Renal Leukemic Infiltration Overlapping Acute Focal Bacterial Nephritis during Myelodysplastic Syndrome: An Autopsy Case Report.

Renal leukemic infiltration is uncommon in myeloid neoplasms, including myelodysplastic syndromes (MDS). A 76-year-old male patient was admitted to our hospital with complaints of fever and dyspnea. He was diagnosed with MDS with multilineage dysplasia and acute focal bacterial nephritis (AFBN) based on clinical, laboratory, and radiological investigations. Antibiotic treatment temporarily improved his condition, but the radiological image of AFBN remained. His condition gradually deteriorated into multiple organ failure, and he unfortunately died on the 31st day of hospitalization. Autopsy findings revealed significantly increased p53-positive blasts in the bone marrow and renal parenchyma overlapping AFBN, suggesting leukemic transformation and renal infiltration. This case emphasizes the need to review the diagnosis when antibiotic treatment is ineffective in MDS patients with AFBN.

Isolated blast crisis relapse in the central nervous system of a patient treating for a chronic myelogenous leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome t (9;22) and the BCR-ABL fusion gene. The condition is relatively rare, accounting for 2.0% to 3.0% of childhood leukemia cases. CML has historically been a triphasic disease. Most patients are diagnosed in chronic phase. Without treatment, it inevitably progresses into a more aggressive accelerated phase and blast crisis. Some proportion of CML cases of blastic transformation develop an extramedullary disease that involves rarely central nervous system. This report describe an extremely rare case of 13-year-old girl with CML and extramedullary blast crisis in the central nervous system. Treatment options and monitoring of disease response are discussed.

New attempts for central nervous infiltration of pediatric acute lymphoblastic leukemia.

The cure rate of acute lymphoblastic leukemia (ALL), the commonest childhood cancer, has been sharply improved and reached almost 90% ever since the central nervous system (CNS)-directed therapy proposed in the 1960s. However, relapse, particularly in the central nervous system (CNS), is still a common cause of treatment failure. Up to now, the classic CNS-directed treatment for CNS leukemia (CNSL) has been aslant from cranial radiation to high-dose system chemotherapy plus intrathecal (IT) chemotherapy for the serious side effects of cranial radiation. The neurotoxic effects of chemotherapy and IT chemotherapy have been reported in recent years as well. For better prevention and treatment of CNSL, plenty of studies have tried to improve the detection sensitivity for CNSL and prevent CNSL from happening by targeting cytokines and chemokines which could be key factors for the traveling of ALL cells into the CNS. Other studies also have aimed to completely kill ALL cells (including dormant cells) in the CNS by promoting the entering of chemotherapy drugs into the CNS or targeting the components of the CNS niche which could be in favor of the survival of ALL cells in CNS. The aim of this review is to discuss the imperfection of current diagnostic methods and treatments for CNSL, as well as new attempts which could be significant for better elimination of CNSL.

Intravitreal Methotrexate for Iris and Ciliary Body Relapse in Acute Lymphoblastic Leukemia.

The authors report a rare unilateral iris and ciliary body relapse in acute lymphoblastic leukemia. Ophthalmologic examination showed reduced visual acuity, pseudohypopyon, and iris irregularity. Ultrasound biomicroscopy and aqueous humor cytology confirmed leukemic infiltration. Lesions were treated with intravitreal methotrexate, which has not been described previously for acute lymphoblastic leukemia. [J Pediatr Ophthalmol Strabismus. 2018;55:e16-e19.].

Cutaneous herald: leukaemia cutis as presenting manifestation of relapse in acute promyelocytic leukaemia.

Leukaemia cutis or cutaneous infiltration of neoplastic myeloid or lymphoid cells is usually seen in the acute myelomonocytic and acute monocytic variants of acute myeloid leukaemia. Here, we report a case of acute promyelocytic leukaemia who achieved remission, presenting with skin lesions, the biopsy of which revealed leukaemia cutis, heralding the relapse of the disease. After establishing the diagnosis with bone marrow analysis, the patient was started on daunorubicin chemotherapy along with arsenic trioxide and all-trans retinoic acid. Afterwards, the skin lesions resolved, and the patient is planned for consolidation with bone marrow transplantation.

Gingival leukemic infiltration as the first manifestation of acute myeloid leukemia.

Leukemic infiltration of the gingival tissue associated or not with gingival enlargement may be the first manifestation of acute leukemia, despite being rarely reported in the literature. A 10-year-old female patient presented with a 1-month history of an asymptomatic, firm, and pinkish-red generalized gingival overgrowth. There was no bone resorption. Incisional biopsy of the gingival tissue was performed, with histopathological examination revealing a diffuse and hypercellular infiltration of monocytoid cells. The patient was referred to a hematologist and underwent a bone marrow biopsy, which led to a conclusive diagnosis of acute myeloid leukemia. The patient was treated with chemotherapy and we observed regression of gingival enlargement after 4 weeks from the initial therapy.

Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor.

In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite nondetectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse-free survival, indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae, including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia-cell entry into the CNS need to be understood to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies. In this study, we analyzed leukemia-cell entry into the CNS using a primograft ALL mouse model. We found that primary ALL cells transplanted onto nonobese diabetic/severe combined immunodeficiency mice faithfully recapitulated clinical and pathological features of meningeal infiltration seen in patients with ALL. ALL cells that had entered the CNS and were infiltrating the meninges were characterized by high expression of vascular endothelial growth factor A (VEGF). Although cellular viability, growth, proliferation, and survival of ALL cells were found to be independent of VEGF, transendothelial migration through CNS microvascular endothelial cells was regulated by VEGF. The importance of VEGF produced by ALL cells in mediating leukemia-cell entry into the CNS and leptomeningeal infiltration was further demonstrated by specific reduction of CNS leukemia on in vivo VEGF capture by the anti-VEGF antibody bevacizumab. Thus, we identified a mechanism of ALL-cell entry into the CNS, which by targeting VEGF signaling may serve as a novel strategy to control CNS leukemia in patients, replacing conventional CNS-toxic treatment.

Dasatinib induces autophagy in mice with Bcr-Abl-positive leukemia.

Dasatinib, a second-generation tyrosine kinase inhibitor, is a highly effective treatment for Bcr-Abl-positive leukemia. However, the mechanism by which dasatinib induces cell death is unclear, particularly in vivo. Autophagy is a lysosomal degradation mechanism essential for cell survival and differentiation. Autophagy also protects cells from the effects of drugs, including those used to treat leukemia. Here, we report that dasatinib induces autophagy in Bcr-Abl-positive leukemia cell lines and further show the induction of autophagy in an immunodeficient mouse model of human Bcr-Abl-positive leukemia with central nervous system (CNS) infiltration. Autophagy was induced in bone marrow (BM) as well as cerebrospinal fluid (CSF). This study is the first to show that autophagy induction is one of the mechanisms underlying cell death in leukemic cells that infiltrate the CNS. Thus, autophagy may represent a novel therapeutic target for the treatment of Bcr-Abl leukemia with CNS infiltration.

Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission. / Infiltración leucémica y retinitis por citomegalovirus en paciente con leucemia linfoblástica aguda tipo T en remisión completa.

CLINICAL CASE: A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. DISCUSSION: Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases.

Cutaneous leukemic infiltration following varicella - a case of Wolf's isotopic response

Abstract Wolf's isotopic response designates the appearance of two subsequent unrelated dermatoses in the same anatomic location. We report the case of a 51-year-old man with a medical history of chronic lymphocytic leukemia without known extra-hematopoietic involvement. The patient developed a disseminated papulo-vesiculous eruption, diagnosed as varicella. Few days after recovering, an erythematous and violaceous papular dermatosis with histopathological examination compatible with leukemic infiltration appeared on the scars of previous herpetic lesions. Complete remission was obtained under systemic corticotherapy, without cutaneous recurrence or blastic transformation. Wolf's isotopic response is attributed to a localized immunologic imbalance following a certain stimulus. In this patient, herpetic infection acted as a local spur for inaugural cutaneous leukemic infiltration, with no impact on the prognosis for the underlying disease.

The immunomodulatory effect of laquinimod in CNS autoimmunity is mediated by the aryl hydrocarbon receptor.

Though several functional properties of laquinimod have been identified, our understanding of the underlying mechanisms is still incomplete. Since the compound elicits similar immunomodulatory effects to ligands of the aryl hydrocarbon receptor (AhR), we compared the efficacy of laquinimod in experimental autoimmune encephalomyelitis (EAE)-afflicted wild-type and AhR-deficient mice. Laquinimod failed to ameliorate clinical symptoms and leukocyte infiltration in AhR-deficient mice; however, treatment exerted neuroprotection by elevation of brain-derived neurotrophic factor (BDNF) independent of genetic profile. Thus, our data identify the AhR pathway in these mutant mice as crucial for the immunomodulatory, but not neuroprotective, efficacy of laquinimod in EAE.