Malignant Hematologic Conditions Research Articles

Comparison of atrial fibrillation prevalence and in-hospital cardiovascular outcomes between patients undergoing allogeneic versus autologous hematopoietic stem cell transplantation: insights from the national inpatient sample

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant hematologic conditions. However, patients undergoing HSCT are at increased risk of developing serious cardiovascular events. Whether cardiovascular risks differ by the type of transplantation strategy used, allogeneic versus autologous HSCT, is unknown. Leveraging the National Inpatient Sample (2016–2019), we assessed the incidence of early cardiovascular events by HSCT mode (allogeneic vs autologous). The primary outcome was the incidence of atrial fibrillation (AF). The secondary outcome was the occurrence of any major adverse cardiac events (MACE), defined as acute heart failure, myocardial infarction (MI), symptomatic atrial or ventricular arrhythmia or heart block, and cardiovascular death. Outcomes were compared between those undergoing allogeneic versus autologous HSCT. Multivariable regression, adjusting for cardiovascular and cancer-related factors, was used to define the association between pre-HSCT factors and MACE. We further assessed the effect of acute cardiovascular events on in-patient mortality by calculating adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI) and p-values. Overall, 64,705 weighted hospitalizations for HSCT were identified, of which 22,655 (35.0%) were allogeneic HSCT and 42,050 (65.0%) were autologous HSCT. The prevalence of AF was 9.1%, and 12.1% for any arrhythmia. In multivariable regression, allogeneic HSCT was associated with higher adjusted odds of peri-HSCT acute heart failure (aOR 2.64; 1.86–3.76; p < 0.0001), QT prolongation (aOR 1.40; 1.04–1.88; p = 0.025), MI (aOR 2.87; 1.16–7.11; p = 0.023), any major cardiovascular complication (aOR 1.16; 1.03–1.32; p = 0.016), and inpatient mortality (aOR 4.87; 3.60–6.58; p < 0.0001). Following cerebrovascular events, AF was the strongest predictor of mortality. Allogeneic HSCT was associated with higher odds of in-hospital cardiovascular complications among patients undergoing HSCT.

Plasmablastic Lymphoma: The 'Rare' Frequency Among Immunocompromised Patients

Limfoproliferations associated with HIV infection/AIDS are rare conditions, with an incidence of malignant lymphomas of approximately 10% among the 25-40% malignancies that can occur in these immunosuppressed patients (1). Plasmablastic lymphoma (PBL), with an incidence of only 2% (out of the total lymphomas), is a borderline form (morphologically and immunophenotypically) between lymphoma and myeloma, defined by its high aggressiveness and unfavorable prognosis (2). Objectives: identifying the clinical, histopathological, and biological characteristics of PBL that require a differential diagnosis within other malignant hematological conditions associated with HIV infection. Materials and Methods: We present three comparative cases of PBL that were observed at the Colțea Hematology Clinic in a short time window (4 months). All patients were diagnosed with PBL in the context of HIV/AIDS infection, with an average age of approximately 41 years, predominantly male (66.6%), and with a symptomatology onset characteristic of immunocompromised individuals (manifesting at the oral, lymph node, and cutaneous levels), but with specific aspects related to associated comorbidities (e.g., psychiatric pathology, dilated cardiomyopathy), risk behaviors (e.g., intravenous drug use for 20 years), and infectious/ non-infectious complications, which influenced the patients' evolution. Conclusions: Plasmablastic lymphoma still represents a highly aggressive condition with an unfavorable prognosis, possibly having a higher clinical incidence than that described in the literature and requiring a adequate multidisciplinary approach.

CD34+ Megakaryocytes Associate with Myelodysplastic Syndromes and Related Cytogenetic Abnormalities, but Not Other Hematological Disorders

Background: CD34 is a transmembrane phosphoglycoprotein that is a marker of hematopoietic stem cells and is used clinically to aid in enumeration of blast cells for identification of advanced myeloid neoplasms. Megakaryocytes are differentiated cells from the myeloid lineage that reside in the bone marrow and generally stain negative for CD34 (CD34-). However, CD34 positive (CD34+) megakaryocytes have been observed in hematological disorders such as myelodysplastic syndrome, myeloproliferative neoplasms, and acute leukemias. CD34+ megakaryocytes are proposed to be relatively specific for malignant hematologic conditions and have been reported to associate with a worse prognosis. However, the general clinical, biochemical, and cytogenic characteristics for bone marrow cases of CD34+ megakaryocytes versus CD34- megakaryocytes remains unclear. Objective: We sought to determine the clinical, biochemical, and cytogenetic characteristics associated with finding CD34+ megakaryocytes on bone marrow biopsies. Methods: We identified 281 independent, index bone marrow biopsy cases between 2011-01-01 and 2017-12-31 from Vancouver General Hospital, Canada that underwent CD34 immunohistochemistry at clinical request. The clinical, biochemical, and cytogenetic characteristics of patients were compared based on megakaryocytes being CD34+ vs CD34- on immunohistochemistry. Cases of CD34+ megakaryocytes were defined as having &amp;gt;5% of megakaryocytes staining CD34+, but sensitivity analyses were performed using different percentage cut-offs of 10, 30, and 50%. Results: Out of 281 cases, 134 had CD34+ megakaryocytes (58.2% male sex; mean age = 64.1 years [SD = 15.2 years]) and 147 had CD34- megakaryocytes (57.1% male sex; mean age = 60.0 years [SD = 16.6 years]). There was a significant difference in the distribution of diagnostic categories observed between cases of CD34+ versus CD34- megakaryocytes: myelodysplastic syndromes 35.1% (n=47) versus 21.8% (n=32), acute myeloid leukemias 20.9% (n=28) versus 21.1% (n=31), non-diagnostic etiology 17.9% (n=24) versus 14.3% (n=21), and myeloproliferative neoplasms 10.4% (n=14) versus 19.7% (n=29) (Figure A; Chi-square p-value=0.0004). Sensitivity analyses using different percentage cut-offs to define cases of CD34+ from CD34- megakaryocytes yielded similar results. The differences in biochemical characteristics between cases of CD34+ versus CD34- megakaryocytes were generally unremarkable. The median (IQR) for biochemical parameters between cases of CD34+ and CD34- megakaryocytes were hemoglobin 99 (28) versus 100 (34) g/L, mean corpuscular volume 94 (14) versus 93 (10) fL, neutrophil count 2.20 (3.68) versus 2.46 (3.63) x10 9/L, platelet count 98 (158) versus 112 (194) x10 9/L, and bone marrow blasts 7 (4) versus 3 (14)%. Lastly, there were notable trends in cytogenetic results associated with 90 cases with CD34+ versus 84 cases with CD34- megakaryocytes including: complex karyotypes for 15.6% (n=14) versus 6.0% (n=5), isolated deletion 5q for 7.8% (n=7) versus 1.2% (n=1), and/or isolated trisomy 8 for 5.6% (n=5) versus 2.4% (n=2). Similar cytogenetic results were observed when cases were restricted to only cases of CD34+ versus CD34- megakaryocytes with a diagnosis of myelodysplastic syndrome (Figure B). Conclusion: The presence of CD34+ megakaryocytes is more common in cases of myelodysplastic syndrome relative to other neoplastic hematologic disorders, but does not appear to help with discriminating between neoplastic and non-neoplastic hematological disorders ( e.g. non-diagnostic etiology). Cases with CD34+ megakaryocytes tend to associate with complex karyotype and deletion 5q abnormalities relative to cases with CD34- megakaryocytes.

International Society for Cell & Gene Therapy Stem Cell Engineering Committee: Cellular therapies for the treatment of graft-versus-host-disease after hematopoietic stem cell transplant

Background aimsAllogeneic hematopoietic stem cell transplant is a curative approach for many malignant and non-malignant hematologic conditions. Despite advances in its prevention and treatment, the morbidity and mortality related to graft-versus-host disease (GVHD) remains. The mechanisms by which currently used pharmacologic agents impair the activation and proliferation of potentially alloreactive T cells reveal pathways essential for the detrimental activities of these cell populations. Importantly, these same pathways can be important in mediating the graft-versus-leukemia effect in recipients transplanted for malignant disease. This knowledge informs potential roles for cellular therapies such as mesenchymal stromal cells and regulatory T cells in preventing or treating GVHD. This article reviews the current state of adoptive cellular therapies focused on GVHD treatment. MethodsWe conducted a search for scientific literature in PubMed® and ongoing clinical trials in clinicaltrial.gov with the keywords “Graft-versus-Host Disease (GVHD),” “Cellular Therapies,” “Regulatory T cells (Tregs),” “Mesenchymal Stromal (Stem) Cells (MSCs),” “Natural Killer (NK) Cells,” “Myeloid-derived suppressor cells (MDSCs),” and “Regulatory B-Cells (B-regs).” All the published and available clinical studies were included. ResultsAlthough most of the existing clinical data focus on cellular therapies for GVHD prevention, there are observational and interventional clinical studies that explore the potential for cellular therapies to be safe modalities for GVHD treatment while maintaining the graft-versus-leukemia effect in the context of malignant diseases. However, there are multiple challenges that limit the broader use of these approaches in the clinical scenario. ConclusionsThere are many ongoing clinical trials to date with the promise to expand our actual knowledge on the role of cellular therapies for GVHD treatment in an attempt to improve GVHD-related outcomes in the near future.

Effects of immune system cells in GvHD and corresponding therapeutic strategies.

Allogeneic tissue transplantation is one of the most effective treatments for several diseases and injuries, in particular, malignant and non-malignant hematological conditions. Following this procedure, transplanted tissue encounters various complications, one of the most serious being graft-versus-host disease (GvHD). The management of GvHD directly affects the success of transplantation and the survival rate of the patient; therefore, many studies have focused on GvHD prevention and control. This review briefly explains the transplantation process, causes of graft rejection, and importance of the human leukocyte antigen system. Initially, we address the pathophysiology and immunobiology of GvHD, the cells involved in this complication, the differences between chronic and acute GvHD, and the importance of graft-versus-leukemia. Interestingly, various types of immune cells are involved in GvHD pathogenesis. After explaining how these cells affect the GvHD process, we discuss the studies conducted to control and reduce GvHD symptoms.

Development of Consensus Guidelines for Hematology Fellow Competency in Peripheral Blood Smear Review Utilizing Nominal Group Technique

INTRODUCTION: Graduate medical education (GME) training in hematology in the United States is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees provide patient care that requires manual review and interpretation of peripheral blood smears (PBS). The ACGME milestones were developed with significant input from the American Society of Hematology (ASH) and mandate fellow competency in the interpretation of peripheral blood smears. However, there are currently no publications that define competency or propose consensus recommendations (CRs) for PBS review. The primary aim of this study was to establish CRs on PBS review with a focus at the GME level. METHODS: Nominal group technique (NGT) and constructivist grounded theory (CGT) were selected given the lack of existing published theory and consensus on the methodology of PBS review or other analogous visuospatial skills within GME. A convenience sample of hematologists with expertise in training and assessing fellows was recruited through the ASH Medical Educators Institute. Goal accrual was 5-10 hematologists. Participants were required to regularly review PBSs as part of their clinical practice and attend two 1-hour virtual focus group sessions. The facilitator guide for session 1 was developed a priori to prompt open discussion on PBS review. Dialogue was transcribed and organized into thematic concepts through inductive coding. Data from session 1 were analyzed using a mixed methods approach and were used to develop a facilitator guide for session 2. Draft CRs were created using CGT. Weak and strong consensus were pre-specified as 50 - 69%, and >70% agreement, respectively. CRs underwent iterative review which would continue for a pre-specified minimum of 2, but no more than 3 rounds. RESULTS: Eight academic hematologists (5 men, 3 women) enrolled in the focus group (Table 1). Duration of clinical practice ranged from 5 to 33 years. Clinical focus spanned classical and malignant hematologic conditions. Half had formally instructed trainees in course work on PBS morphology. All routinely worked with fellows. CRs were generated through CGT. Three rounds of review occurred. Participants provided a statement of agree vs. disagree and offered qualitative suggestions for each statement in which they disagreed. Response rates per round were 87.5%, 87.5%, and 100%. The most commonly identified themes included recognition of morphology suggestive of thrombotic microangiopathies and distinguishing between malignant vs. benign white blood cells (WBC), specifically as it pertains to acute leukemias. Strong consensus was reached on multiple aspects of PBS education, including curricular considerations, method of review, and morphology (Table 2). All agreed that trainees should learn PBS review through a systematic approach, although some agreed that this systematic approach is not always used in clinical practice. The group agreed that trainees should be educated through PBS review of patients under their clinical care as well as through formal slide "libraries". Many discussed the changing landscape of PBS education with the advent of digital microscopy, and formed strong consensus that trainees should understand the benefits and limitations of digital microscopy. Group discussion largely focused on disorders of WBCs and red blood cells (RBC) (43% and 48% of all coded statements respectively). Most discussion focused on disorders in which prompt recognition was imperative to avert significant patient morbidity or mortality. However, all agreed that trainees must also be competent in the identification of common conditions, regardless of the degree of clinical importance, including normal peripheral blood smear morphology. The group was unable to reach consensus on how to balance these competing philosophies. CONCLUSIONS: A formal theory of PBS education was systematically developed using CGT. Experts were able to form strong CRs on almost every aspect of PBS review at the GME level. FUTURE DIRECTIONS: We propose that these guidelines serve as a template for future research and curricular development for both PBS review and other visuospatial tasks in medical education. This framework can also be used by organizations, such as ACGME and ASH, when formally reviewing and codifying guidelines on PBS review. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Demographic Disparities Related to Fertility Preservation Counseling in Patients Undergoing Bone Marrow Transplantation

Infertility is a well-documented adverse effect associated with certain chemotherapeutic agents and radiation therapy.1 High-dose chemotherapy and/or total body irradiation (TBI) are utilized in preparation for bone marrow transplant (BMT), with the intent of achieving complete myeloablation prior to transplant.2 BMT is commonly used as a curative treatment modality for both malignant and benign hematologic conditions. Given this necessary exposure to high-dose chemotherapy and TBI, both male and female patients undergoing BMT are therefore at extremely high risk of impaired fertility later in life. Discussions concerning fertility preservation are often psychologically challenging for patients preparing to undergo BMT. To address these concerns, many institutions have developed fertility preservation counseling programs that aim to provide patients and caregivers with the necessary information to make informed decisions regarding fertility preservation. As is the case with many resources in healthcare, certain populations have more access to these resources than others. The goal of this study was to gain insight into if demographic features such as age, race, socioeconomic status, and underlying diagnosis/indication for BMT impacted the likelihood that a patient received fertility preservation counseling prior to transplant. It was hypothesized that there would be statistically significant differences in the rates of fertility preservation counseling when patients are compared by age, gender, race, socioeconomic status, and underlying diagnosis. A pre-existing database of BMT patients treated at the University of Rochester Medical Center was used to generate a study population of 244 patients between the ages of 0-39 years old who underwent BMT between 2012-2020. Demographic features including age, gender, race, insurance type, zip code, and indication for transplant were extracted from the database. A retrospective chart review was then conducted to identify if patients had a visit with a reproductive endocrinology and infertility (REI) specialist or if any documented fertility preservation counseling occurred prior to transplant. Odds ratios were then calculated for each of the aforementioned independent demographic variables. The overall prevalence of documented fertility preservation counseling was low. Approximately 20% of patients had a documented REI visit, while 47% had any form of documented fertility preservation counseling. There were differences in the prevalence of fertility preservation counseling related to patient age at transplant and median county income. Adult patients (age >18) were more likely than pediatric patients (age <18) to have a documented visit with an REI specialist (OR 2.99, 95% CI 1.37-6.51, p=0.0059) and more likely to have any documented fertility preservation counseling (OR 3.49, 95% CI 1.97-6.16, p<0.0001). Patients living in counties where the median income was >$60,000/year were more likely than patients living in counties with a median income of <$60,000/year to have a visit with an REI specialist (OR 4.25, 95% CI 1.89-9.54, p=0.0005) or any documented fertility preservation counseling (OR 2.72, 95% CI 1.59-4.64, p=0.0002). There were no statistically significant disparities in the prevalence of fertility preservation counseling based on patient gender, race, insurance type, or indication for transplant. These findings demonstrates that there are statistically significant differences in the prevalence of documented fertility preservation counseling based on demographic features, specifically on the basis of age and socioeconomic status. It is unclear if these findings represent the true prevalence of fertility preservation counseling, as some counseling is likely not adequately documented in the electronic medical record. Future studies are needed to design and implement improved fertility preservation counseling mechanisms, and to ensure adequate documentation of this counseling. Footnotes: 1. Rodriguez-Wallberg KA. Principles of cancer treatment: impact on reproduction. Adv Exp Med Biol. 2012;732:1-8. doi:10.1007/978-94-007-2492-1_1 2. Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344-353. doi:10.1182/blood-2014-02-514778

Systematic screening and focused evaluation for veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) following allogeneic stem cell transplant is associated with earlier diagnosis and prompt institution of defibrotide treatment.

Sinusoidal obstructive syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a potentially life-threatening complication following haemopoietic stem cell transplantation (HSCT). The availability of new drugs for malignant hematological conditions has allowed more patients to be eligible for allogeneic haematopoietic stem cell transplants, which has translated into a significant proportion of transplant patients having multiple risk factors for VOD/SOS. Based on these considerations, we undertook a dedicated weekly VOD/SOS ward round, aiming to facilitate early diagnosis of VOD/SOS and pre-emptively identify patients at risk, where a careful evaluation of differential diagnosis is essential. Herein, we present the results of our VOD/SOS ward round; between September 2020 and April 2022, 110 consecutive patients were evaluated in a focused VOD/SOS ward round. From the 110 patients, 108 had undergone HSCT and had at least one known risk factor for developing VOD/SOS. The median number of risk factors present in the VOD/SOS group and non-VOD/SOS group was five (range: three to six) and three (range: zero to seven), respectively. Late-onset VOD/SOS was diagnosed in 45% of our patients. The early identification of patients with multiple risk factors for VOD/SOS allowed an earlier diagnosis and the administration of defibrotide on the same day of diagnosis, which was two days earlier than our previous experience prior to the implementation of this protocol.

Association of enrollment duration on trial outcome in phase 3 randomized controlled trials: A pancancer analysis spanning 67 years.

e13597 Background: Randomized controlled trials (RCTs) inform the standard of care in clinical oncology, yet a substantial proportion yield negative results. Difficulty with patient enrollment is a problem commonly encountered in the conduct of large multicenter RCTs, leading to slow enrollment. Slow enrollment can lead to increased financial costs, delayed reporting, and decreased relevance of trial results if standards of care shift. The effects of slow enrollment on trial success are understudied. We hypothesized that longer enrollment periods would be inversely correlated with trial success, after adjustment for year of study. Methods: Phase 3 RCTs studying malignant hematologic and solid tumor conditions available on the HemOnc.org website through December 31, 2021, were included in the analysis. HemOnc.org contains nearly all phase 3 RCTs of systemic anticancer therapy registered on ClinicalTrials.gov (with results) or with publications indexed in PubMed. Start year and end year of enrollment and comparative efficacy of control and experimental arms of RCTs were extracted. RCTs were deemed positive if the experimental arms were superior in superiority trials or non-inferior in non-inferiority trials, or if control arms were inferior in superiority trials. The remaining RCTs were deemed negative. Logistic regression was used to analyze the relationship between length of enrollment period and trial outcome, adjusted for year of study enrollment start. Results: The analysis included 3072 phase 3 RCTs spanning 99 different cancer types, enrolling from 1955-2019. Breast cancer was the most studied condition (n=554 trials) followed by non-small cell lung cancer (n=314 trials). 1513 (49.2%) of RCTs reported positive trial outcomes. The overall median enrollment period was 4 years (range 1-16 years). Negative trials took 1 year longer, on average, to complete enrollment (Table). The logistic regression model showed that shorter enrollment periods were associated with trial success. Later enrollment start year was also independently associated with trial success (Table). Conclusions: Our study showed that shorter enrollment period was significantly associated with positive trial outcomes. The success rate of trials has also increased over time; this could reflect both more efficacious drugs as well as more conservative enrollment criteria. Our main limitation is that we do not have data on early termination or closure for futility; these two issues might arise in both fast and slow accruing studies, which would bias results towards the null. The results of this analysis emphasize the importance of rapid phase 3 trial enrollment.[Table: see text]

A Warning Call for Fertility Preservation Methods for Women Undergoing Gonadotoxic Cancer Treatment.

Malignant hematological conditions have recognized an increased incidence and require aggressive treatments. Targeted chemotherapy, accompanied or not by radiotherapy, raises the chance of defeating the disease, yet cancer protocols often associate long-term gonadal consequences, for instance, diminished or damaged ovarian reserve. The negative effect is directly proportional to the types, doses, time of administration of chemotherapy, and irradiation. Additionally, follicle damage depends on characteristics of the disease and patient, such as age, concomitant diseases, previous gynecological conditions, and ovarian reserve. Patients should be adequately informed when proceeding to gonadotoxic therapies; hence, fertility preservation should be eventually regarded as a first-intention procedure. This procedure is most beneficial when performed before the onset of cancer treatment, with the recommendation for embryos or oocytes’ cryopreservation. If not feasible or acceptable, several options can be available during or after the cancer treatment. Although not approved by medical practice, promising results after in vitro studies increase the chances of future patients to protect their fertility. This review aims to emphasize the mechanism of action and impact of chemotherapy, especially the one proven to be gonadotoxic, upon ovarian reserve and future fertility. Reduced fertility or infertility, as long-term consequences of chemotherapy and, particularly, following bone marrow transplantation, is often associated with a negative impact of recovery, social and personal life, as well as highly decreased quality of life.

Chronic Graft-Versus-Host Disease (cGVHD) Exacerbation after Sars-Cov-2 Covid Vaccination

INTRODUCTIONAllogeneic hematopoietic cell transplant (allo-HCT) exists as a potential cure to a number of different benign and malignant hematologic conditions. About 50% of patient develop cGVHD, the most important long-term complication of allo-HCT with profound effects on immune recovery. This immunocompromised patient population requires careful consideration regarding approach to vaccination. As the SARS-CoV-2 vaccines were developed and made available at an unprecedented rate, we are learning in real-time how specific vulnerable patient populations are affected, particularly as patients with cGVHD were largely excluded from clinical trials for the SARS-CoV-2 mRNA vaccines. Though the immunomodulatory mechanisms of the Pfizer and Moderna vaccines are poorly understood, societies such as ASH and ASTCT recommend that patients with cGVHD receive it. Here, we report our experience in patients with cGVHD who received the mRNA SARS-CoV-2 vaccine. METHODSWe performed this retrospective analysis of all Huntsman Comprehensive Cancer Center patients who underwent allo-HCT between 2013 and 2020. Patients who had a diagnosis of cGVHD requiring systemic therapy and were alive in December 2020, (when the SARS-CoV-2 vaccine became available), were included in the analysis. The clinical data was queried from the bone marrow transplant (BMT) database, and medical records were individually reviewed for documentation of SARS-CoV-2 mRNA vaccination. Patients meeting criteria were screened in clinic for symptoms post-vaccination. We define worsening or flare of disease as an organ upstage of at least 1 by NIH Consensus Criteria scale, in addition to requirement of intervention with a systemic or topical therapy. All patients were consented under a University of Utah IRB-approved protocol for participation in this study. RESULTSA total of 52 patients at our institution met the inclusion criteria of being alive with cGVHD at the time Covid mRNA vaccinations became available. Of these 52 patients, 65.4% (n=34) had had two doses of SARS-CoV-2 vaccine. Of these 34 patients, 26.5% (n=9) experienced worsening of their cGVHD manifestations after vaccination. All 9 of these patients (100%) received the Pfizer vaccine. Mean time between transplant day 0 and flare date was 1,222 days (95% CI 511-1,933). At the time of flare, 3/9 patients were on systemic treatment for cGVHD, 6/9 patients had been tapered off systemic therapy, and half of them were on topical therapies. Three patients (33.3%) experienced GVHD flare after SARS-CoV-2 vaccine dose #1. The remaining 6 (66.7%) experienced flare after dose #2, with a median time to flare of 1.5 days. Five of the 9 patients (55.6%) required systemic steroid therapy, with 2 patients (22.2%) requiring >30 days of treatment. The most common organs involved were skin and eyes. Six patients (66.7%) had resolution of flare symptoms. One patient (11.1%) subsequently developed Covid pneumonia and had relapse of AML. CONCLUSIONThough reports have emerged highlighting hematologic and other autoimmune disease recrudescence in response to SARS-CoV-2 vaccination, to our knowledge this is the first large case series demonstrating chronic GVHD flare in response to the vaccine. Almost a third of our cGVHD patients experienced disease flare shortly after vaccination, which raises questions of the degree and mechanism of such heightened immunogenicity in an mRNA vaccine. Consistent with prior studies, most of our patients (66.7%) experienced disease flare after receiving the 2 nd mRNA vaccine dose, Although correlation with vaccine administration does not necessary prove causation of GVHD flare, in counseling patients, the possibility of a severe flare should be weighed against risk of Covid infection. [Display omitted] DisclosuresLee: Jazz,: Consultancy; Fresensius Kabi: Consultancy; Kite: Membership on an entity's Board of Directors or advisory committees; Kadmon: Membership on an entity's Board of Directors or advisory committees; CareDx: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding.

Omission of day +11 methotrexate dose and allogeneic hematopoietic cell transplantation outcomes: results of a systematic review/meta-analysis.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for patients with malignant and benign hematologic conditions. Graft-versus-host disease (GVHD) is a known complication of allo-HCT that results in significant morbidity and mortality. A common GVHD prophylaxis strategy combines a calcineurin inhibitor with methotrexate. When mucositis and organ toxicity develop, the day +11 dose is frequently omitted to limit further organ damage. The potential impact of this practice on allo-HCT outcomes is unclear as published data show conflicting results. Thus, we performed a systematic review/meta-analysis of the available literature to assess the impact of omitting day +11 methotrexate on allo-HCT recipients. Data were extracted in relation to benefits (overall survival [OS], progression-free survival [PFS]) and harms (acute and chronic GVHD, non-relapse mortality [NRM], and relapse). Pooled OS rate favored those who received day +11 methotrexate vs. those who did not (HR = 1.21; 95% CI = 1.02-1.43; p = 0.03). There was no significant difference in pooled rates of PFS (HR = 0.96; 95% CI = 0.60-1.52; p = 0.85), acute GVHD (HR = 1.03; 95% CI = 0.35-2.98; p = 0.96), chronic GVHD (HR = 0.83; 95% CI = 0.44-1.57; p = 0.57), NRM (HR = 0.86; 95% CI = 0.67-1.11; p = 0.25), and relapse (HR = 0.97; 95% CI = 0.75-1.26; p = 0.83) between the two groups. Large prospective multicenter studies are needed to better define the significance of day +11 methotrexate omission.

Real-world experiences of nurses administering blood transfusions via a central venous access device (CVAD) concurrently with other intravenous (IV) medications for patients with malignant and non-malignant haematological conditions

Real-world experiences of nurses administering blood transfusions via a central venous access device (CVAD) concurrently with other intravenous (IV) medications for patients with malignant and non-malignant haematological conditions

Telemedicine in Malignant and Nonmalignant Hematology: Systematic Review of Pediatric and Adult Studies.

BackgroundTelemedicine, including video-, web-, and telephone-based interventions, is used in adult and pediatric populations to deliver health care and communicate with patients. In the realm of hematology, telemedicine has recently been used to safely and efficiently monitor treatment side-effects, perform consultations, and broaden the reach of subspecialty care.ObjectiveWe aimed to synthesize and analyze information regarding the feasibility, acceptability, and potential benefits of telemedicine interventions in malignant and nonmalignant hematology, as well as assess the recognized limitations of these interventions.MethodsStudies were identified through a comprehensive Medical Subject Headings (MeSH) search on the PubMed MEDLINE, Controlled Register of Clinical Trials (Cochrane CENTRAL from Wiley), Embase, and CINAHL (EBSCO) databases on February 7, 2018. A second search, utilizing the same search strategy, was performed on October 1, 2020. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the reporting of included evidence. Included studies were original articles researching the feasibility, acceptability, and clinical outcomes of telemedicine or telehealth interventions in pediatric or adult populations with malignant or nonmalignant hematological conditions. Data items in the extraction form included first author name, publication year, country, malignant or nonmalignant hematological condition or disease focus of the study, participant age, participant age subgroup (pediatric or adult), study design and setting, telemedicine intervention type and description, study purpose, and main study outcomes.ResultsA total of 32 articles met the preset criteria and were included in this study. Most (25/32) studies were conducted in adults, and the remaining (7/32) were conducted in the pediatric population. Of the 32 studies, 12 studied malignant hematological conditions, 18 studied nonmalignant conditions, and two studied both malignant and nonmalignant conditions. Study types included pilot study (11/32), retrospective study (9/32), randomized controlled trial (6/32), cross-sectional study (2/32), case study (1/32), pre-post study (1/32), noncomparative prospective study (1/32), and prospective cohort study (1/32). The three main types of telemedicine interventions utilized across all studies were video-based (9/32), telephone-based (9/32), and web-based interventions (14/32). Study results showed comparable outcomes between telemedicine and traditional patient encounter groups across both pediatric and adult populations for malignant and nonmalignant hematological conditions.ConclusionsEvidence from this review suggests that telemedicine use in nonmalignant and malignant hematology provides similar or improved health care compared to face-to-face encounters in both pediatric and adult populations. Telemedicine interventions utilized in the included studies were well received in both pediatric and adult settings. However, more research is needed to determine the efficacy of implementing more widespread use of telemedicine for hematological conditions.

Incidence and Risk Factors of Epstein-Barr Virus Viremia in Patients Undergoing Haploidential Transplantation with Post Translant Cyclophosphamide

INTRODUCTIONHaploidentical stem cell transplants are increasingly performed for a wide variety of malignant and non-malignant hematological conditions. Epstein - Barr virus (EBV) viremia and subsequent development of Post-Transplant Lymphoproliferative Disorder (PTLD) are potential adverse sequelae of the transplantation process and associated immunosuppression. Traditionally, haploidentical transplants have been associated with increased risk of EBV reactivation and subsequent PTLD. This was largely due to graft versus host disease (GVHD) prophylaxis protocols using intense immunosuppression with either Ex-vivo T-cell depletion or in-vivo T- cell depletion with anti-thymocyte globulin (ATG) and Alemtuzumab. However, most haploidentical transplants in recent years have utilized post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis. Rituximab has been used for preemptive treatment of EBV viremia/PTLD, but there is scarce data on its use in this setting, as well as the risk factors and outcomes of EBV viremia associated with haploidentical transplants with PTCy. RESULTSA total of 63 patients with hematological malignancies received haploidentical transplant at our institution from 2013 from 2016. Patient characteristics are summarized in Table 1.All patients received EBV monitoring using plasma viral copies once weekly starting 20 days post-transplant. EBV monitoring continued for 6 months after immunosuppression ended or when CD4 count >200. Among these 63 patients, 18 (28.5%) became EBV DNA positive upon follow-up. Per institutional protocol, EBV titer was confirmed by repeat testing when viral load was 1000 copies/mL and treatment with Rituximab was initiated if repeat titer was >1000 copies/ml.The median time to detection of EBV viremia from the time of transplant was 99 days (range: 20-277). The median peak level for the EBV reactivation cohort was 7650 viral copies /ml. The median time from detection of viremia to peak viremia was 1.5 days (range 0-253).8 of the 18 (44.4%) patients that developed EBV viremia required Rituximab due to rising or persistent EBV viremia. The median EBV level at initiation of therapy was 31,000 copies/ml for the 8 patients that received Rituximab treatment. EBV seronegativity was achieved in 6 patients (75%) with treatment at a median of 13.5 days (range 3-26). The median number of Rituximab cycles administered was 1.5 (range: 1-16). None of the patients in either cohort developed PTLD or other EBV associated diseases.A univariate analysis was performed comparing EBV reactivation cohort and no EBV reactivation cohort to look for risk factors predisposing to EBV reactivation (Table 1) There were no statistically significant differences seen in the variables studied other than patients not in complete remission at the time of transplant were statistically more likely to develop EBV viremia. 9 out of 18 patients (50%) that developed EBV viremia were not in complete remission at the time of transplant, whereas 11 out of the 45 patients (24.44 %) that did not develop EBV viremia were in an incomplete remission at the time of transplant (p value: 0.05) (Table 1).With a median follow up of469 days, there were a total of 22 deaths among the 45 (48.9 %) patients that had no viremia, and 8 deaths amongst the 18 (44.4 %) patients that had viremia (p value: 0.75). There was no statistically significant difference in graft versus host disease (GVHD) incidence (p value: 0.79) or overall survival (555 days for patients with EBV reactivation versus not reached for patients without EBV reactivation, p value: 0.45) between these two groups (p value: 0.79) CONCLUSIONSIn this retrospective study assessing risk factors and outcomes of EBV viremia in patients following haploidentical transplants, we observed a 28.5 percent incidence of EBV viremia. Rituximab was effective in preemptive treatment of EBV viremia. However, no cases of PTLD were observed, even in those patients with sustained elevation in EBV titers. It is unclear how to manage asymptomatic elevations in viral titers after allogeneic transplantation in patients who are otherwise at low risk for development of PTLD. Previous data suggests that even high levels of EBV viremia lacks specificity for prediction of PTLD in post-transplant setting. Given these results, the utility of routine monitoring of EBV viral load after haploidentical transplant should be questioned in those who have received PTCy. [Display omitted] DisclosuresLin:Jazz Pharmaceuticals: Consultancy. Ganguly:Amgen: Other: Advisory Board; Seattle Genetics: Speakers Bureau.

Activity report of the Bone Marrow Transplant Department of the Mohammed VI University Hospital, Marrakech, Morocco, over the period 2012- 2018

Introductionla greffe de cellules souches hématopoïétiques (GCSH) fait partie de l´arsenal de l´immunothérapie cellulaire à but curatif, elle est utilisée dans le traitement de plusieurs affections hématologiques malignes et non malignes ainsi que d´autres pathologies extra-hématologiques. Décrite depuis 1950 et introduite au Maroc depuis les années 2000, la GSCH reste encore jeune dans notre contexte avec plusieurs obstacles juridiques, financiers et organisationnels. L´objectif de notre travail est de rapporter l´expérience en matière de la greffe des cellules souches hématopoïétiques au sein du service d´hématologie clinique et de greffe de moelle osseuse du centre hospitalo-universitaire (CHU) Mohammed VI de Marrakech, étant un exemple d´un service des pays en voie de développement.Méthodesnous avons mené une étude rétrospective descriptive sur une durée de 7 ans.Résultatssoixante-six GCSH ont été réalisées, le myélome multiple représente la première indication dans notre série avec 30 autogreffes. Dans notre série, Le taux de mortalité avoisine les 20%, celui de rechute est à 23% et celui des complications est à 38%. Nos résultats malgré les difficultés restent encourageants, avec un recul assez important.Conclusiondes efforts restent à fournir pour améliorer les résultats de cette thérapie.

Level of Scientific Evidence Underlying the National Comprehensive Cancer Network Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Background: The level of scientific evidence in National Comprehensive Cancer Network (NCCN) guidelines for malignant hematological conditions haven't been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: We reviewed the level of evidence for the 10 most common hematological malignancies by incidence in the United States as of 2020. The NCCN definitions for EC are: category 1, high level of evidence, such as randomized controlled trials, with uniform consensus; category 2A, lower level of evidence with uniform consensus; category 2B, lower level of evidence without a uniform consensus but with no major disagreement; and category 3, any level of evidence but with major disagreement. We compared our results with previously published results from 2011. Results: Of 1353 recommendations, 5%, 91%, 4%, and 1% fell into EC categories 1, 2A, 2B, and 3, respectively, while in 2011 the comparable percentages were 3%, 93%, 4%, and 0%, respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt lymphoma. Of all therapeutic recommendations, 6.3% were category 1 EC, with the majority of these (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were multiple myeloma (12.4%), chronic lymphocytic leukemia/small lymphocytic lymphoma (6.9%), and acute myeloid leukemia (5.6%). Conclusions: Recommendations in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion, underscoring the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders.

Omitting Fluoroquinolones Antibiotic Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation Does Not Increase Gram-Negative Bacteremia Rate or Transplant-Related Mortality

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely utilized as a curative treatment for malignant and non-malignant hematological conditions. Fluoroquinolone prophylaxis (FQ-P) is demonstrated to reduce the rate of blood stream infections (BSI) caused by gram-negative bacteria (GNB) during allo-HSCT and increases overall survival (OS), making this approach the standard of care. The available data show that during the transplantation period, the intestinal microbiome diversity profoundly decreases, which is associated with a significant increase in transplant-related mortality (TRM), acute graft-versus-host disease (aGVHD) related mortality and decrease in OS. FQ-P is reported to be a dominant factor in the perturbation of the gut microbiota, leading some centers to omit or modify transplant antibiotic prophylaxis regimens. The aim of the present study has been to evaluate the effects of FQ-P omission on the prevalence of gram-negative bacteria blood stream infections (GNB-BSI), GNB susceptibility to antibiotic treatment, mortality of patients with sepsis and overall TRM. This retrospective single-center study included all consecutive patients, admitted to the Rambam Department of Hematology for allo-HSCT between 01.01.2017 and 31.12.2019. The fact that at our center, FQ-P in allo-HSCT recipients was discontinued on 01.12.2018 allowed comparison of the outcomes in patients treated with and without such prophylaxis. GNB-BSI events registered within 30 days of admission were analyzed. The proportion of first-time GNB-BSI, the antibiotic susceptibility profile, day 30 and day 90 mortality among patients with GNB-BSI were compared. The assessment also included day 30 and day 90 overall TRM, mortality related to sepsis and aGVHD. During the evaluated period, 189 patients underwent allo-HSCT and were included in the analysis. FQ-P was administered to 125 patients and omitted in 64 individuals. GNB-BSI events occurred in 23 (18.4%) patients receiving FQ-P and in 17 (26.6%) patients who did not receive it (p=0.19). GNB susceptibility to FQ, piperacillin/tazobactam and meropenem increased from 38.1% to 58.8%, from 60% to 70.6% and from 85.7% to 94.1%, respectively, after FQ-P had been stopped (p=non-significant, NS). 30-day and 90-day mortality among patients with GNB-BSI did not increase in the post-FQ-P period (Table 1). Day 30 and day 90 overall TRM rates were 10.6% and 18.9%, respectively, with FQ-P versus 13.5% and 21.9%, respectively, without FQ-P (p=NS). Before FQ-P was stopped, sepsis was the cause of death in 56% of events and aGVHD in 16% and after FQ-P was stopped, the corresponding values were 46% and 23%, respectively (p=NS). FQ-P omission has not significantly increased the rate of GNB-BSI or affected the profile of GNB susceptibility to antibiotic treatment in patients undergoing allo-HSCT. Moreover, it has not significantly changed day 30 and day 90 mortality either among patients with GNB-BSI or in the entire study population. FQ-P omission in allo-HSCT recipients appears to be safe and its implementation could contribute to the preservation of intestinal microbiome diversity, potentially leading to improved post-transplant outcome. The findings of this study need to be further evaluated in large randomized trials. Disclosures No relevant conflicts of interest to declare.

Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines. Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance. Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines. Figure Disclosures No relevant conflicts of interest to declare.

Telehealth Is a Sustainable Population Health Strategy to Lower Costs and Increase Quality of Health Care in Rural Utah.

A telehealth oncology practice was created to care for patients in rural communities to improve access to health care, decrease financial burdens, and save time. Patients with cancer at Sevier Valley Hospital in Richfield, Utah, were treated with a real-time video-based telehealth program under the care of an oncologist at a tertiary medical center. Data on financial savings, travel hours, mileage avoided, carbon emissions reduced, and revenue retained by Sevier Valley Hospital were collected from 2015 to 2018. From 2015 to 2018, 119 patients with cancer in Richfield, Utah, were treated with telehealth for oncology visits, accounting for 1,025 patient encounters. On average, patients saved 4 hours and 40 minutes and 332 miles roundtrip per encounter. In total, patients' savings were estimated to be $333,074. Carbon emissions were reduced by approximately 150,000 kg. Of new patient referrals, 59% were for solid tumors (70 of 119 referrals; 42 metastatic and 28 nonmetastatic cancers), and 41% were hematology consultations (49 of 119 referrals; 28 classical and 21 malignant hematologic conditions). We estimate that Sevier Valley Hospital retained $3,605,500 in revenue over this 4-year period. Using a telehealth program in rural Utah, patients with cancer benefited from substantial time and monetary savings. The local medical center was able to retain revenue it would have otherwise lost to outsourcing cancer care. Recent regulatory changes to address the COVID-19 pandemic should increase the number of patients with cancer treated via telehealth nationwide.