Division Of Hematology Research Articles

Low COAT platelets are frequent in patients with bleeding disorders of unknown cause (BDUC) and can be enhanced by DDAVP

Low COAT platelets are frequent in patients with bleeding disorders of unknown cause (BDUC) and can be enhanced by DDAVP

GDF-15 is associated with atherosclerosis in adults with transfusion-dependent beta-thalassemia.

Objectives: To study serum growth differentiation factor‐15 (GDF‐15) serum level in β‐thalassemia patients and its relation to carotid intima‐media thickness.Background: Thalassemia is a common genetic disease resulting in decreased beta‐chains, leading to manifested anemia. It may be subsequently complicated by iron overload, which induces numerous morbidities and even death. Growth differentiation factor‐15 (GDF‐15) is a strong and independent predictor of mortality and disease progression in patients with atherosclerosis alongside with carotid‐intimal media thickness (CIMT).Patients and methods: This monocentric case‐control study was done on 90 subjects in the period from January 2020 to March 2021. Sixty transfusion‐dependent beta‐thalassemia (TDβT) cases (≥18 years) were selected from the thalassemia clinic of Hematology division at Menoufia University hospitals. We included also 30 sex and age matched healthy as the controls. Routine investigations were done beside. Serum GDF‐15 was measured by ELISA. CIMT was measured by Doppler Ultrasonography.Results: CIMT on both sides was statistically significant higher in cases (median of 0.08 cm) than in the controls (median of 0.04). GDF‐15 was also significantly higher in cases (median of 1839.89 pg/dl) than in controls (median of 256.14 pg/dl). So, we found that GDF‐15 is a predictor of and associated with atherosclerosis in thalassemic adults (OR = 39.198, p value 0.008, 95% CI: 2.576–596.5).Conclusion: GDF‐ 15 is increased in TDβT. CIMT (as a marker of subclinical atherosclerosis) is increased in these patients alongside with GDF‐15, is a predictor, and associated with atherosclerosis in thalassemic adults.

COVID-19 in Patients with Transfusion Dependent Thalassemia (TDT) in Indonesia: Characteristics of the Disease and Patients, and Comparison between Epidemiological Data for COVID-19 and Thalassemia in Indonesia and Southeast Asia.

Background: People living with transfusion dependent thalassemia have a high risk of becoming infected with COVID-19. This can be caused by both internal factors, namely the formation of alloantibodies and autoimmune disorder, and external factors such as routine visits for blood transfusions. Chronic complications of thalassemia also render them more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that thalassemia patients experience less incidence of COVID-19 compared to the general population. Purpose: This study aims to find the correlation between COVID-19 in thalassemia-dependent transfusion patients in Indonesia and Southeast Asia. Patients and Methods: This study used a cross-sectional design. The study was conducted at the Division of Hematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta from May 2020–August 2021. The total sampling method was used involving all thalassemia major patients who had been infected with COVID-19 (obtained directly from medical record and through the thalassemia patients-parents foundation). Results: From 10,397 patients with thalassemia, 67 (0.64%) people were infected by COVID-19 and 2 (2.9%) were deceased. Meanwhile, the incidence of COVID-19 in the general population of Indonesia was 0.87% (more than in the thalassemia population). This means that thalassemia might provide additional protection against COVID-19 due to several mechanisms. This phenomenon has also been seen in other countries with a high prevalence of thalassemia, wherein there are less COVID-19 cases despite the pandemic. On the contrary, countries with low rates of thalassemia had experienced deadly surges of the pandemic. Conclusion: Indonesia and other countries with a high prevalence of thalassemia have lower COVID-19 incidence than countries with low prevalence of thalassemia. Thalassemia might provide additional protection against COVID-19. Well-designed studies are needed to provide better evidence on the protective effect of thalassemia on COVID-19.

COVID-19 in patients with transfusion dependent thalassemia in Indonesia: characteristics of the disease and patients, and comparison between epidemiological data for COVID-19 and thalassemia in Indonesia and South-East Asia

People living with transfusion dependent thalassemia have a high risk of getting infected by COVID-19. This can be caused both by internal factors, namely the formation of alloantibodies and autoimmune disorders, and external factors such as routine visits for blood transfusions. Chronic complications of thalassemia also render the patients more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that thalassemia patients have less incidence of COVID-19 if compared to the general population. This study aims to find the correlation between COVID-19 in thalassemia-dependent transfusion patients in Indonesia and South-East Asia. This research used a cross-sectional design. The study was conducted at the Division of Haematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta, from May 2020 to August 2021. Total sampling method was used involving all thalassemia major patients who had been infected with COVID-19 obtained directly from medical records and through the thalassemia patients’ parents foundation. In 10,397 patients with thalassemia, 67 (0.64%) people were infected by COVID-19 and two (2.9%) died. Meanwhile, the incidence of COVID-19 in the general population of Indonesia was 0.87%, more than in the thalassemia population. This means that thalassemia might provide additional protection against COVID-19 due to several mechanisms. This phenomenon is also seen in other countries with a high prevalence of thalassemia, which show less COVID-19 cases despite the pandemic. On the contrary, countries with low rates of thalassemia carriers had experienced deadly surges of the pandemic. Indonesia and other countries with a high prevalence of thalassemia have lower COVID-19 incidence than countries with a low prevalence of thalassemia. Thalassemia might provide additional protection against COVID-19. Well designed studies are needed to provide better evidence on the protective effect of thalassemia against COVID-19.

Impact of Body Mass Index on 5-Year Survival Rates in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Background:Cancer survival is associated with body mass index (BMI). However, the impact of patients’ baseline characteristics on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes remains unclear. This study aimed to examine the baseline clinical factors associated with 5-year survival rates in patients undergoing allo-HSCT.Material and Methods:This was a retrospective exploratory observational study. Patients (n = 113, 52 women; average age: 55 years) who underwent allo-HSCT at the Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, between January 2008 and March 2015, were included in the present study.Results:Patients with low BMI (<18.5 kg/m2) had significantly lower 5-year survival rates than those with normal (18.5-24.9 kg/m2) and high (⩾25.0 kg/m2) BMI. The 5-year survival rate was poorer for patients with sarcopenia (41.5%) than that for those without sarcopenia prior to allo-HSCT (P = .05). The 5-year survival rate was poorer for patients with geriatric nutritional risk index (GNRI < 98) (34.5%) than that for those without GNRI prior to allo-HSCT (P < .01).Conclusions:Low BMI before allo-HCST pre-treatment was a predictor of 5-year survival rates in this study. Patients undergoing allo-HSCT may require nutritional interventions during pre-treatment to reduce the risk of sarcopenia and GNRI (<98), which affects their survival rates.

Influence of RBC Indices on HbA1c Measurement by Capillary Electrophoresis and HPLC Methods.

HbA1c is the gold standard of diabetic surveys to monitor the long-term glycemic control. Anemia is cited as a major confounder to HbA1c analysis; however, the effect of RBC indices influences on HbA1c analysis is not known. The aim of this study is to compare ion-exchange high-performance liquid chromatography, and capillary electrophoresis to evaluate the influence of RBC parameters on HbA1c values in anemia patients. Erythrocyte parameters were collected from the 307 randomly selected specimens from the Hematology division. HbA1c was measured on the same specimen using Tosoh G8 and Capillarys 2 Flex Piercing on the same day. There is acceptable concordance between the results of capillary electrophoresis and HPLC methods (R2 = 0.953, p < 0.001). However, significant differences in HbA1c value between the two assay methods were obtained in the patients with abnormal RBC indices (p < 0.001). Our results demonstrated HbA1c differences were significantly different in the patients with low Hb (≤ 8 g/dL) and high RDW-CV (≥ 13.7%). It is suggested that in the analysis of HbA1c level in anemia patients, simultaneous testing for hemoglobin level is needed. In addition, development of a new reference value of HBA1c for patients with severe anemia should be considered.

Is the treatment of inflammatory arthritis different in sickle cell disease?

Musculoskeletal findings are common in sickle cell patients and may be confused with inflammatory arthritis. In addition, complications such as frequent infections may create difficulties while choosing drugs such as steroids, methotrexate, or antiTNFs. Our aim is to reveal whether the treatment is different in sickle cell patients with rheumatic diseases such as rheumatoid arthritis. Patients followed by Rheumatology and Hematology divisions of Hatay Mustafa Kemal University Hospital were retrospectively screened. Excluding patients with musculoskeletal findings associated with sickle cell disease (SCD), patients with chronic or acute inflammatory arthritis were enrolled into study. Demographic data, disease activities, the drugs used, frequency of infection, and sickle cell-related crisis before and after rheumatic disease diagnosis-treatment of the patients were examined. Inflammatory rheumatic disease was detected in 14 of 28 sickle cell patients evaluated in the rheumatology department for musculoskeletal complaints. Twelve of the patients were female and 2 were male. The median duration of rheumatic disease was 27 months (16.5). Eight of these patients had rheumatoid arthritis, 1 had ankylosing spondylitis, reactive arthritis, gout, connective tissue disease, undifferentiated monoarthritis, and 1 patient had undifferentiated oligoarthritis. For rheumatic disease, 11 (78.6%) of the patients were using steroids, 8 (57.1%) hydroxychloroquine, 4 (28.6%) methotrexate and sulfasalazine, 2 (14.3%) leflunomide, 1 (7.1%) anti-TNF (etanercept), and 1 allopurinol and colchicine. The frequency of SCD-related crisis and annual serious infections before and after rheumatic disease treatment were similar (p = 0.31). The clinical manifestations of inflammatory arthritis such as rheumatoid arthritis and sickle cell disease may overlap. The use of drugs such as steroids, methotrexate, or anti-TNF in sickle cell patients with rheumatic disease is the same as in patients without sickle cell disease. However, treatment should be individualized in patients with complications such as infection.

Venetoclax and hypomethylating agents in older/unfit patients with blastic plasmacytoid dendritic cell neoplasm

Venetoclax and hypomethylating agents in older/unfit patients with blastic plasmacytoid dendritic cell neoplasm

Hematology Patient Explorer - an Informatics Infrastructure and Web Application Empowering Clinicians and Researchers to Use Electronic Health Record Information to Identify Clinical Cohorts of Interest

Introduction: The widespread adoption of electronic health records (EHR) in the US (Adler-Milstein and Jha 2017) presents an opportunity to transform healthcare into rapidly learning health organizations and systems (Etheredge 2007; Abernethy et al. 2010) that use routinely collected clinical data in the course of care to generate evidence, address information disparities in patients underrepresented in clinical trials, such as those who are older, belong to ethnic minorities, or are in medically underserved areas, and continuously improve the quality of care delivered.(Rivera et al. 2019; Penberthy, Rivera, and Ward 2019) Unfortunately, this potential remains largely unrealized due to deficiencies in EHR interoperability (Holmgren, Patel, and Adler-Milstein 2017) and usability.(Dunn Lopez et al. 2021) EHR information remains largely unstructured due to the nature of the patient-clinician interaction and current user interfaces where structured data entry is burdensome.(Khairat et al. 2019) At the University of Utah Huntsman Cancer Institute division of Hematology, clinicians as well as clinical and translational researchers often need detailed information on patients seen at the cancer center to plan and conduct research and evaluate and improve the quality of care delivered. Previous efforts to address these needs relied on a clinical data science and health informatics staff working with clinicians to identify patient cohorts of interest. As part of an effort to improve the efficiency of this service, decrease the latency in information provision, and serve a larger number of clinicians and researchers, we designed and implemented a highly usable, scalable, health information technology solution that allows clinicians and researchers to identify, in near real time, cohorts of interest, based on patient and disease characteristics.Methods: Common information needs at the division were assessed by identifying key stakeholders, including division leadership, clinicians, researchers, and health informatics leadership and staff. A team was formed to include overlapping expertise in Hematology, clinical informatics and data science, and prior experience in extraction of clinical information from EHR data warehouses to generate evidence on patient practices and outcomes. Information sources and architectures were evaluated on their comprehensiveness, validity, extensibility, and ability to integrate multiple data sources. A modern web-based interface was designed to mirror the steps clinicians and clinical researchers frequently used to identify cohorts of interest, provide guidance for these users, and generate population level and patient level information. Usability testing included rounds of initial internal testing, followed by a round of closed beta testing.Results: A data lake architecture was implemented to ingest, harmonize and stage information from various data sources, including the Enterprise Data Warehouse, Tumor Registry, and other data silos. Data cleaning and harmonization was done using Python. A web application using ‘Dash’ was implemented with four steps split into four consecutive panes. The first two focused on cohort identification using diagnosis (first pane), and patient and disease characteristics (pane 2). Users first input keywords that allow them to identify diagnoses of interest based on ICDO-3 codes. Users can select multiple codes at this stage. In the next step, users can filter down their cohort based on patient and disease characteristics, such as sex, age, year of initial diagnosis, grade and stage of disease, and others. Once all desired refinements to the pilot cohort are made, users move on to the third tab, which displays customizable population level information, such as number of diagnoses by year, sex, or age. Finally, the fourth tab presents individual level data such as Patient Medical Record Numbers, age, or ICDO-3 diagnosis descriptions. Based on this output, users can return to the initial selection criteria and adjust them. Users are able to download or export selection criteria and query results for future work.Conclusion: We describe the process, roles, and informatics infrastructure and tools to implement a web interface that allows clinicians and researchers to leverage EHR information to identify cohorts of patients for research and quality improvement. Further research will focus on tool usability and scope. DisclosuresDeininger: Sangamo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Fusion Pharma, Medscape, DisperSol: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Part of a Study Management Committee, Research Funding; SPARC, DisperSol, Leukemia & Lymphoma Society: Research Funding; Novartis: Consultancy, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Blueprint Medicines Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Part of a Study Management Committee, Research Funding.

Association of Race, Ethnicity, Age and Socioeconomic Status with Access to Virtual Visits within the Brigham & Women's Hospital Division of Hematology during the COVID-19 Pandemic

Background: The COVID-19 pandemic prompted an expedited shift towards expanding telemedicine services. Historically, telemedicine has been shown to increase healthcare access for those in rural communities but widen care gaps for other vulnerable populations by exacerbating existing digital divides and clinician biases in offering telemedicine services. The purpose of this study is to understand the demographic and socioeconomic characteristics of patients completing telephone, video, and in-person visits at the Brigham and Women's Hospital Division of Hematology (BWH DOH) during the COVID-19 pandemic.Methods: This was a retrospective chart review of patients who completed clinical encounters within the BWH DOH between March 19, 2020, when the division switched to virtual visits, and December 31 st, 2020 (pandemic). Patients who completed visits between January 1, 2019 and March 18, 2020 (pre-pandemic) served as a comparator group. Differences in socio-demographic composition of patients completing telephone only (TO), video only (VO), or a mix of in-person and telemedicine visits (IPTM) were tested for significance using Kruskal-Wallis and Chi-square tests.Results: A total of 8307 pre-pandemic visits and 5910 pandemic visits were included in analysis. Almost all visits (99.8%) were in-person pre-pandemic compared to 32.4% in-person, 42.6% by telephone, and 25% by video during pandemic. Median age was significantly different between patients who had only pre-pandemic visits, only pandemic visits, and both (55 vs 52 vs 58 years; p=0.003). Otherwise, there was no significant difference in racial and median income distributions pre-pandemic to pandemic. Table 1 shows the socio-demographic characteristics of patients who completed TO (1536), VO (1065), or IPTM (1518) visits during the pandemic. VO patients were significantly younger than TO and IPTM patients (p<0.001). The majority of patients identified as White (61.3%) with Black and Hispanic patients accounting for 13.8% and 11.4% of the pandemic population, respectively. A higher proportion of White patients had VO visits (29.9%) compared to Black (15.2%) and Hispanic patients (13%) who both had a higher proportion of TO visits (34.7% vs 40.4% vs 50.9%, p<0.001). More patients with a college (29.9%) or post-graduate (34.3%) degree had VO visits than patients with a high school (16.3%) or other levels of education (21.5%) who were more likely to have TO visits (p<0.001). Median household incomes approximated from patient zip codes were significantly higher in patients with VO visits than those with TO or IPTM visits (p<0.001).Discussion: This study shows that during the COVID-19 pandemic, there were significant differences in the socio-demographic composition of patients completing VO versus TO versus IPTM visits within the BWH DOH. Overall, individuals from groups that historically experience health inequities in the United States including the elderly, African Americans, Hispanics, and those with lower educational levels and socioeconomic status had fewer VO visits and more TO visits compared to patients who were younger, White, and had higher levels of education and socioeconomic status. These differences have important implications as VO visits may offer better clinical interaction when compared to TO visits. The younger age of patients seen during the pandemic compared to pre-pandemic suggests that some older adults lost access to hematology care altogether during the pandemic. This disparity pre-pandemic to pandemic was not observed in other demographic subsets. Our work reveals a need to focus on digital inclusion efforts centered around device access, internet access, and digital literacy. Additionally, while TO and VO visits are temporarily equally reimbursed as in person visits under the U.S government's COVID emergency declaration, there has already been a return to markedly lower reimbursement for TO visits. Many practices and hospital system have lost significant revenue due to the pandemic and this differential reimbursement may disincentivize providing care through TO, even if that is the patient's only means of access. This could pose as a further barrier to telemedicine access for individuals from vulnerable populations and exacerbate structural racism, ageism, and other inequities. Care must be taken moving forward that actions to cope with the pandemic or modernize health care serve all patients. [Display omitted] DisclosuresNeuberg: Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Other: Stock ownership. Achebe: Fulcrum Therapeutics: Consultancy; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Gender Differences in Psychosocial, Religious, and Spiritual Aspects in Coping: A Cross-Sectional Study with Cancer Patients.

Background: There is a growing awareness of religiosity and/or spirituality (R/S) as a possible resource in coping with cancer. Gender differences in religious coping have not yet been thoroughly examined. This study aimed to analyze differences in religious coping between men and women with cancer and compare the impact of R/S on anxiety and depression symptoms.Methods: This cross-sectional study was conducted at the Divisions of Hematology and Oncology of the Medical University of Vienna. In total, 352 patients with a cancer diagnosis, who regarded themselves as religious and/or spiritual, were interviewed at Vienna's university hospital with standardized questionnaires. To answer our research questions, we used the Hospital Anxiety and Depression Scale (HADS), the Benefit Through Spirituality/Religiosity (Benefit) questionnaire, and collected demographic characteristics.Results: Of 689 cancer patients, 51% (352) regard themselves as religious and/or spiritual. Women with cancer tend toward R/S more significantly (57%) than men (45%). In patients with an R/S belief, women scored higher in almost all items of the Benefit questionnaire and showed higher prevalence of anxiety (p < 0.001) and depression than men. Regarding the socioeconomic characteristics, more women were widowed, and had significantly lower income than men.Conclusions: The results show a significant gender gap concerning the importance of R/S for cancer patients and the effect on psychological well-being.Women in this study were more religious/spiritual than men and scored higher on anxiety and depression. We support the notion that the gender perspective is essential and can contribute to better patient care in identifying gender-specific concerns.

Do platelet indices play a role in assessing severity of pre-eclampsia and eclampsia?

Background: Pre-eclampsia and eclampsia is a multisystem disorder affecting approximately 2-7% of all pregnancies and is a significant cause of maternal and fetal morbidity and mortality. Many hemostatic abnormalities have been reported in association with hypertensive disorder of pregnancy. We conducted this prospective case-control study to assess and analyze the platelet parameters in 3rd-trimester normotensives, pre-eclamptic, and eclamptic pregnant women. Materials and methods: This study was conducted in the hematology division of the Department of Pathology, in a rural population-based medical institute over 2 years. In all subjects (cases and controls) 2 ml of blood sample was collected in EDTA vials for platelet counts and platelet indices. The blood samples were run on an automated blood cell counter (Beckman coulter) within 2 hours of collection. The data obtained were tabulated and statistical analyses were performed. Results: The mean platelet count was significantly decreased in cases as compared to controls with increased frequency of thrombocytopenia associated with progression of the disease. Platelet indices, mean platelet volume, and platelet distribution width were increased, whereas the plateletcrit was decreased in cases as compared to the controls. However, the statistically significant difference was found only in platelet distribution width and plateletcrit. Conclusions: We concluded that platelet indices like platelet distribution width and plateletcrit can be useful along with platelet count in early detection of pre-eclampsia and eclampsia instead of relying on platelet count alone.

Evaluation of ADAM28 expression in adult Egyptian Acute Myeloid Leukemia patients and its impact on outcome

Background: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is fatal as a result of primary refractoriness, relapse, and treatment-related mortality. Although the majority of patients with AML enter remission upon induction chemotherapy, the risk of relapse is considerable. Aim of the Work: To evaluate ADAM28 expression in newly diagnosed adult Egyptian Acute Myeloid Leukemia patients and to assess its impact on outcome Patients and Methods: This was a prospective case control study was conducted at Ain Shams university hospitals. Clinical hematology division of internal medicine department including 60 participants: 30 adult patients with newly diagnosed AML and 30 healthy age and sex matched control. The duration of the study was 6 months. Results: The main findings of the study revealed that: There was no statistically significant difference between the studied groups as regard demographic data, according to FAB score there were 8 (26.7%) M1, 10 (33.3%) M2, 8 (26.7%) M3 and 4 (13.3%) M4, there was high statistically significant difference between the studied groups as regard WBCs, Plts and ESR and statistically significant difference as regard Hb, there was no statistically significant difference between the studied groups as regard Liver and kidney function tests, according to Cytogenetic risk category there were 4 (13.3%) favorable, 18 (60%) intermediate and 8 (26.7%) unfavorable, there was high statistically significant difference between the studied groups as regard ADAM-28m and ADAM-28s, according to response to chemotherapy in the induction phase there were 13 patients in remission and 11 patients did not respond to chemotherapy and there were 6 who died . Conclusion: There was high statistically significant difference between the studied groups as regard ADAM-28m and ADAM-28s. There was significant correlation between ADAM-28 and response to chemotherapy. ADAM28 improved the growth and dissemination of AML.

AML-345: Algorithmic Diagnostic Approach and Spectrum of Hematological Malignancies in Patients with Germline Predisposition Syndromes

Context: Germline predisposition syndromes (GPS) are genetic disorders that increase the risk of all types of malignancies, with a growing list of genes associated specifically with hematological malignancies. Although many of these conditions have syndromic features, some GPS patients present without identifiable traits. We have established a hematology GPS clinic that uses an algorithmic approach to diagnose GPS patients. Objective: To illustrate the heterogeneity of GPS and the benefits of an algorithmic approach to identify non-syndromic GPS patients. Design: Medical records were reviewed retrospectively from patients diagnosed with GPS at our institution from 1994 to 2018. Prospectively, we investigated new pediatric and adult patients with GPS from 2017 to 2020 using an algorithmic approach summarized as follows: 1) Evaluation of relevant family history, 2) phenotype-specific functional assays (telomere measurement, breakage assay, erythrocyte adenosine deaminase testing), 3) germline genetic testing through a custom-designed gene panel, and 4) research whole exome sequencing for negative cases. Both a detailed explanation of the algorithm and the methodology for genetic variant interrogation are included in Mangaonkar et al. MC Proc 2019. Setting: This study was carried out at the Division of Hematology at Mayo Clinic. Patients or Other Participants: GPS was investigated in pediatric and adult patients with one or more first-degree relatives with hematological/visceral malignancies, in those with antecedent thrombocytopenia, or in those with specific features indicative of inherited bone marrow failure (IBMF) (short telomere syndromes, GATA2 haploinsufficiency, Fanconi anemia, Schwachman-Diamond syndrome). Interventions: N/A Main Outcomes Measures: The number of patients diagnosed with GPS both retrospectively and prospectively were tallied and compared. Results: A total of 146 individuals were included in the study divided as follows: 28 (19.4%) presented with hematological malignancy with precedent thrombocytopenia, 27 (18.8%) without precedent thrombocytopenia, 74 (51.3%) showed IBMF, and 15 (10.4%) showed general cancer predisposition syndrome. Eighty-five patients were retrospectively included, while 61 were prospectively evaluated through our algorithmic approach. Among retrospective patients, 7.1% (6 patients) did not present syndromic features, while this value increased to 14.7% (9 patients) when using the algorithmic approach. Conclusions: By using an algorithmic approach, we can identify a higher percentage of GPS patients without syndromic features.

Lymphocyte Doubling Time As A Key Prognostic Factor To Predict Time To First Treatment In Early-Stage Chronic Lymphocytic Leukemia.

The prognostic role of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was recognized more than three decades ago when the neoplastic clone’s biology was almost unknown. LDT was defined as the time needed for the peripheral blood lymphocyte count to double the of the initial observed value. Herein, the LDT prognostic value for time to first treatment (TTFT) was explored in our prospective O-CLL cohort and validated in in two additional CLL cohorts. Specifically, newly diagnosed Binet stage A CLL patients from 40 Italian Institutions, representative of the whole country, were prospectively enrolled into the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540). Two independent cohorts of newly diagnosed CLL patients recruited respectively at the Division of Hematology in Novara, Italy, and at the Hospital Clinic in Barcelona, Spain, were utilized as validation cohorts. In the training cohort, TTFT of patients with LDT >12 months was significantly longer related to those with a shorter LDT. At Cox multivariate regression model, LDT ≤ 12 months maintained a significant independent relationship with shorter TTFT along with IGHV unmutated (IGHVunmut) status, 11q and 17p deletions, elevated β2M, Rai stage I-II, and NOTCH1 mutations. Based on these statistics, two regression models were constructed including the same prognostic factors with or without the LDT. The model with the LTD provided a significantly better data fitting (χ2 = 8.25, P=0.0041). The risk prediction developed including LDT had better prognostic accuracy than those without LDT. Moreover, the Harrell’C index for the scores including LDT were higher than those without LDT, although the accepted 0.70 threshold exceeded in both cases. These findings were also confirmed when the same analysis was carried out according to TTFT’s explained variation. When data were further analyzed based on the combination between LDT and IGHV mutational status in the training and validation cohorts, IGHVunmut and LDT>12months group showed a predominant prognostic role over IGHVmut LTD ≤ 12 months (P=0.006) in the O-CLL validation cohort. However, this predominance was of borden-line significance (P=0.06) in the Barcelona group, while the significant prognostic impact was definitely lost in the Novara group. Overall, in this study, we demonstrated that LDT could be re-utilized together with the more sophisticated prognostic factors to manage the follow-up plans for Binet stage A CLL patients.

Autoimmune Cytopenias in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib in Routine Clinical Practice at an Academic Medical Center

INTRODUCTIONThe effects of ibrutinib treatment on the natural history of autoimmune cytopenias (AIC) among chronic lymphocytic leukemia (CLL) patients (pts) treated on clinical trials suggests: i) a low rate of treatment-emergent (TE) AIC (~2%, Rogers, Leukemia 2016; Montillo, BCJ 2017) and ii) improved control of pre-existing AIC at the time ibrutinib is initiated with the ability to discontinue immunosuppressive therapies (~69%, Vitale, Haematologica 2016). Confirmation of these findings in CLL pts treated in routine clinical practice requires further investigation. METHODSBetween 4/2012 and 1/2017, 286 CLL pts treated with ibrutinib outside the context of a clinical trial were seen in the Division of Hematology at Mayo Clinic. The CLL Database and medical records of these pts were reviewed for details of past history of AIC and TE AIC; the diagnosis of AIC was determined by the treating physician. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals for the association of history of TE AIC with progression-free (PFS) and overall (OS) survival. Time-dependent Cox regression models were used to look at the association of TE AIC with PFS and OS. Fisher's Exact test was used to test for the association of clinical variables with TE. RESULTSAmong the 286 pts, 242 (85%) pts were treated for relapsed CLL and 44 (15%) pts for previously untreated CLL. The median age at ibrutinib start was 68 years, and 72% were males. Twenty-two percent had TP53 disruption (either del17p or TP53 mutation) and 78% had unmutated IGHV genes. We identified 37/286 (13%) pts with a history of AIC prior to ibrutinib start, including 15 pts with autoimmune hemolytic anemia (AIHA), 11 pts with immune thrombocytopenia (ITP), 5 pts with Evans syndrome, 3 pts with pure red cell aplasia (PRCA), 2 pts with autoimmune neutropenia, and 1 pt with aplastic anemia.Eleven (4%) pts developed TE AIC (including two pts with past history of AIC who developed a different AIC after ibrutinib therapy) including: AIHA (n=4), ITP (n=4), PRCA (n=1), aplastic anemia (n=1), and autoimmune neutropenia (n=1). This occurred after a median of 30 days following the initiation of ibrutinib (range, 8-325 days). Eight pts were able to continue ibrutinib after either temporarily holding ibrutinib (n=6), ibrutinib dose reduction (n=1), or no modification to ibrutinib therapy (n=1). Three of the 11 pts (ITP n=2, aplastic anemia n=1) permanently discontinued ibrutinib as a result of the AIC.Twenty-two of the 37 pts with a prior history of AIC had a remote history of AIC and were not on any AIC treatment and 15/37 pts were receiving AIC directed therapy at ibrutinib start. Among the 15 pts who were on AIC directed therapy at the time of ibrutinib initiation, 6 pts had uncontrolled disease, for which they were receiving ≥20 mg prednisone daily, and 9 pts had controlled AIC on therapy consisting of <20 mg of prednisone daily or equivalent. Five (33%) of the 15 pts on therapy were able to discontinue AIC therapy at a median of 2 months (range, 0-25), an additional 5 (33%) pts were able to reduce the dose and schedule of AIC therapy, and 3 (20%) pts continued AIC therapy with no changes. Two (14%) pts not previously on rituximab were started on the therapy due to continued steroid dependence and inability to taper off steroids. None of these 15 pts had worsening of their underlying AIC as a consequence of initiating ibrutinib therapy. See Figure 1 for temporal relationship of ibrutinib treatment.The median OS and PFS from time of ibrutinib start was not significantly different between pts with a history of AIC and those with no history of AIC (Figures 2 and 3). There was no statistically significant association between age, gender, TP53 disruption, IGHV mutation status, and history of AIC with development of TE or recurrent AIC (p-values all > 0.05). The PFS and OS were not significantly different among pts with TE AIC compared to those pts who did not develop TE AIC. CONCLUSIONIn this large retrospective cohort of ibrutinib treated CLL pts outside the context of clinical trials, we found that 1 out of every 25 pts developed TE AIC. Nonetheless, ~75% pts were still able to continue ibrutinib treatment. Improved control of AIC with discontinuation or de-escalation of AIC treatments in ~67% of pts on AIC directed therapy at ibrutinib start supports previous findings. We did not identify any risk factors for the development of TE AIC in our study. [Display omitted] DisclosuresDing:Merck: Research Funding. Kay:Gilead: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Tolero Corporation: Research Funding. Shanafelt:Genentech: Research Funding; GlaxoSmithKline: Research Funding; Celgene: Research Funding; AbbVie: Research Funding; Hospira: Research Funding; Jannsen: Research Funding; Pharmacyclics: Research Funding. Parikh:AstraZeneca: Honoraria; Pharmacyclics: Honoraria; Pharmacyclics: Research Funding.

Effect of Proteasome Inhibitors and/or Immunomodulatory Drugs on the Risk of Early Death of 991 Newly Diagnosed Symptomatic Multiple Myeloma Patients: A Single Centre Retrospective Analysis

Introduction and aim : Several clinical trials have shown that the incorporation of novel agents (i.e., proteasome inhibitor, bortezomib and immunomodulatory drugs, thalidomide and lenalidomide) in the treatment of newly diagnosed symptomatic multiple myeloma (MM) patients improves their time to first response and survival outcomes. Nevertheless, some patients still die within 3 months (early death, ED) from starting treatment. Thus, we investigated the effect of novel agents- containing first line treatments on the risk of ED of MM patients.Study design : retrospective analysis of a cohort of 991 newly diagnosed symptomatic MM patients consecutively treated at a single Institution from 1997 until 2015 at the Hematology Division of the Ospedale Papa Giovanni XXIII (formerly, Ospedali Riuniti) of Bergamo, Italy.Results : during the entire period of analysis (18 years), 708 patients (71.4%) died. They were 374 men and 334 women, aged 25-94 years (median 68 years). Types of MM were: IgG (n=357), IgA (n=138), light chain (n=125), plasmacytoma (n=23), non-secretory (n=16), plasma cell leukemia (n=11), IgD (n=6), IgM (n=4), unknown (n=28). Durie and Salmon clinical stages were: I (n=75), II (n=111), III (n=479), unknown (n=43). A/B stages were: A (n=518, 73%), B (n=147, 21%), unknown (n=43, 2%). Treatments were as follows: conventional chemotherapy (CC) (n=255, 36%), CC + autotransplantation (ASCT) (n=150, 21%), novel agents (n=181, 26%), novel agents + ASCT (n=122, 17%). Ninety-two patients (9.3%) experienced an early death (ED cohort) and the other 616 patients died > 90 days from starting treatment (late death, LD, cohort) (91.7%). Univariate and multivariate analysis (Table) showed that patients in the ED cohort were significantly older and had more commonly stage B MM compared to patients in the LD cohort. Incorporation of at least a novel agent in the first line treatment resulted in a significant reduction of ED. This beneficial effect was only seen in patients not enrolled in ASCT programs (p<0.001, Odds Ratio, OR, 0.37, 95% Confidence Interval, CI, 0.20-0.69 and p=0.009, OR 0.42, 95%CI 0.22-0.81, by univariate and multivariate analysis, respectively). Progression of MM was the cause of all ED events. Only one patient in the ED cohort started a second line of treatment.Conclusions : Administration of first line regimens containing at least a novel agent significantly reduced the ED rate of patients with MM. Particularly, this improved survival was beneficial in patients not enrolled in ASCT programs. [Display omitted] DisclosuresRambaldi:Novartis, Amgen, Celgene, Sanofi: Other: Travel, Accomodations, Expenses; Novartis, Roche/Genentech, Amgen, Italfarmaco: Consultancy.

RECURRENT APHTHOUS STOMATITIS ASSOCIATED WITH MYELODYSPLASTIC SYNDROME: A CASE REPORT

<h3>Objective</h3> The aim of this report is to present the process of diagnosis and management of a patient with myelodysplastic syndrome afflicted with recurrent aphthous stomatitis (RAS). <h3>Background</h3> RAS is one of the most common lesions of the oral mucosa seen in adolescents. Although the exact etiology of RAS is still unknown, different hematinic deficiencies have been proposed. <h3>Case Report</h3> A 71-year-old male patient with multicomorbidities suffered from frequent oral ulcerations for many years. Hematologic investigation showed normal iron serum concentration and higher folate levels. In addition, his serum zinc concentration was low. Although his vitamin B12 level was normal, his homocysteine level was slightly high. Furthermore, his red blood cell count, hemoglobin, and hematocrit were low, and mean corpuscular volume, mean corpuscular hemoglobin, and red blood cell distribution width were high, which were related to megaloblastic anemia. Treatment with prednisolone, zinc gluconate, hydroxocobalamin, and nystatin led to rapid improvement. Nevertheless, fluctuations in the state of his RAS occurred within 6 months. Hence, we consulted the Division of Hematology and Oncology for further evaluation. The hematology and oncology doctor arranged blood tests and bone marrow biopsy and prescribed ferrous gluconate-B. The bone marrow biopsy showed myelodysplastic syndrome, refractory cytopenia with multilineage dysplasia, and iron store deficiency. After iron supplementation, his recovery rate improved. <h3>Clinical Implication</h3> When patients have RAS, consider checking iron, vitamin B12, and folate levels and treating patients if levels are low. Such treatment could reduce some varieties of RAS. However, in patients with hematological diseases, further tests, such as bone marrow biopsy, may be needed.

In Memoriam: José Baselga's Journey in Cancer Medicine.

In Memoriam: José Baselga's Journey in Cancer Medicine.

Crowdsourcing in a Pandemic: Pearls and Pitfalls From the Trainee Experience.

Crowdsourcing in a Pandemic: Pearls and Pitfalls From the Trainee Experience.