-
Frontiers in Oncology 2024Acute promyelocytic leukemia (APL) is rarely caused by the fusion gene. While APL patients with fusion commonly exhibit diverse hematologic symptoms, the presentation...
BACKGROUND
Acute promyelocytic leukemia (APL) is rarely caused by the fusion gene. While APL patients with fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.
CASE PRESENTATION
A 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic fusion gene, confirming the diagnosis of APL.
CONCLUSION
In the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.
PubMed: 38835381
DOI: 10.3389/fonc.2024.1375737 -
Discover Oncology Jun 2024The treatment of myeloid sarcoma (MS) is challenging and has not markedly improved patient prognosis. The introduction of venetoclax (VEN) has changed the treatment of...
BACKGROUND
The treatment of myeloid sarcoma (MS) is challenging and has not markedly improved patient prognosis. The introduction of venetoclax (VEN) has changed the treatment of MS, and venetoclax-based therapy has been described as very promising in several case reports.
METHODS
In this retrospective study, we analyzed the treatment outcomes of 14 patients with MS treated with venetoclax-based therapy at The First Affiliated Hospital of Xiamen University from January 2020 to October 2023 RESULTS: The cohort consisted of 7 (50%) women and 7 (50%) men with an average age of 37.5 years. Four patients (28.6%) had isolated MS de novo, 2 (14.2%) were diagnosed synchronously with AML, and 8 (57.2%) had isolated extramedullary relapse. The most common sites for MS in our cohort were the skin and lung, followed by the spinal canal, soft tissue, bone and kidney. Five patients were affected at more than three sites. Nine patients received VEN in combination with azacytidine, and 5 patients received VEN in combination with other agents. The median number of venetoclax therapies administered was 2 cycles (range: 1-10 cycles). A response was observed in all patients included in the study, with 8 patients (57.2%) achieving a CR and 3 patients (21.4%) achieving a PR, corresponding to an ORR (including CR and PR) of 78.6%. The median follow-up time for all patients was 13 months (range 1-44 months), and the 1 year OS for all patients was 67.7%.
CONCLUSIONS
Venetoclax-based therapy shows excellent efficacy and safety in MS patients in the "real world" at a single institution, and a corresponding prospective study is needed to verify this conclusion.
PubMed: 38834922
DOI: 10.1007/s12672-024-01068-z -
Oncology Letters Jul 2024Myeloid sarcoma (MS) is a rare extramedullary tumor mass that carries a high risk of progression to acute myeloid leukemia (AML), and patients with MS are commonly...
Myeloid sarcoma (MS) is a rare extramedullary tumor mass that carries a high risk of progression to acute myeloid leukemia (AML), and patients with MS are commonly treated with the AML regimen. However, MS is frequently misdiagnosed due to its lack of clinical specificity. Patients with MS who harbor tumor protein p53 (TP53) mutations and complex karyotypes are considered to have a poorer prognosis. The present study reports a case of lymph node MS with TP53 (V173G)-related myelodysplastic syndrome (MDS). The mass was first considered to be a lymphoma and treated as such. However, following immunohistochemical analysis, which revealed cells positive for CD43, myeloperoxidase and CD117, the patient was later diagnosed with MS combined with MDS. The patient went into complete remission after the first cycle of chemotherapy, and showed a decrease in platelet, red blood cell and white blood cell counts following the second cycle of chemotherapy. After the third chemotherapy, agranulocytosis occurred, leading to refractory pneumonia and eventually death due to respiratory failure. MS with TP53-related MDS has a low incidence rate, a poor prognosis and a short survival time. The clinical manifestations of MS are non-specific and easy to misdiagnose, leading to delayed diagnosis and treatment, and ultimately worsening the prognosis of the patients. Therefore, a lymph node biopsy should be performed as soon as possible for patients with lymph node enlargement, and early treatment should be carried out to prolong the survival period.
PubMed: 38807682
DOI: 10.3892/ol.2024.14458 -
Infection and Drug Resistance 2024Mucormycosis is a fatal invasive fungal infection that commonly affects immunocompromised children. The aim of our study was to investigate the clinical manifestations,...
BACKGROUND
Mucormycosis is a fatal invasive fungal infection that commonly affects immunocompromised children. The aim of our study was to investigate the clinical manifestations, treatments, and prognosis of pediatric patients with mucormycosis.
METHODS
We conducted a retrospective search in Shenzhen Children's Hospital from July 2013 to July 2023 for all patients with mucormycosis. The clinical manifestation, pathogen detection, radiology, treatments, and prognosis were analyzed.
RESULTS
Four cases were identified. Underlying conditions included acute myeloid leukemia with myeloid sarcoma (n = 1), thalassemia (post-allogeneic hematopoietic stem cell transplantation; n = 1), systemic lupus erythematosus (n = 1), and bilateral nephroblastoma (post-bilateral nephrectomy; n = 1). Two patients were disseminated mucormycosis, one case was pulmonary mucormycosis, and one case was cerebral mucormycosis. Fever, cough, and dyspnea were the main clinical symptoms of pulmonary mucormycosis, headache was the main clinical symptom of cerebral mucormycosis. Lung CT findings included consolidation, multiple nodules, halo sign, air crescent sign, and pleural effusion. The contrast-enhanced CT showed pulmonary artery and pulmonary vein occlusions in two patients and pseudoaneurysm in two patients. Amphotericin B formulations were administered as first-line therapy in all cases; in three cases, Triazole was administered in combination with amphotericin B.
CONCLUSION
Mucormycosis is a life-threatening disease involving multiple systems. Aorta pseudoaneurysm is a rare and fatal complication, enhanced CT can assist in diagnosis. Early diagnosis and appropriate therapeutic strategies are needed.
PubMed: 38779351
DOI: 10.2147/IDR.S462725 -
MedRxiv : the Preprint Server For... May 2024HiC sequencing is a DNA-based next-generation sequencing method that preserves the 3D conformation of the genome and has shown promise in detecting genomic...
UNLABELLED
HiC sequencing is a DNA-based next-generation sequencing method that preserves the 3D conformation of the genome and has shown promise in detecting genomic rearrangements in translational research studies. To evaluate HiC as a potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia and sarcoma specimens previously positive for clinically significant genomic rearrangements. Archived specimen types tested included viable and nonviable frozen leukemic cells, as well as formalin-fixed paraffin-embedded (FFPE) tumor tissues. Initially, pediatric acute myeloid leukemia (AML) and alveolar rhabdomyosarcoma (A-RMS) specimens with known genomic rearrangements were subjected to HiC analysis to assess analytical concordance. Subsequently, a discovery cohort consisting of AML and acute lymphoblastic leukemia (ALL) cases with no known genomic rearrangements based on prior clinical diagnostic testing were evaluated to determine whether HiC could detect rearrangements. Using a standard sequencing depth of 50 million raw read-pairs per sample, or approximately 5X raw genomic coverage, 100% concordance was observed between HiC and previous clinical cytogenetic and molecular testing. In the discovery cohort, a clinically relevant gene fusion was detected in 45% of leukemia cases (5/11). This study demonstrates the value of HiC sequencing to medical diagnostic testing as it identified several clinically significant rearrangements, including those that might have been missed by current clinical testing workflows.
KEY POINTS
HiC sequencing is a DNA-based next-generation sequencing method that preserves the 3D conformation of the genome, facilitating detection of genomic rearrangements.HiC was 100% concordant with clinical diagnostic testing workflows for detecting clinically significant genomic rearrangements in pediatric leukemia and rhabdomyosarcoma specimens.HiC detected clinically significant genomic rearrangements not previously detected by prior clinical cytogenetic and molecular testing.HiC performed well with archived non-viable and viable frozen leukemic cell samples, as well as archived formalin-fixed paraffin-embedded tumor tissue specimens.
PubMed: 38765974
DOI: 10.1101/2024.05.10.24306838 -
Journal For Immunotherapy of Cancer May 2024Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and...
BACKGROUND
Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.
METHODS
We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed.
RESULTS
We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy.
CONCLUSIONS
This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect.
TRIAL REGISTRATION NUMBER
ACTRN12613000198729.
Topics: Humans; Melanoma; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Male; Female; Middle Aged; Gangliosides; Adult; Aged; T-Lymphocytes; Treatment Outcome
PubMed: 38754916
DOI: 10.1136/jitc-2023-008659 -
Frontiers in Oncology 2024Osteolytic lesions are infrequently observed in adult patients with acute myeloid leukemia (AML). This report details the case of a 66-year-old male patient who...
Osteolytic lesions are infrequently observed in adult patients with acute myeloid leukemia (AML). This report details the case of a 66-year-old male patient who presented with myeloid sarcoma (MS), osteolytic lesion and pancytopenia. Effective treatments were delayed due to diagnostic challenges and the rapid progression of the disease. It is essential to consider AML in the differential diagnosis when faced with a patient presenting osteolytic lesions and pancytopenia.
PubMed: 38751817
DOI: 10.3389/fonc.2024.1364266 -
Cureus Apr 2024Testicular myeloid sarcoma (TMS) is a challenging pathology often posing diagnostic difficulties due to the poorly differentiated nature of tumor cells at the initial...
Testicular myeloid sarcoma (TMS) is a challenging pathology often posing diagnostic difficulties due to the poorly differentiated nature of tumor cells at the initial presentation. The delay in diagnosis significantly impacts patient life expectancy, emphasizing the need for prompt identification and treatment initiation. In certain cases, the presence of the Fms-like tyrosine kinase () mutation adds complexity to the disease, requiring tailored therapeutic approaches. In this report, we present a unique case of bilateral TMS with tyrosine kinase domain () mutation. The patient exhibited an aggressive clinical course, initially misdiagnosed with orchitis during the initial evaluation. Subsequent reevaluation of the testicular biopsy at a second center led to an accurate diagnosis, highlighting the importance of thorough examination in challenging cases. Given the emerging significance of mutations in myeloid sarcomas, comprehensive testing for all variants is crucial to determine the appropriate treatment modality. This case underscores the need for increased awareness among healthcare professionals regarding the diagnostic nuances and potential genetic variations associated with TMS. Furthermore, the inclusion of tyrosine kinase inhibitors, such as midostaurin or gilteritinib, especially in the presence of mutations, may significantly impact treatment outcomes. This report contributes to the growing body of literature on TMS and highlights the importance of considering mutations in the diagnostic and therapeutic decision-making process for improved patient care.
PubMed: 38738062
DOI: 10.7759/cureus.58140 -
Cureus Apr 2024We report a case of pancreatic myeloid sarcoma (MS), an extremely rare manifestation of acute myeloid leukemia (AML), in a 35-year-old male who presented with epigastric...
We report a case of pancreatic myeloid sarcoma (MS), an extremely rare manifestation of acute myeloid leukemia (AML), in a 35-year-old male who presented with epigastric pain and watery stools. Initial diagnostic testing was inconclusive; however, following an extensive evaluation, endoscopic biopsies suggested AML, which was confirmed by a bone marrow biopsy. Given that few cases are documented in the literature, pancreatic MS without a preexisting hematologic malignancy poses a significant diagnostic challenge.
PubMed: 38725771
DOI: 10.7759/cureus.57880 -
Clinical Case Reports May 2024Myeloid sarcoma (MS) is a rare extramedullary infiltration of acute myeloid leukemia (AML). We present a case of 19-year-old male with AML-M2 who relapse with AML...
Myeloid sarcoma (MS) is a rare extramedullary infiltration of acute myeloid leukemia (AML). We present a case of 19-year-old male with AML-M2 who relapse with AML sarcoma in brain and optic nerve. MS as AML extramedullary relapse had a poor prognosis.
PubMed: 38721563
DOI: 10.1002/ccr3.8861