The Diagnostic Value of 18F-FDG PET/CT Bone Marrow Uptake Pattern in Detecting Bone Marrow Involvement in Pediatric Neuroblastoma Patients

Objectives. To explore the diagnostic value of 18F-FDG PET/CT bone marrow uptake pattern (BMUP) in detecting bone marrow involvement (BMI) in pediatric neuroblastoma (NB) patients. Methods. Ninety-eight NB patients were enrolled in BMI analysis. Four patterns of bone marrow uptake were categorized based on pretreatment cF-FDG PET/CT images. Some crucial inspection indexes and 18F-FDG PET/CT metabolic parameters were analyzed. The BMUP was divided into BMUP1, BMUP2, BMUP3, and BMUP4. Paired-like homeobox 2b (PHOX2B) of bone marrow and blood, bone marrow biopsy (BMB) result, and 18F-FDG PET/CT were compared to detect BMI. All patients were followed up for at least six months. Results. BMUP had excellent consistency among different physicians. Kappa coefficients of two residents and two attending physicians and between the resident and attending physician, were 0.857, 0.891, and 0.845, respectively. The optimal cut-off value of SUVmax-Bone/Liver was 2.08 to diagnose BMI for BMUP3 patients, and the area under curve (AUC) was 0.873. AUC of PHOX2B of bone marrow (PHOX2B of BM), PHOX2B of blood, BMB, and 18F-FDG PET/CT were 0.916, 0.811, 0.806, and 0.904, respectively. There was no significant difference between PHOX2B of BM and PET/CT. Positive predictive value, negative predictive value, sensitivity, and specificity in diagnosis of BMI were 92.9%, 92.9%, 97.0%, and 83.9% for PET/CT and 96.7%, 80.6%, 89.6%, and 93.5% for PHOX2B of BM, respectively. Conclusions. BMUP of pretreatment 18F-FDG PET/CT is a simple and practical method, which has a relatively high diagnostic efficiency in detecting BMI and might decrease unnecessary invasive inspections in some pediatric NB patients.

FDG PET/CT versus Bone Marrow Biopsy for Diagnosis of Bone Marrow Involvement in Non-Hodgkin Lymphoma: A Systematic Review

The management of non-Hodgkin lymphoma (NHL) patients requires the identification of bone marrow involvement (BMI) using a bone marrow biopsy (BMB), as recommended by international guidelines. Multiple studies have shown that [18F]FDG positron emission tomography, combined with computed tomography (PET/CT), may provide important information and may detect BMI, but there is still an ongoing debate as to whether it is sensitive enough for NHL patients in order to replace or be used as a complimentary method to BMB. The objective of this article is to systematically review published studies on the performance of [18F]FDG PET/CT in detecting BMI compared to the BMB for NHL patients. A population, intervention, comparison, and outcome (PICO) search in PubMed and Scopus databases (until 1 November 2021) was performed. A total of 41 studies, comprising 6147 NHL patients, were found to be eligible and were included in the analysis conducted in this systematic review. The sensitivity and specificity for identifying BMI in NHL patients were 73% and 90% for [18F]FDG PET/CT and 56% and 100% for BMB. For aggressive NHL, the sensitivity and specificity to assess the BMI for the [18F]FDG PET/CT was 77% and 94%, while for the BMB it was 58% and 100%. However, sensitivity and specificity to assess the BMI for indolent NHL for the [18F]FDG PET/CT was 59% and 85%, while for the BMB it was superior, and equal to 94% and 100%. With regard to NHL, a [18F]FDG PET/CT scan can only replace BMB if it is found to be positive and if patients can be categorized as having advanced staged NHL with high certainty. [18F]FDG PET/CT might recover tumors missed by BMB, and is recommended for use as a complimentary method, even in indolent histologic subtypes of NHL.

Follicular Lymphoma

Follicular lymphoma (FL) is one of the most common type of indolent non- Hodgkin’s lymphoma. It originates from germinal center B cells and has characteristic translocation t(11,14) involving immunoglobulin heavy chain gene (chromosome 14q32) and Bcl2 gene (chromosome 18q21) in 90% of patients. FL presents with lymphadenopathy and/or bone marrow involvement. Diagnosis is confirmed by histological examination of lymph nodes. FL is a slow growing tumor with frequent remission and relapses. Follicular lymphoma international prognostic index (FLIPI) and progression of disease within 24 months (POD24) are most important prognostic markers. Early-stage disease is usually treated with radiotherapy. Management of advanced stage depends on disease burden. Patients with advanced stage disease may be observed in case of low burden disease and those with high disease load require treatment with chemo-immunotherapy.

Kết quả điều trị u lympho tế bào B trưởng thành bằng phác đồ LMB 96 tại Bệnh viện Nhi Trung ương

TÓM TẮT Đặt vấn đề: U lympho tế bào B trưởng thành (B - NHL) là bệnh lý ác tính và tiến triển nhanh ở trẻ em. Kết quả điều trị đã được cải thiện đáng kể bằng phác đồ đa hóa chất liều cao. Nghiên cứu này nhằm đánh giá kết quả điều trị bệnh nhân B - NHL bằng phác đồ LMB 96 tại Bệnh viện Nhi Trung ương (BVNTƯ). Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang các bệnh nhân dưới 16 tuổi được chẩn đoán B - NHL dưới 16 tuổi được điều trị tại BVNTƯ từ 01/01/2015 đến thời điểm kết thúc điều trị trước 30/06/2021, không bao gồm các bệnh nhân không theo dõi được. Kết quả: 84 bệnh nhân B - NHL được điều trị theo phác đồ LMB 96 trong thời gian 6 năm. 23 bệnh nhân tử vong (27,4%). Nguyên nhân tử vong chính là do nhiễm trùng nặng liên quan đến giảm bạch cầu hạt độ 4 (11,9%). Xác suất sống toàn bộ (OS) và xác suất sống không bệnh (EFS) 6 năm lần lượt là 69,6% và 63,9%. OS và EFS 6 năm của nhóm bệnh nhân giai đoạn 3 là 77,2% và 76,7%; giai đoạn 4 là 46,4% và 35,7%, thấp hơn giai đoạn 1 và 2 (p = 0). OS và EFS 6 năm của nhóm bệnh nhân có LDH ≥ 1000 UI/ml là 58,2% và 52,6%, thấp hơn nhóm có LDH < 1000 UI/ml (p ≤ 0,05). OS và EFS 6 năm của nhóm có thâm nhiễm tủy xương thấp hơn nhóm không thâm nhiễm tủy xương (p ≤ 0,05). Hội chứng ly giải u gặp ở 10,7% bệnh nhân trước điều trị và 11,9% bệnh nhân sau khi bắt đầu điều trị, xuất hiện chủ yếu trên bệnh nhân có LDH ≥ 1000 UI/ml, thể Burkitt, giai đoạn 3 và 4. Kết luận: Kết quả điều trị bệnh nhân B - NHL theo phác đồ LMB 96 tại BVNTƯ tương đương với các nước đang phát triển nhưng thấp hơn các nước phát triển. Các biện pháp điều trị hỗ trợ cần cải thiện hơn để nâng cao tỉ lệ sống cho bệnh nhân. ABSTRACT OUTCOME OF MATURE B CELL LYMPHOMA TREATED BY LMB 96 PROTOCOL IN VIETNAM NATIONAL CHILDREN’S HOSPITAL Mature B cell lymphoma (B - NHL) is a highly aggressive and fast - growing human disease in children. The outcome of childhood B - NHL treatment has improved steadily through the use of intensive multi -agent chemotherapy regimens. This study aims to reveal the outcome of treatment according to LMB 96 protocol in Vietnam National Children’s Hospital (VNCH). Objective and methods: A descriptive study was carried out in all B - NHL patients under 16 years old that start their treatment in VN CH since 01 January 2015 and end before 30 June 2021, excluding patients can’t follow up. Results: Eighty - four patients were diagnosed with B - NHL, who underwent chemotherapy by the LMB96 protocol and followed up in 6 years. Twenty - three patients (27.4%) died. The main cause of death was severe sepsis related to grade IV neutropenia in 11.9% of the patients. The 6 years OS and EFS were 69.6% and 63.9%, respectively, for the whole groups of patients. The 6 years OS and EFS were 77.2% and 76.7% at stage III; 46.4% and 35.7% at stage 4, lower than at stage Iand II (p = 0). The 6 years OS and EFS in the group with LDH ≥ 1000 UI/ml were 58.2% and 52.6%, worse than in the group with LDH < 1000 UI/ml (p ≤ 0,05). OS and EFS in the non - bone marrow involvement group were much lower than the bone marrow involvement patients (p ≤ 0,05). Tumor lysis syndrome was seen in 10.7% of the patients before starting chemotherapy and 11.9% of those after the beginning of treatment, mostly occurs in patients with LDH ≥ 1000 UI/ml, Burkitt lymphoma, stage 3 and 4. Conclusion: The outcome of treatment mature B cell lymphoma in VNCH according to LMB 96 protocol was similar to other results in developing countries but lower than those in developed countries.Supportive care needs to improve to increase the survival rate. Keywords: Mature B cell lymphoma, outcome, Vietnam National Children’s Hospital

The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis

Patients with anaplastic large cell lymphoma (ALCL) rarely develop a leukemic phase of the disease. The reported leukemic ALCL cases are almost all ALK-positive, which are frequently associated with small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Rare leukemic ALK-negative ALCL cases have been reported. In the present study, we investigated the clinical and pathologic features and outcomes of nine patients with leukemic ALK-negative ALCL and compared these features with 39 patients without leukemic disease. Compared with the non-leukemic ALK-negative ALCL group, patients with leukemic disease more often had absolute lymphocytosis (50% vs. 0%, p = 0.008), thrombocytopenia (60% vs. 11%, p = 0.03), bone marrow involvement (50% vs. 14%, p = 0.04), and CD7 positivity (71% vs. 19%, p = 0.02). Four of five (80%) patients with leukemic ALK-negative ALCL had a complex karyotype, which was significantly higher than that of the patients in the non-leukemic group. A fluorescence in situ hybridization for TP53 was performed on six leukemic ALK-negative ALCL cases and all (100%) had TP53 deletion. There were no significant differences in the other clinicopathologic features, treatment, and complete remission rates between patients in the leukemic versus non-leukemic group (all p > 0.05). The median follow-up of this cohort was 18 months with a range of 0.3–140 months. Eight of nine (90%) patients with leukemic ALK-negative ALCL died, and their overall survival was significantly shorter than that of the patients with non-leukemic disease (median 15.5 vs. 60 months, p = 0.001). In conclusion, we show that the leukemic phase of ALK-negative ALCL is associated with high-risk biologic features and, in particular, a complex karyotype and TP53 deletion. Compared with the non-leukemic ALK-negative ALCL patients, the patients with a leukemic phase of disease have poorer survival and may require more aggressive treatment.

Flow cytometry of bone marrow aspirates from neuroblastoma patients is a highly sensitive technique for quantification of low-level neuroblastoma

Background: Bone marrow involvement is an important aspect of determining staging of disease and treatment for childhood neuroblastoma. Current standard of care relies on microscopic examination of bone marrow trephine biopsies and aspirates respectively, to define involvement. Flow cytometric analysis of disaggregated tumour cells, when using a panel of neuroblastoma specific markers, allows for potentially less subjective determination of the presence of tumour cells. Methods: A retrospective review of sequential bone marrow trephine biopsies and aspirates, performed at Great Ormond Street Hospital, London, between the years 2015 and 2018, was performed to assess whether the addition of flow cytometric analysis to these standard of care methods provided concordant or additional information. Results: There was good concurrence between all three methods for negative results 216/302 (72%). Positive results had a concordance of 52/86 (61%), comparing samples positive by flow cytometry and positive by either or both cytology and histology. Of the remaining samples, 20/86 (23%) were positive by either or both cytology and histology, but negative by flow cytometry. Whereas 14/86 (16%) of samples were positive only by flow cytometry. Conclusions: Our review highlights the ongoing importance of expert cytological and histological assessment of bone marrow results. Flow cytometry is an objective, quantitative method to assess the level of bone marrow disease in aspirates. In this study, flow cytometry identified low-level residual disease that was not detected by cytology or histology. The clinical significance of this low-level disease warrants further investigation.

Spine Myeloid Sarcoma: A Case Series with Review of Literature

Myeloid sarcoma (MS) is a malignant extramedullary tumor consisting of immature cells of myeloid origin. It may precede, present concurrently or follow acute myeloid leukemia (AML) in de novo case or may also be present and might be the only manifestation of recurrent AML, myelodysplastic syndrome, or chronic myeloid leukemia. It frequently involves skin, orbit, bone, periosteum, lymph nodes, and gastrointestinal tract, soft tissue, central nervous system, and testis. Because of its different localization and symptoms, and the lack of diagnostic algorithm, MS is a real diagnostic challenge particularly in patients without initial bone marrow involvement. The correct diagnosis of MS is important for optimum therapy, which is often delayed because of a high misdiagnosis rate. We reported three cases of MS derived from spine presented with back pain, paraplegia, paraparesis, respectively, and reviewed the relevant literature.