After completing this course, the reader will be able to:1. Cite the primary concerns of oncologists regarding influenza vaccination for their cancer patients.2. Describe research showing that cancer patients, whether taking myelosuppressive chemotherapy or not, are able to generate an immune response to the H1N1 vaccine similar to that of healthy controls.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTBackground. The immune response of patients who have cancer, who may be receiving immunosuppressive therapy, is generally considered to be decreased. This study
5070 Title: A case of Hemophagocytic Lymphohistiocytosis with Acute Myelofibrosis Case report: A 60 year old previously healthy male was admitted for a four week history of non-productive cough, and intermittent fever which was getting worse since 1 week prior to presentation. He also had runny nose and nasal stuffiness 2 months prior to presentation. The patient also had significant weight loss of 30 lbs over the past month. Physical examination was remarkable for a temperature of 38°C. Patient was alert and oriented. No Lymphadenopathy or hepatosplenomegaly was found. Rest of the physical examination was otherwise unremarkable. Laboratory findings on admission: hemoglobin 10.1 g/dl, white blood cell count 1000 /ml (with 58.5% neutrophils, 36.9% lymphocytes 3.4% monocytes), platelet count 111,000 /ml, reticulocyte count 1.3 % and an erythrocyte sedimentation rate 4 mm, total bilirubin 0.8 mg/dL (with 0.4 mg/dL conjugated), alkaline phosphatase 62 U/L, AST 113 U/L, ALT 137 U/L, triglyceride 388 mg/dL, LDH 513 IU/L, ferritin was > 2000 ng/mL, PT 12.2 sec PTT 26.8 sec and fibrinogen 154 mg/dl No pathogens were isolated from throat, urine, feces, or blood. H1N1 testing; serological studies for hepatitis A, B, D, and E; Quantiferon test for tuberculosis; Serological studies for Human immunodeficiency virus (HIV), Cytomegalovirus (CMV), Epstein-Bar virus (EBV), parvovirus; antinuclear antibody, rheumatoid factor, lupus anticoagulant were all negative. Peripheral blood examination revealed normochromic-normocytic anemia. There was no evidence of micro-angiopathy or other marrow infiltration. A bone marrow biopsy was performed which showed a hypercellular marrow, with absence of myeloid precursors and decrease in erythroid cells. The predominant components were atypical megakaryocytes, plasma cells and eosinophils Reticulin stain showed marked increase in coarse reticulin. Occasional large histiocytes were visualized with engulfed lymphocytes, polymorphonuclear and red blood cells. Flow cytometry was negative for a myeloproliferative disorder. The platelet and WBC count nadirs were 73,000/mL and 800/mL (53% polymorphonuclear cells) at days 5–7 of admission. He continued to have cytopenias with intermittent febrile episodes despite being on broad spectrum antibiotics and antifungals. Based on pancytopenia, intermittent fever, elevated liver enzymes, very high ferritin level, high triglyceride level and evidence of hemophagocytosis on bone marrow exam a diagnosis of Hemophagocytic Lymphohistiocytosis was made. Patient received IV Ig for 2 days along with high dose steroids with prophylaxis with IV proton pump inhibitors, after which his fever resolved. LDH decreased from a peak of 900 to 300 and his leucopenia resolved with a WBC count of 3,000 /ml 5 days after 1st dose of IV Ig. Patient seemed to be responding very well to the treatment, but he had an episode of massive GI bleed on the fifteenth day of hospitalization with malena and he could not be resuscitated. No autopsy was performed. Discussion: We describe a case of possible secondary Hemophagocytic Lymphohistiocytosis (HLH) with Acute Myelofibrosis. A diagnosis of HLH was made based on the proposed diagnostic criteria, 2009 by Dr. Filipovich. Acute Myelofibrosis was evidenced by marked increase in reticulin stain with absence of splenomegaly or tear drop cells on peripheral blood smear. Viral infection could have been a trigger for HLH in this patient as he had runny nose 2 months before presentation. The patient responded very well to IVIg and high dose steroids as evidenced by an increase in WBC and platelet count, resolution of fever and decrease in LDH. HLH is a rare and potentially fatal condition with excessive activation of macrophages and T cells with an overwhelming systemic inflammatory reaction. Viruses are implicated as the most common triggers for secondary HLH. Our case adds to the literature on the rare disease and will help in understanding the disease better. Disclosures: No relevant conflicts of interest to declare.
1743 Introduction: Effective vaccinations against 2009 H1N1 have been reported in healthy individuals; however, the response of immunocompromised patients, particularly patients who have hematologic malignancies and who also may be taking cytotoxic myelosuppressive and immunosuppressive treatments, is unclear and is generally considered to be decreased. Methods: We conducted a prospective study to test the immunogenicity of H1N1 vaccination in patients with hematologic malignancies. We enrolled 22 patients, all of them received inactivated monovalent H1N1 2009 vaccine made by Sanofi. Antibody responses were measured by hemaglutination inhibition assay (HAI) at 4–6 weeks and 6–16 weeks. Results: Among the 22 patients, there were 15 males, 7 females, median age 61.5y (range 35–86y). Sixteen patients had active disease, with MGUS+MM (n=4), CLL+NHL (n=5), MDS+AML (n=4) and MPD (n=3), while the other 6 patients were in remission (within 3 years of initial diagnosis), including MM (n=1), CLL+NHL+HD (n=3), AML (n=1) and MPD (n=1). Eleven patients were receiving treatment (within 28 days before or after vaccination) with drugs that have myelosuppressive potential (91%), and 54.5% of the patients were also receiving drugs that have immunosuppressive potential. The median interval of treatment prior to vaccination was 6 days (range 0–84 d) and the median interval of treatment after vaccination was 14 days (0-28 d). At baseline, 23.0% (95% confidence interval [CI], 4–42%) patients had antibody titer ≥ 1:40, and the geometric mean titer was 18.2 (95%CI, 8.6–38.7); at 4–6 weeks, the geometric mean titer was 197.0 (95%CI, 86.5–448.4), and the geometric mean ratio was 12.1 (95%CI 5.28–27.9). The seroconversion rate (4 fold increase in the antibody titer and ≥1:40) was 75% (95%CI, 54–96%), and the post-vaccination seroprotection rate (titer ≥1:40) was 90% (95%CI, 77–100%). When re-tested at 6–16 weeks, the results were not significantly different. Among the 5 patients (25%) who did not show seroconversion, 2 had very high baseline protection titers, 2 did not attain seroprotective titers after vaccination, another one did not show protective titer at 6 weeks, but mounted a titer of 1:40 at 10 weeks. No serious adverse events or hospital admissions from H1N1 infection were documented at 6 months of follow up. Subgroup analyses were performed to evaluate the influence on seroconversion rates of potential factors including (1) the presence or absence of active disease, (2) lymphoproliferative disorders versus myeloid disorders, (3) myelosuppressive drugs, (4) immunosuppressive drugs, and none showed a significant difference. Three patients were treated with Rituximab based chemotherapy, 1 patient who had R-CHOP for NHL showed robust response at 4–6 weeks, while 1 patient who had CLL treated with FCR, and another one with NHL treated with R-Bendamustine failed to develop response. These are the only 2 patients who did not show seroconversion or seroprotective titers in this study. Conclusion: Patients with hematologic malignancies are able to generate an immune response to the H1N1 vaccine. The lower boundaries of CI of seroconversion rate (54%) and that of seroprotection rate (77%) are above what are recommended by the US FDA for an effective vaccine. Among the patients who developed an immune response, all but one demonstrated response within 4–6 weeks. Patients receiving Rituximab based treatment nevertheless can generate an effective immune response. Disclosures: No relevant conflicts of interest to declare.
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