scholarly journals Comparison of three different methods to detect bone marrow involvement in patients with neuroblastoma

2021 ◽  
Author(s):  
Felix Schriegel ◽  
Sabine Taschner-Mandl ◽  
Marie Bernkopf ◽  
Uwe Grunwald ◽  
Nikolai Siebert ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Involvement ◽  
Prognostic Significance ◽  
Cost Effective ◽  
Study Entry ◽  
Diagnostic Tools ◽  
Number Of Patients ◽  
A Prospective Study ◽  
Positive Results

Abstract Purpose Neuroblastoma (NB) is the most frequent extracranial tumor in children. The detection of bone marrow (BM) involvement is crucial for correct staging and risk-adapted treatment. We compared three methods regarding the detection of NB involvement in BM. Methods Eighty-one patients with NB were included in this retrospective study. BM samples were obtained at designated time points at study entry and during treatment or follow-up. The diagnostic tools for BM analysis included cytomorphology (CM), flow cytometry (FCM) and automatic immunofluorescence plus fluorescence in situ hybridization (AIPF). Results We analyzed 369 aspirates in 81 patients in whom AIPF, CM, and FCM were simultaneously available. During the observation period, NB cells were detected in 86/369 (23.3%) cases, by CM in 32/369 (8.7%), by FCM in 52 (14.1%), and by AIPF in 72 (19.5%) samples. AIPF and/or FCM confirmed all positive results obtained in CM and detected 11 additional positive BM aspirates in 294 CM negative samples (p < 0,001). Survival of patients with BM involvement at study entry identified solely by FCM/AIPF was 17.4% versus 0% for patients in whom BM involvement was already identified by CM. Conclusion The combination of AIPF/FCM yielded the highest detection rate of NB cells in BM. AIPF was the single, most sensitive method in detecting these cells. Although CM did not provide any additional positive results, it is still a useful, readily available and cost-effective tool. The prognostic significance of FCM and AIPF should be confirmed in a prospective study with a larger number of patients.

scholarly journals Comparison of Three Different Methods to Detect Bone Marrow Involvement in Patients with Neuroblastoma

2021 ◽  
Author(s):  
Felix Schriegel ◽  
Sabine Taschner-Mandl ◽  
Marie Bernkopf ◽  
Uwe Grunwald ◽  
Nikolai Siebert ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Involvement ◽  
Diagnostic Tools ◽  
Solid Malignancy ◽  
Additional Information ◽  
The Central Nervous System ◽  
Positive Results ◽  
Observation Period

Abstract Purpose Neuroblastoma (NB) is the most frequent solid malignancy in children outside the central nervous system. Detection of bone marrow (BM) involvement is crucial for correct staging and risk-adapted treatment. We compared three different methods regarding the detection of NB involvement in BM. Methods Eighty-one patients with NB were included in this retrospective study. BM samples were obtained at designated time points at study entry and during treatment or follow-up. The diagnostic tools for BM analysis included cytomorphology (CM), flow cytometry (FCM) and automatic immunofluorescence plus fluorescence in situ hybridization (AIPF). Results We analyzed 369 aspirates in 81 patients in whom AIPF, CM, and FCM were simultaneously available. During the observation period, NB cells were detected in 86/369 (23.3%) cases, by CM in 32/369 (8.7%) samples, by FCM in 52 (14.1%) samples, and by AIPF in 72 (19.5%) samples. AIPF and/or FCM confirmed all positive results obtained in CM and detected 11 additional BM aspirates with NB cells in 294 CM negative samples (p < 0,001). Survival of patients with BM involvement at entry into the study identified solely by FCM / AIPF was 17.4% versus 0% for patients in whom BM involvement was already identified by CM. Conclusion The combination of AIPF and FCM yielded the highest detection rate of NB cells in BM. AIPF was the single, most sensitive method in detecting NB cells in BM. Although CM did not contribute additional information, it is still a useful tool because of its rapid availability and cost-efficiency.

scholarly journals An Unsuspected Finding of t(9;22): A Rare Case of Philadelphia Chromosome-Positive B-Lymphoblastic Lymphoma

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Prajwal Boddu ◽  
C. Cameron Yin ◽  
Rashmi Kanagal-Shamanna ◽  
Guillin Tang ◽  
Beenu Thakral ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
Philadelphia Chromosome ◽  
Lymphoblastic Lymphoma ◽  
Accurate Diagnosis ◽  
Biopsy Specimens ◽  
B Lymphoblastic Lymphoma ◽  
Prophylactic Chemotherapy

While rare, cases of isolated extramedullary disease of B-cell Lymphoblastic Lymphoma (B-LBL) without morphologic bone marrow involvement have been described. In this report, we illustrate the case of an elderly gentleman who presented with isolated testicular and vertebral LBL involvement but had no morphologic bone marrow involvement. The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence in situ hybridization (FISH) and PCR testing for BCR-ABL1 rearrangements were being performed on the marrow specimens as a part of routine diagnostic workup. While the FISH returned negative, PCR testing unexpectedly detected BCR-ABL1 fusion transcripts at a low level of 0.48%. Given their presence, we performed FISH for BCR/ABL1 rearrangement in both testicular and L5 vertebral specimens which were 80–90% positive. He subsequently received rituximab, hyper-CVAD, and dasatinib, along with prophylactic intrathecal prophylactic chemotherapy. The patient achieved a prolonged remission but eventually relapsed, 4 years later. Had it not been for this fortuitous discovery, the patient would not have been treated with tyrosine kinase inhibitors. We emphasize that FISH and PCR testing for BCR-ABL1 rearrangement are integral to arriving at an accurate diagnosis and should be routinely tested on B-LBL biopsy specimens.

scholarly journals The Importance of Bone Marrow Biopsy in the Staging of Patients With Lymphosarcoma

Blood ◽  
1973 ◽  
Vol 41 (6) ◽  
pp. 913-920 ◽  
Author(s):  
Vincent Vinciguerra ◽  
Richard T. Silver
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Clinical Stage ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
Valuable Procedure ◽  
Physical Findings ◽  
Positive Results ◽  
Extent Of Disease ◽  
Initial Staging

Abstract The frequency of bone marrow involvement in patients with lymphosarcoma (LSA) and the particular value of the marrow biopsy, as compared with the aspiration smear technique, in the initial staging of this disease were investigated. Certain physical findings and laboratory studies were analyzed to determine whether the presence of marrow invasion could be predicted. Of 75 patients, 47 (63%) were found to have a positive marrow examination. The clinical stage of 40 of these 75 patients was changed to stage IV as a result of bone marrow biopsy; these included four of nine (44%) stage I patients, 9 of 12 (75%) stage 5 patients, and 27 of 41 (65%) stage III patients. Bone marrow biopsy more often yielded positive results (62%) than did aspiration smears (38%). Little correlation was found between extent of disease on initial physical examination and marrow involvement. A normal hematocrit, white blood cell count, and/or platelet count did not preclude the presence of marrow invasion. The technique of bone marrow biopsy is a simple and valuable procedure in the staging of lymphosarcoma. It uncovers unsuspected and widespread diseases in those patients whose illness appears restricted to even one or two node groups. The high frequency of marrow involvement in patients with LSA is evidence that many patients have widespread disease at the time of diagnosis; thus, marrow biopsy, when positive, is an invaluable test for their initial staging. We urge that it be performed routinely in all patients, irrespective of apparent clinical extent of disease.

The Pro-Inflammatory IL23/IL23R/IL17 Axis Is Active in IL23R-Expressing Circulating CLL Cells in Patients with Poor Prognosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3889-3889
Author(s):  
Fortunato Morabito ◽  
Giovanna Cutrona ◽  
Anna Grazia Recchia ◽  
Sonia Fabris ◽  
Serena Matis ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Lymphoid Cells ◽  
Fish Analysis ◽  
Number Of Patients ◽  
Significant Difference

Abstract Abstract 3889 Inflammatory cytokines play a biological role in the pathogenesis of Chronic lymphocytic leukemia (CLL). IL23 is a pro-inflammatory cytokine involved in T-cell responses and in tissue remodeling. It has been shown that the IL23 receptor (IL23R) is up-regulated in primary acute lymphoblastic leukemia (ALL) cells, and that IL23 inhibits ALL cell growth. Nevertheless, the anti-tumor function of IL23 still remains controversial. The role of the IL23R/IL23 axis in CLL has not been investigated so far. Herein we evaluated the expression pattern of IL23R/IL23 axis and its correlation with progression free survival (PFS) in CLL patients. A total of 233 newly diagnosed Binet stage A CLL cases from Italian institutions (clinicaltrials.gov NCT00917540) were studied for IL23R expression by flow-cytometry (FC) (median percentage IL23R expression=22.7, range 1.2–91.1). The median follow-up was 23 months (range 1–47). PFS information was obtained in 203 patients. Using the median value of 23% of IL23R as threshold, 8/102 IL23Rneg and 23/101 IL23Rpos CLL cases progressed with therapy requirement. The 2-year PFS probability of IL23Rneg patients was 89.7% as compared to 80.7% of IL23Rpos cases [χ2 7.7, P=.006; HR=3.0, 95%CI (1.3–6.6)]. Cases were then stratified according to IL23R positivity [IL23Rneg (102 cases) versus IL23Rpos (101 cases)]. No significant difference in terms of CD38 and ZAP-70 positive cases was observed, however, the IGVH mutational status could distinguish the two groups: IGHV-mutated in 92 (78.6%) of IL23Rneg vs 70 (61.9%) IL23Rpos and IGHV-unmutated in 25 (21.4%) vs 43 (38.1%), p=.006]. FISH analysis showed that IL23Rneg and IL23Rpos cases carrying 13q14.3 were respectively 53 (51.4%) and 44 (42.7%), while the number of patients with trisomy 12 were 8 and 10 respectively in cases with low and high IL23R expression. Deletion of 11q was detected in 3.9% (4/103) of IL23Rneg and in 8.7% (9/103) of IL23Rpos cases. Only 3 cases with 17p deletion were seen in this cohort of early CLL patients and all belonged to the IL23Rpos group. Overall, no significant differences in the incidence of the major genetic lesions were observed between the two groups. Il23R expression still remained independently associated with PFS also in multivariate analysis. In situ expression analysis of IL23R and of its ligand IL23 was then performed by immunohistochemistry (IHC) in 16 CLL samples [10 lymph node (LN) and 6 bone marrow (BM) biopsies] collected on diagnosis and in 8 control biopsies (4 lymph nodes with reactive follicular hyperplasia and 4 normal BM biopsies). IL23R was variably expressed in CLL and significantly expressed in the neoplastic clones of 9 (6 lymph nodes and 3 BM biopsies) of the 16 cases tested; IL23R was diffusely present along the membrane and cytoplasm of neoplastic cells effacing the lymph node or BM architecture (Fig. 1, upper-left). In CLL cases with low IL23R expression, IL23R was detected in few scattered lymphoid cells intermingling with neoplastic lymphocytes (Fig. 1, upper-right). IL23 was also detected, with a variable staining intensity (Fig. 1, middle-left), paralleling in part that of IL23R. Double-marker analysis confirmed the concomitant expression of IL23 and IL23R in CLL neoplastic infiltrates highlighting the co-localization of the two markers (Fig.1 middle-right) and suggesting the possibility of an autocrine IL23/IL23R loop in CLL clones. We speculated that the microenvironment of CLL cases rich in IL23R and IL23 could be enriched in IL17-producing cells. The IHC expression of IL17 in CLL cases with low or high IL23R and IL23 expression showed that CLL cases rich in IL23Rpos cells, also characterized by high IL23 expression, displayed significantly higher numbers of IL17pos infiltrating cells (Fig. 1 bottom-left), as compared with CLL cases with no or low expression of IL23R or IL23 (Fig. 1 bottom-right). In conclusion, our study shows that high IL23R expression predicts a worse PFS. Furthermore, we linked this picture with, the in situ engendering of a clone-related microenvironment characterized by the preponderancy of pro-inflammatory signals such as those of the IL23/IL23R/IL17 axis, and its correlates in the peripheral blood (i.e. IL23R expression on circulating CLL cells), may endorse its strong prognostic significance. This analysis prompts further investigation into the specific function of the IL23/IL23R/IL17 axis and its targets in the context of CLL. Figure 1. Figure 1. Disclosures: No relevant conflicts of interest to declare.

Prognostic Significance of Bone Marrow Involvement in Hodgkin Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5370-5370 ◽  
Author(s):  
Ankit Mangla ◽  
Muhammad Umair Mushtaq ◽  
Rohit Kumar ◽  
Nikki Agarwal ◽  
Sibgha Gull Chaudhary ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hodgkin Lymphoma ◽  
Bone Marrow Involvement ◽  
Prognostic Significance ◽  
Albumin Level ◽  
Stage Iii ◽  
Inverse Association ◽  
Care Hospital ◽  
Advanced Stage ◽  
Histologic Subtype

Abstract Background: The utility of bone marrow biopsy (BMB) in patients with Hodgkin lymphoma (HL) has been a controversial topic. Clinical stage 4 (CS4) has been shown to be an independent poor prognostic marker and is also included in the International Prognostic Scoring (IPS) index for predicting both progression-free survival (PFS) and overall survival (OS). The current guidelines still recommend performing a BMB in patients with stage IIB (with unfavorable risk factors), III and IV HL, mainly for staging purposes. Though bone marrow involvement (BMI) upstages the HL to stage IV, the prognostic significance of BMI remains unclear. The study was aimed to determine the prognostic significance of BMI in underserved patients with HL and to determine the prognostic importance of other blood parameters. Methods: The study was conducted at John H. Stroger Hospital of Cook County, an inner city tertiary care hospital providing care to the underserved population of Chicago. Charts of 241 patients diagnosed with HL were screened from tumor registry. Patients with incomplete charts were not included in the study. Socio-demographic, clinical and pathologic factors were recorded at the time of diagnosis. For comparative purpose, CS4 disease did not include patients with BMI. Kaplan-Meier and bivariate analyses were performed. Cox regression analyses were conducted to explore predictors of OS and PFS. Hazard ratios (HR) with 95% confidence intervals (CI) were obtained. Results: The study included 192 patients of which 41% were Afro-Americans, 34% were Hispanics and 21% were Caucasians. Median age was 34 years with 25.5% patients being older than 45 years and 68% patients being women. Seventeen percent patients were positive for HIV. Nodular sclerosis was the most common histologic subtype (55%), bulky disease was recorded in 19% patients and 61.5% patients had B-symptoms. CS4 disease was seen in 12% patients while 28% patients were stage III, 47% were stage II and 13% were stage I. Single-site BMB was done in 96% patients. BMB was positive for involvement with HL in 19% patients (n=37). Out of these 37 patients, 84% (n=31) had advanced stage (III & IV) HL. BMI was seen in 5% patients with early-stage HL (stages I-II) and 41% patients with advanced-stage HL. Median IPS score was 2 (range 0-6). Median values for clinical factors were: hemoglobin-11.8 g/dL, platelets 314.5 x103/uL, leukocytes 8.3 x103/uL, neutrophils 6x103/uL, lymphocytes 1.2 x103/uL and albumin 3.7 g/dL. Mean OS was 143 months (95% CI 126-160) with 5-year OS of 89%. Significant correlates of OS included: age 45 years or older (HR 2.83, 95%CI 1.25-6.43, P =0.013), HIV (HR 2.80, 95%CI 1.19-6.61, P =0.019), nodular sclerosistype (HR 0.29, 95%CI 0.12-0.71, P =0.006), CS4 disease (HR 3.05, 95%CI 1.20-7.77, P =0.019), BM positive for involvement with HL (HR 5.76, 95%CI 2.56-12.98, P <0.001), IPS score (HR 1.57, 95%CI 1.20-2.06, P =0.001), hemoglobin <10.5 g/dL (HR 3.57, 95%CI 1.56-8.19, P =0.003), platelets <150 x103/uL (HR 5.32, 95%CI 2.19-12.96, P <0.001) and lymphocytes <0.6 x103/uL (HR 2.97, 95%CI 1.21-7.28, P =0.017). Gender, albumin level, leukocytosis (>15 x103/uL) and relative lymphopenia (<8%) did not have a significant association with OS. When adjusted for CS4 disease, BMI remained an independent predictor of OS (HR 2.17, 95%CI 1.04-4.55, P =0.039). Mean PFS was 105 months (95% CI 97-117) with 5-year PFS of 78%. BMI (HR 2.38, 95%CI 1.21-4.67, P =0.012), albumin level (HR 0.71, 95%CI 0.53-0.94, P =0.017) and albumin-globulin ratio (HR 0.41, 95%CI 0.18-0.93, P =0.032) predicted PFS. None of the other factors had a significant association with PFS. BMI had inverse association with OS (mean OS 97.5 months vs. 164 months, P <0.001; 5-year OS 70% vs. 93.5%, P<0.001) and PFS (mean PFS 74 months vs. 112 months, P = 0.004; 5-year PFS 65% vs. 81%, P=0.030). Conclusion: BMI in HL indicates disseminated disease. Our study shows that BMI in patients with HL has a significant inverse relation with OS and PFS, independent of stage. Our data indicates that in patients with HL important prognostic information can be achieved by demonstrating BMI and it should be considered for inclusion in the IPS score. The rate of BMI is higher in our cohort, for both early and advanced stage HL, when compared with literature and maybe a limitation of our retrospective study. However our results still warrant that long term prospective studies should be designed to explore the prognostic significance of BMI. Disclosures No relevant conflicts of interest to declare.

scholarly journals BONE MARROW IN FOLLICULAR LYMPHOMA PROGNOSIS

2016 ◽  
Vol 15 (3) ◽  
pp. 99-102 ◽  
Author(s):  
N. N. Tupitsyn ◽  
N. A. Falaleeva ◽  
A. V. Mozhenkova ◽  
A. I. Pavlovskaya
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Follicular Lymphoma ◽  
Histological Study ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Prognostic Role ◽  
Long Time

Background. Bone marrow is the mostfrequent metastatic site in follicular lymphoma, 40-70 % cases. It’s unfovourable prognostic role is stated in the index FLIPI-2 (Follicular Lymphoma International Prognostic Index-2). Objective. To study both prognostic role of bone marrow involvement and it’s relation to erythropoiesis peculiarities in follicular lymphoma was the purpose of this research. Materials and methods. Histological study was performed in 269 follicular lymphoma patients. Erythropoiesis peculiarities were studied in that patients according to standard myelogram analysis. Results. Bone marrow involvement was noted according to trephine biopsy section staining in 37,9 % of follicular lymphoma case (102 from 269). Bone marrow involvement did not influenced the prognosis (overall survival) in all period of observation (p = 0,18). Longterm survival (more than 48 months) was negatively influenced by bone marrow involvement (p = 0,04). Intertrabecular pattern of follicular lymphoma growth in bone marrow was negative prognostic factor (p = 0,02). We noted negative correlation between bone marrow involvement and the elevation of orthochromic normoblasts in bone marrow of patients with follicular lymphoma. In cause of bone marrow such elevation was noted in 67 %, and in the absense of involvement - in 78 % (p = 0,043). Elevation of orthochromic normoblasts did not influenced the overall survival of follicular lymphoma patients (p = 0,89). Conclusion. Bone marrow involvement in follicular lymphoma plays prognostically unfavourable role in long-time observation periods (later than 48 months). The most unfavourable are the intertrabecular patchy lesions. Involvement of bone marrow is in opposite relations to elevation of orthochromic normoblast, but the latter sign is of no prognostic significance.

Clinical and prognostic significance of bone marrow involvement in patients with diffuse aggressive B-cell lymphoma.

1995 ◽  
Vol 13 (6) ◽  
pp. 1336-1342 ◽  
Author(s):  
Y Yan ◽  
W C Chan ◽  
D D Weisenburger ◽  
J R Anderson ◽  
M A Bast ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Term Survival

PURPOSE We studied the effect of morphology and extent of bone marrow (BM) infiltrate on the survival of patients with diffuse aggressive B-cell non-Hodgkin's lymphoma (NHL), along with clinical features. PATIENTS AND METHODS Sixty adult patients with diffuse aggressive B-cell NHL and BM involvement at the time of presentation were studied. All patients were uniformly staged and treated with a curative high-dose chemotherapy regimen. BM involvement was assessed according to the cytology, pattern of infiltration, and extent of involvement, and was correlated with overall survival (OS) and failure-free survival (FFS). RESULTS Patients with BM involvement that consisted of > or = 50% large cells or BM involvement of > or = 70% had a poorer OS (P = .065 and P = .055, respectively). Those who presented with an infiltrate of less than 50% large cells and an international prognostic index (IPI) of < or = 3 had a significantly longer postrelapse survival time (P = .003). A diffuse or interstitial pattern of BM involvement was predictive of both poor OS and FFS (P = .008 and .009, respectively). Multivariate analysis indicated that only IPI (P = .0005) and pattern of BM infiltration (P = .009) were independent predictors of OS, and only the former was predictive of FFS (P = .03). CONCLUSION The IPI is predictive of OS and FFS, while BM involvement with a diffuse or interstitial pattern is associated with significantly poorer OS. Patients with BM infiltration that involved > or = 70% of the marrow or contained > or = 50% large cells had poor OS, but more patients need to be studied to determine the significance. Two parameters, IPI < or = 3 and BM large cells less than 50%, identify a group of patients with long-term survival after relapse.

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