Effect of cumulative dose of brentuximab vedotin maintenance in relapsed/refractory classical Hodgkin lymphoma after autologous stem cell transplant: an analysis of real-world outcomes.

Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma demonstrated an improved 2-year progression-free survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse <12 months (RL<12) from the end of frontline therapy. Cohort 1 had patients with >75% of the planned total cumulative dose, cohort 2 with 51-75% of dose, and cohort 3 with ≤50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL<12, and 39% had END. Forty-four percent of patients had prior exposure to BV and 65% were in complete remission before ASCT. Only 14% of patients received the full planned BV dose. Sixty-one percent of patients discontinued maintenance early and majority of those (72%) were due to toxicity. The 2-year PFS for the entire population was 80.7%. The 2-year PFS was 89.2% for cohort 1 (n=39), 86.2% for cohort 2 (n=33), and 77.9% for cohort 3 (n=46) (P=0.70). These data are reassuring for patients who require dose reductions or discontinuation to manage toxicity.

Anakinra versus etoposide-based therapy added to high-dose steroids for the treatment of secondary hemophagocytic lymphohistiocytosis.

OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening, hyperinflammatory syndrome usually treated with high-dose steroids (HDS), often complemented with adjunct therapies, such as etoposide (HLH-94 protocol). Anakinra has been reported to effectively treat HLH; however, has not been comparatively examined with etoposide-based therapies. We sought to evaluate the effectiveness and durability of these treatment approaches. METHODS: We performed a retrospective analysis of all adult patients diagnosed with secondary HLH between January 2011 and November 2022 who received anakinra and HDS, the HLH-94 protocol, HDS alone, or supportive care. RESULTS: Thirty adult patients with secondary HLH were included. Cumulative incidence (CI) of response at 30 days was 83.3%, 60%, and 36.4% for patients treated with anakinra, the HLH-94 protocol, and HDS alone, respectively. CI of relapse at 1 year was 50%, 33.3%, and 0% with the HLH-94 protocol, HDS, and anakinra and HDS, respectively. Overall survival at 1 year was higher with anakinra and HDS compared to the HLH-94 protocol, yet was not statistically significant (77.8% vs. 33.3%; hazard ratio: 0.29; p = .25). CONCLUSION: Treatment with anakinra and HDS in adults with secondary HLH was associated with higher response rates with longer survival compared with alternative therapies and should be further investigated in this setting.

Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas.

There is a pressing need for more effective therapies to treat patients with T-cell lymphomas (TCLs), including first-line approaches that increase the response rate to cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) chemotherapy. We characterized the mitochondrial apoptosis pathway in cell lines and patient-derived xenograft (PDX) models of TCL and assessed the in vitro efficacy of BH3 mimetics, including the BCL2 inhibitor venetoclax, the BCL2/BCL-xL inhibitor navitoclax, and the novel MCL1 inhibitor AZD5991. The abundance of antiapoptotic BCL2 family members based on immunoblotting or RNA transcript levels correlated poorly with the activity of BH3 mimetics. In contrast, the functional approach BH3 profiling reliably predicted sensitivity to BH3 mimetics in vitro and in vivo. We used BH3 profiling to select TCL PDX that were dependent on MCL1. Mice xenografted with these PDX and treated with AZD5991 had markedly improved survival. The combination of AZD5991 and CHOP achieved synergy based on survival improvement beyond a mathematical "sum of benefits" model. Thus, MCL1 inhibition is a promising strategy as both a single agent and in combination with chemotherapy for patients with TCL and functional dependence on MCL1.

Hemophagocytic Lymphohistiocytosis in the Emergency Department: Recognizing and Evaluating a Hidden Threat.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematologic disorder resulting from an ineffective and pathologic activation of the immune response system that may mimic common emergency department presentations, including sepsis, acute liver failure, disseminated intravascular coagulation, and flu-like illnesses such as coronavirus disease 2019 (COVID-19). OBJECTIVE: This narrative review provides a summary of the disease and recommendations for the recognition and diagnostic evaluation of HLH with a focus on the emergency clinician. DISCUSSION: Though the condition is rare, mortality rates are high, ranging from 20% to 80% and increasing with delays in treatment. Importantly, HLH has been recognized as a severe variation of the cytokine storm associated with COVID-19. Common features include a history of infection or malignancy, fever, splenomegaly or hepatomegaly, hyperferritinemia, cytopenias, coagulopathies, abnormal liver enzymes, and hypertriglyceridemia. Using specific features of the history, physical examination, laboratory studies, and tools such as the HScore, HLH-2004/2009, and hyperferritinemia thresholds, the emergency clinician can risk-stratify patients and admit for definitive testing. Once diagnosed, disease specific treatment can be initiated. CONCLUSION: This review describes the relevant pathophysiology, common presentation findings, and a framework for risk stratification in the emergency department.

The Acute Hemolytic Anemias: The Importance of Emergency Diagnosis and Management.

BACKGROUND: Hemolytic anemias are defined by the premature destruction of red blood cells. These anemias have many causes that are mostly due to chronic diseases, but, occasionally, cases of acute life-threatening hemolysis can occur. OBJECTIVE: The objectives of this article were to review the pathophysiology of hemolytic anemias, to discuss the general emergency department (ED) evaluation, and to discuss the assessment and treatment of important and "cannot miss" hemolytic diseases. DISCUSSION: Because hemolytic anemias are rarely seen, the emergency physician may consider a patient's anemia as due to blood loss rather than hemolysis, and the workup and treatment may not be appropriate. The primary goal for the emergency provider is to resuscitate, but he or she also must recognize that a hemolytic process is present. Appropriate laboratory work and specialist consultation should be obtained. While focused treatment is rarely necessary in the ED, the avoidance of certain treatments, such as early platelet transfusion in thrombotic thrombocytopenic purpura, may be necessary. CONCLUSIONS: Hemolytic anemias are rare, but should still be considered in the ED differential diagnosis of low hemoglobin. Emergency physicians should first resuscitate, but should also be able to identify the presence of hemolysis and obtain the appropriate laboratory tests. Occasionally, specific treatments are needed but should be discussed in conjunction with a specialist.

Review of recently approved alternatives to anticoagulation with warfarin for emergency clinicians.

BACKGROUND: Dabigatran and rivaroxaban are novel anticoagulants that have been approved for the prevention of thromboembolic events in atrial fibrillation. These medications are attractive to both patients and clinicians, as, unlike warfarin, they do not require laboratory monitoring or dietary restrictions. However, they carry bleeding risks similar to that of warfarin and are without a reliable reversal agent. OBJECTIVES: The objectives of this article are to 1) summarize the pivotal trials leading to the U.S. Food and Drug Administration approvals of dabigatran (Pradaxa; Boehringer Ingelheim, Ridgefield, CT) and rivaroxaban (Xarelto; Janssen Pharmaceuticals, Inc., Titusville, NJ); 2) present the limited data available regarding the management of bleeding patients on these agents; and 3) provide suggestions to guide emergency providers given the limited data. DISCUSSION: Dabigatran and rivaroxaban were approved based on large, non-inferiority trials comparing the new agents to warfarin with stroke or systemic embolism as the primary outcome. Traditional coagulation studies cannot be used to determine the degree of anti-coagulation produced by these agents. Fresh frozen plasma is unlikely to be effective in patients on these drugs who are acutely bleeding. Prothrombin complex concentrate can be considered in patients on rivaroxaban. Dabigatran is renally cleared, so dabigatran could be removed by hemodialysis. Theoretically, DDAVP (Sanofi-Aventis U.S. LLC, Bridgewater, NJ), aminocaproic acid, tranexamic acid, or recombinant activated factor VII could also be used in an attempt to control bleeding. CONCLUSION: There is a need for assays for the degree of anticoagulation produced by drugs such as dabigatran and rivaroxaban. Additionally, studies are needed to evaluate reversal agents that could be effective in the setting of acute bleeding.

Looking to achieve cure the first time around for DLBCL patients who are older and/or with co-morbidities.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive but often curable malignancy. Older patients, especially those 80 years and older, have poor outcomes compared to those < 60, likely due to a number of reasons including disease biology, comorbidities, and treatment intolerance. Prospective data informing the treatment of older patients and those with multiple co-morbidities is limited. Here, we intend to review available data for regimens other than standard R-CHOP (rituximab, cyclophosphamide, adriamycin, prednisone) or R-pola-CHP (rituximab, polatuzumab vedotin [pola], cyclophosphamide, adriamycin, prednisone), tools available that may aid in treatment selection, and future directions, including the incorporation of newer treatment modalities into therapy for more vulnerable patients.

Impact of Thiotepa-Based Autologous Hematopoietic Cell Transplantation in Primary Central Nervous System Lymphoma in First Complete Remission: A University of California Hematologic Malignancies Consortium Retrospective Analysis.

BACKGROUND: The choice between nonmyeloablative chemotherapy (NMA-C) or autologous hematopoietic cell transplantation (autoHCT) as consolidation in primary central nervous system lymphoma (PCNSL), and timing of autoHCT differs among centers. We aimed to clarify these points. METHODS: We retrospectively analyzed PCNSL adult patients who received consolidation in CR1 or underwent autoHCT during their treatment course. Cohort A included those who underwent autoHCT in CR1, cohort B included those who underwent NMA-C in CR1, and cohort C included patients who underwent autoHCT in CR2+. We compared cohorts A and B, and cohorts A and C. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), treatment-related mortality (TRM) and cumulative incidence of relapse (CIR). RESULTS: 36 patients were included in cohort A, 30 in cohort B, and 14 in cohort C. The 5-year OS for cohorts A vs B and vs C were 90.7% vs 62.8% (P = .045) and vs 77.9% (P = .32), respectively. The 5-year PFS from diagnosis for cohorts A vs B was 87.8% vs 37.3% (P < .001). The 5-year PFS from autoHCT for cohorts A vs C was 87.6% vs 58.4% (P = .023). The 5-year TRM and CIR in cohorts A vs B was 9.4% vs 9.5% (P = .674), and 2.9% vs 53.2% (P < .001), respectively. The 5-year TRM and CIR in cohorts A vs C from the time of autoHCT was 9.5% vs 22.1% (P = .188), and 2.9% vs 19.5% (P = .104), respectively. CONCLUSION: Despite the limitations, thiotepa-based autoHCT in CR1 appears to improve outcomes in eligible patients with PCNSL.

Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study.

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 dose (RP2D) for phase 2 expansion. Phase 2 patients (n = 30) received RP2D (nanatinostat 20 mg daily, 4 days per week with valganciclovir 900 mg orally daily) for 28-day cycles. The primary end points were safety, RP2D determination (phase 1b), and overall response rate (ORR; phase 2). Overall, 55 patients were enrolled (B-non-Hodgkin lymphoma [B-NHL], [n = 10]; angioimmunoblastic T-cell lymphoma-NHL, [n = 21]; classical Hodgkin lymphoma, [n = 11]; and immunodeficiency-associated lymphoproliferative disorders, [n = 13]). The ORR was 40% in 43 evaluable patients (complete response rate [CRR], 19% [n = 8]) with a median duration of response of 10.4 months. For angioimmunoblastic T-cell lymphoma-NHL (n = 15; all refractory to the last prior therapy), the ORR/CRR ratio was 60%/27%. The most common adverse events were nausea (38% any grade) and cytopenia (grade 3/4 neutropenia [29%], thrombocytopenia [20%], and anemia [20%]). This novel oral regimen provided encouraging efficacy across several EBV+ lymphoma subtypes and warrants further evaluation; a confirmatory phase 2 study (NCT05011058) is underway. This phase 1b/2 study is registered at www.clinicaltrials.gov as #NCT03397706.

Eponyms in Malignant Hematology.

Eponyms have been traditionally used in the field of medicine to honor the contributions of an individual or group of individuals in understanding a disease. However, many eponyms have come under scrutiny given the personal backgrounds of individuals for whom they intend to honor. As we previously reviewed commonly used eponyms in medical oncology, we now aim to review commonly used eponyms in malignant hematology in order to highlight the individuals for whom they are named after. In this review, we discuss the pathophysiology of each disease, epidemiology, and the historical background for the individual or individuals for which the eponym honors.

Eponyms in medical oncology.

Eponyms have historically been used to honor individual contributions or discoveries in the field of medicine. More recently, some eponyms have been criticized for imprecision or for being misnomers. Eponyms attributed to discoveries made by Nazi German scientists have also fallen out of favor. However, despite these criticisms, eponyms remain popular for their ease of use. Eponyms generate interest in medical history and may help humanize the study of medicine. Here, we describe several eponyms in medical oncology with a focus on basic disease pathophysiology, epidemiology, and brief background on the individuals for whom the eponym was named.

Sinonasal lymphoma: A primer for otolaryngologists.

Objective: Sinonasal lymphomas are a rare entity that commonly present with nonspecific sinonasal symptoms and are often recognized immediately. Through this review, we aim to summarize important principles in diagnosis and treatment of sinonasal lymphomas, with the goal of disseminating the current knowledge of this under-recognized malignancy to otolaryngologists. Methods: Systemic review using PRISMA guidelines of foundational scholarly articles, guidelines, and trials were reviewed focusing on clinical characteristics of key sinonasal lymphoma subtypes, along with available treatments in the otolaryngology, medical oncology, and radiation oncology literature. Results: Sinonasal lymphoma are derived from clonal proliferation of lymphocytes at various stages of differentiation, of which diffuse large B-cell lymphoma (DLBCL) and extranodal natural killer/T-cell lymphoma (ENKTL) are the most common. Diagnosis and staging require biopsy with immunohistochemistry in conjunction with imaging and laboratory studies. Treatment is ever evolving and currently includes multi-agent chemotherapy and/or radiation therapy. Conclusion: Otolaryngologists may be the first to recognize sinonasal lymphoma, which requires a comprehensive workup and a multidisciplinary team for treatment. Symptoms are nonspecific and similar to many sinonasal pathologies, and it is crucial for otolaryngologists to keep a broad differential. Level of Evidence: 5.

R-CHOP Vs DA-EPOCH-R for Double-Expressor Lymphoma: A University of California Hematologic Malignancies Consortium Retrospective Analysis.

BACKGROUND: Managing double-expressor lymphomas (DEL) is controversial given the dearth of data and lack of standardized guidelines on this high-risk subset of lymphomas. No prospective and few retrospective studies limited by either their sample size or short follow-up address the question of initial treatment of choice for DEL. We performed the largest analysis to date exploring R-CHOP vs DA-EPOCH-R in DEL. METHODS: Adults with DEL diagnosed from 6/2012-2/2021 at 4 unique sites were retrospectively analyzed. Progression-free survival (PFS) was the primary endpoint. Key secondary endpoints include overall survival (OS), overall and complete response rates (ORR and CRR), cumulative incidence of relapse, and autologous hematopoietic cell transplantation (autoHCT) utilization. RESULTS: 155 patients were included, 61 treated with R-CHOP and 94 with DA-EPOCH-R. 3-year PFS and OS were similar between R-CHOP and DA-EPOCH-R, 33.2% vs 57.2%,(P = .063), and 72.2% vs 71.6% (P = .43) after median follow-up times of 2.43 and 2.89 years, respectively. Patients <65 had improved PFS with DA-EPOCH-R, hazard ratio 0.41 (P = .01). CRR and ORR rates were also similar. Relapse rates were not statistically different, 51.9% vs 28.6% (P = .069). AutoHCT utilization was higher with R-CHOP vs DA-EPOCH-R, 23.0% vs 8.5% (P = .017). CONCLUSIONS: Our findings do not support the use of DA-EPOCH-R over R-CHOP for DEL. Patients <65 years may experience longer PFS with DA-EPOCH-R, but limitations to the analysis make this interpretation difficult.

SWOG 1918: A phase II/III randomized study of R-miniCHOP with or without oral azacitidine (CC-486) in participants age 75 years or older with newly diagnosed aggressive non-Hodgkin lymphomas - Aiming to improve therapy, outcomes, and validate a prospective frailty tool.

Diffuse large B cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy; however, cure is highly dependent on the ability to deliver intensive, anthracycline-based chemoimmunotherapy. Nearly one third of cases of DLBCL occur in patients over age 75 years, and advanced age is an important adverse feature in prognostic models. Despite this incidence in older patients, there is no clear accepted standard of care due to under-representation of this group in large randomized clinical trials. Furthermore, insufficient assessments of baseline frailty and prediction of toxicity hamper clinical decision-making. Here, we present an ongoing randomized study of R-miniCHOP chemoimmunotherapy with or without oral azacitidine (CC-486, Onureg) for patients age 75 and older with newly diagnosed DLBCL and associated aggressive lymphomas. The incorporation of an oral hypomethylating agent is based on increased tumor methylation as a biologic feature of older patients with DLBCL and a desire to minimize the injection burden for this population. This is the first randomized study in this population conducted in North America by the National Clinical Trials Network (NCTN) and will enroll up to 422 patients including 40 patients in a safety run-in phase. This study incorporates an objective assessment of baseline frailty (the FIL Tool) and a serial comprehensive geriatric assessment (CGA). Key correlative tests will include circulating tumor DNA (ctDNA) assays at pre-specified timepoints to explore if ctDNA quantity and methylation patterns correlate with response. S1918 has the potential to impact future trial design and to change the standard of care for patients 75 years and older with aggressive lymphoma given its randomized design, prospective incorporation of geriatric assessments, and exploration of ctDNA correlatives. Trial registration: The trial is registered with ClinicalTrial.gov Identifier NCT04799275.

Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas.

Bcl-2 proteins represent a rheostat that controls cellular viability. Obatoclax, a BH3-mimetic, has been designed to specifically target and counteract anti-apoptotic Bcl-2 proteins. We evaluated the biological effects of obatoclax on the anti-tumour activity of rituximab and chemotherapy agents. Obatoclax induced cell death of rituximab/chemotherapy-sensitive (RSCL), -resistant cell lines (RRCL) and primary tumour-cells derived from patients with B-cell lymphomas (N=39). Obatoclax also enhanced the activity of rituximab and had synergistic activity when combined with chemotherapy agents. The ability of Obatoclax to induce PARP cleavage varied between patient samples and was not observed in some RRCL. Inhibition of caspase activity did not affect obatoclax activity, suggesting the existence of caspase-independent death pathways. Autophagy was detected by LC3 conversion and/or electron microscopy in RRCL and in patient-derived tumour cells. Moreover, obatoclax activity was inhibited by Beclin-1 knockdown. In summary, obatoclax is an active Bcl-2 inhibitor that potentiates the activity of chemotherapy agents and, to a lesser degree, rituximab. Defining the molecular events triggered by obatoclax is necessary to further its clinical development and identify potential biomarkers that are predictive of response.

Thrombotic thrombocytopenic purpura.

In 1924, Dr Eli Moschcowitz described a 16-year-old adolescent girl with abrupt onset of petechiae, hemolytic anemia, followed by paralysis, coma, and death. Autopsy showed widespread hyaline thrombi in the terminal arterioles and capillaries of various organs. The syndrome described by Moschowitz is now known as thrombotic thrombocytopenic purpura.

Treatment Modalities and Survival Outcomes for Sinonasal Diffuse Large B-Cell Lymphoma.

OBJECTIVES/HYPOTHESIS: This study utilizes a large population national database to comprehensively analyze prognosticators and overall survival (OS) outcomes of varying treatment modalities in a large cohort of sinonasal diffuse large B-cell lymphoma (SN-DLBCL) patients. STUDY DESIGN: Retrospective database study. METHODS: The National Cancer Database was queried for all SN-DLBCL cases diagnosed from 2004 to 2015. Kaplan-Meier log-rank test determined differences in OS based on clinical covariates. Cox proportional-hazards analysis was used to determine clinical and sociodemographic covariates predictive of mortality. RESULTS: A total of 2,073 SN-DLBCL patients were included, consisting of 48% female with a mean age of 66.0 ± 16.2 years. Overall, 82% of patients were Caucasian, 74% had early-stage disease, and 49% had primary tumors in the paranasal sinuses. Early-stage patients were more likely to receive multi-agent chemoradiotherapy compared to multi-agent chemotherapy alone (P < .001). Multivariable Cox proportional-hazards analysis revealed chemoradiotherapy to confer significantly greater OS improvements than chemotherapy alone (hazard ratio [HR]: 0.61; P < .001). However, subset analysis of late-stage patients demonstrated no significant differences in OS between these treatment modalities (P = .245). On multivariable analysis of chemotherapy patients treated post-2012, immunotherapy (HR = 0.51; P = .024) demonstrated significant OS benefits. However, subset analysis showed no significant advantage in OS with administering immunotherapy for late-stage patients (P = .326). Lastly, for all patients treated post-2012, those receiving immunotherapy had significantly improved OS compared to those not receiving immunotherapy (P < .001). CONCLUSIONS: Treatment protocol selection differs between early- and late-stage SN-DLBCL patients. Early-stage patients receiving chemotherapy may benefit from immunotherapy as part of their treatment paradigm. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2727-E2735, 2021.

Oncologic Emergencies: Immune-Based Cancer Therapies and Complications.

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation.

Considerations for the Treatment of Diffuse Large B Cell Lymphoma in the Elderly.

PURPOSE OF REVIEW: Diffuse large B cell lymphoma (DLBCL) is a curable and common malignancy in elderly population. Elderly patients, especially those 80 and older, have poor outcomes compared with those < 60. This may be due to the disease biology, comorbidities, and/or functional limitations. RECENT FINDINGS: Prospective data, and especially randomized data, are limited. The FIL tool objectively categorizes patients as fit, unfit, or frail. Fit and unfit patients can benefit from chemoimmunotherapy with curative intent. Evidence guiding treatment of frail patients is limited, but it appears that frail patients have similar survival regardless of treatment with curative or palliative intent. For fit and unfit patients, treatment options include rituximab with dose-attenuated CHOP or regimens with adriamycin alternatives if there is concern for cardiovascular adverse effects (AEs). Frail patients are extremely sensitive to toxicity from therapies. Frail patients and those 80 and older could greatly benefit from trials incorporating novel agents.

Hemophagocytic lymphohistiocytosis in the setting of HELLP Syndrome.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper activation of the immune system. Rare cases associated with HELLP syndrome and other similar conditions in pregnancy have been reported. Despite the improved survival rates with etoposide and dexamethasone-based regimens, HLH remains a challenging disease. Experience in pregnant patients is exceedingly rare.