Background: Hemophagocytic lymphohistiocytosis [HLH], is a rare life-threatening syndrome of excessive immune activation. It can be primary due to genetic predisposition or secondary due to infections, immune disorders or malignancies. With nonspecific clinical presentation, a high index of suspicion is required to make the diagnosis. Prompt treatment of underlying etiology and HLH specific therapy is warranted to prevent adverse clinical outcome. Methods: After IRB approval, we conducted a retrospective chart review of adult patients (pts) ≥ 18 years diagnosed with HLH between January 1st, 2010 and June 30th, 2019. We recorded age at diagnosis, gender, cause of HLH, symptoms, laboratory testing, bone marrow pathology, imaging, treatment and outcome. Results: We found a total of 15 patients in the time interval. Pt age ranged from 22 to 64 years with a median of 46 years. 60% were females and 40% were males. 14 pts had secondary HLH and one pt tested positive for HLH gene mutations. Etiology of HLH was malignancy in 6 (40%), infection in 5 (33%), rheumatological disease in 3 (20%) and cause was unclear in one pt but suspected to be an infection. One pt had prior allogenic stem cell transplant and one pt developed HLH even after completion of treatment for lymphoma. On presentation, 14 (93%) had fever, 6 (40%) had respiratory symptoms, 6 (40%) had neurological symptoms, 2 (13%) had a skin rash, 2 (13%) had bleeding manifestations and 3 (20%) required pressor support. Hemoglobin ranged from 5.5 to 13.3 g/dL on presentation, with median of 10.1 g/dL and 14 (93%) had Hb <9 g/dL. Absolute neutrophil count ranged from 0.3 to 16.94 x 103/uL with median of 2.87x103/uL and decreased to < 1000x103/uL in 11 (73%) and < 500x103/uL in 7 (46%). Platelet counts on presentation ranged from 18 to 244x103/uL with median of 82x103/uL and decreased to <100x103/uL in 14 (93%) and <20x103/uL in 8 (53%). 14 (93%) had bicytopenia. Initial ferritin levels ranged from 1,552 to 2,62,080 ng/ml with median of 5,515 ng/ml and increased to >10,000 ng/ml in 10 (66%) and highest level was 4,57,970 ng/ml. All 15 pts had some degree of hepatic dysfunction and one pt had acute kidney injury. Triglyceride levels were >265 mg/dL in 6 (40%). 10 (66%) had laboratory evidence of disseminated intravascular coagulation (DIC), one pt had clinical DIC. Blood cultures were negative in everyone, except 2 pts who developed infection during the hospital course, one with Candida krusei and the other with methicillin sensitive staphylococcus aureus. Bone marrow biopsy was performed in 14 (93%) and all of them demonstrated hemophagocytosis. 3 (20%) underwent lumbar puncture and 2 had elevated CSF protein. 11 (73%) had immunological testing and all of them had elevated soluble IL-2 receptor alpha (sCD25 or sIL-2R). Of the 3 pts who had HLH genetic testing, one had HLH associated mutations. Organomegaly was noted in 11 (73.3%) (4 had hepatosplenomegaly, 6 had splenomegaly, one had hepatomegaly). 6 (40%) had lung infiltrates. MRI brain was done in 5 (33%) and 2 had patchy hyperintensities. 11 (73.3%) were treated with HLH-94 protocol with etoposide and dexamethasone. One pt had matched unrelated donor Allogenic stem cell transplant. 13 (86.6%) had initial recovery. At the time of data cut off, 10 (66%) were alive. Of the 3 pts who initially recovered, one pt died of relapsed lymphoma, one died of HLH relapse and one developed Clostridium difficile infection with bowel perforation. [Refer to Table 1]. Conclusion: Even though literature suggests that malignancy associated HLH has a worse prognosis, our small series did not suggest that. We also noted that HLH associated with rheumatological diseases leads to a superior outcome if the underlying disease is adequately treated. The most significant finding in our series was a patient with diffuse large B cell lymphoma who was diagnosed to have primary HLH with HLH associated mutations. Typically, primary HLH presents in the first few years of life. This patient case points to the fact that patients with primary HLH can have a late presentation and can also be associated with immunological disorders with a predisposition to malignancy. This finding suggests that all patients diagnosed with HLH should have genetic testing done for HLH associated mutations, as this will impact treatment decisions and these patients will benefit from more intense treatment which may include an allogenic stem cell transplant. Disclosures No relevant conflicts of interest to declare.
Immunotherapies such as the cytotoxic T-lymphocyte–associated protein 4 inhibitor ipilimumab and the programmed cell death protein 1 inhibitor nivolumab have become ubiquitous in cancer treatment. Recently, the FDA approved nivolumab with or without ipilimumab for the treatment of refractory small cell lung cancer. Immunotherapies increase the immune response to cancer cells by interfering with inhibitory molecular pathways that prevent tumor cell killing, thus augmenting tumor cell death without many of the cytotoxic side effects associated with chemotherapy. However, this augmented immune response may result in unwanted immune-mediated inflammation of different organs and are therefore associated with immune-related adverse events, unlike traditional chemotherapies or targeted therapies. Here, we describe 1 patient with advanced small cell lung cancer who developed grade III–IV acute inflammatory demyelinating polyradiculoneuropathy after treatment with ipilimumab and nivolumab. The patient was treated with intravenous immunoglobulin alone and showed symptomatic improvement.
e14735 Background: Hormone receptor and HER2 status have both predictive and prognostic implications in breast cancer (BC). Studies report differences of 3% to 54% for Estrogen receptor (ER), 5% to 78% for Progesterone receptor (PR), and 0% to 34% for HER2 between primary (P) and recurrent/metastatic breast cancer (RMBC). To evaluate this difference, we conducted an observational single institution study in adult patients (pts) ≥ 18 years with RMBC. Methods: After IRB approval, we conducted a retrospective chart review of pts diagnosed with RMBC between January 1st, 2010 and October 31st, 2018, with history of PBC. We recorded age at PBC diagnosis, stage, tumor type, receptor status, initial treatment, age at RMBC diagnosis, if biopsy performed, receptor status and survival. We studied the differences in ER, PR and HER2 receptors between P and RMBC. Descriptive statistics was used for analysis. Results: We found a total of 179 pts in the time interval. Median age was 54 ± 13.2 years at PBC diagnosis, 98.9% females, 1.1% males. 187 events were recorded. At PBC diagnosis, 27.4% had Stage I, 37.4% had Stage II and 31.8% had Stage III disease. Tumor type was ductal in 83.8% and lobular in 12.2%. 78.8% was ER+, 68.7% was PR+ and 14% was HER2+. 70.9% received chemotherapy, 12.8% received HER2 therapy and 67% received hormonal therapy. Age at RMBC was median of 61 ± 13.1 years. Biopsy was done in 93.3%. Time between PBC and RMBC ranged from 7 and 324 months. 31.3% had local recurrence and 68.7% had distant disease. In RMBC, 59.2% was ER+, 41.9% was PR + and 13.4% was HER2 +. 58.7% are alive and 38% deceased. With RMBC, 19.2% who were ER+ became ER-, 4.9% who were ER- became ER+, 37.5% who were PR+ became PR-, 8.6% who were PR- became PR+, 23.1% who were HER2+ became HER2-, 4.5% who were HER2 - became HER2+. In pts who became ER-/PR-, 88.5% received hormonal therapy and 61.5% received chemotherapy at the time of PBC. In pts who became HER2-, 83.3% received HER2 therapy at the time of PBC. Conclusions: In our study, we found a difference of 24.1% in ER, 46.1% in PR and 27.6% in HER2 between PBC and RMBC. It is recommended that patients with RMBC should have a biopsy to evaluate the receptor status as it would impact treatment and survival.
Transformation of germ cell tumor to an alternate malignancy is rare; and it is believed to be secondary to teratomatous elements of the initial tumor surviving chemotherapy and subsequently proliferating. Here, we describe a patient with transformation of a nonseminomatous germ cell tumor to adenocarcinoma. A 55-year-old male with history of nonseminomatous germ cell tumor of the left testicle, previously resected, followed by four cycles of BEP chemotherapy, on active surveillance, presented nearly 20 years later with nausea and rising alpha-fetoprotein levels. Computed tomography (CT) abdomen revealed bulky retrocrural lymphadenopathy with increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan. Biopsy revealed metastatic adenocarcinoma, staining strongly positive for SALL4 and CDX2, with focal rare positivity for CK20 in the tumor cells, consistent with germ cell origin. FOL-FOX therapy was therefore initiated. This is one of few documented cases showing transformation of nonseminomatous germ cell tumor to adenocarcinoma, for which surgical resection is favored as primary therapy. However, aggressive adjuvant chemotherapy may be considered and should be directed towards the most aggressive found histology.
BackgroundMany co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC).MethodsWe carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC.ResultsOne hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival.ConclusionsOur results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.
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