[Minimal residual disease assessment and progress in multiple myeloma].

With the rapid iteration of multiple myeloma therapeutics over the last two decades, as well as increasing remission rates and depth of remission in patients, traditional methods for monitoring disease response are insufficient to meet the clinical needs of new drugs. Minimal residual disease (MRD) is a more sensitive test for determining the depth of response, and data from multiple clinical trials and meta-analyses show that a negative MRD correlates with a better prognosis than a traditional complete response. MM is at the forefront of MRD evaluation and treatment. MRD detection methods have been continuously updated. The current MRD assessment has three dimensions: bone marrow-based MRD testing, MRD testing based on images of residual metabolic of focal lesions, and peripheral blood-based MRD testing. The various MRD assessment methods complement one another. The goal of this article is to discuss the currently used MRD assays, the progress, and challenges of MRD in MM, and to provide a reference for clinicians to better use the techniques.

Clinical characterization of hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors: a review of published cases.

OBJECTIVE: An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments. METHODS: Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases. RESULTS AND DISCUSSION: Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26-86). The mean time to the onset of symptoms was 10.3 weeks (7 days-14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described. CONCLUSION: HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

Severe Infection Mimicking AML due to Bone Marrow Suppression: a Diagnostic Challenge.

BACKGROUND: Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML). METHODS: We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis. CONCLUSIONS: To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.

Leukemia circulation kinetics revealed through blood exchange method.

Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1-2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

A case report of prostate cancer with leptomeningeal metastasis and bone marrow involvement.

BACKGROUND: Prostate cancer is the second most common cancer in men. Central nervous system (CNS) involvement in prostate cancer which manifests as cerebral, leptomeningeal, or dural involvement is uncommon and occurs late in the course of disease. CASE: A 60-year-old patient with castration resistant prostate cancer (CRPC) presented with headache and fatigue. Evaluation revealed bone marrow and leptomeningeal involvement. The patient treated by whole brain radiotherapy, leuprolide, weekly docetaxel and daily 1000 mg abiraterone. Complete blood count (CBC) and CNS symptoms improved and the patient is alive after 11 months with excellent performance status. CONCLUSION: Leptomeningeal involvement in prostate cancer is rare and is associated with a poor prognosis but the possibility of such event should be considered in patients with new onset progressive CNS symptoms. New treatment strategies such as combination of docetaxel and abiraterone added to androgen deprivation therapy (triplet therapy) might improve outcome in these patients.

Recurrent leishmaniasis infection isolated in the pleural fluid.

We present a rare case of recurrent leishmaniasis infection in a female in her 80s who re-presented with a pleural effusion. The patient was initially investigated as an outpatient for cytopenia and underwent a bone marrow biopsy which subsequently diagnosed visceral leishmaniasis. Following full treatment, and apparent recovery, she re-presented with pleural effusion, hypoalbuminaemia and cytopenia. Leishmania was eventually isolated in a pleural fluid sample obtained on therapeutic drainage, and she was treated for a recurrence at a tertiary infectious disease unit. This interesting and challenging case demonstrates the importance of suspecting leishmaniasis recurrence in previously treated cases and the diagnostic benefit of pleural fluid analysis in the context of suspected leishmaniasis.

The KIR2DL family serves as prognostic biomarkers and correlates with immune infiltrates in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.

Pre-treatment [18F]FDG PET/CT for assessing bone marrow involvement and prognosis in patients with newly diagnosed peripheral T-cell lymphoma.

PURPOSE: To explore the value of [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in assessing bone marrow involvement (BMI) and prognosis in newly diagnosed peripheral T-cell lymphomas (PTCLs) before treatment. METHODS: This retrospective study included 201 eligible PTCLs who received pre-bone marrow biopsy (BMB) and PET/CT. The status of bone marrow (BM) by PET was assessed using a visual examination and a quantitative index (the maximal standardized uptake value [SUVmax] of BM divided by the SUVmax of the liver [M/L]). RESULTS: Totally 148 patients had no evidence of BMI by PET or BMB; BMI was detected by both methods in 16 patients. The sensitivity and specificity of PET/CT for patients with confirmed BMI by BMB were 43.2% and 90.2%, respectively (κ = 0.353). In addition, 25 patients assessed by PET/CT staging (having stage I to II disease) had no evidence of BMI detected by both PET/CT and BMB. Image-guided biopsy was also recommended when PET/CT showed a focal FDG uptake outside the iliac crest. Survival analysis revealed that BMB was significant for overall survival (OS) (P = 0.020) while M/L for both progression free survival (P = 0.002) and OS (P < 0.001). In multivariate analysis, M/L (HR 1.825, 95% CI 1.071-3.110, P = 0.027) was an independent prognostic factor for OS. There were no statistical differences at the genetic level about BMI confirmed by PET or BMB. CONCLUSION: PET/CT has a complementary role in assessing BMI and an ability to predict prognosis in PTCL patients.

Poly-L-lactic acid/gelatin electrospun membrane-loaded bone marrow-derived mesenchymal stem cells attenuate erectile dysfunction caused by cavernous nerve injury.

Radical prostatectomy (RP) can cause neurogenic erectile dysfunction (ED), which negatively affects the quality of life of patients with prostate cancer. Currently, there is a dearth of effective therapeutic strategies. Although stem cell therapy is promising, direct cell transplantation to injured cavernous nerves is constrained by poor cell colonization. In this study, poly-L-lactic acid (PLLA)/gelatin electrospun membranes (PGEM) were fabricated to load bone marrow-derived mesenchymal stem cells (BM-MSCs) as a patch to be placed on injured nerves to alleviate ED. This study aimed to establish a promising and innovative approach to mitigate neurogenic ED post-RP and lay the foundation for modifying surgical procedures. Electrospinning and molecular biotechnology were performed in vitro and in vivo, respectively. It was observed that PGEM enhanced the performance of BM-MSCs and Schwann cells due to their excellent mechanical properties and biocompatibility. The transplanted PGEM and loaded BM-MSCs synergistically improved bilateral cavernous nerve injury-related ED and the corresponding histopathological changes. Nevertheless, transplantation of BM-MSCs alone has been verified to be ineffective. Overall, PGEM can serve as an ideal carrier to supply a more suitable survival environment for BM-MSCs and Schwann cells, thereby promoting the recovery of injured cavernous nerves and erectile function.

The quantitative parameters based on marrow metabolism derived from synthetic MRI: A pilot study of prognostic value in participants with newly diagnosed multiple myeloma.

BACKGROUND: The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. METHODS: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Splenic B-cell lymphoma/leukemia with prominent nucleoli: A three-case series of the newly named old entity and review of literature.

CONTEXT: Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) aka hairy cell leukemia variant (HCL-v) is a rare B-cell chronic lymphoproliferative disorder. The main diagnostic challenge is to differentiate SBLPN from Classical hairy cell leukemia (HCL-c), as the former faces inferior responses to therapies and a poor prognosis. AIMS: The aim is to discuss the clinic-hematological and immunophenotyping findings of three cases of SBLPN. SETTINGS AND DESIGN: This is a retrospective observational study. METHODS AND MATERIAL: From the year 2011 to 2021, flow cytometry of all the cases with HCL diagnosis was reviewed, and three cases with negative or dim CD25 and hematological presentation matching with SBLPN were picked up. STATISTICAL ANALYSIS USED: Descriptive statistics is used. RESULTS: All the cases were male. The age ranges from 43 to 64 years. Median hemoglobin concentration, total leucocyte count, and platelet count were 8.6 g/dL, 6.9 × 109/L, and 53 × 109/L, respectively. The atypical cells were medium to large. All three showed prominent nucleoli. Bone marrow biopsies showed an interstitial pattern of infiltration in all the cases. The hairy cells were positive for CD20, CD11c, and CD103. CD25 was dim positive in one case. Annexin A1 was negative in all three cases. BRAF V600E mutation analysis was done in one case and turned out negative for the mutation. CONCLUSIONS: SBLPN is a rare entity, usually on-flow cytometry CD25 negative. However, in dim CD25-positive cases, BRAFV600E mutational analysis helps in discerning SBLPN diagnosis and differentiating it from HCL-c.

Different evasion strategies in multiple myeloma.

Multiple myeloma is the second most common malignant hematologic malignancy which evolved different strategies for immune escape from the host immune surveillance and drug resistance, including uncontrolled proliferation of malignant plasma cells in the bone marrow, genetic mutations, or deletion of tumor antigens to escape from special targets and so. Therefore, it is a big challenge to efficiently treat multiple myeloma patients. Despite recent applications of immunomodulatory drugs (IMiDS), protease inhibitors (PI), targeted monoclonal antibodies (mAb), and even hematopoietic stem cell transplantation (HSCT), it remains hardly curable. Summarizing the possible evasion strategies can help design specific drugs for multiple myeloma treatment. This review aims to provide an integrative overview of the intrinsic and extrinsic evasion mechanisms as well as recently discovered microbiota utilized by multiple myeloma for immune evasion and drug resistance, hopefully providing a theoretical basis for the rational design of specific immunotherapies or drug combinations to prevent the uncontrolled proliferation of MM, overcome drug resistance and improve patient survival.

Bone marrow-derived mesenchymal stem cells mitigate chronic colitis and enteric neuropathy via anti-inflammatory and anti-oxidative mechanisms.

Current treatments for inflammatory bowel disease (IBD) are often inadequate due to limited efficacy and toxicity, leading to surgical resection in refractory cases. IBD's broad and complex pathogenesis involving the immune system, enteric nervous system, microbiome, and oxidative stress requires more effective therapeutic strategies. In this study, we investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell (BM-MSC) treatments in spontaneous chronic colitis using the Winnie mouse model which closely replicates the presentation and inflammatory profile of ulcerative colitis. The 14-day BM-MSC treatment regimen reduced the severity of colitis, leading to the attenuation of diarrheal symptoms and recovery in body mass. Morphological and histological abnormalities in the colon were also alleviated. Transcriptomic analysis demonstrated that BM-MSC treatment led to alterations in gene expression profiles primarily downregulating genes related to inflammation, including pro-inflammatory cytokines, chemokines and other biomarkers of inflammation. Further evaluation of immune cell populations using immunohistochemistry revealed a reduction in leukocyte infiltration upon BM-MSC treatment. Notably, enteric neuronal gene signatures were the most impacted by BM-MSC treatment, which correlated with the restoration of neuronal density in the myenteric ganglia. Moreover, BM-MSCs exhibited neuroprotective effects against oxidative stress-induced neuronal loss through antioxidant mechanisms, including the reduction of mitochondrial-derived superoxide and attenuation of oxidative stress-induced HMGB1 translocation, potentially relying on MSC-derived SOD1. These findings suggest that BM-MSCs hold promise as a therapeutic intervention to mitigate chronic colitis by exerting anti-inflammatory effects and protecting the enteric nervous system from oxidative stress-induced damage.

Prognostic marker CD27 and its micro-environmental in multiple myeloma.

BACKGROUND: The Cluster of Differentiation 27 (CD27) is aberrantly expressed in multiple myeloma (MM) -derived. This expression facilitates the interaction between tumor and immune cells within TME via the CD27-CD70 pathway, resulting in immune evasion and subsequent tumor progression. The objective of this study is to investigate the correlation between CD27 expression and the prognosis of MM, and to elucidate its potential relationship with the immune microenvironment. METHODS: In this research, CD27 expression in T cells within the 82 newly diagnosed MM microenvironment was assessed via flow cytometry. We then examined the association between CD27 expression levels and patient survival. Subsequent a series of bioinformatics and in vitro experiments were conducted to reveal the role of CD27 in MM. RESULTS: Clinical evidence suggests that elevated CD27 expression in T cells within the bone marrow serves as a negative prognostic marker for MM survival. Data analysis from the GEO database has demonstrated a strong association between MM-derived CD27 and the immune response, as well as the hematopoietic system. Importantly, patients with elevated levels of CD27 expression were also found to have an increased presence of MDSCs and macrophages in the bone marrow microenvironment. Furthermore, the PERK-ATF4 signaling pathway has been implicated in mediating the effects of CD27 in MM. CONCLUSIONS: We revealed that CD27 expression levels serve as an indicative marker for the prognosis of MM patients. The CD27- PERK-ATF4 is a promising target for the treatment of MM.

Lactate acid promotes PD-1+ Tregs accumulation in the bone marrow with high tumor burden of Acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) displayed poor response to programmed death-1 (PD-1) blockade therapy. Regulatory T cells (Tregs) was one of major immunosuppressive components in Tumor microenvironment and plays a vital role in the resistance of immunotherapy. Coinhibitory receptors regulate function of regulatory Tregs and are associated with resistance of PD-1 blockade. However, the coinhibitory receptors expression and differentiated status of Tregs in AML patients remain to be unclear. METHODS: Phenotypic determination of Tregs and CD8+ T cells in bone marrow of healthy donors and AML patients was performed by flow cytometry. Coculture experiments of AML and Tregs in vitro were performed and the concentrations of lactate acid (LA) in the supernatant were examined by ELISA. RESULTS: More Tregs differentiated into effector subsets in AML patients. However, PD-1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression on Tregs were comparable in healthy donors and AML patients. Further analysis showed that PD-1+ and PD-1+TIGIT+Tregs are more abundant in the bone marrow of patients with higher leukemic load. Moreover, PD-1+ Tregs accumulation was associated with higher level of senescent CD4+ T cells and increased frequencies of exhausted CD4+ as well as CD8+ T cells. Notably, neither Tregs nor their effector subsets were decreased among patients in complete remission. PD-1 expression was significantly downregulated in Tregs after achieving complete remission. Mechanistically, both AML cell line (KG-1α) and primary AML blasts produced high concentration of LA. Blockade of LA by lactate transporter inhibitor abrogated the upregulation of PD-1 by AML cells. CONCLUSION: PD-1+ Tregs accumulation in bone marrow in higher leukemic burden setting was linked to lactate acid secreted by AML blasts and decreased after disease remission. Our findings provided a novel insight into Tregs in AML and possible mechanism for resistance of PD-1 blockade in AML.

Validation of Human Bone Marrow-derived Mesenchymal Stem Cells and MCF-7 Breast Cancer Cells Co-culture Using a 3D Perfused Biomimetic Microfluidic Platform.

BACKGROUND/AIM: Microfluidic experimental models allow to study the mutual interrelation between tumor development and the microvasculature avoiding animal use and lacking interspecies differences. This study aimed to develop and characterize a 3D tissue culture model employing a two-compartment microfluidic chip-perfused platform to visualize and quantify human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and MCF-7 breast cancer cell-cell interactions in real time. MATERIALS AND METHODS: MCF-7 cells were implanted in the tumor chamber and hBM-MSCs were injected into microvascular channels. hBM-MSCs culture media was perfused into microvascular compartments. The microfluidic device was microscopically examined weekly for four weeks. RESULTS: VE- and E-cadherin immunofluorescence validated hBM-MSCs differentiation into endothelial cells and MCF-7 cell tumor formation. hBM-MSCs differentiation was highly heterogeneous along the microvascular channels, due to different perfusion flow. hBM-MSCs lining microvascular channels acquired VE-cadherin positive endothelial phenotype and continuously covered microchannels as an endothelium like layer. MCF-7 cells were constantly grown as spheroidal aggregates and later formed a compact area of E-cadherin-positive tumor cells inside tumor compartment. CONCLUSION: Our study provides valuable knowledge on the properties of hBM-MSCs as vasculogenesis-supporting cells when co-cultured with MCF-7 cells on a 3D perfused biomimetic microfluidic device. This newly established model may serve as an experimental platform for testing anti-tumor/anti-angiogenic drugs.

Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

BACKGROUND: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. METHODS: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. RESULTS: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. CONCLUSIONS: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Modeling skeletal dysplasia in Hurler syndrome using patient-derived bone marrow osteoprogenitor cells.

Dysostosis multiplex is a major cause of morbidity in Hurler syndrome (mucopolysaccharidosis type IH [MPS IH], OMIM #607014) because currently available therapies have limited success in its prevention and reversion. Unfortunately, the elucidation of skeletal pathogenesis in MPS IH is limited by difficulties in obtaining bone specimens from pediatric patients and poor reproducibility in animal models. Thus, the application of experimental systems that can be used to dissect cellular and molecular mechanisms underlying the skeletal phenotype of MPS IH patients and to identify effective therapies is highly needed. Here, we adopted in vitro/in vivo systems based on patient-derived bone marrow stromal cells to generate cartilaginous pellets and bone rudiments. Interestingly, we observed that heparan sulphate accumulation compromised the remodeling of MPS IH cartilage into other skeletal tissues and other critical aspects of the endochondral ossification process. We also noticed that MPS IH hypertrophic cartilage was characterized by dysregulation of signaling pathways controlling cartilage hypertrophy and fate, extracellular matrix organization, and glycosaminoglycan metabolism. Our study demonstrates that the cartilaginous pellet-based system is a valuable tool to study MPS IH dysostosis and to develop new therapeutic approaches for this hard-to-treat aspect of the disease. Finally, our approach may be applied for modeling other genetic skeletal disorders.

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding. A Phase 2 trial of MEC chemotherapy combined with uproleselan for relapsed/refractory AML showed a median overall survival of 8.8 months and low (2%) rates of severe oral mucositis. Clinical trials seek to confirm activity in AML and mitigation of neutrophil-mediated adverse events (mucositis and diarrhea) after intensive chemotherapy. In this review we summarize E-selectin biology and the rationale for uproleselan in combination with other therapies for hematologic malignancies. We also describe uproleselan pharmacology and ongoing clinical trials.

Extranodal NK/T-cell lymphoma with localized relapse in bone marrow of lower leg detected using PET-CT.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma (NHL) with poor prognosis, particularly in relapsed or refractory patients. Thus, timely detection of relapse and appropriate disease management are crucial. We present two patients with ENKTL, wherein positron emission tomography-computed tomography (PET-CT) with total-body coverage after induction therapy, detected newly relapsed regions in the bone marrow of the lower leg prior to progression. Case 1: A 47-year-old woman with nasal obstruction, showing 18F-fluoro-deoxyglucose (FDG) uptake in the nasal cavity (Lugano stage IE). After induction therapy (RT-2/3 DeVIC), PET-CT revealed abnormal uptake only in the right fibula. Case 2: A 68-year-old man with a skin nodule/ulcer and an enlarged right inguinal lymph node was diagnosed with advanced ENKTL. A PET-CT scan revealed abnormal uptake in the subcutaneous mass of the right medial thigh, lymph nodes, and descending colon (Lugano stage IV). After induction therapy, PET-CT revealed new abnormal uptake only in the left tibia. In both patients, CT-guided biopsy confirmed ENKTL recurrence. Moreover, PET-CT with whole-body coverage was useful for the timely assessment of relapse and detection of asymptomatic bone involvement. This approach allowed for modifications to treatment strategies in certain patients.