Bone Marrow Infiltration Of Lymphoma Research Articles

Utility of 18F-fluorodeoxyglucose PET-CT scan in detecting bone marrow involvement in lymphoma

Background & objectives:Evaluation of bone marrow infiltration in lymphoma is usually done by bone marrow biopsy (BMB). This study analyzed the utility of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) to detect bone marrow involvement (BMI) compared to BMB.Methods:Treatment-naïve lymphoma patients underwent both 18F-FDG PET/CT scan and BMB before treatment initiation. BMI detected on PET/CT was compared with BMB.Results:The study population consisted of 80 patients and comprised 37 Hodgkin’s lymphoma (HL) patients, 30 aggressive non-HL (NHL) and 13 indolent NHL patients. The majority of the aggressive NHLs were diffuse large B-cell lymphoma (20/30) and major indolent lymphoma was follicular lymphoma (5/13). When compared to BMB, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of focal (±diffuse) marrow FDG uptake on 18F-FDG PET/CT were 100, 61.3, 33.3 and 100 per cent, respectively, for HL; 100, 65.4, 30.8 and 100 per cent, respectively, for aggressive NHL and 75, 80, 85.7 and 66.7 per cent, respectively, for indolent NHL. When comparing marrow involvement on 18F-FDG PET/CT to baseline BMB and/or resolution of bone marrow FDG uptake at interim/end-of-treatment 18F-FDG PET/CT, the sensitivity, specificity, PPV and NPV were 100 per cent each for HL and aggressive NHL and 77.3, 100, 100 and 66.7 per cent, respectively, for indolent NHL.Interpretation & conclusions:18F-FDG PET/CT has a good sensitivity and NPV for detecting BMI in HL and aggressive lymphoma. The low specificity and PPV improved if marrow uptake pattern on interim or end-of-treatment 18F-FDG PET/CT scan was analyzed. In patients with HL who are staged with18F-FDG PET/CT at baseline and followed up with an interim/end-of-treatment PET/CT, baseline BMB may be avoided. For all other lymphoma subtypes, BMB may be essential if there is no marrow FDG uptake on PET/CT scan performed at baseline.

Clinicopathological Study of Bone Marrow Infiltration in Lymphoma

Clinicopathological Study of Bone Marrow Infiltration in Lymphoma

The Role of Texture Analysis and Radiomics in Prediction of Bone Marrow Infiltration in Patients with Lymphoma

Purpose. To explore the ability of image-based parameters with texture parameters in the differentiation of bone marrow infiltration by positron emission tomography-computed tomography (PET/CT). Procedures. We retrospectively evaluated the baseline PET/CT scan of 44 patients with histologically proven lymphoma. Seventy-three of features were extracted using CGITA software and statistical analysis were carried out on SPSS program. Results. Spearman correlation analysis revealed a strong positive correlation between conventional PET metrics and texture features (19 significant association features) and inverse correlation was found (one parameter significant association feature). Area under the curve and p-value of receive operating characteristics showed that (HILRE (4-bin), HILZE (64-bin), LRE (64-bin), LZE (64-bin), max spectrum (8-bin), busyness (64-bin),code similarity (32-bin & 64-bin)) were significant discriminator of bone marrow infiltration among other features (AUC>0.682, p < 0.05). Univariate analyses of texture features showed that code similarity and LRE (both 64 bin) has significant prediction to BMI. Multivariate analyses revealed that LRE (64 bin) p= 0.031; odds ratio: 1.022; 95% CI, 1.002-1.043) were independent variables for bone marrow infiltration. Conclusions. Significant associations emerged between PET features and bone marrow infiltration in lymphoma. Texture analysis on PET/CT shows potential to differentiate between bone marrow infiltration in patients with Lymphoma.

Bone marrow infiltration pattern in patients with intravascular large B-cell lymphoma diagnosed by random skin biopsy.

We retrospectively analyzed bone marrow (BM) infiltration pattern in consecutive 30 intravascular large B‐cell lymphoma (IVLBCL) patients diagnosed by random skin biopsy (RSB). BM infiltration of lymphoma was observed in 18 patients (60.0%), including five patients with the intrasinusoidal pattern with minimal extravasation, eight patients with the mixed of intrasinusoidal and scattered/interstitial or nodular infiltration, and five patients with the nodular/diffuse pattern. Twelve patients were negative for lymphoma infiltration. BM histology of patients with IVLBCL were diverse and frequently discordant with those of other site of IVLBCL lesions. BM biopsy had a poorer diagnostic performance for detecting intravascular features.

Clinical analysis of 20 patients with non-Hodgkin lymphoma and autoimmune hemolytic anemia: A retrospective study.

Non-Hodgkin lymphoma (NHL) can co-exist with autoimmune hemolytic anemia (AIHA), a phenomenon known as AIHA-associated NHL (AIHA/NHL). However, few studies have reported AIHA/NHL incidence or its clinical characteristics. We conducted a retrospective analysis of 20 AIHA/NHL patients treated at our hospital from 2009 to 2018. AIHA/NHL was presented by only 0.91% of the NHL and 9.8% of the AIHA patients. In addition, AIHA occurred most frequently with angioimmunoblastic T-cell lymphoma (AITL) (7.31%), followed by marginal zone B-cell lymphoma (MZBL) (6.25%), B-cell lymphoma-unclassified (BCL-U) (4.25%), chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL) (2.50%), and mantle cell lymphoma (MCL) (2.30%). In addition to the CLL/SLL patients with impaired bone marrow, 66.7% of the AIHA/NHL patients had lymphoma bone marrow infiltration (LBMI), of which 4 patients presented LBMI in bone marrow smears (BMS) but not in bone marrow biopsy (BMB) and 6 were positive for BMB but not BMS. The 1-, 3- and 5-year survival rates of AIHA/NHL patients were 70%, 30% and 20%, respectively, and they responded poorly to chemotherapy. In conclusion, AIHA can co-exist with various NHLs and the defining clinical characteristic of AIHA/NHL is the high incidence of LBMI. However, both BMS and BMB should be performed to avoid missed diagnosis.

The Value of Pelvic Magnetic Resonance Imaging in Detecting Bone Marrow Infiltration of Lymphoma

The Value of Pelvic Magnetic Resonance Imaging in Detecting Bone Marrow Infiltration of Lymphoma

Clinical significance of bone marrow immunopathologic detection: analyses of 266 newly diagnosed lymphoma cases

Objective To investigate the clinical significance of bone marrow immunopathogenesis in the diagnosis and staging of lymphoma. Methods Clinical data of 266 patients with newly diagnosed lymphoma admitted to Department of Hematology in the First Hospital of Jilin University from August 2015 to December 2017 were retrospectively analyzed. The results of lymphoma diagnosis and staging in different bone marrow detection methods were compared, SPSS 22.0 software was used to make statistical analysis and χ 2 test was used to compare the positive rates of lymphoma bone marrow infiltration in different methods. Results In the 266 patients, 64 cases (24.1%) were diagnosed with lymphoma by using bone marrow detection on the condition that no lymph node pathology was available and all the immunophenotypes of 64 cases were identified by bone marrow immunopathology. Bone marrow infiltration was identified in 121 patients (45.5%), among which the rate of bone marrow infiltration was 0 (0/12) in Hodgkin lymphoma (HL) and 47.6% (121/254) in non-Hodgkin lymphoma (NHL). The rate of bone marrow infiltration was 50.0% (105/210) and 36.4% (16/44) in B type and T type NHL respectively. The positive rate of bone marrow infiltration detected by bone marrow smear, bone marrow biopsy, bone marrow flow cytometry and bone marrow immunopathology were 78.5% (95/121), 87.6% (106/121), 89.3% (108/121), 96.7% (117/121) respectively. Bone marrow immunopathology was more advantageous than any other methods, and there was a statistical difference (χ 2= 18.38, 9.09, 3.76; all P < 0.05). Among 121 patients who were identified with bone marrow infiltration by bone marrow detection, the staging of 42 patients (34.7%) were amended, including the staging of 39 amended patients (32.2%) through bone marrow immunopathologic detection. Conclusion Bone marrow immunopathology can be used for the diagnosis and classification of lymphoma, which has an obvious advantage in detecting bone marrow infiltration of lymphoma compared with bone marrow smear, bone marrow biopsy, bone marrow flow cytometry, and it can be used to amend the clinical staging. Key words: Lymphoma; Bone marrow; Immunopathology

Preliminary evaluation of PET-CT and DWI for the detection of lymphoma bone marrow infiltration

Objective: To evaluate the clinical value of PET-CT and DWI for the detection of bone marrow infiltration of lymphoma. Methods: The bone marrow samples of 93 untreated patients with pathologically diagnosed lymphoma were retrospectively analyzed. 61 patients underwent PET-CT examination, and other 32 underwent DWI examination. With bone marrow biopsy results as "gold standard" , the rates and sites of bone marrow infiltration of various lymphoma subtypes were analyzed, and the detection rates of the two imaging techniques were compared according to different lymphoma subtypes. Results: 39 patients were diagnosed as bone marrow infiltration based on pathological examination of bone marrow biopsies from routine sampling sites and bone marrow pathological examination of biopsies guided by PET-CT and DWI. The sensitivity, specificity, accuracy, positive and negative predictive values of PET-CT for lymphoma bone marrow infiltration were 80.8%, 88.6%, 85.3%, 84.0% and 86.1%, respectively; for DWI examination, these rates were 84.6%, 89.5%, 87.5%, 84.6% and 89.5%, respectively. The detection rates of the two imaging techniques for aggressive lymphoma were 37.5% (18/48) and 38.1% (8/21), respectively, which were slightly higher than those for the indolent lymphoma [23.1% (3/13) and 27.3% (3/11)], although the differences were not statistically significant (P=0.521, P=0.660). For both aggressive lymphoma and indolent lymphoma, the detection rates of DWI were numerically slightly higher than those of PET-CT(P=0.963, P=1.000). Conclusions: PET-CT and DWI have important and similar diagnostic value for bone marrow infiltration of lymphoma. None of PET-CT and DWI can replace bone marrow biopsy (BMB). However, image-guided bone marrow biopsies can improve the detection rate of bone marrow infiltration of lymphoma.

The clinical utility of 18F-FDG PET-CT for detection of bone marrow infiltration in lymphoma

Bone marrow infiltration in lymphoma is crucial to the disease diagnosis, staging, treatment options and prognostic evaluation. Although bone marrow biopsy is the main detecting method, it has high false negative rate. At present, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) technology which is integrating morphological characteristics with metabolic function provides a new way for the diagnosis, staging and prognostic evaluation of bone marrow infiltration in lymphoma due to its advantages of high sensitivity, high specificity and functional image. Key words: Lymphoma; Bone marrow; Fluod deoxyglucose F18; Positron-emission tomography

Comparison of ¹⁸F-FDG PET/CT and large-scale DWI for evaluation of non-Hodgkin lymphoma bone marrow infiltration

To compare the diagnostic value of ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and large-scale diffusion weighted imaging (DWI) for evaluation of non-Hodgkin lymphoma (NHL) bone marrow (BM) infiltration. A total of 79 patients with pathologically diagnosed NHL underwent ¹⁸F-FDG PET/CT, large scale DWI and BM pathological examination. BM examination as the "gold standard", the performance (the sensitivity, specificity, accuracy, positive and negative predictive value) of ¹⁸F-FDG PET/CT and large scale DWI for evaluation of BM infiltration was compared and the risk of BM infiltration of different subtypes and sources of NHL was analyzed. 25 of 79 cases were diagnosed as BM infiltration by pathological examination with 57 BM sites. Abnormal high BM metabolisms were identified in 22 cases with 56 BM sites by ¹⁸F-FDG PET/CT and 25 cases with 58 BM sites by large-scale DWI. The sensitivity, specificity, accuracy, positive and negative predictive value of ¹⁸F-FDG PET/CT were 80.0%, 96.3%, 91.1%, 90.9%, 91.2%, respectively. And they were 84.0%, 92.6%, 89.9%, 84.0%, and 92.6% by large-scale DWI, respectively. A receiver operating characteristic (ROC) analysis demonstrated that there was no statistical difference in ¹⁸F-FDG PET/CT and large-scale DWI (P>0.05). The area under ROC curve for ¹⁸F-FDG PET/CT and large-scale DWI were 0.911 and 0.883 respectively. The incidences of BM infiltration in aggressive NHL patients by ¹⁸F-FDG PET/CT (21/69, 30.4%) and large-scale DWI (23/69, 33.3%) were higher than those (PET/CT: 10.0%; large-scale DWI: 20.0%; P>0.05) in indolent NHL patients. ¹⁸F-FDG PET/CT and large-scale DWI had important clinical value in diagnosing BM infiltration of NHL. A combination of ¹⁸F-FDG PET/CT, large-scale DWI and pathological examination could improve the positive rate of BM infiltration in NHL.

Bone marrow infiltration of lymphoma

Bone marrow infiltration of lymphoma

The Utility of Positron Emission Tomography (PET) with 18Fluorodeoxyglucose (18F-FDG) Compared to Standard Procedures in Detecting Bone Marrow Infiltration in Diffuse Large B-Cell Lymphoma in Developing Countries.

Abstract 5015 BackgroundComputed tomography (CT) scanning and bone marrow biopsy (BMB) are the most used methods for initial staging in Diffuse Large B-cell Lymphoma (DLBCL) in developing countries. In the United States and Europe, 18-FDG PET has demonstrated to be an essential imaging modality for initial staging, early response and final therapeutic assessment in DLBCL patients. Afterward BM biopsy (BMB) is the gold standard to detect BM infiltration in lymphoma. However the ability of the FDG-PET to assess bone marrow (BM) positivity in DLBCL has been investigated and remains a controversial issue in the literature. For that reason we retrospectively compared the BM infiltration by bilateral BMB with FDG-PET at diagnosis in DLBCL patients. MethodsWe evaluated retrospectively 38 patients with DLBCL reporting the number of true-positive, false-positive, true-negative, and false-negative BM positivity by FDG-PET having the bilateral BMB as a reference standard. ResultsOut of 38, BM(+) was detected in 4 (10.5%) patients by BMB and in 14 (36.8%) patients by FDG-PET. The sensitivity and specificity of FDG-PET to recognize BM infiltration were respectively 100% and 71%. Negative and positive predictive values of the FDG-PET to identify BM(+) were respectively 100% and 28.5%. In negative-BMB patients, a positive FDG-PET BM was found in iliac 1 (10%), vertebra 5 (50%), sternum 2 (20%), scapula 1 (10%) and femur 1 (10%). The 18FDG mean maximum standardized uptake value (SUVmax) was 6.85 ± 3.9 in negative-BMB group and 9.77 ± 3.2 in positive-BMB group, p=0,208. ConclusionThese results suggest that FDG-PET has a good sensitivity in detecting bone marrow infiltration in this type of aggressive lymphoma when compared to bilateral BMB to our knowledge the standard procedure to evaluate BM infiltration in lymphoma staging. Even though this study has several limitations such as one single center experience, a small number of patients and the lack of FDG-PET BM(+) confirmation by guided biopsy in previously negative-BMB patients, the majority of publications have been made in developed countries, and moreover we believe many issues still remain to be answered such as data regarding the FDG-PET cost-effectiveness out of clinical trails, specially in developing countries, in order to elucidate whether these results will be translated into a real benefit in overall survival for these patients. DisclosuresNo relevant conflicts of interest to declare.

The Anti-CD19 Bispecific T-Cell Engager (BiTE) MT103 (MEDI-538), Induces Dose-Dependent Complete and Partial Responses in Relapsed Non-Hodgkin Lymphoma (NHL): Phase I Study MT103-104.

MT103 (MEDI-538), a bispecific, single chain construct specific for CD19 and CD3, is a member of a novel class of highly active antibody derivatives that direct T-cells to target cells. The primary objective of this study is to evaluate the safety and tolerability of a 4- to 8-week continuous intravenous infusion at increasing dose levels in patients with relapsed NHL, starting at dose level 1 (DL1) of 0.5μg/m2/24h. Dose-limiting toxicities (DLTs) were assessed during the first 2 weeks of infusion. To date, 31 patients have been included up to a dose level of 30μg/m2/24h. No DLTs were observed from DL1 to DL3 (5μg/m2/24h. At DL4 (5μg/m2/24h on day 1, followed by 15 μg/m2/24h maintenance dose), 7 patients (pts) were treated. One of the 7 pts had elevated liver enzymes up to CTC grade 3 after 2 weeks, and another patient showed reversible confusion, assessed as a DLT on the 2nd treatment day. For further optimization of safety and convenience of the initiation phase, the stepwise increase was modified to a constant infusion rate. This regimen was well tolerated and showed a favorable safety profile. Due to these modifications a total of 13 pts were treated at 15μg/m2/24h. At 30μg/m2/24h, 6 pts were treated; one DLT (metabolic acidosis, grade 4) was recorded. Confounding factors for this event were pre-existing renal insufficiency, fever and increasing anemia. The adverse events (AEs) were transient and the most common ones observed so far in all cohorts, regardless of causality, were (overall/grade 3 or 4) leucopenia (63%/37%), lymphopenia (59%/59%), pyrexia (55%/7%) elevated liver enzymes (44%/4%). At the dose level of 15μg/ m2/24h, MT103 induced 1 complete (CR) and 2 partial responses (PRs) in indolent lymphoma, which had not been observed at the previous dose levels. A total of 5 pts including the responders at this dose level had bone marrow involvement by indolent lymphoma. MT103 induced complete disappearance of lymphoma cells from the bone marrow in 3 and partial reduction in 2 of the 5 cases. One of these 5 patients had lymphoplasmocytoid lymphoma pre-treated with fludarabine. MT103 induced a 60% reduction of paraprotein. At the dose level of 30μg/m2/24h, clinical benefit was observed in mantle cell lymphoma (MCL), which had not been noted at the previous dose levels. One out of 3 evaluable pts with MCL enrolled at this dose level experienced a CR and one showed complete disappearance of lymphoma cells from the bone marrow. Best responses in the 26 evaluable pts overall were 2 CRs, 2 PRs, 2 minimal responses (MRs) and 13 SDs. Best responses in 14 evaluable patients starting at the dose level of 15μg/m2/24h were 2 CRs, 2 PRs, 2 MRs and 5 SDs.Conclusions: The current data suggest a favorable safety profile of MT103 administered as continuous 4 to 8 week infusion. MT103 induces CRs and PRs in relapsed indolent lymphoma and MCL in an apparently dose dependent fashion. Pronounced effects on lymphoma bone marrow infiltration have further demonstrated the clinical activity of MT103. Determination of the optimal biological dose is ongoing.