Factors affecting response to 5-azacytidine and prognosis of myelodysplastic syndrome. Is long-term survival a realistic goal?

The introduction of hypomethylating agents (HMAs) 5-azacytidine and decitabine has altered the prognosis of patients with myelodysplastic syndrome (MDS). Over the past few years, the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) have been used both to define the prognosis of patients with MDS and to select patients to be treated with HMAs. Nevertheless, the prognosis of individual patients with MDS can differ considerably from the one calculated with the use of the above-mentioned prognostic systems. Thus, some patients may achieve long-term survival irrespective of their initial prognostic score. Several factors besides those used to define the IPSS/IPSS-R are analyzed in this review article; these include age and gender, the baseline hematologic characteristics, the comorbidities, the cytogenetic and molecular profile of the patients, as well as their response to treatment with 5-azacytidine. Thus, insight into a more personalized way of managing patients with MDS is given and long-term survival is set as a more realistic goal of treatment with 5-azacytidine. © 202

Post-Myelofibrosis Acute Myeloid Leukemia Effectively Treated with a Combination of Ruxolitinib and 5-Azacytidine

Background: Leukemic transformation is an unfavorable event emerging in a minority of patients with myelofibrosis (MF) and carrying a poor prognosis. Patients with post-MF acute myeloid leukemia (AML) may be treated with curative or noncurative intent, but there is no standard of care. The use of hypomethylating agents has been correlated with limited activity and low overall survival rates, while ruxolitinib has been proven to have modest antileukemic activity. Case Presentation: In this case study, we present the case of a 67-year-old female patient with post-polycythemia vera MF who developed AML and was successfully treated with a combination of 5-azacytidine and ruxolitinib, without any significant toxicity. Summary: To our knowledge, this is the first report of a patient with post-MF AML achieving a complete remission with a combination of ruxolitinib and a hypomethylating agent. This combination is actively studied in phase I/II clinical trials and may be proven effective in this hard-to-treat group of patients. © 2019 S. Karger AG, Basel

Significance of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in multiple myeloma

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a member of the CC chemokine family and is primarily associated with cell adhesion and migration. It is produced by myeloma (MM) cells and directly stimulates osteoclast formation and differentiation in a dose dependent way. MIP-1 alpha protein levels were elevated in the bone marrow plasma of MM patients and correlated with disease stage and activity. MIP-1 alpha was also elevated in the serum of myeloma patients with severe bone disease and correlated positively with bone resorption markers providing evidence for a causal role of MIP-1 alpha in the development of lytic bone lesions in MM. MIP-1 alpha has also been found to stimulate proliferation, migration and survival of plasma cells. Mice, which were inoculated with myeloma cells and treated with a monoclonal rat anti-mouse MIP-1 alpha antibody, showed a reduction of both paraprotein and lytic lesions. In addition, MIP-1 alpha enhanced adhesive interactions between myeloma and marrow stromal cells, increasing the expression of RANKL and IL-6, which further increased bone destruction and tumor burden. Myeloma patients with high MIP-1 alpha serum levels have poor prognosis. The positive correlation between MIP-1 alpha and beta(2)-microglobulin that has been observed in MM patients at diagnosis further supports the notion that MIP-1 alpha is not only a chemokine with osteoclast activity function but is also implicated in myeloma growth and survival. Therefore, MIP-1 alpha pathway may serve as a target for the development of novel anti-myeloma therapies

A case report of Hodgkin lymphoma in a patient treated with ustekinumab for psoriasis

RATIONALE: Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been case reports that raise concerns about its oncogenic potential. We are the first authors to report a case of Hodgkin lymphoma in a psoriatic patient receiving ustekinumab. PATIENT CONCERNS: A 22-year-old asymptomatic female patient presented to our department to investigate an enlarged cervical lymph node. Her past history was unremarkable, except for psoriasis since age 13. Two months before presentation the decision to administer Ustekinumab was taken and the patient had already received 3 doses. DIAGNOSES: During workup a Stage IV Hodgkin lymphoma was discovered. INTERVENTIONS: Ustekinumab administration was discontinued. The patient received treatment with the ABVD regimen. OUTCOMES: The patient's disease was refractory to the above-mentioned treatment. Therefore, a more aggressive regimen (BEACOPP escalated) was administered. LESSONS: Growing postmarketing surveillance data and case reports indicate that further research is warranted in order to elucidate a potential association between Ustekinumab and malignancy

Molecular analysis of immunoglobulin genes in multiple myeloma

The study of immunoglobulin genes in multiple myeloma over the last five years has provided important information regarding biology, ontogenetic location, disease evolution, pathogenic consequences and tumor-specific therapeutic intervention with idiotypic vaccination, Detailed analysis of V-H genes has revealed clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and peripheral blood. V-H gene usage is biased against V4-34 (encoding antibodies with cold agglutinin specificity; anti-l/i) explaining the absence of autoimmune phenomena in myeloma compared to other B-cell lymphoproliferative disorders. V-H genes accumulate somatic hypermutations following a distribution compatible with antigen selection, but with no intraclonal heterogeneity. V-L genes indicate a bias in usage of V kappa I family members and somatic hyper mutation, in line with antigen selection, of the expressed V kappa genes is higher than any other B-cell lymphoid disorder. A complementary imprint of antigen selection as evidenced by somatic hypermutation of either the V-H or V-L clonogenic genes has been observed. The absence of ongoing somatic mutations in either V-H or V-L genes gives rise to the notion that the cell of origin in myeloma is a post-germinal center memory B-cell. Clinical application of sensitive PCR methods in order to detect clonal immunoglobulin gene rearrangements has made relevant the monitoring and follow-up of minimal residual disease in stem cell autografts and after myeloablative therapy. The fact that surface immunoglobulin V-H and V-L sequences consitute unique tumor-specific antigenic determinants has stimulated investigators to devise strategies aiming to generate active specific immunity against the idiotype of malignant B-cells in myeloma by constructing vaccines based on expressed single-chain Fv fragments, DNA plasmids carrying V-H+V-L clonogenic genes for naked DNA vaccination, or dendritic cell-based vaccination armed with the tumor-specific idiotype

Unusual complications of infective endocarditis

Case series Patients: Female, 65-year-old • Female, 74-year-old Final Diagnosis: Endocarditis Symptoms: Dyspnea Medication: — Clinical Procedure: — Specialty: Cardiology • Infectious Diseases Objective: Unusual clinical course Background: Despite advances in management, infective endocarditis remains a condition with high in-hospital and post-discharge mortality, especially when it is complicated by perivalvular extension and heart failure (HF). Case Reports: Herein we describe two illustrative cases of endocarditis. The first case was complicated by left ventricle to right atrial fistula. The second cased was complicated by valvular perforation with a “windsock” appearance. Both patients developed acute HF. Conclusions: Fistulas and severe valvular regurgitation are among the major causes of acute HF in the setting of infective endocarditis. In such cases, surgery should be considered to decrease mortality. © Am J Case Rep, 2020

A case report of a fulminant Aeromonas hydrophila soft tissue infection in a patient with acute lymphoblastic leukemia harboring a rare translocation

Introduction: Aeromonads are gram-negative opportunistic bacteria, mainly found in aquatic environments. Hematologic patients are particularly at risk of Aeromonas soft tissue infections and septicemia, especially during chemotherapy-induced neutropenia. Case description: A 46-year-old man was diagnosed with acute lymphoblastic leukemia characterized by the rare t(12;17)(p13;q21)/TAF15-ZNF384 aberration. On day 22 of chemotherapy, he developed febrile neutropenia followed by necrotizing fasciitis in his upper right extremity. Despite appropriate antibiotic therapy and prompt surgical intervention, he died within 36 h after the appearance of a fever. A multi-sensitive Aeromonas hydrophila was isolated from all cultural sites. Discussion and conclusions: In a previous paper we characterized the patient’s aberration with cytogenetic and FISH analysis. Here, we provide details regarding the patient’s rapidly progressing infection and underline the importance of maintaining high clinical suspicion of Aeromonas infections in acute leukemia. Given the unusually rapid progression of an infection caused by a rare non-resistant pathogen, and after considering data on the implication of metalloproteinase function in immune system regulation, a correlation between risk of severe infection and TAF15-ZNF384 aberrated acute lymphoblastic leukemia cannot be ruled out. © 2022 Informa UK Limited, trading as Taylor & Francis Group