2-[18F]-FDG PET/CT Semiquantitative and Radiomics Predictive Parameters of Richter's Transformation in CLL Patients.

Background and Objectives: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in developed countries, which can evolve into aggressive lymphoma variants, a process called Richter transformation (RT). The aim of this retrospective study was to analyze the role of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT) and its semiquantitative and radiomics features in detecting RT and evaluate the impact on overall survival (OS). Materials and Methods: One hundred and thirty-seven patients with histologically proven CLL were retrospectively recruited. PET/CT images were qualitatively and semiquantitatively examined by estimating the main metabolic parameters (the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-blood-pool SUV ratio (L-BP SUV R), lesion-to-liver SUV ratio (L-L SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and radiomics first- and second- order variables of the lesion with highest uptake. The role of these parameters in predicting RT and OS was analyzed. Results: One hundred and thirty (95%) PET/CT scans were positive, showing an increased tracer uptake at the site of disease, whereas the remaining 7 (5%) scans were negative. SUVbw, SUVlbm, SUVbsa, L-L SUV ratio, and L-BP SUV ratio were significantly higher in the RT group (p < 0.001 in all cases). Radiomics first- and second-order features were not significantly associated with RT. After a median follow-up of 44 months, 56 patients died; OS was significantly shorter in patients with RT than patients without RT (28 vs. 34 months; p = 0.002). Binet-stage, RT, and L-BP SUV R were shown to be independent prognostic features. Conclusions: Semiquantitative PET/CT parameters such as SUVbw, SUVlbm, SUVbsa, L-L SUV ratio and L-BP SUV ratio may be useful in discriminating patients with a high risk of developing RT, whereas Binet-stage, RT, and L-BP SUV R are also significant in predicting OS.

Diffuse Bone Uptake of 131 I and Effect on Blood Counts in a Patient With Papillary Thyroid Carcinoma and Chronic Lymphocytic Leukemia.

ABSTRACT: A 57-year-old woman with history of chronic lymphocytic leukemia was referred to our center for adjuvant 131 I therapy following complete thyroidectomy for differentiated thyroid cancer. Posttherapeutic scintigraphy revealed atypical diffuse osteomedullar uptake. A major drop in lymphocyte count was observed, from 117.7 g/L to 4.8 g/L 8 weeks after 131 I therapy. Bone marrow uptake is presumed to be related to tracer sequestration in leukemic cells. White blood cell count normalization suggests a high sensitivity of leukemic cells to beta emission. This scintigraphic pattern may act as a pitfall for nuclear medicine physician.

Leukemic pulmonary infiltrates in chronic lymphocytic leukemia: Clinical and imaging features.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. Although various patterns of lung involvement with CLL have been reported, data on clinicoradiologic presentation are sparse. METHODS: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 and had leukemic pulmonary infiltrates (LPI) with CLL demonstrated on lung biopsy. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features. RESULTS: Among 13 patients, median age was 77 years (range: 60-88) and included 10 men (77 %). All patients were known to have CLL with a median duration of 96 months (range: 50-408), and none were on treatment. Most common symptoms were dyspnea (62 %), cough (54 %), and fatigue (46 %); 2 patients (15 %) were asymptomatic. Dominant abnormality on CT consisted of single or multiple nodular/mass-like opacities in 10 patients (77 %), while diffuse centrilobular nodules, pleural mass, and diffuse bronchial wall thickening were each seen in one patient, respectively; intrathoracic lymphadenopathy was present in all. After diagnosis of LPI, treatment for CLL was administered to 7 patients (54 %); 6 patients (86 %) exhibited improvement. During follow-up (median 41 months), 8 (62 %) patients died. Causes of death included progressive CLL or treatment-related complications (2 patients), pneumonia (1 patient), unrelated causes (3 patients), and unknown in 2 patients. CONCLUSIONS: LPI in CLL is generally encountered in patients with known untreated CLL. The main imaging feature is single mass-like opacity or multiple nodular/mass-like opacities, associated with intrathoracic lymphadenopathy.

Clinical Application of 18F-FDG-PET Quantification in Hematological Malignancies: Emphasizing Multiple Myeloma, Lymphoma and Chronic Lymphocytic Leukemia.

Most hematological malignancies display heightened glycolytic activity, leading to their detectability through 18F-FDG-PET imaging. PET quantification enables the extraction of metabolic information from tumors. Among various PET measurements, maximum standardized uptake value (SUVmax), which indicates the highest value of 18F-FDG uptake within the tumor, has emerged as the commonly used parameter in clinical oncology. This is because of SUVmax ease of calculation using most available commercial workstations, as well as its simplicity and independence from observer interpretation. Nonetheless, SUVmax represents the increase in activity within a specific small area, which may not fully capture the overall tumor uptake. Volumetric PET parameters have been identified as a potential solution to overcome certain limitations associated with SUVmax. However, these parameters are influenced by the low spatial resolution of PET when assessing small lesions. Another challenge is the high number of lesions observed in some patients, leading to a time-consuming process for evaluating all focal lesions. Some institutions recently have started advocating for CT-based segmentation as a method for measuring radiotracer uptake in the bone marrow and overall bone of the patients. This review article aims to provide insights into clinical application of PET quantification specifically focusing on 3 major hematologic malignancies: multiple myeloma, lymphoma, and chronic lymphocytic leukemia.

68Ga-DOTATATE PET/CT Incidentally Detects Relapsed Chronic Lymphocytic Leukemia in Patient With Metastatic Neuroendocrine Tumor.

ABSTRACT: A 54-year-old man with metastatic well-differentiated neuroendocrine tumor of the pancreas underwent 68Ga-DOTATATE PET/CT scan to evaluate treatment response. Patient was known for remote history of chronic lymphocytic leukemia (CLL), previously treated. Scan revealed diffusely increased abnormal tracer uptake throughout the marrow of the axial and proximal appendicular skeleton. Bone marrow biopsy revealed relapsed CLL. We present a rare case of relapsed CLL incidentally detected on 68Ga-DOTATATE PET/CT.

Lung Adenocarcinoma with Chronic Lymphocytic Leukemia Mimicking Bone Metastasis.

A 77-year-old man was referred to our hospital for abnormal thoracic radiographs. Computed tomography (CT) revealed a 20-mm subpleural ground-glass opacity in the right S6 area. A CT-guided biopsy revealed lung adenocarcinoma. Fluorodeoxyglucose-positron emission tomography revealed multiple abnormal bone accumulations, and a subsequent biopsy of a left iliac bone lesion revealed chronic lymphocytic leukemia. A right lower lung lobectomy was performed for the lung adenocarcinoma (cT1bN0M0, stage IA2). An aggressive biopsy of the bone lesion confirmed a rare case of double primary malignancies, which determined the patient's treatment and outcomes.

Splenic Size and Volume Measurements in Patients with Chronic Lymphocytic Leukemia.

RATIONALE AND OBJECTIVES: To determine which methods of assessment of splenic size most accurately represent the actual spleen volume in patients with Chronic Lymphocytic Leukemia (CLL). MATERIALS AND METHODS: The Abdominal Computed Tomography images of 48 patients with CLL enrolled on a phase 2 clinical trial at two time-points before and after 2-months of continuous acalabrutinib treatment were analyzed. Linear one-dimensional measurements of the spleen were taken in different planes. Two-dimensional and three-dimensional measurements were calculated from the linear measurements using mathematical formulae. The spleen volume was determined by manual segmentation as the ground truth. Data derived were analyzed using Pearson correlation and statistical significance was set at p < 0.05. RESULTS: Among the single-dimensional measurements, the strongest correlation with the segmented splenic volume was the sagittal long axis diameter (LAD) (r = 0.89, p < 0.05), followed closely by Coronal LAD (r = 0.87, p < 0.05) and cephalocaudal length (iwCLL) (r = 0.84, p < 0.05). For the two-dimensional indices, the sum of LAD and short axis diameter (SAD) of the spleen in axial plane showed good correlation with the splenic volume (r = 0.77, p < 0.05). Among the three-dimensional indices, the splenic index (0.523 x axial LAD x axial SAD x coronal height) and a formula for volume (30 + 0.58 x axial LAD x axial SAD x coronal height) had the strongest correlation (both r = 0.92, p < 0.05) with the spleen volume. CONCLUSION: The three-dimensional formulae showed the strongest correlation with volumetric reference spleen measurement. Among unidimensional measurements, the sagittal LAD had the best correlation with the actual splenic volume. The two-dimensional calculation methods were less reliable.

Unusual Illustration of Richter Transformation in Chronic Lymphocytic Leukemia on FDG PET/CT.

ABSTRACT: A man with history of chronic lymphocytic leukemia (CLL) in remission had multiple rapidly growing lumps in recent 2 months. FDG PET/CT demonstrated disseminated FDG-avid nodal and extranodal lesions including those in unusual locations such as the nasopharynx, salivary glands, lungs, gastric wall, peritoneum, bones, and muscles. Subsequent biopsy of the right axillary mass showed absolute lymphocytosis with focus of large B-cell lymphoma. Flow cytometric immunophenotyping demonstrated κ-restricted CLL and B-cell lymphoma, consistent with Richter transformation of CLL. FDG PET/CT images of this case illustrated the most severe and most disseminated nodal and extranodal involvements of Richter transformation in CLL.

Ileal plasmablastic lymphoma presenting as intestinal occlusion in an HIV-negative patient with chronic lymphocytic leukemia.

We report the case of a 56-year-old male with a history of chronic lymphocytic leukemia (CLL), RAI 0 and Binet Stage A in therapeutic abstention, who presented to the Emergency Department with a two-week history of low abdominal pain and constipation. Physical examination was unremarkable except for mild diffuse abdominal pain on palpation. Laboratory studies revealed lymphocytosis and anemia (Hb: 10.2 g/dl). An abdominal computed tomography (CT) scan showed a partial small bowel obstruction secondary to a proximal ileal neoplasm.

Using 18F-FDG PET/CT to rule out Richter transformation as cause of deterioration in a patient with chronic lymphatic leukemia and severe COVID-19: A case report.

RATIONALE: This case report demonstrates the use of flourine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) to rule out Richter transformation (RT) as the cause of clinical deterioration in a patient with chronic lymphatic leukemia (CLL) and severe COVID-19. 18F-FDG PET/CT can be used to establish the diagnosis of RT in patients with CLL, but the use of 18F-FDG PET/CT to exclude RT as the cause of clinical deterioration in patients with CLL and severe COVID-19 has not previously been described. PATIENT CONCERNS: A 61-year-old male with CLL and COVID-19 developed increased dyspnea, malaise and fever during hospitalization for treatment of severe and prolonged COVID-19. DIAGNOSES: 18F-FDG PET/CT ruled out RT and revealed progression of opacities in both lungs consistent with exacerbation of severe acute respiratory syndrome coronavirus 2 pneumonia. INTERVENTIONS: 18F-FDG PET/CT imaging. OUTCOMES: The patient was discharged at day 52 without the need of supplemental oxygen, with normalized infection marks and continued care for CLL with venetoclax. LESSONS: 18F-FDG PET/CT ruled out RT as the cause of deteriorations in a patient with CLL and severe COVID-19, enabling directed care of exacerbation of severe acute respiratory syndrome coronavirus 2 pneumonia.

A 58-year-old man with B-cell chronic lymphocytic leukemia and multiple strokes.

A 58-year-old male with B-cell chronic lymphocytic leukemia presented with fever, chest pain, and acute-onset neurological deficits suggestive of multiple strokes (A). Brain autopsy revealed softening areas in the brain parenchyma (B, C) corresponding to extensive necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F) necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F).

Chronic lymphocytic leukaemia and Richter's transformation: multimodal review and new imaging paradigms.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults. It is a malignancy of CD5 B-cells characterised by small, mature-appearing lymphocytes accumulating in the blood, bone marrow, and lymphoid tissues. Richer transformation (RT) is an important adverse complication. Detection of RT is critical to allow initiation of appropriate therapy. CLL staging and response evaluation is complicated and nuanced. From our extensive tertiary centre experience of several hundred CLL cases over the last decade, we detail key computed tomography (CT) and positron-emission tomography (PET) imaging features of the natural history of CLL. The authors present an original imaging-based patient-management paradigm for the investigation of potential RT, which will inform global practice. Potential applications of whole-body diffusion weighted imaging, novel PET radiotracers, minimal residual disease, and ct-DNA are addressed.

The Pattern of Use of PET/CT Scans in the Clinical Management of Chronic Lymphocytic Leukemia.

BACKGROUND: The study aimed to evaluate the utilization patterns of positron emission tomography/computed tomography (PET/CT) in chronic lymphocytic leukemia (CLL) patients and to investigate whether the results of these scans influenced treatment decisions. PATIENTS: and Methods: In this observational study, we analyzed patients with CLL or small lymphocytic leukemia (SLL) who underwent at least one PET/CT scan from 2007 to 2018. Patients were divided into two groups: (1) patients who had at least one fluorodeoxyglucose-avid PET/CT scan, and (2) patients who had all negative scans. PET/CT results were retrieved from patients' medical files and were revised by an expert radiologist according to visual score scale, SUVmax/SUVliver mean ratio, and the SUVmax. RESULTS: Of the 524 patients, 160 patients (30.5%) had PET/CT scans, and 120 patients met the inclusion criteria. A total of 219 eligible scans were analyzed; 62 of these scans (28.3%) were reported as positive, and 167 of these scans (76.3%) were performed for staging. There was a significant association between PET/CT results and change of therapy (P < .001); however, 62.9% of the positive PET/CT scans were not followed by a change of treatment. Survival time was not different between the two groups. The SUVmax/SUVliver mean ratio was negatively significantly associated with lymphocytes percent (r = -0.237, P = .042) and positively associated with lactate dehydrogenase levels (r = 0.338, P = .008) among CLL patients. CONCLUSION: Despite the fact that the use of surveillance PET/CT for patients with CLL/SLL is not in the guidelines and that it is not useful for disease management, in practice the test is in frequent use in Israel.

Hypercalcaemia, renal failure, anaemia and osteolytic lesions (CRAB) in chronic lymphocytic leukaemia mimicking multiple myeloma.

Classical CRAB features (hypercalcaemia, renal failure, anaemia, osteolytic lesions) have been traditionally defined in patients with plasma cell dyscrasia. But these can be rare and uncommon presentations of other chronic lymphoproliferative disorders (CLPD). The pathophysiological basis of CRAB features in other CLPD need to be explored further for better outcomes and therapeutic interventions. These can present a diagnostic dilemma and requires extensive workup to rule out coexisting malignancy and myeloma. Here, we report an unusual case of B CLPD in a middle-aged male who presented with classical CRAB features along with a brief literature review. After detailed investigations, he was diagnosed as chronic lymphocytic leukaemia, without any second malignancy and responded well to ibrutinib-based therapy.

Concurrent BK polyomavirus, adenovirus and cytomegalovirus infections in a patient treated for chronic lymphocytic leukaemia.

A 58-year-old woman with chronic lymphocytic leukaemia (CLL) presented with 2 weeks of fever and haematuria following chemo-immunotherapy. CT scan showed thickening of her left urethra and bladder, suggesting pyleo-ureteritis with cystitis. The patient was initially treated for suspected bacterial urinary tract infection although repeated blood and urine cultures remained negative. She then received multiple transfusions for chemotherapy-induced pancytopenia while her urinary symptoms did not improve. Due to her immunocompromised status, she was tested for viral infection, which revealed, BK polyomavirus, adenovirus and cytomegalovirus in serum and urine. Cidofovir was initially administered to treat these infections while ganciclovir was used with filgrastim due to neutropenia. The patient subsequently improved. This case represents a diagnostic and therapeutic challenge due to the multiple concurrent viral infections causing haematuria as well as the combined post-chemo-immunotherapy and antiviral myelotoxicity in a CLL patient.

A platform trial in practice: adding a new experimental research arm to the ongoing confirmatory FLAIR trial in chronic lymphocytic leukaemia.

BACKGROUND: The FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success. METHODS: FLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial. RESULTS: The changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres. CONCLUSIONS: FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community. TRIAL REGISTRATION: ISRCTN Registry ISRCTN01844152 . Registered on August 08, 2014.