Reduced-Intensity Anthracycline-Free Chemoimmunotherapy in Elderly Patients With Newly Diagnosed or Relapsed Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL); it has a cure rate of approximately 50% with standard anthracycline-based chemoimmunotherapy. However, the clinical outcomes of elderly unfit/frail DLBCL patients remain suboptimal due to poor tolerance of anthracycline-containing regimens. Herein, we report a series of seven elderly unfit patients with DLBCL who were treated with a reduced-intensity anthracycline-free chemoimmunotherapy (rituximab, cyclophosphamide, vincristine, and prednisone) regimen combined with lenalidomide (

Primary Diffuse Large B-Cell Lymphoma of the Bone

Primary lymphoma of the bone (PLB) is a rare lymphoproliferative neoplasm that can present either as solitary or multiple bone lesions. We report four patients with PLB who were successfully treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by consolidative radiotherapy. All patients achieved a complete remission and had excellent long-term outcomes. PLB has a favorable response to combined modality treatment with chemoimmunotherapy and radiation. Long-term outcomes of PLB tend to be better than those of non-osseous diffuse large B-cell lymphoma

Durable Remission in Hodgkin Lymphoma Treated With One Cycle of Bleomycin, Vinblastine, Dacarbazine and Two Doses of Nivolumab and Brentuximab Vedotin.

A 49-year-old woman with systemic lupus erythematosus, lupus nephritis and chronic congestive heart failure presenting with bulky cervical lymphadenopathy was diagnosed with classic Hodgkin lymphoma (HL) stage IIIB (positron emission tomography-computed tomography (PET-CT) scan and bone marrow biopsy). She received one cycle of bleomycin, dacarbazine, and vinblastine to debulk the tumor. Given her advanced heart failure, doxorubicin was not administered. After the first cycle of chemotherapy, she was switched to nivolumab plus brentuximab vedotin (BV) and received two doses 4 weeks apart, finishing in July 2019. A restaging PET-CT in June 2019 showed a complete remission (CR). After the second course of treatment, she was unable to tolerate more treatments and hence was placed on a surveillance program. She remains in CR after a follow-up of 3 years. This case highlights the role of a tailored treatment approach to optimize clinical outcomes in uniquely complex clinical circumstances. BV in combination with nivolumab is a reasonable alternative regimen in HL ineligible for cytotoxic chemotherapy

Synchronous Presentation of Autoimmune Hepatitis and Multiple Myeloma

Autoimmune hepatitis (AIH) is a rare immune-mediated disease predominantly seen in women and triggered by various environmental factors. Rarely, AIH can be triggered by an underlying malignancy. We report a woman in her 60s who presented with markedly abnormal liver biochemical tests. Serology was positive for anti-smooth muscle antibodies and a liver biopsy confirmed AIH. During the hospital course, she developed sepsis and acute renal failure requiring dialysis support. Serum protein electrophoresis (SPEP) showed a monoclonal IgG kappa protein of 1.92 g/dL and a bone marrow biopsy revealed 7% clonal plasma cells. She had lytic lesions on skeletal survey confirming the diagnosis of a coexisting multiple myeloma (MM). Given her markedly abnormal liver chemistries, we decided to treat the AIH first and use the steroids (an important anti-myeloma therapy) as a bridge to the specific treatment of the MM once her clinical condition improved. She was treated with oral prednisone and azathioprine for AIH. One month later, a marked improvement in liver biochemical test results was noted and she was started on oral ixazomib, lenalidomide and dexamethasone. She received palliative radiotherapy to the lumbar spine (L2), left femur, and ischium lesions. This case highlights a rare co-occurrence of AIH and MM, the underlying mechanism of which is unknown

Synchronous Presentation of Autoimmune Hepatitis and Multiple Myeloma

Autoimmune hepatitis (AIH) is a rare immune-mediated disease predominantly seen in women and triggered by various environmental factors. Rarely, AIH can be triggered by an underlying malignancy. We report a woman in her 60s who presented with markedly abnormal liver biochemical tests. Serology was positive for anti-smooth muscle antibodies and a liver biopsy confirmed AIH. During the hospital course, she developed sepsis and acute renal failure requiring dialysis support. Serum protein electrophoresis (SPEP) showed a monoclonal IgG kappa protein of 1.92 g/dL and a bone marrow biopsy revealed 7% clonal plasma cells. She had lytic lesions on skeletal survey confirming the diagnosis of a coexisting multiple myeloma (MM). Given her markedly abnormal liver chemistries, we decided to treat the AIH first and use the steroids (an important anti-myeloma therapy) as a bridge to the specific treatment of the MM once her clinical condition improved. She was treated with oral prednisone and azathioprine for AIH. One month later, a marked improvement in liver biochemical test results was noted and she was started on oral ixazomib, lenalidomide and dexamethasone. She received palliative radiotherapy to the lumbar spine (L2), left femur, and ischium lesions. This case highlights a rare co-occurrence of AIH and MM, the underlying mechanism of which is unknown

Middle Meningeal Artery Embolization in Acute Leukemia Patients Presenting With Subdural Hematoma

Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients with acute leukemia may develop subdural hematoma (SDH) spontaneously or secondary to trauma. In patients with acute leukemia and SDH, the surgical evacuation of the hematoma causes significant morbidity and mortality. New approaches and strategies to reduce the need for surgical evacuation are needed to improve outcomes in patients with acute leukemia and intracerebral hemorrhage. We report two cases of acute SDH in patients with acute leukemia successfully treated with middle meningeal artery embolization, a minimally invasive interventional radiology technique, obviating the need for a surgical intervention. The first patient with acute promyelocytic leukemia (APL) presented with coagulopathy and developed an acute SDH after a fall. The second patient with acute myeloid leukemia presented with gum bleeding and also sustained an acute SDH after a fall. Both patients underwent middle meningeal artery embolization for treating their SDHs while actively receiving induction chemotherapy for acute leukemia. Both patients had resolution of their acute SDH and are in remission from their acute leukemia. Middle meningeal artery embolization is a very effective, and within the context of this setting, a novel, minimally invasive technique for management of SDH in acute leukemia patients, which can prevent the need for surgical interventions with its associated comorbidities and high risk of fatal outcomes in patients with acute leukemia and acute SDH

Antibody Therapies for the Treatment of Acute Myeloid Leukemia: Exploring Current and Emerging Therapeutic Targets

INTRODUCTION: Acute myeloid leukemia (AML) is the most common and deadly type of leukemia affecting adults. It is typically managed with rounds of non-targeted chemotherapy followed by hematopoietic stem cell transplants, but this is only possible in patients who can tolerate these harsh treatments and many are elderly and frail. With the identification of novel tumor-specific cell surface receptors, there is great conviction that targeted antibody therapies will soon become available for these patients. AREAS COVERED: In this review, we describe the current landscape of known target receptors for monospecific and bispecific antibody-based therapeutics for AML. Here, we characterize each of the receptors and targeted antibody-based therapeutics in development, illustrating the rational design behind each therapeutic compound. We then discuss the bispecific antibodies in development and how they improve immune surveillance of AML. For each therapeutic, we also summarize the available pre-clinical and clinical data, including data from discontinued trials. EXPERT OPINION: One antibody-based therapeutic has already been approved for AML treatment, the CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin. Many more are currently in pre-clinical and clinical studies. These antibody-based therapeutics can perform tumor-specific, elaborate cytotoxic functions and there is growing confidence they will soon lead to personalized, safe AML treatment options that induce durable remissions

Predictors for functional and anatomic outcomes in macular edema secondary to non-infectious uveitis

Aims We aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis. Material and methods We conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of > 300 mu m as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm(2) area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or < 300 mu m) within a 12 month period. Results Fifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis. Conclusion Available treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.This work was supported by grants from: Spanish Ministry of Economy, Industry and Competitivity, Carlos III Health Institute, cofinanced by the European Regional Development Fund, identification number: PI13/02148, Principal Investigator: AA; http://www.eng.isciii.es/ISCIII/es/contenidos/fd-investigacion/financiacion.shtml.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript