ALBERT

Description: Hodgkin lymphoma (HL) occurs in HIV-infected individuals more frequently than in the HIV-negative population and the incidence is rising. Patients (pts) with non-Hodgkin’s lymphoma in HIV appear to have improved outcomes if they receive HAART with chemotherapy (CT). ABVD is standard CT for HL and is frequently administered with HAART in pts with HIV-HL. However, some components of the ABVD regimen may interact with antiretroviral (ARV) medications to alter metabolism and increase toxicity. In particular, vinblastine (VBL) is metabolized by CYP3A4 and protease inhibitors, particularly ritonavir (RTV), appear to inhibit this cytochrome potentially leading to higher VBL exposure. Little definitive information is available regarding how interactions might affect clinical outcome. We conducted a retrospective review of 36 pts with HIV-related HL to identify the frequency of neurotoxicity (NT), hematologic toxicity (HT), and lung toxicity (LT), to identify risk factors for severe (grade III–IV) toxicity, and to determine its clinical significance. Clinical data were collected from the CFE database and by chart review from 3 centers. The median age at HL diagnosis (dx) was 41 (range 29–66) years and 34 (94%) were male. HL was advanced stage in 28 (78%). Hasenclever score could be calculated in 23 pts and was 0–4 and ≥5 in 15 and 8 pts respectively. ECOG PS was 0–1 in 13 and ≥2 in 8 (n=21). HIV risk factor was: sexual, n=21 and other, n=5 (n=26). Median CD4 count at HL dx was 210 (2–660) cells/ul (n=31). Median HIV viral load (VL) was undetectable (

Description: Introduction: Nearly one in five cancer survivors report limitations in ability to work following diagnosis, with poor work-related outcomes particularly noted in the hematologic cancers. Although much is known about the efficacy, toxicity and direct costs of treatment for follicular lymphoma, there is no data assessing the impact of this diagnosis on productivity of affected individuals. Methods: We conducted a consecutive cross-sectional study of patients attending a malignant hematology clinic at a large multi-disciplinary cancer centre. Patients with a diagnosis of FL or other indolent NHL were asked to complete questionnaires assessing demographics, health status (EQ-5D), and work productivity and activity impairment (WPAI questionnaire). Results: Eighty-four patients completed the survey study (〉95% response rate). Mean age was 58.7 (+/−13.8 SD) and 55% were male. Diagnoses included FL (55%), CLL (25%), and other indolent NHL (20%). The majority of patients presented in advanced stage (stage III–IV; 65%) and had received some therapy, although 29% were still being observed without having received therapy by the time of survey administration. The median disclosed income was $40,000–$59,000; 76% had pursued post-secondary education. Over 61% were working full-time prior to diagnosis while 14% were retired. Patients reported a minimal impact on their work productivity (1.9+/−3.2 on a scale of 0 to 10; 0=no effect and 10=complete impairment of activity) and on their daily activities (2.4+/−3.1) attributable to their cancer diagnosis. However, following diagnosis of NHL (and at the time of survey completion), only 33% were able to continue full-time work, 7% were working part-time, 10% required disability, and 37% were retired. Of those still working, a mean of 2.1 days (+/−6.9) were missed due to illness in the preceding 4 weeks, with a mean of 16 days (+/−8.7) worked in that period. Only 6% received paid assistance, while 17% required unpaid care from a partner/spouse, relative, or friend. Unpaid caregivers missed a mean of 11.3 days (+/−16.2) of work and provided a mean of 9.8 days (+/−13.4) of care. There was a significant inverse correlation between daily activity scores (high values=complete impairment) and health status ratings (high values=excellent health status/utilities) ascertained by the EQ-5D instrument (Spearman correlation coefficient −0.69; p5) was predicted by poor self-rated health status (OR 32.1; 95% CI 5.9–174.2; p

Description: Introduction Systemic mastocytosis (SM) represents a heterogeneous group of disorders characterized by accumulation of neoplastic mast cells (MCs) in one or more organ systems. Patients with SM present with a broad range of symptoms resulting from excessive mast cell mediator release, especially histamine, that frequently overlap with those of allergic disease. Episodes of life-threatening anaphylaxis are a recognized feature of SM. Here at St. Michael's Hospital we currently follow more than 50 SM patients, the largest patient cohort in Canada. Omalizumab is a subcutaneously administered monoclonal antibody which acts on circulating IgE, reducing binding to the high-affinity IgE receptor (FCεR1) on mast cells, thereby reducing the potential reactivity of these cells. At St. Michael's Hospital, omalizumab is used as an add-on, off-label therapy in SM patients at risk for recurrent anaphylaxis. The efficacy of omalizumab treatment for SM patients remains unclear. Typically, highly symptomatic patients who are refractory to all other medication are candidates for omalizumab therapy. Objectives Our primary objective was to describe the response to treatment by omalizumab in patients with SM in a tertiary care centre. Our secondary objective was to compare the markers of disease in SM patients between those who were non-responsive versus responsive to omalizumab. The clinical and biological markers to be studied are symptoms and tryptase levels. Methods This is an observational, retrospective study (n=6) of SM patients treated with omalizumab at St. Michael's Hospital between January, 2014 and June, 2018. Electronic medical records were reviewed for mastocytosis treatment, symptom progression and tryptase levels, if available. All patients included in the study were diagnosed with SM according to the 2016 WHO criteria by undergoing a bone marrow biopsy. A baseline was established 2-5 months pre omalizumab exposure, as well as two follow-ups, each ranging from 2-8 months post omalizumab exposure (av. 4.7 months). The Brown Anaphylaxis score was used to capture severity of anaphylaxis. Mild (1), moderate (2), and severe (3) scores were associated with cutaneous manifestations, systemic (GI, respiratory, cardiovascular) involvement and systemic (hypoxia, hypotension, neurological compromise) collapse, respectively. Results Our study consisted of 4 females and 2 males, with an average age of 49 years old [IQR 36-74]. All 6 patients were diagnosed with indolent SM, the more moderate of the six SM subtypes. In every system, except for respiratory, it appears that symptoms decreased once therapy began. From baseline to first follow-up: all three patients who were experiencing systemic symptoms, three of the six manifesting cutaneous symptoms, and two of the three with cardiovascular involvement, responded fully to treatment. At second follow-up, patient 1 presented to clinic asymptomatically. Overall, 100% of patients responded to treatment with responses ranging from 17% to 100% improvement of mastocytosis-related symptoms. The grading of anaphylaxis severity reported three of the six patients improving from scores of 3 (severe) to 1 (mild). The other three patients remained at scores of 2. Patients 1 and 2 (only patients with available tryptase levels at both baseline and follow-up) saw a decrease in tryptase level from 134 to 84.1 and 11.4 to 8.3, respectively. Conclusions Omalizumab appears to be an effective therapy for patients with SM with anaphylaxis and reduces tryptase levels. It should be readily considered in the management of this population. Next steps include following these patients prospectively to better capture the efficacy of omalizumab within this population. Disclosures No conflicts of interest to declare Disclosures No relevant conflicts of interest to declare.

Description: Background Iron deficiency (ID) is the most common and widespread nutritional deficiency in both developing and developed countries (WHO, 2001; Mei et al., 2011). Women of child bearing age are at the highest risk, but this risk increases even more during pregnancy. The expansion of blood volume, growth of the fetus and placenta increase demand for iron to approximately 5.0mg/day by the third trimester (Met et al., 2011). Common symptoms of ID during pregnancy include fatigue, shortness of breath, and difficulty concentrating (WHO, 2001). Poor prenatal iron status is associated with diminished cognitive performance, language ability, and motor functions in the child (Tamura et al, 2002). For the mother, it is associated with risk of blood transfusion and post-partum depression. Despite international recommendations and guidelines on the management of ID in pregnancy, it remains a problem of epidemic proportions and is often unrecognized and left untreated. To increase awareness of ID, a quality improvement project, IRON Deficiency project in Pregnancy: Maternal Iron Optimization (IRON MOM) was implemented January 1st, 2017 at St. Michael's Hospital (SMH), in Toronto, Canada. Phase 1 of the project involved adapting lab requisitions and workflow in the obstetrics clinic to incorporate routine measurement of ferritin in week 12, 16 and 28 of pregnancy. As part of the IRON MOM, laboratory requisitions were modified to include ferritin as part of routine screening for all pregnant women. Objective The primary objective of this study was to assess the prevalence of ID in pregnant women consistently screened for ID after the implementation of the IRON MOM quality improvement project at a tertiary hospital in Toronto, Canada. Methods Administrative laboratory data was collected from the electronic medical record system at SMH, Toronto, Canada between January 1 and December 31, 2017. Suboptimal iron stores was defined as serum ferritin between 30-50μg/L. ID was defined as serum ferritin between 15-29μg/L, and severe ID was defined as

Description: Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based method, ASH has identified 5 tests and treatments that in some circumstances are not well supported by evidence and which in certain cases involve a risk of adverse events and financial costs with low likelihood of benefit. The ASH Choosing Wisely® recommendations focus on avoiding liberal RBC transfusion, avoiding thrombophilia testing in adults in the setting of transient major thrombosis risk factors, avoiding inferior vena cava filter usage except in specified circumstances, avoiding the use of plasma or prothrombin complex concentrate in the nonemergent reversal of vitamin K antagonists, and limiting routine computed tomography surveillance after curative-intent treatment of non-Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated benefits of the identified tests and treatments before performing them.

Description: High-dose therapy and autologous stem cell transplantation (HDT/ASCT) and rituximab immunotherapy have been increasingly applied in the management of non-Hodgkin’s lymphomas (NHL). Although both approaches have been individually associated with B-cell depletion and hypogammaglobulinemia, the incidence, time course, and predictors of prolonged deficiencies following a combined treatment approach is unknown. Methods: We completed a series of prospective phase II studies of HDT/ASCT combined with rituximab for patients with relapsed follicular lymphoma (FL) or diffuse large B cell lymphoma (DLBCL). In two phase II trials of patients with FL (R/Tx and R-IFN/Tx), patients received 9 infusions of rituximab 375mg/m2 as both an in vivo purge and as maintenance post HDT/ASCT. In a trial with relapsed DLBCL or transformed lymphoma, patients received 8 infusions with rituximab 375mg/m2 only as part of the salvage chemotherapy regimen (R-ESHAP/Tx). Immunoglobulin levels were expressed as percentages with 100% representing the lower limit of normal at the institutional lab. Hypogammaglobulinemia was defined as 3 months) infections included herpes zoster reactivation (n=7) and pneumonia (n=8). One individual in the R-ESHAP/Tx study died of PCP pneumonia 4 months post HDT/ASCT. A relationship between grade III-IV infections and prolonged hypogammaglobulinemia was not evident on univariate analysis (data not shown). Conclusions: Patients with follicular lymphoma undergoing high dose therapy and stem cell transplantation together with rituximab maintenance are likely to experience a prolonged hypogammaglobulinemia whereas this is less likely with patients with aggressive-histology lymphoma undergoing similar doses of rituximab as part of their salvage therapy. Further research is required to elucidate the relative contributions of disease histology, bone marrow involvement, baseline hypogammaglobulinemia, timing of rituximab infusions or other factors not yet identified. Figure Figure Figure Figure

Description: Introduction and Objective The activated partial thromboplastin time (aPTT) and prothrombin time/ international normalized ratio (PT/INR) are the most commonly used coagulation tests (Chee et al 2008) and have become ubiquitous in medical practice despite only having been validated for very specific clinical indications (Capoor et al 2015, Pilsczek et al 2005). Indiscriminate use of these tests increases costs with little anticipated benefit for patients, and reliance on these test results to predict bleed risk may mislead care (Chee et al 2008). While staff education and development of revised practice guidelines may reduce unnecessary testing (Shojania & Grimshaw 2005), a simple process change to order panels has been shown to be associated with meaningful reductions in coagulation testing and associated costs without obvious adverse effects (Merkeley et al 2016). A prospective quality improvement initiative was conducted in the Emergency Department (ED) at St. Michael's Hospital in Toronto Canada. The ED was targeted as this was an area where coagulation test volumes were particularly high. The following strategies were implemented in order to enhance appropriate utilization of coagulation tests: PT/PTT testing options were uncoupled, ED order panels were revised, and educational materials were distributed to relevant stakeholders. These simple process changes resulted in significant reductions in unnecessary testing and meaningful cost savings. Weekly rates of PT/INR testing and aPTT per 100 ED patients decreased (17.2 vs. 38.4, rate ratio=0.45 (95% CI 0.43-0.47), p

Description: Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched Pubmed and EMBASE up to August 20, 2020, to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of ICU admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RR), and 95% confidence intervals (CI) were calculated using a random-effects model. 34 adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14/34 adult studies included only hospitalized patients). The risk of death amongst adult patients was 34% (95% CI 28-39, N=3240) in this sample of predominantly hospitalized patients. Patients aged 〉60 years had a significantly higher risk of death than patients 60 years have significantly higher mortality, and pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

Description: Abstract 4677 Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening form of microangiopathic hemolysis that can be associated with HIV infection, and has previously been reported to be associated with low CD4 counts. The existing literature on HIV-TTP is very small and largely made up of small case series generated through databases of patients with HIV. As a result, reports have tended to focus on HIV parameters with limited information available regarding the presentation, management and outcome of the TTP itself. We conducted a retrospective review of TTP cases referred to the pheresis units St. Michael’s Hospital and Vancouver General Hospital in Vancouver between July 1993 and May 2011. Ten cases of HIV associated TTP were identified (8 male; 2 female). Median age at presentation was 38 years. One patient had been previously diagnosed and treated for TTP at a different institution. Average duration of HIV infection prior to TTP diagnosis was 5 years (range 0 to 11). Median CD4 count at TTP diagnosis was 79 × 106/ml (range 2 to 326). Median platelet count at presentation was 14 × 106/ml (range 5 to 233), median haemoglobin was 74 g/L (range 61 to 133), all patients had an LDH 〉 2x the upper limit of normal, and all for whom data was available (8/10) had fragmentation on blood film. Creatinine was elevated in 9 of 10 patients. ADAMTS13 was assessed in 3 of 10 patients and was deficient in one. Five of 10 patients had fever. At presentation, 6 of 10 patients had neurological symptoms (most commonly seizures and/or confusion), but none suffered permanent neurological deficits. All patients were treated with plasmapheresis and received a median of 16 exchanges (2-56). Four patients received concurrent steroids, two patients received IVIG, and one patient received pheresis, steroids IVIG, vincristine and rituximab. Eight of 10 patients achieved complete remissions, one patient achieved a partial response, and one died on treatment. Four of the responding patients subsequently relapsed (0.6 to 13.8 months after the initial episode of TTP); two achieved second remissions, and two died on treatment. In conclusion, our series of HIV associated-TTP confirms previous reports that HIV-TTP tends to occur in patients with CD4 counts less than 200. Complete remissions can be achieved with standard management. However, based on our small series, relapses may be more common and mortality greater than in the general TTP population. Disclosures: Leitch: Novartis Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Description: Abstract 4675 Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening form of microangiopathic hemolysis that can be associated with pregnancy. Although the association between TTP and pregnancy is well recognized, the presentation, natural history, and ideal treatment of TTP in this population remain poorly understood. St. Michael's Hospital is a regional referral centre for TTP in Ontario, Canada. We conducted a retrospective review of all cases of TTP referred to our pheresis unit between July 1993 and May 2010. Ninety-four cases were identified, of these, ten patients were pregnant or up to one week post-partum at the time of TTP diagnosis. Median age at presentation was 34 (29-36). Only one patient had been previously diagnosed with TTP and then developed a TTP relapse while pregnant. At presentation, all patients had thrombocytopenia (platelets: 〈 3 to 124 × 106/ml), anemia (hemoglobin: 60 to 99 mg/L), elevated LDH (1.3 to 12.5 × ULN), and fragmentation on blood film. ADAMTS13 was assessed in six of ten patients. It was normal in four patients, and deficient in two patients. Seven patients had neurological symptoms at presentation, one of whom suffered permanent right sided paralysis. Six patients had depressed glomerular filtration ratio (GFR) at presentation, four of these six recovered normal GFR. Hypertension was present in only one patient, and no patients had abnormal coagulation parameters at presentation. ALT was normal in six patients, mildly elevated in two patients, and unavailable in two patients. There were no patient deaths in this series. Patients were treated with a median of 17 plasma exchanges (range: 9 to 55) using either fresh frozen plasma or cryosupernatant. Eight patients achieved complete remission with plasma exchange. Two patients had refractory disease which ultimately responded to splenectomy and rituximab respectively. There were two fetal deaths, one a first trimester miscarriage, and the second an intrauterine death in the second trimester. In conclusion, in our series of pregnancy associated-TTP, there were no maternal deaths and most women responded to a short course of plasma exchange. ADAMTS13 deficiency was uncommon in our series. Nonetheless, in our series, TTP was not difficult to distinguish from preeclampsia and/or disseminated intravascular coagulation using routine laboratory parameters. Disclosures: No relevant conflicts of interest to declare.