Use of cardiac radiation therapy as bridging therapy to CAR-T for relapsed pediatric B-cell acute lymphoblastic leukemia.

The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with B-ALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CAR-T infusion. Using this approach, he successfully tolerated CAR-T with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in B-ALL.

[Chronic lymphoid leukemia and renal complication: Report on 10 cases from Marseille over 16 years]. / Néphropathies au cours de la leucémie lymphoïde chronique : à propos d'une étude monocentrique de 10 cas.

INTRODUCTION: Chronic lymphoid leukemia (CLL) is a hematological malignant disease, associated with a clonal B cell proliferation. The incidence is 4400 new cases per year in France. The prevalence increases with age with a median age at diagnostic of 65 years. Renal involvement is rare and estimated at 1.2% of patients with CLL. Renal pathological diagnoses associated with CLL are variable and are not always related to the hematological disease. We report here on cases of patients with CLL who underwent a renal biopsy over the past 16 years in Marseille. METHODS: All cases of renal biopsies performed in patients with CLL between2000 and 2016 in Marseille were included. Pathological analysis was performed by the same experimented pathologist. Data were collected at the time of biopsy and after treatment. RESULTS: Ten patients were included in this study. The reason for renal biopsy was acute kidney injury or the onset of nephrotic syndrome. We report on 4 cases of membranous nephropathy, 1 minimal change disease, 1 cryglobulinemia-related membrano-proliferative glomerulonephritis, 1 light chain amyloidosis, 1 fibrillary glomerulonephritis, 1 interstitial monoclonal infiltration and one case of non-specific tubular lesions. Only one patient was treated before the biopsy, 7 patients received a specific hematological treatment of CLL because of its renal involvement. Renal and hematological responses were variable. CONCLUSION: Renal involvement of CLL is rare and is not mentioned in the Binet classification. Yet, it can be severe, with acute kidney injury or nephrotic syndrome, and can lead to the initiation of a specific treatment. The most frequent presentation this series was secondary MN, which differs from previous series.

Pancytopenia and Hypothyroidism in a Patient With Leukemic Infiltration of the Thyroid as the First Presentation of Acute Lymphoblastic Leukemia.

We report the case of a 16-year-old female patient with hypothyroidism, goiter, and pancytopenia. Biopsy of the thyroid showed leukemic infiltration. After confirmation of the diagnosis of B-lymphoblastic leukemia, treatment was started. Histologic follow-up at day 33 and 79 showed no residual signs of leukemic infiltration. Hypothyroidism persisted despite successful antileukemic treatment. Leukemic infiltration of the thyroid should be considered as a differential diagnosis in patients with hypothyroidism, goiter, and pancytopenia. We suggest that follow-up of thyroid function and histology should be incorporated in the follow-up of rare patients with acute lymphoblastic leukemia with thyroid infiltration.

Asymptomatic Leukemic Optic Nerve Infiltration as Presentation of Acute Lymphoblastic Leukemia Relapse.

The authors report a case of asymptomatic leukemic optic neuropathy as the first sign of acute lymphoblastic leukemia relapse in a 4-year-old boy. Routine ophthalmologic examination showed normal visual acuity and pupillary function in the presence of a tumoral mass covering the left optic disc. The mass resolved with preservation of vision after intrathecal chemotherapy. A routine ophthalmological examination is recommended for all patients with a history of acute lymphoblastic leukemia to exclude optic nerve involvement without systemic symptoms or signs. Vision can be preserved and radiation avoided by using targeted chemotherapy. [J Pediatr Ophthalmol Strabismus. 2017;54:e60-e62.].

Thoracic Complications in Chronic Lymphocytic Leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder worldwide. Although thoracic complications are frequent in CLL, only limited data exist regarding the etiologies of these complications. MATERIALS AND METHODS: A retrospective chart review was performed on all patients admitted to a tertiary care, CLL referral center, with CLL and a respiratory complaint from 2001 through 2013, to categorize pulmonary complaints and diagnoses. RESULTS: There were 277 patients with CLL admitted on 409 occasions with respiratory complaints. The median age was 73 years, with a male to female ratio of 2:1. The majority of patients had a high-risk Rai classification and had received prior treatment. Common presenting symptoms included dyspnea, cough, and sputum production. The most common diagnoses were pneumonia (62.8%), with an identified organism in 44.7%, pleural effusions (31.8%), lung cancer (6.9%), and leukemic infiltrates (5.9%). Invasive procedures were performed 138 times: 70 bronchoscopies, 24 surgical lung biopsies, 10 computed tomography-guided lung biopsies, and 34 thoracenteses. In-hospital mortality was 24.9%. In a multivariable analysis, an elevated blood urea nitrogen level and creatinine, thrombocytopenia, and a presenting symptom of dyspnea correlated significantly with in-hospital mortality. CONCLUSION: Thoracic manifestations in CLL are common among hospitalized patients. Although infectious pneumonia remains most common, unusual or opportunistic infections may be increasing, and direct lung damage owing to CLL itself or to newer biologic agents are being diagnosed with lung tissue sampling. Recognition of these complications will allow earlier diagnosis, which may change management including removal of offending biologic agents or augmentation of treatment for CLL when infiltrative leukemic cells are present.

Laparoscopy Reveals a Diversity of Peritoneal Change in Patients with Long-Term Vintage of Peritoneal Dialysis.

BACKGROUND: Although laparoscopy may provide more detailed morphological and histological information about peritoneal damage, its significance in patients with long vintage of peritoneal dialysis (PD) is not elucidated. METHODS: Findings in 12 patients with PD vintage of 7.3 (5.0-8.4) years who had undergone laparoscopy between 2007 and 2011 were reviewed. Macroscopic (peritoneal change, hypervascular change, adhesion, encapsulation) and histopathological peritoneal findings (interstitial fibrosis, microvascular change, fibrin deposition, inflammatory cell infiltration) were scored and summed as Macro-total score (Macro-TS) and Micro-total score (Micro-TS), respectively. Factors associated with these scores and the relationship between these scores were investigated. RESULTS: Neither Macro-TS nor Micro-TS were related to PD vintage (p = 0.069 and p = 0.769, respectively); moreover, Macro-TS varied from patient to patient regardless of similar PD vintage. However, Macro-TS showed a significant association with duration of acidic dialysate (p = 0.003). CONCLUSION: Macroscopic and microscopic findings via laparoscopy may help the assessment of peritoneal damage in patients with long PD vintage.

Erythrodermic Leukemia Cutis in a Patient With Pre-B-Cell Acute Lymphoblastic Leukemia.

The clinical differential diagnosis of erythroderma is extensive and includes both benign and malignant causes. The authors present an exceptional case of erythroderma secondary to pre-B-cell lymphoblastic leukemia cutis, with diagnostic findings on biopsy.

Bilateral peripheral facial palsy and mastoid infiltration as symptoms of relapsed acute myeloid leukemia.

BACKGROUND: Although Bell's palsy (BP) is the most common cause of peripheral facial palsy (PFP), other etiologies merit investigation. CASE REPORT: A 60-year-old female patient presented with recurrent bilateral PFP. Although the patient had a history of acute myeloid leukemia (AML), she had initially been diagnosed with BP-related PFP and had been treated accordingly. When the PFP recurred, additional diagnostic tests were performed. The resulting immunohistochemical profile included CD3 positivity in a few reactive T lymphocytes; positivity for myeloperoxidase in atypical cells; and focal positivity for CD34 and proto-oncogene c-kit proteins in neoplastic cells, thus confirming the suspicion of mastoid infiltration caused by relapsed AML. CONCLUSION: In patients with neoplastic disease, a finding of PFP calls for extensive investigation in order to rule out the involvement of the temporal bone.

Extramedullary disease in APL: a real phenomenon to contend with or not?

In the last 2 decades an increasing number of patients reported with extramedullary involvement among relapsed acute promyelocytic leukemia (APL) patients. Several investigators related this phenomenon to the relatively new treatment of all-trans-retinoic-acid (ATRA). In this review article we will examine what has been reported in the medical literature on extramedullary disease in APL: the common sites to be involved, the clinical risk factors to its development, the role of ATRA and arsenic tri-oxide and the recommended treatment.

Respiratory events at the earliest phase of acute myeloid leukemia.

Acute myeloid leukemia (AML) can result in acute respiratory failure (ARF) during the first days, requiring intensive care unit (ICU) admission in half the cases. We describe three leukemia-specific syndromes responsible for ARF: leukostasis, pulmonary leukemic infiltration (PLI) and acute lysis pneumopathy (ALP). We retrospectively analyzed clinical and laboratory data from 114 patients admitted to a medical ICU within 10 days after a diagnosis of AML. Respiratory events (REs) occurred in 95 patients and were leukemia-specific in 58 patients (61%). Day-28 mortality was 34.5% in patients with leukemia-specific REs (leukostasis, 41%; PLI, 23%; and ALP, 31%) and 48.6% in patients with other REs. By multivariate analysis, independent risk factors for death were age > 50 (odds ratio, 13; 95% confidence interval, 3-51), Eastern Cooperative Oncology Group (ECOG) status ≥ 2 (5.4; 1.8-17) and need for invasive mechanical ventilation (19; 5-75). Dexamethasone therapy was protective (0.26; 0.09-0.8), suggesting a role as a preventive treatment in patients with AML-related non-infectious pulmonary involvement.

The combined treatment of Copaxone and Salirasib attenuates experimental autoimmune encephalomyelitis (EAE) in mice.

EAE is a common animal model for multiple sclerosis (MS). Immunomodulatory treatments such as glatiramer acetate (GA, Copaxone) are beneficial in EAE but are not universally effective in the clinic. The Ras inhibitor farnesylthiosalycylic acid (FTS, Salirasib), efficiently ameliorate EAE as well. Here we demonstrate a synergistic beneficial effect of the combined GA and FTS treatment on EAE; 22.5% of the combined-treatment mice developed disease compared to 87.5%, 77.5% and 82.5% of mice treated with vehicle, GA and FTS, respectively, results supported by MRI, histological, immunological and biochemical data. Such a combined treatment may improve clinical outcome in MS patients.