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.

Diffuse Large B-Cell Lymphoma: Risk Stratification and Management of Relapsed Disease

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 252-259 ◽  
Author(s):  
John W. Sweetenham
Keyword(s):  
Gene Expression ◽  
Risk Stratification ◽  
B Cell ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Molecular Techniques ◽  
High Dose ◽  
Large B Cell

Abstract The clinical factors described by the International Prognostic Index (IPI) provide a model for risk stratification in diffuse large B-cell lymphomas (DLBCLs). However, there is variability in outcome within IPI risk groups, indicating the biological and clinical heterogeneity of these diseases. Studies of gene expression profiling (GEP) in DLBCL are uncovering biological heterogeneity with prognostic significance. Various gene expression signatures with predictive value independent of the IPI are now recognized. Immunophenotypic features of DLBCL have also been shown to have prognostic value. The use of fluorodeoxyglucose–positron emission tomography (FDG-PET) scanning may provide additional predictive information when used at diagnosis or soon after initiation of treatment. Future prognostic models in DLBCL are likely to incorporate functional imaging, immunophenotype and GEPs as well as clinical data in risk stratification and choice of treatment. Treatment of relapsed DLBCL remains a major problem. High-dose therapy (HDT) and stem cell transplantation (SCT) has been shown to produce superior overall survival (OS) compared with conventional dose salvage therapy in patients with relapsed, chemosensitive DLBCL. However, only 20% to 30% of patients are cured by this approach, and the effectiveness of HDT and SCT in patients treated with rituximab-based combinations as first-line therapy is unknown. Although new transplant techniques including non-myeloablative allogeneic SCT are being investigated, their role is unclear. New treatment strategies are needed for these patients. The use of molecular techniques such as GEP is identifying many potential new therapeutic targets in DLBCL including histone deacetylase, HLA-DR, bcl-2, bcl-6, mTOR and TRAIL.

High Incidence of Asian Variant Intravascular Large B-Cell Lymphoma (IVL) among IVL in Japan: Clinicopathologic Study of 95 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1365-1365
Author(s):  
Takuhei Murase ◽  
Ritsuro Suzuki ◽  
Motoko Yamaguchi ◽  
Masataka Okamoto ◽  
Yumiko Sato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
B Cell ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Serum Lactate Dehydrogenase

Abstract IVL is a rare form of aggressive B-cell lymphoma characterized by multifocal and predominant growth within vessels. Although its neurologic and dermatologic manifestations at diagnosis have been well documented, clinical courses of IVL are protean by patients. Systematic strategies for diagnosis and treatment of IVL are still to be established. To address these issues, we retrospectively analyzed a series of patients with IVL. This study was conducted by a refractory lymphoma study group, supported by the Ministry of Labor, Health and Welfare of Japan, and approved by the institutional review board of each participating institution. Both histopathological findings of IVL and positive reactions for at least one B-cell antigens (CD20, CD19 or CD79a) were required for inclusion. There were 95 patients (49 males and 46 females), with a median age of 67 years old (range 41–85). Most patients of IVL were associated with poor prognostic factors; i.e., 95% had more than 1 site of extranodal involvement, 91% had stage III/IV disease, 82% showed performance status greater than 1, and 94% had serum lactate dehydrogenase higher than normal level. Eighty-five percent was classified to the high-risk group of the International Prognostic Index (IPI). Therefore, IPI is not useful for the prognostification of IVL. Thirty-five patients (37%) were positive for CD5. Hemophagocytosis in the bone marrow, a key pathologic criterion for Asian variant of IVL (AIVL; Murase et al: Brit J Haematol 2000), was noted in 53 of 79 patients (67%) with available information. All these 53 patients met the clinical and laboratory criteria for AIVL, including anemia, thrombocytopenia, hepatosplenomegaly, and absence of tumor formation. In contrast, no hemophagocytosis was observed in 13 patients who did not meet the criteria. Patients with IVL were further characterized by the presence of B symptoms (76%), neurologic abnormality (27%), skin lesion (13%), and leukocytopenia (&lt;4x109/L; 27%). Bone marrow involvement was identified in 76% of the patients. Leukemic lymphoma cells were noted in 28% of the patients. Since 16 patients were diagnosed at autopsy, and 4 died shortly after the diagnosis or failed to follow, 75 were enrolled for analyses of prognostic factors. Univariate analyses for overall survival showed no use of anthracycline containing regimen (p=0.001), older age (p=0.005), lower platelet count (&lt;100x109/L; p=0.006), and higher serum soluble IL-2 receptor (5x103U/mL or more; p=0.017) as unfavorable prognostic factors. Multivariate analysis using Cox regression model revealed that all these three factors were independent and significant prognostic factors (no anthracycline regimen: p=0.002, Hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.53–6.90; age by 10 years: p=0.014, HR 1.36, 95%CI 1.07–1.66; and platelet &lt;100x109/L: p=0.037, HR 2.12, 95%CI 1.05–4.31). These findings suggest patients with IVL should be treated chemotherapy containing anthracyclines.

Detection of B-Cell Clonality in Bone Marrow Is Independent Predictor of Outcome in De Novo Diffuse Large B-Cell Lymphoma Patients Treated with High-Dose Chemotherapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2967-2967
Author(s):  
Olga A. Gavrilina ◽  
Eugene E. Zvonkov ◽  
Elena N. Parovichnikova ◽  
Andrey B. Sudarikov ◽  
Alla M. Kovrigina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
De Novo ◽  
Independent Predictor ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
Chain Gene ◽  
High Dose ◽  
Cell Clonality

Abstract Introduction: Detection of bone marrow involvement (BM) is a factor of poor prognosis for diffuse large B-cell lymphoma (DLBCL), since DLBCL BM is characterized by aggressive course and low response level to standard chemotherapy (CT), and 5-year overall survival (OS) rate for this group is less than 30% after ÑHOP-like CT. Intensification of therapy in this group of patients can improve the results, except patients with bone marrow involvement at diagnosis. Bone marrow involvement is a poor prognostic factor for patients treated with high-dose chemotherapy. Bone marrow involvement in DLBCL by histology is detected in 10-30% patients. The importance of B-cell clonality examination in bone marrow as prognostic and staging factor has not been described in the literature. Aim: To evaluate the significance of the immunoglobulin heavy chain gene rearrangement analysis performed by PCR for identification of the bone marrow involvement frequency and its value for staging and prognosis in patients with de novo DLBCL treated with high-dose chemotherapy (HDC). Patients and methods: We performed a pilot prospective trial, including 175 consecutive adult patients (median age 45 years, range 18–67) with newly diagnosed DLBCL who were enrolled in HDC protocol (mNHL-BFM-90 program or scheme R-EPOCH/R-HMA) since June 2007 till July 2014. Their clinical characteristics included such factors as IPI and phenotype DLBCL by immunohistochemical study. Out of the 175 patients, 85 had a GCB phenotype and 90 - non-GCB; 36 patients (20%) had low IPI risk, 40 patients (23%) had low-intermediate, 38 patients (22%) had high-intermediate, 61 patients (35%) had high risk. B-cell clonality was evaluated using PCR amplification by IGH (FR1, FR2, FR3) and IGK (Vκ-Jκ, Vκ/intron-Kde) gene rearrangements with multiplex BIOMED-2 primer sets and subsequent fragment analysis using ABI PRISM 3130 Genetic Analyzer (Applied Biosystems).In 105 of 175 patients the study by BIOMED-2 multiplex polymerase chain reaction protocol of B-cell clonality of bone marrow was fulfilled. Statistical analysis was done using JMP ver. 10.0 (SAS, Cary, NC). Results: Histological and immunohistochemical studies validated bone marrow involvement in 19 patients (10.8%), including: concordant in - 12 patients (63%), and discordant - in 7 patients (37%). In 14 of these patients the B-cell clonality detection was performed and confirmed immunoglobulin (IG) heavy chain gene rearrangement in all cases. In 26 out of 105 patients, bone marrow involvement (24.7%) was revealed: in 14 patients bone marrow involvement was identified by histological examination and in 12 patients only by clonality of bone marrow. 12 patients with only B-cell clonality in bone marrow were classified by IPI: 4 (33%) patients had high IPI, 6 (50%) patients - high-intermediate IPI and low-intermediate IPI - 2 (17%) patients. So, in 17% patients had to change the risk group according to bone marrow involvement. Thus, 31 patients with bone marrow involvement signs were identified. Univariate analysis of the entire cohort (n = 175) revealed that both IPI and phenotype were not of prognostic significance (p > 0.05). In multivariate analysis, detection of B-cell clonality in bone marrow was an independent predictor of OS and relapse-free survival (RFS) (p < 0.005). (Fig.1-2). OS, RFS in patients with histological detection bone marrow involvement and with only B-cell clonality in the bone marrow did not differ. Conclusion:Detection of B-cell clonality in the bone marrow seems to be an independent predictor of outcome in de novo DLBCL pts, treated with high-dose chemotherapy, while IPI and phenotype DLBCL cannot be considered as risk factors for this group of pts. It seems to be reasonable to include the detection of B-cell clonality in the bone marrow in primary diagnostics of the DLBCL for staging and predicting response in HDC. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chidamide combined with ibrutinib improved the prognosis of primary bone marrow diffuse large B cell lymphoma

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093605 ◽  
Author(s):  
Chen Tian ◽  
Zehui Chen ◽  
Yueyang Li
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Primary Bone ◽  
Primary Bone Marrow

Primary bone marrow diffuse large B cell lymphoma (DLBCL) is an independent pathologic type with a poor prognosis when treated with standard chemoimmunotherapy. Generally, rituximab-based high-dose chemotherapy regimens such as dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) can be administered to young patients, followed by autologous stem cell transplantation. For elderly patients, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen is well tolerated, but it is an insufficient induction therapy for this group. Herein, we reported an elderly patient diagnosed with primary bone marrow DLBCL, germinal center B-cell-like subtype. Considering tolerance, the R-CHOP regimen was administered. However, his disease progressed after two treatment cycles. Then, the rituximab, gemcitabine, dexamethasone, cisplatin, lenalidomide regimen was administered, but the patient still experienced disease progression. Subsequently, the histone deacetylase (HDAC) inhibitor chidamide and Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib were concurrently administered, and the patient achieved complete remission. We found that the response of primary bone marrow DLBCL to chemotherapy was poorer than that of de novo DLBCL. High-dose chemotherapy regimens such as DA-EPOCH should be administered to young patients in combination with rituximab. For elderly patients, new targeted drugs such as HDAC and BTK inhibitors appear to produce favorable outcomes.

Impact of Concordant and Discordant Bone Marrow Involvement on Outcome in Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2011 ◽  
Vol 29 (11) ◽  
pp. 1452-1457 ◽  
Author(s):  
Laurie H. Sehn ◽  
David W. Scott ◽  
Mukesh Chhanabhai ◽  
Brian Berry ◽  
Anna Ruskova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Bone Marrow Biopsies ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose In diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant bone marrow involvement with DLBCL portends a poorer prognosis, whereas discordant bone marrow involvement with small B-cell lymphoma does not. We examined the significance of bone marrow involvement in patients treated in the current era of therapy including rituximab. Patients and Methods We performed a retrospective analysis of the prognostic impact of bone marrow involvement in an unselected population of patients with newly diagnosed DLBCL treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in British Columbia and Auckland, New Zealand, with complete clinical information and evaluable staging bone marrow biopsies. Results In total, 795 patients were identified. Six hundred seventy (84.3%) of 795 had a negative bone marrow, 67 patients (8.4%) had concordant and 58 (7.3%) had discordant involvement. Median follow-up was 41 months (range, 1 to 115). Progression-free survival (PFS) was inferior in those with concordant (P < .001) and discordant (P = .019) involvement while overall survival (OS) was inferior in those with concordant involvement (P < .001) only. In a multivariate analysis controlling for the International Prognostic Index (IPI) score, concordant involvement remained an independent predictor of PFS (P < .001) and OS (P = .007). Discordant involvement was associated with older age, elevated lactate dehydrogenase, advanced stage, and increased number of extranodal sites and was not a negative prognostic factor independent of the IPI score. Conclusion The negative prognostic impact of discordant involvement is adequately represented by the IPI score, while the risk with concordant involvement is greater than that encompassed by this predictor. The results emphasize the need for accurate staging assessment of bone marrow involvement in DLBCL.

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.

Prognostic significance of metallothionein in B-cell lymphomas

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3514-3519 ◽  
Author(s):  
Christian Bjørn Poulsen ◽  
Rehannah Borup ◽  
Niels Borregaard ◽  
Finn Cilius Nielsen ◽  
Michael Boe Møller ◽  
...  
Keyword(s):  
B Cell ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Significant Risk ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Significant Risk Factor ◽  
Sustained Remission ◽  
B Cell Lymphomas ◽  
Lymphoma Cells

Abstract We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure. This was confirmed in 2 independent series, which showed significantly shorter 5-year survival in DLBCL with high versus low MT-IIa levels. By immunohistology, MT was shown to be present in both macrophages and lymphoma cells. The proportion of MT-positive macrophages did not correlate with the survival. In contrast, in 115 DLBCLs, MT labeling of more than 20% lymphoma cells was associated with a significantly poorer 5-year survival, independent of the age, stage, or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by more than 20% lymphoma cells constitute independent risk factors in DLBCL.

The prognostic significance of bone marrow involvement in diffuse large B cell lymphoma according to the flow cytometry

2019 ◽  
Vol 60 (10) ◽  
pp. 2477-2482 ◽  
Author(s):  
Uri Greenbaum ◽  
Itai Levi ◽  
Odelia Madmoni ◽  
Yotam Lior ◽  
Kayed Al-Athamen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 478-485 ◽  
Author(s):  
Takuhei Murase ◽  
Motoko Yamaguchi ◽  
Ritsuro Suzuki ◽  
Masataka Okamoto ◽  
Yumiko Sato ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Clinicopathologic Study ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Intravascular large B-cell lymphoma (IVLBCL) is pathologically distinct with a broad clinical spectrum and immunophenotypic heterogeneity. A series of 96 patients with IVLBCL (median age, 67 years; range, 41-85 years; 50 men) was reviewed. Anemia/thrombocytopenia (84%), hepatosplenomegaly (77%), B symptoms (76%), bone marrow involvement (75%), and hemophagocytosis (61%) were frequently observed. The International Prognostic Index score was high or high-intermediate in 92%. For 62 patients receiving anthracycline-based chemotherapies, median survival was 13 months. CD5, CD10, Bcl-6, MUM1, and Bcl-2 were positive in 38%, 13%, 26%, 95%, and 91% of tumors, respectively. All 59 CD10− IVLBCL cases examined were nongerminal center B-cell type because they lacked the Bcl-6+MUM1− immunophenotype. CD5 positivity was associated with a higher prevalence of marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic abnormalities among patients with CD10−IVLBCL. Compared with 97 cases of de novo CD5+CD10−diffuse LBCL, 31 cases of CD5+CD10−IVLBCL exhibited higher frequencies of poor prognostic parameters, except age. Multivariate analysis in IVLBCL revealed that a lack of anthracycline-based chemotherapies (P < .001, hazard ratio [HR]: 9.256), age older than 60 years (P = .012, HR: 2.459), and thrombocytopenia less than 100 × 109/L (P = .012, HR: 2.427) were independently unfavorable prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity, IVLBCL constitutes a unique group with aggressive behavior.

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