Egyptian sample)

Abstract Background Hematopoietic stem cell transplantation is now established as a standard therapeutic modality for different malignant and benign diseases. Hematopoietic stem cell transplantation has many complications. Infection and graft-versus-host disease (GVHD) remain the major source of morbidity and mortality in patients who undergo BMT. Aim The aim of this work was to investigate the effect of hepatitis B and hepatitis C (HCV) viral infection on the outcome of fully matched sibling donor peripheral blood stem cell transplantation in patients with acute myeloid leukemia (AML). Patients and methods A total of 328 patients with AML who received allogeneic PBSC transplantation using BU/CY or FLU/BU conditioning regimen after the consent of the Ethical Committee of Nasser Institute Hospital during the period from 1997 to December 2016 were included in this study with a follow-up of 12 months. Results In seropositive patients, neutrophil engraftment was reached at a median of 14.57 days and platelet engraftment was reached at a median of 12.7. However, in seronegative patients, neutrophil engraftment was reached at a median of 14.3 (P=0.287) and platelet engraftment was reached at a median of 12.66 (P=0.917). In seropositive patients, the incidence of SOS was 2.1%, acute GVHD grades 2–4 was reported in eight patients, whereas chronic GVHD was reported in nine patients. In seronegative patients, the incidence of SOS was 0.70% (P=0.33), acute GVHD grades 2–4 was reported in 30 patients (P=0.184), whereas chronic GVHD was reported in 45 patients (P=0.54). Overall survival for HCV seronegative and seropositive patients was 58.4 and 44.6%, respectively (P=0.001), whereas disease-free survival for HCV seronegative and seropositive patients was 56.9 and 43.4%, respectively (P=0.0001). Conclusion Analysis of 46 HCV-positive adult AML patients and 282 HCV seronegative patients who had peripheral blood stem cell transplantation shows that HCV infection does not affect platelet or neutrophil engraftment or the incidence of SOS. HCV viremia did not show a significant effect on the incidence of acute and chronic GVHD. We also documented that there is a significant effect of HCV on both the disease-free survival and overall survival.

Clonal Hematopoiesis of Indeterminate Potential: Current Understanding and Future Directions.

This article summarizes the current knowledge about clonal hematopoiesis of indeterminate potential (CHIP), its association with cardiovascular disease (CVD), and other outcomes, pathogenesis, postulated mechanisms of various pathologies, current knowledge gaps, possible targets of intervention, and therapeutic implications. Recently, a common age-related hematological entity known as CHIP has been identified as the independent risk factor for CVD. CHIP is defined as the presence of clonally expanded blood cells involving leukemogenic mutations without the evidence of malignancy. CHIP is known to increase the inflammatory state which in turn is thought to be responsible for increased risk of CVD. Apart from CVD and malignancy, CHIP is also associated with pulmonary embolism, COPD, CKD, stroke, altered metabolism, obesity, liver disease, and increased all-cause mortality. At the same time surprisingly, CHIP is found to have positive outcomes in bone marrow transplant patients and similar reciprocal association with Alzheimer's disease. The risk of CVD and cancer increases with the advancing age, and these two are the leading causes of death in the USA. CHIP is an independent risk factor for CVD development. Most patients with CHIP have somatic clonal mutations in epigenetic regulators, DNA repair genes, or regulatory tyrosine kinases without evidence of overt hematological malignancy. CHIP portends increased risk for leukemia development and carries twofold increased risk of CVD including CAD, MI, and poor prognosis in heart failure. CHIP is associated with various other pathologies making CHIP an area of active research interest in recent years. Current research efforts aim to bridge many knowledge gaps in understanding of CHIP that still exist.