Leukemic Infiltration Research Articles

Sudden Hearing Loss as the Initial Manifestation of Chronic Myeloid Leukemia

Sudden hearing loss rarely presents as an initial manifestation of a hematologic disorder, although it can result from various factors. A 48-year-old male had sudden hearing loss in both ears. The pure tone audiometry and audiometry brainstem response revealed profound hearing loss in both ears. Further examination indicated an elevated leukocyte count, and a temporal bone magnetic resonance image suggested potential bleeding in the cochlear and labyrinth of both ears. Upon consultation with hematologic oncology, chronic myeloid leukemia was diagnosed. Hearing loss in leukemia patients is attributed to leukemic infiltration, hemorrhage, infection, and hyperviscosity. Following treatment using tyrosine kinase inhibitor for chronic myeloid leukemia, the leukocyte count was normalized. However, on the 90th day of treatment, both profound hearing loss persisted. We suspect that the cause of sudden hearing loss may be related to hemorrhage in both cochlear and labyrinth. Accurate diagnosis and treatment are essential for preventing complications.

Leukemic occult infiltrative optic neuropathy presenting as optic neuritis: a case report

Isolated ocular relapses of leukemia are rare and typically present as infiltrative lesions of the optic nerve. This report presents a case of an isolated ocular relapse of leukemia in a female patient, characterized by occult infiltrative optic neuropathy. Despite the absence of leukemic cell infiltration on MRI, a 33-year-old female patient presented with optic neuritis, which resolved after intrathecal administration of chemotherapeutic agents. However, due to her non-compliance with the treatment regimen, leukemia progressed to infiltrative optic neuropathy. She refused radiation therapy, and while intrathecal injections provided temporary stabilization, they were insufficient for sustained disease control. This case uniquely documents the extended progression of an isolated ocular relapse of leukemia, evolving from an occult infiltrative lesion initially presenting as optic neuritis to a more pronounced infiltrative lesion. It suggests that leukemic optic nerve infiltration can occur in patients with leukemia even in the absence of MRI-detectable abnormalities. Radiation therapy emerges as a critical modality in the management of infiltrative lesions of the optic nerve.

Diagnosis of leukemic lung infiltration mimicking fungal infection by transbronchial lung cryobiopsy: the first case report

BackgroundWe here report the first case of leukemic lung infiltration diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the leukemic cells infiltrated tissues. TBLC is generally considered a superior diagnostic method compared to transbronchial lung forceps biopsy (TBLB) because it utilizes cryotechnology to obtain larger specimens, increasing the likelihood of capturing tissues infiltrated with leukemic cells.Case presentationA 69-year-old male patient with acute myeloid leukemia presented with a fever. His initial chest CT scans revealed consolidative lesions, raising suspicion of fungal infection such as angioinvasive aspergillosis or mucormycosis. TBLC and TBLB were conducted to achieve a precise diagnosis, and eventually, leukemic lung infiltration was identified exclusively in the tissues obtained from TBLC. Two cycles of chemotherapy was administrated to patient, showing improvements in symptoms and chest CT findings.ConclusionsTBLC has greater potential as a differential diagnostic method for pulmonary lesions than TBLB in leukemia patients facing therapeutic challenges due to its higher diagnostic yield.

RWC Update: Two Dropped IOLs, One Rigid IOL in Sulcus and Choroidal Detachment; Is AI Ready for the Clinical Retina Practice?; Pseudopapilledema From Leukemic Optic Nerve Infiltration.

RWC Update: Two Dropped IOLs, One Rigid IOL in Sulcus and Choroidal Detachment; Is AI Ready for the Clinical Retina Practice?; Pseudopapilledema From Leukemic Optic Nerve Infiltration.

Central nervous system complications during treatment in childhood acute leukemia.

Central nervous system (CNS) complications can be seen in patients with leukemia, depending on the disease itself and the chemotherapeutic agents used. This study focused on CNS complications during treatment in children with acute leukemia in a single pediatric institution. CNS complications were evaluated retrospectively in 115 patients with ALL and AML. Patients with CNS leukemia infiltration at the time of diagnosis or during a neurological event, late-onset encephalopathy, peripheral neuropathy, or a previous history of neurological abnormalities were excluded from the study. A total of 115 children's clinical records with acute leukemia over a four-year period were reviewed. Acute CNS complications developed in 23.1% of acute myeloid leukemia (AML) patients and in 13.5% of acute lymphoblastic leukemia (ALL) patients. CNS complications developed most frequently during the induction phase of the treatment (66.7%). Seizures were the most common symptom (9 patients, 50%), followed by hemiparesis (4 patients, 22.2%) and headache (4 patients, 22.2%). Six patients (33.3%) had chemotherapy-induced toxic leukoencephalopathy, two (11.1%) had Wernicke's encephalopathy, and one patient (5.6%) each had sinus vein thrombosis, posterior reversible encephalopathy syndrome, and CNS infection. Sequelae occurred in three patients (16.7%), and only one patient (5.6%) died due to a CNS complication. Awide variety of symptoms can be observed in childhood leukemia, depending on the disease itself, the chemotherapeutic agents used and a lot of other conditions such as nutritional problems. Our research shows that several CNS complications might manifest with similar symptoms; differentiated diagnosis between the underlying etiological reasons can be made by neuroimaging.

Severe Leukemic Retinopathy due to Acute Lymphoblastic leukemia

Leukaemia is a myeloproliferative disorder which commonly affects the eye. The retina is most commonly affected by leukaemia. Both acute and chronic leukaemia can develop retinopathy. Patients can develop anaemia and thrombocytopenia. The ophthalmic features include white-centred retinal haemorrhages (Roth spot), cotton wool spots, macular haemorrhages and vitreous haemorrhages. CNS involvement through the optic nerve can cause papillo-oedema and cranial nerve palsy. Opportunistic infection can occur after chemotherapy. A young female patient was diagnosed with Acute Lymphoblastic leukaemia (ALL); she presented with pain and blurred vision in both her eyes. In coloured fundus photograph (CFP) shows dilated, tortuous blood vessels and grey-white streaks along vessels due to perivascular infiltrate. Large whitish opacity all over the fundus. Optic nerve infiltration is also present. Vascular occlusion like CRVO occurs due to hyperviscosity. OCT shows leukaemic infiltration of the retina, causing detachment. The modalities of the Management of leukaemia involve chemotherapy, immunotherapy or radiotherapy, but the Management of leukaemic retinopathy is symptomatic. ALL is treated with vincristine, prednisolone and L-asparagine. Eye treatment was done by intravitreal injection of methotrexate. Patients with acute lymphoblastic leukaemia (ALL) may be asymptomatic and develop vision loss (VL). CBMJ 2024 July: vol. 13 no. 02 P: 277-281

Ophthalmic Manifestations of Leukemia and Their Management

Patients with leukemia often have ophthalmic manifestations. These occur either from direct infiltrations of neoplastic cells or from indirect or secondary causes. Nearly all ocular structures can be affected by leukemia. Sometimes, ophthalmic involvement can be the first sign of disease relapse. This review article aims to highlight different ocular manifestations of leukemia along with treatment. It involves studying the available material in textbooks, printed and online journals. As there is high prevalence of ocular findings in leukemia, it can be a standard practice that all leukemic patients should have screening by ocular examination. Awareness of the clinical spectrum of leukemic infiltration of ocular region is essential for rapid diagnosis, prompt initiation of treatment and better outcome. If prompt diagnosis and treatment can be done, worsening of vision may be minimized or prevented. Mugda Med Coll J. 2024; 7(1): 36-41

Role of MRI in Assessment of Central Nervous System Lesions and Post Treatment Complications in Pediatric Patents with Leukemia

Abstract Background In terms of pediatric oncology, leukemia is one of the most frequent deadly illnesses. Early CNS problem identification and appropriate therapy were enhanced by MRI. Aim Describe the MRI results brought on by leukemia's involvement in CNS structures and treatment-related CNS side effects, and evaluate their efficacy for early therapy and preventing long-term adverse effects. Patients and Methods A prospective observational study included 52 children with leukemia. All patients undergone MR examination including conventional MRI, MR diffusion imaging and MR venography (MRV). Results Regarding MRI finding of CNS, leukemic infiltration was found in 57.7%, sub volimic changes in mild manner in 50% and about 26% in a moderate manner while absent in 23.1%, PRES was present in 19.2%, venous thrombosis present in 30.8% and post treatment complications were found in 7.7%. Conclusion Diffusion-weighted MRI proved very helpful in the early diagnosis and distinction of various CNS lesions seen in young patients with leukemia and post-treatment CNS sequelae. These techniques included conventional, post- contrast, MR venography, and diffusion-weighted MRI.

Bridging the gap: understanding contemporary autopsies in acute leukemia by comparing ante-mortem and post-mortem profiles

This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009–2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.

Beyond the Marrow: Unveiling Uncommon Sites of ALL Relapse with 18F-FDG PET/CT

AbstractExtramedullary infiltration of acute lymphoblastic leukemia/lymphoma (ALL) to genital organs is extremely rare. Here, we present a case report of an asymptomatic 49-year-old female, known case of precursor B-cell ALL, who was incidentally detected with thickened and heterogeneously hyperechoic endometrium on sonography. Contrast magnetic resonance imaging detected large polypoidal enhancing lesions showing intense diffusion restriction occupying the endometrial cavity and similar lesions in the left adnexa, left ovary, and fallopian tube which were suspicious for leukemic infiltration because of the clinical history and atypical appearance of the lesions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was done which revealed intensely metabolically active lesion in the endometrial cavity, left adnexa, omental nodules, retroperitoneal lymph node, pancreatic lesion, and few irregular nodules in the right lower lobe. Biopsy findings confirmed extramedullary relapse of ALL. Hence, 18F-FDG PET/CT can act as a good whole body survey to look for extramedullary sites of relapse.

The FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia

BackgroundAbnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain.MethodsThe FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining.ResultsWe report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice.ConclusionsThese findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.

Chronic lymphocytic leukemia infiltration of a transplanted kidney successfully treated with venetoclax and obinutuzumab: a case report

Chronic lymphocytic leukemia infiltration of a transplanted kidney successfully treated with venetoclax and obinutuzumab: a case report

Bilateral optic nerve infiltration and leukemic retinopathy as initial signs of leukemia relapse with central nervous system involvement in an adult: a case report

BackgroundWe describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement.Case presentationA 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased.ConclusionsTo the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Acute Kidney Injury Secondary to Leukemic Infiltration of the Kidneys in M3 Acute Myeloid Leukemia

Acute Kidney Injury Secondary to Leukemic Infiltration of the Kidneys in M3 Acute Myeloid Leukemia

A Case of Rhegmatogenous Retinal Detachment in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by uncontrolled proliferation of granulocytes, caused the BCR-ABL1 fusion gene. While ocular manifestations of CML are rare, the presentations can range from asymptomatic to sudden vision loss. CML associated ocular findings that have been reported include retinal hemorrhages, leukemic infiltrates, and optic disc edema, but a rhegmatogenous retinal detachment (RRD) in the setting of CML has not been described. Case report. A 21-year-old man presented with intermittent vision loss in his right eye, tinnitus in the right ear, and abdominal distension. Work up revealed significant leukocytosis, splenomegaly, and a positive BCR-ABL1 mutation. He was diagnosed with CML and started on systemic therapy. Exam of the right eye revealed a large intraocular mass. After two weeks of systemic treatment, the large elevation in the right eye had improved, allowing visualization of diffuse subretinal whitening. At follow up, an RRD secondary to an atrophic hole in an area of prior subretinal infiltrates were noted. He underwent repair with a scleral buckle. Postoperative course was complicated by redetachment with proliferative vitreoretinopathy, which led to an unrepairable detachment, despite multiple surgeries with silicone oil tamponade. Ocular findings related to CML are rare, with the lowest incidence when compared to other leukemias, and are associated with worse outcomes. Posterior segment findings include intraretinal hemorrhages, Roth spots, and retinal infiltrates. This unique case describes an RRD in CML retinopathy with an aggressive course and poor anatomical result.

Ultraviolet Light-Emitting Diode Radiation Kills Leukemia Cells Without Affecting Hematopoiesis of Hematopoietic Stem Cells in Mice.

The eradication of leukemia cells while sparing hematopoietic stem cells in the graft before autologous hematopoietic stem cell transplant is critical to prevention of leukemia relapse. Proliferating cells have been shown to be more prone to apoptosis than differentiated cells in response to ultraviolet radiation; however, whether leukemia cells are more sensitive to ultraviolet LED radiation than hematopoietic stem cells remains unclear. We compared the in vitro responses between murine leukemia L1210 cells and murine hematopoietic stem cells to 280-nm ultraviolet LED radiation. We also investigated the effects of ultraviolet LED radiation on the tumorigenic and metastatic capacity of L1210 cells and hematopoietic stem cell hematopoiesis in a mouse model of hematopoietic stem cell transplant. L1210 cells were more sensitive to ultraviolet LED radiation than hematopoietic stem cells in vitro, as evidenced by significantly reduced colony formation rates and cell proliferation rates, along with remarkably increased apoptosis rates in L1210 cells. Compared with corresponding unirradiated cells, ultraviolet LED-irradiated L1210 cells failed to generate palpable tumors in mice, whereas ultraviolet LED-irradiated bone marrow cells restored hematopoiesis in vivo. Furthermore, transplant with an irradiated mixture of L1210 cells and bone marrow cells showed later onset of leukemia, milder leukemic infiltration, and prolonged survival in mice, compared with unirradiated cell transplant. Our results suggest that ultraviolet LED radiation can suppress the proliferative and tumorigenic abilities of leukemia cells without reducing the hematopoietic reconstitution capacity of hematopoietic stem cells, serving as a promising approach to kill leukemia cells in autograft before autologous hematopoietic stem cell transplant.

Organomegalies as a predictive indicator of leukemia cutis in patients with acute myeloid leukemia.

Leukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC. We conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses. The study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC). AML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.

Uncommon bilateral orbital lesion in leukemic patient: is it cutis leukemia, celullitis or both?

Introduction : Acute Myeloblastic Leukemia can infiltrate any parts of the body including the orbit and periocular area. This article was aimed to report uncommon sign of cutis leukemia representing as orbital cellulitis.
 Case Illustration : Male, 35 yo with chief complained progressive lesion in his bilateral upper and lower eyelid since 4 days before admission. He felt pain and stingy sensation around lesion. There was history of toothache. He was diagnosed with acute myeloblastic leukemia since 2 month before. Ophthalmology examination showed his visual acuity was 6/6 in both eyes with good ocular motility.His bilateral upper and lower eyelid were edematous and spasm with multiple vesicles, papule and pustule. Conjunctival injection was found in both eyes. The reminder of ophthalmology examination was unremarkable. There were other hyperemic nodules in left mandibulae and right mastoid bone. Laboratory examination showed increased leukocyte, procalcitonin and C-Reactive Protein level. Orbital CT scan revealed edema in cutis and subcutis area in both superior and inferior bilateral palpebra. Board spectrum and anaerobe antibiotic along with steroid were administered intravenously. Biopsy was performed. After two weeks medication, lesion around both palpebra was decreased. Unfortunately, because of his poor systemic condition, he was readministered to our hospital and hospitalized in ICU. He was passed away after 8 days of hospitalization.
 Discussion : Male patient is more likely to develop orbital infiltration of leukemia, and it necessitates significant morbidity and mortality condition.
 Conclusion : Leukemia with orbital invasion should bring more awareness from both ophthalmologist and hematooncologist as it indicates more mortality and morbidity.

A murine model to evaluate immunotherapy effectiveness for human Fanconi anemia-mutated acute myeloid leukemia.

Fanconi anemia (FA)-mutated acute myeloid leukemia (AML) is a secondary AML with very poor prognosis and limited therapeutic options due to increased sensitivity to DNA-damaging agents. PD-1 immune checkpoint inhibitors upregulate T-cell killing of cancer cells and is a class of promising treatment for FA-AML. Here, we developed a novel FA-AML murine model that allows the study of human AML with a humanized immune system in order to investigate immunotherapeutic treatments in vivo. FA-AML1 cells and non-FA-mutated Kasumi-1 cells were injected into 8-10 week old NSG mice. Once leukemic engraftment was confirmed by HLA-DR expression in the peripheral blood, human peripheral blood mononuclear cells (hPBMCs) were injected into the mice. One week post-hPBMCs injection, Nivolumab (PD-1 inhibitor) or PBS vehicle control was administered to the mice bi-weekly. In our Nivolumab treated mice, FA-AML1, but not Kasumi-1-engrafted mice, had significantly prolonged overall survival. Both FA-AML1 and Kasumi-1 engrafted mice had decreased spleen weights. Higher leukemic infiltration into vital organs was observed in FA-AML1 engrafted mice compared to Kasumi-1 engrafted mice. In conclusion, our novel humanized murine model of FA-mutated AML is an attractive tool for supporting further studies and clinical trials using PD-1 inhibitors to treat FA-mutated AML.

Outcomes for pediatric acute lymphoblastic leukemia patients with intestinal perforation.

Intestinal perforation during acute lymphoblastic leukemia (ALL) treatment in children is rare, but represents a severe complication with possible long-term consequences. In this study, we aim to provide an overview of the epidemiology and clinical characteristics of these patients; analyze surgical pathology findings for possible causes; and determine its impact on patients' therapy, nutritional status, and outcome. Historical chart review from January 2000 to October 2020 of children with ALL and intestinal perforation during therapy diagnosed at a single institution. Data collected included patient demographics, anthropometric measurements, ALL characteristics, diagnosis and surgery of intestinal perforation, pathology, adjustments to treatment plan, and outcome. Of 1840 ALL patients, 13 (0.7%) presented with intestinal perforation during treatment. Perforation occurred during induction phase in 91% of cases. Most patients underwent laparotomy with ostomy creation, and no patient died from the intervention or developed malnutrition. Pathology mainly revealed inflammation at the perforation site. Two samples showed leukemic infiltration and presence of microorganisms. Patients were able to resume ALL therapy in all cases. A total of eight patients (73%) were in first remission at last follow-up, with a median follow-up time of 42months (interquartile range=42). Early surgical intervention is a successful treatment approach for intestinal perforation in ALL patients. There is a clear predilection for induction phase in the occurrence of intestinal perforation in ALL patients. No specific cause was identified. Patients can receive bridging chemotherapy during surgical recovery and proceed with their treatment without apparent impact on outcome.