A Case of Hemophagocytic Lymphohistiocytosis in a Patient with Chronic Lymphocytic Leukemia after Treatment with Fludarabine, Cyclophosphamide, and Rituximab Chemotherapy, with Autopsy Findings

Hemophagocytic lymphohistiocytosis (HLH) is rarely described in association with chronic lymphocytic leukemia (CLL), mostly triggered by disease progression or concurrent infection. A 68-year-old male received 4 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) for CLL and achieved a complete response. Twenty-four days after the last chemotherapy, he presented with febrile neutropaenia and was diagnosed with HLH. The diagnosis was based upon persistent fever, pancytopenia, hyperferritinemia, splenomegaly, and hemophagocytosis on bone marrow aspirate. He began treatment with dexamethasone, cyclosporine, and etoposide. Fever resolved and hyperferritinemia improved but pancytopenia persisted. He died 13 days later from septic shock with positive blood cultures. A limited postmortem examination was performed and biopsies were taken from bone marrow, liver, and spleen. Biopsies demonstrated abundant hemophagocytosis by the activated macrophage as stained by CD68. There was no evidence of residual CLL as demonstrated by the lack of lymphocytes which was confirmed by the negative staining of CD79a. Chemotherapy appears to be responsible for the development of HLH in this patient. This is the second reported case of HLH developing after a rituximab-containing chemotherapy

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

Danazol: An Effective Option in Acquired Amegakaryocytic Thrombocytopaenic Purpura

Acquired amegakaryocytic thrombocytopaenic purpura (AATP) is a rare haematological condition characterised by isolated thrombocytopaenia with normal other cell lines. It is often initially misdiagnosed as immune thrombocytopaenic purpura but has characteristic bone marrow findings of reduced megakaryocyte numbers. The optimal treatment of AATP is not clearly defined but revolves around immunosuppressive therapies. We report a case of successful treatment of AATP with danazol, an antioestrogenic medication. We also review the aetiologies and pathogenesis of the disorder and suggest that danazol should be considered as an effective alternative to potent immunosuppression in AATP

A Case of Hemophagocytic Lymphohistiocytosis in a Patient with Chronic Lymphocytic Leukemia after Treatment with Fludarabine, Cyclophosphamide, and Rituximab Chemotherapy, with Autopsy Findings

Hemophagocytic lymphohistiocytosis (HLH) is rarely described in association with chronic lymphocytic leukemia (CLL), mostly triggered by disease progression or concurrent infection. A 68-year-old male received 4 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) for CLL and achieved a complete response. Twenty-four days after the last chemotherapy, he presented with febrile neutropaenia and was diagnosed with HLH. The diagnosis was based upon persistent fever, pancytopenia, hyperferritinemia, splenomegaly, and hemophagocytosis on bone marrow aspirate. He began treatment with dexamethasone, cyclosporine, and etoposide. Fever resolved and hyperferritinemia improved but pancytopenia persisted. He died 13 days later from septic shock with positive blood cultures. A limited postmortem examination was performed and biopsies were taken from bone marrow, liver, and spleen. Biopsies demonstrated abundant hemophagocytosis by the activated macrophage as stained by CD68. There was no evidence of residual CLL as demonstrated by the lack of lymphocytes which was confirmed by the negative staining of CD79a. Chemotherapy appears to be responsible for the development of HLH in this patient. This is the second reported case of HLH developing after a rituximab-containing chemotherapy

A Blockwise Empirical Likelihood Test for Gaussianity in Stationary Autoregressive Processes

A new and simple blockwise empirical likelihood moment-based procedure to test if a stationary autoregressive process is Gaussian has been proposed. The proposed test utilizes the skewness and kurtosis moment constraints to develop the test statistic. The test nonparametrically accommodates the dependence in the time series data whilst exhibiting some useful properties of empirical likelihood, such as the Wilks theorem with the test statistic having a chi-square limiting distribution. A Monte Carlo simulation study shows that our proposed test has good control of type I error. The finite sample performance of the proposed test is evaluated and compared to some selected competitor tests for different sample sizes and a variety of alternative applied distributions by means of a Monte Carlo study. The results reveal that our proposed test is on average superior under the log-normal and chi-square alternatives for small to large sample sizes. Some real data studies further revealed the applicability and robustness of our proposed test in practice

Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL) representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia) with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site