Bone Marow (BM) Involvement in Diffuse Large B Cell Lymphoma (DLBCL): Clinical Impact of Discordant Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2031-2031
Author(s):  
Mukesh Chhanabhai ◽  
Joseph Connors ◽  
Wayne Seville ◽  
Dan Matso ◽  
Randy Gascoyne
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Clinical Impact ◽  
Low Grade ◽  
Large B Cell Lymphoma ◽  
Clinical Records ◽  
Large B Cell

Abstract Background and Methods: Most published studies have suggested that survival of de novo DLBCL with discordant BM involvement by small B cell lymphoma is indistinguishable from patients having a negative staging BM. The aim of the study was to investigate the incidence and clinical impact of BM involvement by concordant and discordant B cell lymphoma in patients with DLBCL seen in a single institution over a 5 year period (1\1\2000 – 31\12\2004). The cases were identified from pathology records and BCCA Lymphoid Cancer Database. Results: The group of interest for this study comprised 652 patients with de novo DLBCL with staging marrow available for review. 60 of 652 (9.2%) of patients with DLBCL had concordant large B-cell lymphoma in their bone marrow. 523 (80.2%) were negative, 16 patients showed what we considered to be atypical lymphoid (ALH) infiltrates lacking definitive features of malignancy. In 50 patients (7.7%) the bone marrow showed discordant histology with predominantly small B-cells, some showing paratrabecular localization. In total there were five cases of TCRBCL in the study, three with marrow involvement. Furthermore, all 54 cases of primary mediastinal B-cell lymphoma (PMBCL) had a negative BM. Of the 652 cases with DLBCL with staging bone marrows available, merging the pathology and clinical databases resulted in 599 patients with complete clinical records. Of these, bone marrows were either not done or deemed inadequate in 101 cases. Therefore, there were 488 patients with DLBCL with an interpretable marrow of which 344 had advanced stage disease. Staging marrows in these patients were negative = 264, positive 41, discordant 28, and ALH 11. The overall survival and progression free survival were strongly affected by the IPI score for these 344 cases (P<0.00001) (see figure). Compared to those without BM involvement patients with concordant large B-cell lymphoma in their BM (n=41) had the worst outcome and those with discordant small B-cell lymphoma in the bone marrow (n=28) had an inferior but intermediate outcome (median survivals (months) = not reached;12 and 20, respectively). Conclusion: Diffuse large B-cell lymphoma is a heterogenous group of lymphomas as demonstrated by gene expression profiling. Our data suggests that discordant low grade B-cell lymphoma in patients who have coincident DLBCL has a poorer prognosis and the presence or absence of BM disease has clinical significance. Though we had very few cases, TCRBCL show a higher incidence of BM involvement in keeping with the reported literature. The absence of marrow disease in PMBCL is consistent with recent data indicating it is a biologically distinct form of DLBCL. Figure Figure

Diffuse Large B-Cell Lymphoma (DLBCL) Patients with Composite Histology Have Improved Early Outcome Compared to De Novo DLBCL When Treated with R-CHOP

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2819-2819
Author(s):  
Matthew J. Maurer ◽  
Thomas E. Witzig ◽  
William R. Macon ◽  
Sergei I. Syrbu ◽  
James R. Cerhan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: A significant percentage of DLBCL patients present with a composite histology, often seen as a node containing both follicular lymphoma and DLBCL or DLBCL in the node and discordant indolent lymphoma in the bone marrow. Literature from the pre-rituximab era suggests DLBCL patients with transformed lymphoma or composite histology have worse outcome than de novo DLBCL. Here we report on early events in a cohort of R-CHOP treated patients. Goal: To determine whether patients with composite lymphoma have an inferior event free survival (EFS) and overall survival (OS) compared to de novo diffuse large B-cell lymphoma when treated with R-CHOP. Methods: Newly diagnosed patients treated with an R-CHOP containing regimen were prospectively enrolled in our Lymphoma SPORE registry from 9/2002 through 6/2007. Pathology was centrally reviewed. All patients were followed for retreatment, disease progression, and death. Results: 401 DLBCL patients were enrolled; 14% (57/401) had a composite histology. 33 patients had DLBCL and another histology, predominantly follicular lymphoma (n=29), in the same node. 20 patients had a non-DLBCL histology in a distinct location from the DLBCL; this was primarily indolent lymphoma in the bone marrow (n=15). 4 patients had both. 19% (75/401) of patients died during follow-up and 30% (121/401) had an event (death due to any cause, progression, or retreatment). Median follow-up for living patients was 34 months (range, 5–73). Composite DLBCL patients had higher event-free (3 year EFS = 79%) and overall (3 year OS = 93%) survival then de novo DLBCL (3 year OS = 66%, 3 year EFS 79%), p=0.05 and p=0.005 respectively. These differences remained statistically significant after adjusting for the International Prognostic Index (IPI): EFS HR = 0.53, 95% CI: 0.29–0.97, p=0.02; OS HR=0.28, 95% CI: 0.10–0.76, p=0.002. OS and EFS for composite DLBCL more closely resembled R-CHOP treated grade III follicular lymphoma (A,B) from the same cohort (3 year EFS = 81%, 3 year OS = 93%). Improved outcome for composite DLBCL was consistent whether the additional histology was in the same node or distinct from the DLBCL. Conclusions: R-CHOP treated DLBCL patients with indolent discordant bone marrow involvement or other composite histology have improved early OS and EFS compared to de novo DLBCL. Further follow-up is needed to assess the long-term prognosis of composite DLBCL in the rituximab era. Histology N Age &gt; 60 Stage III/IV LDH &gt; ULN PS &gt; 1 &gt;2 EN Sites 3 YR EFS 3 YR OS * Denotes statistically significant difference at p=0.05 de novo DLBCL 344 58% 56% 56% 17% 22% 66% 78% Composite DLBCL 57 65% 77%* 34%* 18% 32% 79%* 93%* Figure Figure

scholarly journals A Case ofDe NovoCD5+ Disseminated Intravascular Large B-Cell Lymphoma Presenting as Multiorgan Failure

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Daulath Singh ◽  
Devika Kapuria ◽  
Suparna Nanua ◽  
Rakesh Gaur
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Bone Marrow Biopsy ◽  
De Novo ◽  
Cell Lymphoma ◽  
Multiorgan Failure ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Intravascular large B-cell lymphoma is an extremely rare extranodal lymphoma that proliferates in the lumen of the blood vessels while sparing the organ parenchyma. It usually presents with CNS and skin involvement. A 65-year-old Caucasian female presented with fevers and chills of 3-4 months’ duration. Bone marrow biopsy done 3 months prior showed no significant myelodysplasia or lymphoid aggregates. The patient later died due to multiorgan failure. A bone marrow biopsy showed 20–30% CD5+ B cells consistent with infiltrative large B-cell lymphoma. An autopsy performed revealed diffuse intravascular invasion by lymphoma cells. Multiorgan involvement by intravascular B-cell lymphoma is very rare. Based on our literature review and to the best of our knowledge, there are only 5 case reports describing the presentation of this lymphoma with multiorgan failure. The immunophenotypic studies performed revealed that our patient hadde novoCD5+ intravascular large B-cell lymphoma which is known to be aggressive with very poor prognosis. Although it is an extremely rare lymphoma, it should be considered as a potential cause of multiorgan failure when no other cause has been identified. A prompt tissue diagnosis and high-dose chemotherapy followed by ASCT can sometimes achieve remission.

scholarly journals An unusual case of primary hepatic lymphoma with dramatic but unsustained response to bendamustine plus rituximab and literature review

2017 ◽  
Vol 5 ◽  
pp. 2050313X1770919 ◽  
Author(s):  
Sih-Han Liao ◽  
Yin-Kai Chen ◽  
Shan-Chi Yu ◽  
Ming-Shiang Wu ◽  
Hsiu-Po Wang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Hepatic Tumors ◽  
Primary Hepatic Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Objectives: Primary hepatic lymphoma is an uncommon cause of hepatic space-occupying lesions. Methods: We describe the case of a 73-year-old man with primary hepatic lymphoma, who presented with a low-grade fever and lower limb weakness which had progressed in the past 2 months. Results: Abdominal ultrasound and computed tomography showed multiple small hepatic tumors. Echo-guided biopsy of the hepatic tumor demonstrated primary hepatic diffuse large B cell lymphoma. Moreover, bone marrow was uninvolved, but the bone marrow smear disclosed hemophagocytosis, which is uncommon in diffuse large B cell lymphoma. Chemotherapy with bendamustine and rituximab treatment was initiated with a dramatic response: hepatic tumors markedly shrank in size shown by follow-up computed tomography and the patient returned to his normal life. Nevertheless, the response was sustained for only 8 months. Finally, the disease resisted further chemotherapy and this patient died of a severe Klebsiella pneumoniae infection. Conclusion: Chemotherapy with bendamustine and rituximab has shown a dramatic, but not durable, response in the present case with old age and multiple comorbidities.

High Grade Transformation in Splenic Marginal Zone Lymphoma: A Description of a Series of 8 Cases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4599-4599
Author(s):  
Moez R. Dungarwalla ◽  
Andrew Wotherspoon ◽  
Gareth Morgan ◽  
Daniel Catovsky ◽  
Claire E. Dearden ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Splenic Marginal Zone Lymphoma ◽  
High Grade ◽  
Large B Cell Lymphoma ◽  
High Grade Transformation ◽  
Large B Cell

Abstract Splenic marginal zone lymphoma (SMZL) without or with villous lymphocytes (SLVL) is a low grade B cell non-Hodgkin’s lymphoma that comprises &lt;1% of lymphoid malignancies. SLVL is indistinguishable histologically from SMZL and it is believed that the 2 entities represent different phases of the same process in the spleen and the bone marrow. Characteristic features of SMZL are splenomegaly, moderate lymphocytosis, immunophenotype with a CLL score &lt; 2 and nodular/intrasinusoidal pattern of bone marrow infiltration. Despite its slow clinical course, and response to splenectomy, approximately 50% of deaths in patients with SMZL are caused by progressive disease. As in other low grade lymphoproliferative disorders, SMZL may undergo high grade transformation. We describe 8 cases of SMZL that showed clinical, morphological and histological features of progression to large B cell lymphoma. These 8 cases represent 19% of our series of 41 SMZL patients followed up between 1996 and 2006. Patients were aged between 44 and 76 years, and there were 4 men and 4 women. Progression to high grade B cell lymphoma occurred between 1 and 48 months from diagnosis. The cases can be divided into 2 distinct groups on the basis of the site of transformation. Those cases with high grade transformation in the bone marrow had a median overall survival of 10 months, although 1 patient did attain a complete remission with combination chemotherapy (R-CHOP) and is alive at 12 months. In contrast, there were 3 cases of transformation in peripheral lymph nodes with a median overall survival of 60 months. Large B cell lymphoma was also diagnosed in the spleen in the initial stages of the disease in 1 case. This patient achieved a complete remission with R-CHOP post splenectomy, and is still alive at 36 months follow up. In a previous report of transformation to large B cell lymphoma in SMZL (Camacho et al, Am J Surg Pathol 2001) a 13% incidence was reported. In our series of 8 cases the incidence of transformation is 19%. Hence it appears that while the incidence of large B cell transformation seems to be higher than in CLL (1–10%) it is lower than that reported in follicular lymphoma (25–60%). Two of the 4 cases of high grade transformation in the bone marrow had previously been treated with fludarabine in the year prior to their progression to large B cell lymphoma. In 1 of these cases Epstein Barr Virus encoded RNA was detected in the malignant cells at the time of transformation. This may suggest that EBV is involved in the pathology of SMZL transformation, and treatment with immunosuppressive agents such as the purine analogues, may increase this risk. In our series of 41 patients, 6 have received fludarabine therapy and the risk of high grade transformation in this small group is significantly higher at 33% (2/6).

Prognostic Impact, Phenotypic and Molecular Characterization of Concordant and Discordant Bone Marrow Involvement in Patients with Diffuse Large b-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3871-3871
Author(s):  
Sara Alonso ◽  
Miguel Alcoceba ◽  
Oscar Blanco ◽  
Julio Davila ◽  
Juan Carlos Caballero ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Free Survival ◽  
Clonal Relationship ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract INTRODUCTION: In the rituximab era, the prognostic influence of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) has been hardly studied. In this retrospective observational study, we aim to investigate the prognostic influence of concordant and discordant BM infiltration in patients with histological diagnosis of DLBCL. In addition, we analyzed the possible clonal relationship between BM and lymph node tumor cells in the cases with discordant histology. PATIENTS AND METHODS: All patients diagnosed of DLBCL in our center from January 1, 1999 were included in the study. Histological BM infiltration pattern was classified as concordant (DLBCL infiltration) or discordant (small or low-grade B-cell lymphoma) based on the diagnostic reports from the Pathology department. All cases were reviewed for this purpose by an expert pathologist. To further characterize the discordant cases, flow cytometry (FCM) reports of BM infiltration were reviewed. In the discordant cases, the clonal IGH rearrangement was studied in both BM and lymphadenopathy, by amplification of the VDJ genes as recommended in the BIOMED-2 protocol. For survival analysis, only patients treated with R-CHOP or similar were included. RESULTS: 236 patients diagnosed of DLBCL were included in the study; of them, 31 (13%) had concordant histological BM infiltration and 18 (7.6%) discordant. Phenotypic characterization by FCM of the discordant cases was heterogeneous: chronic lymphocytic leukemia (N = 2), follicular lymphoma (N = 5), marginal zone lymphoma (N = 2), non-specific phenotype (N = 5) or non-infiltration (N = 2). Clonality studies were performed in the discordant cases. Good quality DNA was obtained in 17 out of 18 patients. We confirmed the same clone in both BM and lymphadenopathy in 12 patients (70%); different clones were observed in two, and a polyclonal pattern was obtained in the remaining three patients. Survival analyzes were conducted only in the 186 patients treated with R-CHOP or similar. With a median follow up of 58 (1-135) months, PFS was significantly worse in patients with concordant (35% at 5 years, p = 0.001) or discordant (35% at 5 years, p = 0.04) histology, compared to patients without infiltration (64% at 5 years) (Figure 1). OS was significantly lower in patients with concordant histology (53% at 5 years, p = 0.05), whereas there was no significant difference between patients with discordant infiltration (62% at 5 years, p = 0.8) and non-affected BM (75% at 5 years). In the multivariate analysis, concordant BM infiltration (HR = 2.25, 95% CI 1.2 to 4.3, p = 0.01) had a negative influence on PFS (but not on OS), independently of the age, ECOG and LDH, while discordant histology was close to statistical significance (RR = 2; 95% CI 0.95 to 3, p = 0.1) CONCLUSIONS: Our results indicate that BM infiltration, both concordant and discordant, is associated with a lower PFS in DLBCL patients treated with R-CHOP or similar. Cases with discordant BM infiltration have a very heterogeneous phenotype, but we found a clonal relationship between the two different histologies in a high proportion of cases, indicating a probable histologic transformation from a low-grade lymphoma. Further studies are needed to determine the sequence of biological events that might be involved in this transformation. Figure 1. Progression free survival (PFS) according to the concordant or discordant histology of the BM Figure 1. Progression free survival (PFS) according to the concordant or discordant histology of the BM Disclosures No relevant conflicts of interest to declare.

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome

1999 ◽  
Vol 105 (4) ◽  
pp. 1133-1139 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Toshiyuki Ohno ◽  
Kouji Oka ◽  
Masanori Taniguchi ◽  
Motohiro Ito ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Outcome ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Molecular Markers ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Significant Finding ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.

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