Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Utility of hemoglobin electrophoresis to distinguish between severe delayed hemolytic transfusion reaction versus hyperhemolysis syndrome.

Delayed hemolytic transfusion reaction (DHTR) and hyperhemolysis syndrome (HHS) are both complications of red blood cell transfusions in patients with sickle cell disease.Clinically, both present with hemolysis and can be difficult to differentiate. Hemoglobin electrophoresis may aid in the diagnosis. Herein we describe a case in which a patient with hemoglobin SC disease presented with features of severe hemolysis several days after initiation of red blood cell exchange. Increase in reticulocyte count and complete absence of hemoglobin A on electrophoresis during this event supported the diagnosis of severe DHTR, indicating a rapid and selective destruction of the transfused red blood cells. Ability to interpret the hemoglobin electrophoresis can help clinicians distinguish between these two severe transfusion complications in patients living with sickle cell disease. It is important to identify the presence or absence of concomitant HHS, as patients with HHS tend to have a worse prognosis and there is a higher rate of recurrence of HHS with subsequent transfusions. Accurate diagnosis can lead to prompt management and decrease morbidity and mortality.

The impact of bridging therapy prior to CD19-directed chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma.

In the relapsed/refractory setting for treatment of large B-cell lymphoma (LBCL), chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective treatment modality. Patients often have aggressive disease that requires prompt treatment in the form of bridging therapy (BT) for disease stabilisation while CAR-T cells are manufactured. Patients (n = 75) undergoing CAR-T therapy infusion for LBCL at our institution were identified. A total of 52 (69·3%) received BT and 23 (30·7%) received no BT (NBT). BT modalities included systemic BT (SBT) in 28 patients, radiation BT (RBT) in 14, and high-dose steroid BT (HDS) in 10. There was no difference in incidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome between BT and NBT (P = 0·18 and P = 0·53 respectively). Prolonged cytopenias at Day 180 were more common in BT than NBT (50% vs. 13·3%, P = 0·04). The SBT and RBT subgroups had more cytopenias at Day 180 compared to the HDS and NBT subgroups (58·3% and 57·1% vs. 20% and 13·3% respectively, P = 0·04). Disease response at last follow-up, progression-free survival and overall survival were similar between BT, NBT, and BT subgroups. In summary, BT can be safely considered in patients undergoing CAR-T therapy. However, those undergoing BT with SBT or RBT are at higher risk of prolonged cytopenias after CAR-T therapy.

Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear. METHODS: 1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3). RESULTS: 7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18-25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.21) and Group 3 (HPV-/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.012) and Group 3 (HPV-/unknown) (p = 0.002). CONCLUSIONS: There was no observed difference in the time to development of DM between the HPV-/unknown and HPV+ HNSCC groups. However, the HPV+ HNSCC group showed a higher rate of DM to the lung compared to the HPV-/unknown -HNSCC group (p = 0.002).

Multi-Organ Failure as the Initial Presentation of Lymphocyte-Depleted Hodgkin Lymphoma in Two Patients with Human Immunodeficiency Virus.

Patients with HIV-associated lymphocyte-depleted Hodgkin lymphoma (HIV-HL) often present with advanced, extranodal disease and aggressive clinical features, limiting definitive therapeutic intervention. Here we report two patients with HIV-HL who presented with multi-organ dysfunction as an initial manifestation of their malignancy. Both were initially treated with brentuximab vedotin (BV), which led only to a temporary partial response, highlighting the challenges of treatment. One patient was eventually started on nivolumab and responded very well to the immune checkpoint inhibitor. To our knowledge, this is the first case to describe successful use of nivolumab in a patient with relapsed lymphocyte-depleted HIV-HL. Prompt recognition of multi-organ dysfunction as an initial presentation of lymphocyte-depleted HIV-HL is essential to ensure rapid provision of therapy. While use of BV remains a reasonable option, earlier introduction of immunotherapy in the treatment of HL may provide an additional option in critically ill patients with lymphocyte-depleted HIV-HL.

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management.

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD), yet the optimal pharmacologic anticoagulant is unknown. METHODS: A retrospective single-institution cohort study of patients with SCD complicated by first VTE from January 2009 through July 2017 was performed using ICD 9/10 codes. Data collected included the anticoagulant used, VTE recurrence, and incidence of bleeding. RESULTS: 109 patients with VTE were identified. SCD genotypes included HbSS in 92 (84%), HbSC in 13 (12%), and HbS-ß+ thalassemia in 4 (4%). After the initial VTE event, 32 patients received a vitamin K antagonist (VKA), 34 for low-molecular-weight heparin (LMWH), and 43 for direct oral anticoagulants (DOACs). 16 patients (15%) experienced a clinically significant bleeding event, including 9 on VKA, 5 on LMWH, and 2 on DOACs. At a median follow-up of 11.8 (range, 3.4-60) months, 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH, and 13 on DOACs (p = 0.833). Bleeding incidence was least with the DOACs, which were associated with fewer bleeding events (OR 0.22), and greatest with VKA (OR 1.55) (p < 0.05). CONCLUSION: There was no difference between VTE recurrence and choice of anticoagulation in SCD patients with VTE. Bleeding events were lower for DOACs compared to VKA or LMWH.

Relapsed Philadelphia Chromosome-Positive Pre-B-ALL after CD19-Directed CAR-T Cell Therapy Successfully Treated with Combination of Blinatumomab and Ponatinib.

Adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with conventional chemotherapy have dismal outcomes. Novel immunotherapies targeting CD19, including the bispecific T-cell engager blinatumomab and chimeric antigen-receptor T (CAR-T) cells, have revolutionized the treatment of R/R B-ALL. Robust response rates to CAR-T cell therapy after blinatumomab have recently been reported, but it is unknown whether blinatumomab can be effective following failure of anti-CD19 CAR-T cell therapy. Herein, we describe a patient with Philadelphia chromosome-positive B-ALL who relapsed after CD19-directed CAR-T therapy, but subsequently responded to the combination of blinatumomab and the tyrosine kinase inhibitor ponatinib, with the achievement of a complete remission lasting 12 months.

Thrombotic microangiopathy in the setting of human immunodeficiency virus infection: High incidence of severe thrombocytopenia.

BACKGROUND: Human immunodeficiency virus (HIV) infection increases the risk of thrombotic microangiopathy (TMA), but TMA in the setting of HIV infection is not well characterized. The experience with TMA in the setting of HIV infection at the University of Maryland Medical Center was reviewed. STUDY DESIGN AND METHODS: Patients undergoing therapeutic plasma exchange (TPE) for TMA from January 1, 2000 through December 31, 2012 were reviewed. Those with known HIV-positive and -negative status were compared. RESULTS: Among 102 patients with known HIV status, 28 (27%) were HIV-positive, including 3 with previously undiagnosed HIV. HIV-positive patients had a median viral load of 89 500 copies/mL (range, 0->750 000 copies/mL) and a median CD4 count of 58 cells/µL (range, 2-410 cells/µL). Compared to HIV-negative patients, HIV-positive patients more frequently presented with concurrent infections (60.7% vs. 23.7%; P = .0007), had a trend toward lower median platelet counts (3000/µL vs. 15 000/µL; P = .07) and more frequently had platelet counts less than 10 000/mcL (P = .02). Nevertheless, number of TPE procedures required for remission, remission rate, mortality, and relapse incidence were similar in HIV-positive and HIV-negative patients. CONCLUSIONS: The incidence described herein of HIV infection among TMA patients is the highest reported outside of South Africa. More severe thrombocytopenia in HIV-positive patients may reflect TMA in the setting of preexisting HIV-associated thrombocytopenia. HIV should be considered in patients with TMA, and TMA should be considered in HIV-positive patients with severe thrombocytopenia.

Successful Use of Veno-Venous Extracorporeal Membrane Oxygenation in an Adult Patient with Sickle Cell Anemia and Severe Acute Chest Syndrome.

A 25-year-old female with sickle cell anemia presented with respiratory failure due to acute chest syndrome (ACS). Given her severely compromised cardiopulmonary status, she was started on veno-venous extracorporeal membrane oxygenation (VV-ECMO). After 20 days, the patient's respiratory status improved and she was successfully decannulated. Veno-venous extracorporeal membrane oxygenation can be utilized for severe ACS in adult patients with sickle cell disease. Prompt initiation of this modality may improve outcomes in adult patients with sickle cell disease complicated by life threatening ACS.

Use of the APACHE II score to assess impact of therapeutic plasma exchange for critically ill patients with hypertriglyceride-induced pancreatitis.

OBJECTIVES: Hypertriglyceridemic (HTG) pancreatitis carries significant morbidity and mortality and often requires intensive care unit (ICU) admission. Therapeutic plasma exchange (TPE) rapidly lowers serum triglyceride (TG) levels. However, evidence supporting TPE for HTG pancreatitis is lacking. METHODS: Ten patients admitted to the ICU for HTG pancreatitis underwent TPE at our institution from 2005-2015. We retrospectively calculated the Acute Physiology and Chronic Health Examination II (APACHE II) score at the time of initial TPE and again after the final TPE session to assess the impact of triglyceride apheresis on morbidity and mortality associated with HTG pancreatitis. RESULTS: All 10 patients had rapid reduction in TG level after TPE, but only 5 had improvement in their APACHE II score. The median APACHE II score decreased from 19% to 17% after TPE, correlating with an 8% and 9% decrease in median predicted non-operative and post-operative mortality, respectively. The APACHE II score did not differ statistically before and after TPE implementation in our patient group (p=0.39). CONCLUSION: TPE is a clinically useful tool to rapidly lower TG levels, but its impact on mortality of HTG pancreatitis as assessed by the APACHE II score remains uncertain.

Evaluating the Quality and Usability of Open Data for Public Health Research: A Systematic Review of Data Offerings on 3 Open Data Platforms.

CONTEXT: Government datasets are newly available on open data platforms that are publicly accessible, available in nonproprietary formats, free of charge, and with unlimited use and distribution rights. They provide opportunities for health research, but their quality and usability are unknown. OBJECTIVE: To describe available open health data, identify whether data are presented in a way that is aligned with best practices and usable for researchers, and examine differences across platforms. DESIGN: Two reviewers systematically reviewed a random sample of data offerings on NYC OpenData (New York City, all offerings, n = 37), Health Data NY (New York State, 25% sample, n = 71), and HealthData.gov (US Department of Health and Human Services, 5% sample, n = 75), using a standard coding guide. SETTING: Three open health data platforms at the federal, New York State, and New York City levels. MAIN OUTCOME MEASURES: Data characteristics from the coding guide were aggregated into summary indices for intrinsic data quality, contextual data quality, adherence to the Dublin Core metadata standards, and the 5-star open data deployment scheme. RESULTS: One quarter of the offerings were structured datasets; other presentation styles included charts (14.7%), documents describing data (12.0%), maps (10.9%), and query tools (7.7%). Health Data NY had higher intrinsic data quality (P < .001), contextual data quality (P < .001), and Dublin Core metadata standards adherence (P < .001). All met basic "web availability" open data standards; fewer met higher standards of "hyperlinked to other data." CONCLUSIONS: Although all platforms need improvement, they already provide readily available data for health research. Sustained effort on improving open data websites and metadata is necessary for ensuring researchers use these data, thereby increasing their research value.

Diagnosis and management of chronic thromboembolic pulmonary hypertension (CTEPH) in sickle cell disease: A review.

Pulmonary hypertension in sickle cell disease (SCD) is a complex phenomenon resulting from multiple overlapping etiologies, including pulmonary vasoconstriction in the setting of chronic hemolytic anemia, diastolic dysfunction, and chronic thromboembolic disease. The presence of pulmonary hypertension of any cause in SCD confers a significant increase in mortality risk. Evidence to guide the management of patients with sickle cell disease and chronic thromboembolic pulmonary hypertension (CTEPH) is scant and largely the realm of case reports and small case series. Centered on a discussion of a complex young patient with hemoglobin hemoglobin SC who ultimately underwent treatment with pulmonary thromboendarterectomy, we review the available literature to guide management and discuss and overview of treatment of CTEPH in SCD, considering the unique considerations and challenges facing patients suffering from this multisystem disease.

Clinical outcomes of patients with acute myeloid leukemia and cardiovascular disease.

Incidence of both acute myeloid leukemia (AML) and cardiovascular disease (CVD) increases with age. We evaluated whether pre-existing CVD impacts clinical outcomes in AML. We retrospectively evaluated 291 consecutive adult AML patients treated at our institution, 2014-2020. Pretreatment comorbidities were identified by chart review. Outcomes included complete remission (CR) and CR with incomplete count recovery (CRi) rates, disease-free survival (DFS), overall survival (OS) and incidence of cardiovascular adverse events. CVD was present in 34% of patients at AML diagnosis. CVD patients had worse performance status (p=0.03) and more commonly had secondary AML (p=0.03) and received hypomethylating (HMA) agent-based therapy (72% vs 38%, p< 0.001). CVD (0.45 vs 0.71, p<0.001) and diabetes mellitus (HR= 0.24, 95% CI: 0.08 - 0.8, p= 0.01) were associated with lower probability of achieving CR/CRi. Accounting for age, performance status (PS), complex karyotype, secondary disease and treatment, CVD patients had shorter OS (HR=1.5, 95% CI: 1.1-2.2, p=0.002), with 1- and 3-year OS 44% vs 67% and 25% vs 40%, respectively, but there was no difference in cumulative incidence of relapse between patients with vs without CVD. Thus, CVD is an independent risk factor for lower response rate and shorter survival in AML patients.

Fulminant Hepatic Failure as the Initial Presentation of Hodgkin Lymphoma in 4 Patients With Human Immunodeficiency Virus.

In the era of antiretroviral therapy (ART), Hodgkin Lymphoma (HL) is a common non-AIDS-defining cancer with increasing incidence in people with human immunodeficiency virus (PWH). Through review of these cases, we identify clinical patterns such as declining CD4 count despite ART, hyperbilirubinemia and recurrent fever, which preceded diagnosis. Identifying these important signs and symptoms may lead to earlier diagnosis and initiation of therapy. Fulminant hepatic failure limits the ability to give standard of care chemotherapy, likely jeopardizing outcomes in this patient population. Alternative bridging therapies should be considered until hepatic function improves.