Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a critical element in the B-cell receptor signaling pathway. Syk is also a key component in signal transduction from other immune receptors like Fc receptors and adhesion receptors. Several oral Syk inhibitors including fostamatinib (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659 are being assessed in clinical trials. The second generation compound, entospletinib, showed promising results in clinical trials against B-cell malignancies, mainly chronic lymphoid leukemia. Syk inhibitors are being evaluated in combination regimens in multiple malignancies.
BackgroundBabesiosis is endemic in selected areas in North America. Babesia infection is commonly associated with anemia, thrombocytopenia, hyponatremia and elevated liver enzymes. Autoimmune hemolytic anemia (AIHA) is known to be caused by parasitic and viral infections but has not been well characterized.Case presentationWe describe two cases diagnosed with babesiosis triggering severe AIHA. One case had history of splenectomy, and the other was an elderly patient. Older, immunocompromised and asplenic patients may be particularly at risk for post-babesiosis AIHA (PB-AIHA).ConclusionsThe pathogenesis for conventional AIHA and PB-AIHA appears to be different, since splenectomy is a treatment for conventional AIHA, whereas PB-AIHA is seen more often in asplenic patients. Further investigation into this intriguing mechanism of host immune response to babesiosis may help to elucidate the overall mechanism of infection- triggered AIHA.
Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP). In addition to antibiotics treatment for babesiosis, ITP therapy was administered. ITP in the present case was most likely triggered by the babesia infection. The severity of ITP in this case was not proportional to the severity of parasitemia. The neoantigen triggering the autoimmune response in babesiosis requires further characterization.
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by widespread inflammation due to massive immune activation and cytokine release. It is of 2 types, primary or familial and secondary or acquired. Diagnosis is made by fulfilling 5 of 8 criteria as determined by the Histiocyte Society. Treatment includes etoposide, dexamethasone, with or without intrathecal methotrexate in the presence of neurologic involvement as well as treating the underlying cause in secondary HLH. We present a case of a 23-year-old female with congenital human immunodeficiency virus (HIV) infection who presents with nonspecific signs and symptoms of cough, fever, leukopenia, and anemia, and a high-serum parvovirus B19 DNA, later diagnosed with HLH and treated with etoposide and dexamethasone. She made clinical improvements and was successfully discharged to home after 26 days of admission.
The V617F mutation of Janus-associated kinase 2 (JAK2) is commonly seen in myeloproliferative neoplasms (MPN). Transformation of JAK2 positive MPNs to acute leukemia has been reported. We here report a case of acute promyelocytic leukemia which was later confirmed to have a co-existing JAK2 V617F positive MPN. In addition, the patient was found to have FLT3-TKD mutation, which, together with PML/ RARa, could play a role in the MPN transformation to APL.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. Fludarabine-based regimens demonstrate higher response rates in younger patients but have a significant risk of infection and are thus poorly tolerated by older, frail patients. Anti-CD20 monoclonal antibodies have added to the efficacy of chemotherapy in CLL. Obinutuzumab is a potent Type II anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular toxicity and direct cell death compared with rituximab. In Phase I studies, infusion reactions and neutropenia were the predominant toxicities. Phase II studies demonstrated efficacy both as a single agent and in combination with chemotherapy in patients with CLL. The CLL11 trial was a Phase III randomized trial of chlorambucil alone or with either obinutuzumab or rituximab in elderly, unfit patients. Progression-free survival (the primary end point) was 26.7 months for patients receiving obinutuzumab plus chlorambucil versus 16.3 months for those receiving rituximab plus chlorambucil and 11.1 months for those receiving chlorambucil alone (P<0.001). Overall survival was improved for patients receiving obinutuzumab plus chlorambucil versus chlorambucil alone (P=0.002). This trial led to the US Food and Drug Administration (FDA) approval of obinutuzumab in this patient population.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease.
6123 Background: Loss to follow-up (LFU) of cancer patients is a serious dilemma, and has only been narrowly studied. Lincoln Medical and Mental Health Center (LMMHC) serves South Bronx (SB), the poorest district in the nation. The purpose of this study was to assess rates of LFU and correlate it with age, sex, ethnicity, race, cancer types, and stage at diagnosis. Methods: We collected data from 1,552 patients diagnosed with invasive cancer in LMMHC between 2006-2010. The data collected were age, sex, ethnicity, race, type of cancer, stage, LFU, treatment, and vital status. Results: From the 1,552 patients, roughly 25 % were LFU, with 50% receiving some initial form of treatment. The remaining percentages are shown below (Table). A higher rate of LFU was with patients younger than 65 (OR: 1.38, 95% CI: 1.08-1.76). There was no correlation between sex and LFU. Non-Hispanics were more likely to be LFU compared to Hispanics (OR: 1.39, 95% CI: 1.07 – 1.8). Blacks were more likely to be LFU compared to non-Blacks (OR: 1.43, 95% CI: 1.12–1.82). There was no significance between LFU and stage at diagnosis. Looking at cancer specific data, colon cancer (C) and head and neck cancers (HN) had the highest percentage of LFU (30% each). There was higher LFU rate for C compared to breast cancer (B) (OR: 1.7, 95% CI: 1.03-2.8), prostate cancer (P) (OR: 1.88, 95% CI: 1.18-3.02), and lung cancer (L) (OR: 1.64 95% CI: 0.94- 2.8). HN patients were more likely LFU compared to B (OR: 2.4, 95% CI: 1.13-5.2), P (OR: 2.69, 95 % CI: 1.28-5.68), and L (OR: 2.3, 95% CI: 1.05-5.19) patients. There was no significant difference between C and HN patients in respect to LFU. Conclusions: In the SB, LFU rates are related to age, ethnicity, race, and type of cancer. Younger patients, blacks, non-Hispanics, and those with C and HN cancers were most likely to be LFU, the latter likely due to the lack of a HN surgeon at LMMHC. We hope that with focus on race, ethnicity, and cancer-specific disparities in LFU rates, we will improve the retention rate of our cancer patients in the future. [Table: see text]
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