Concordant Bone Marrow Involvement Research Articles

CNS relapse in high-grade B-cell lymphoma with MYC and BCL2 rearrangements and dark-zone signature–expressing DLBCL

AbstractHigh-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), or “double-hit lymphoma,” has been associated with a high risk of central nervous system (CNS) relapse. However, historic estimates are impacted by selection bias. We report CNS relapse rates associated with HGBCL-DH-BCL2 from a population-based cohort with complete fluorescence in situ hybridization testing, as well as diffuse large B-cell lymphoma morphology (DLBCL) tumors expressing the dark-zone gene expression signature (DZsig), which was originally derived from HGBCL-DH-BCL2. The 2-year CNS relapse risk in HGBCL-DH-BCL2 was 6.8%. CNS relapses were early, predominantly leptomeningeal (73%), and co-occurred with systemic relapse (64%). High-risk CNS International Prognostic Index (CNS-IPI) and concordant bone marrow involvement were associated with an elevated CNS relapse risk in HGBCL-DH-BCL2. The “refined cell-of-origin” classification assigned 20% of DLBCL morphology tumors with germinal center B-cell–like phenotype (GCB-DLBCL) into a distinct subgroup based on DZsig expression (DZsig+). CNS relapse risk in DZsig+ (2 year: 6.4%) was independent of HGBCL-DH-BCL2 status and was further stratified by the CNS-IPI. CNS relapse in DZsig-negative GCB-DLBCL was rare (2-year risk, 1.4%; P = .04 vs DZsig+) and exclusively parenchymal. Altogether, the CNS relapse risk in HGBCL-DH-BCL2 is lower than previously reported, and DZsig refines risk stratification in GCB-DLBCL.

Prognostic impact of concordant and discordant bone marrow involvement on diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), bone marrow (BM) involvement includes two types that are concordant involvement and discordant involvement. It has been reported that concordant BM involvement has a worse prognosis than discordant involvement in previous studies. However, the prognostic effects of concordant or discordant BM involvement on DLBCL still need further research. In this work, DLBCL cases with BM involvement were collected and analyzed to better reflect the prognostic implications of concordant and discordant BM involvement. We reviewed the cases with newly diagnosed DLBCL and BM involvement from April 2018 to April 2022 in Northern Jiangsu People's Hospital. Overall survival (OS) and progression-free survival (PFS) were accessed by the Kaplan-Meier method and compared between groups by the log-rank test. A multivariate regression analysis based on Cox proportional hazard model was used to test the independent effect of each variable on survival. In total, 32 patients were included and 15 (46.9%) patients had concordant BM involvement and 17 (53.1%) patients had discordant BM involvement. Compared with the discordant group, the concordant group tended to be older and had elevated lactate dehydrogenase level. The outcome of patients with concordant BM involvement was worse than the discordant subset, including OS (P=0.04) and PFS (P=0.03). Furthermore, the discordant BM involvement was excluded to acquire a BM-adjusted International Prognostic Index (IPI) score. The significance of BM-adjusted IPI scores to predict OS was improved greatly compared with the previous IPI scores (P=0.053 vs. P=0.16). Multivariate analysis showed that the BM-adjusted IPI was an independent predictor for OS [hazard ratio =3.406; 95% confidence interval (CI): 1.145-10.127; P=0.03]. These results highlight the requirement for identifying BM infiltration type accurately and then adjusting the IPI score by excluding discordant BM involvement since concordant involvement can partly predict a poor prognosis of DLBCL with BM involvement other than discordant involvement.

Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes

Isolated Extramedullary (EMD) Blastic Transformation of Chronic Myeloid Leukemia (CML-BP) in the TKI Era: Characteristics, Treatments and Outcomes

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy.

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negative BM status. Compared with negative BM disease, concordant BM adversely impacted overall and progression-free survival, independent of the International Prognostic Index (IPI) and cell-of-origin classification. Once BM is concordantly involved, poor prognosis was not associated with the extent of BM involvement. Conversely, patients with discordant BM showed favorable overall survival similar to stage I-II DLBCL. A BM-adjusted IPI, using three parameters: concordant BM involvement, age >60 years, and performance status >1, improves the risk stratification for DLBCL with positive BM. Intensive immunochemotherapy seemingly rendered survival benefit for patients with concordant BM, as did rituximab maintenance for the discordant BM group. Frequently revealing adverse clinical and molecular characteristics, patients with concordant BM demonstrated gene expression signatures relevant to tumor cell proliferation, migration and immune escape. In conclusion, clinical and biological heterogeneity is seen in DLBCL with positive BM but concordant BM involvement represents a distinct subset with unfavorable gene signatures, high-risk clinicopathologic features and poor prognosis.

High Ki-67 expression in involved bone marrow predicts worse clinical outcome in diffuse large B cell lymphoma patients treated with R-CHOP therapy.

Approximately 10-25 % of patients with diffuse large B cell lymphoma (DLBCL) at the time of diagnosis exhibit bone marrow involvement (BMI). After introduction of rituximab, immunohistochemistry (IHC) markers lost to prognostic value in DLBCL patients. However, the specimens used have mainly been diagnostic tissues, not bone marrow (BM). It would thus be useful to determine the prognostic value of specific IHC markers of pathologic BM in DLBCL patients with BMI in the rituximab era. In the present study, a total of 580 DLBCL patients were analyzed 67 of whom had BMI. CD10, Bcl-6, MUM-1, Bcl-6 and Ki-67 dyeing on pathologic BM were applied. Bcl-2 positivity was more frequent in discordant BMI (P = 0.039) and high Ki-67 expression was more frequent in concordant BMI (P = 0.016). High Ki-67 expression independently predicted poor prognosis between the negative BMI group and each of the following BMI-positive groups: entire BMI (PFS, P < 0.001; OS, P < 0.001), concordant BMI (PFS, P = 0.024; OS, P = 0.007), and discordant BMI (PFS, P = 0.033; OS, P = 0.026). We found that Ki-67 expression in pathologic BM is a novel significant prognostic parameter of worse prognosis in DLBCL patients with BMI in the rituximab era.

Impact Of Bone Marrow Involvement On Outcome Of Young Patients With High-Risk Diffuse Large B-Cell Lymphoma (DLBCL) Treated In The Phase III Randomized Trial (DLCL04) With Rituximab Dose-Dense Chemotherapy Followed By Intensified High-Dose Chemotherapy and Autologous Stem Cell Transplantation (HDC+ASCT) Or Standard Rituximab Dose Dense Chemotherapy: A Study of The Fondazione Italiana Linfomi (FIL)

IntroductionThe role of bone marrow (BM) involvement as prognostic factor in untreated young patients with diffuse large B-cell lymphoma at poor prognosis is still a matter of debate. Recent data showed an adverse prognostic role of BM involvement in DLBCL including patients both at low and high IPI score (Sehn L et al, J Clin Oncol 2011). On this basis, FIL analyzed the impact of BM involvement in the prospective randomized phase III trial DLCL04 (Vitolo U et al, Blood, ASH annual Meeting 2012) that included only young patients at high-risk age-adjusted IPI (aa-IPI) score 2 or 3. Patients and MethodsInclusion criteria were: age 18-65; untreated DLBCL or follicular grade IIIb; aa-IPI score 2 or 3. Patients were stratified according to aa-IPI and randomized at diagnosis to receive: R-CHOP14 x 8 cycles; R-MegaCHOP14 (1200 mg/sqm Cyclophosphamide, 70 mg/sqm Doxorubicin, standard dose Vincristine and Prednisone) x 6; R-CHOP14 x 4 + R-HDC (Rituximab + High Dose Cytarabine + Mitoxantrone + Dexamethasone) followed by BEAM and ASCT; R-MegaCHOP14 x 4 + R-HDC + BEAM and ASCT. BM biopsy and aspirate were mandatory at diagnosis; at the end of treatment, BM assessment was mandatory only in case of positivity at baseline. BM involvement was defined as concordant if marrow was involved by large B-cell and discordant if involved by small B-cells. Flow cytometry, immunohistochemistry, and/or molecular studies were utilized to confirm a clonal B-cell population. ResultsFrom June 2005 to September 2010, 399 patients were randomized to receive: 199 R-HDC+ASCT and 200 R-dose-dense chemotherapy without ASCT. All patients were evaluable for analysis. BM involvement was reported in 84 patients (21%): 39 (20%) in the R-HDC+ASCT group and 45 (22%) in the R-dose-dense chemotherapy group. Pattern of involvement was: concordant in 63 patients, discordant in 14 and not specified in 7 patients. Patients with BM involvement (BM positive: 84) compared to those without BM involvement (BM negative: 315) were significantly older (median age 53 years vs 47 years, p<.001) and at higher aa-IPI score (aa-IPI 3: 36% vs 24%, p .024); whereas other clinical characteristics were well balanced between the two groups (ECOG PS >1 43% vs 45%, bulky 25% vs 33%, extranodal sites > 1 26% vs 33%, LDH higher than normal value 93% vs 89%). With a median follow-up of 49 months, 3-year PFS for the whole series of 399 patients enrolled in the trial was: 67% (95% CI: 62-72). Three-year PFS was significantly worse in BM positive vs. BM negative: 46% (95% CI:35-56%) vs. 73% (95% CI:67-77%) p<.001 (Figure 1). In a Cox-model for PFS including type of treatment (ASCT vs no-ASCT, RCHOP vs R-MegaCHOP), age, gender, aa-IPI, performance status, histology and BM involvement, the adverse prognostic impact of BM involvement was maintained with an adjusted Hazard Risk (aHR) of 2.22 (95% CI:1.54-3.22, p<.001).Three-year OS rates in BM positive vs. BM negative were: 65% (95% CI:53-74%) vs. 83% (95% CI:78-87%) with an aHR 1.94 (95% CI:1.23-3.05; p=.004). The adverse prognostic impact of BM involvement on PFS was not affected by the type of treatment and the application of HDC+ASCT: 3-year PFS in BM positive patients treated with R-dose-dense chemotherapy 42% (vs. 69% BM negative) with an aHR of 2.19 (95% CI: 1.35-3.54, p<.001); 3-year PFS in BM positive patients treated with HDC+ASCT 51% (vs. 77% BM negative ) with an aHR of 2.27 (95% CI:1.30-3.97, p<.004). We further analyzed the prognostic impact of the pattern of BM involvement (concordant vs discordant). With the limits of small sample size of the discordant group, concordant BM involvement maintained an adverse prognostic impact on PFS whereas discordant involvement did not affect PFS: in a Cox-model assuming BM negative as reference, the risk of progression was significantly increased in the concordant involvement group with an aHR of 2.48 (95% CI: 1.68-3.67, p<.001) and not affected by discordant involvement (aHR 1.05; 95% CI:0.41-2.71, p=.916). [Display omitted] ConclusionsBone marrow involvement, namely concordant pattern, is a strong adverse predictor of outcome in young patients with untreated DLBCL at poor prognosis treated with R-chemotherapy regardless of intensification with HDC+ASCT. New treatment approaches are needed for these high-risk patients at poor prognosis. Disclosures:Vitolo:Roche: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau.

Diffuse large B‐cell lymphoma and mantle cell lymphoma of the ocular adnexal region, and lymphoma of the lacrimal gland: An investigation of clinical and histopathological features

Diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) constitute two distinct subtypes of non-Hodgkin lymphoma (NHL) associated with considerable morbidity and mortality. Marked diversities with regard to molecular biology and clinical features are recognized in different subsets of the two lymphomas. Because these differences could be related to the location of the lymphoma, it is of interest to investigate the clinical and histopathological features of DLBCL and MCL involving the ocular adnexal region (i.e. the orbit, eyelids, conjunctiva, lacrimal gland and lacrimal sac). Similarly, the lacrimal gland is the only glandular structure within the orbit. Because the lacrimal gland represents an important part of the immunological system, it is of interest to investigate lymphomas involving this location with regard to clinical and histological characteristics. To characterize the clinical and histopathological features of Danish patients with DLBCL of the ocular adnexal region between 1980 and 2009 and of Danish ocular adnexal MCL patients from 1980 to 2005. Furthermore, the aim of this PhD was to review all specimens from patients with lymphoma of the lacrimal gland in Denmark between 1975 and 2009 to determine the distribution of lymphoma subtypes of the lacrimal gland and to describe the clinicopathological features of these patients. A total of 34 patients with DLBCL and 21 with MCL of the ocular adnexal region were identified. Twenty-seven patients had lacrimal gland lymphoma, including four DLBCLs and three MCLs from studies I and II. Elderly patients predominated in all three groups, with median ages of 78, 75 and 69 years in the DLBCL, the MCL and the lacrimal gland lymphoma groups, respectively. MCL patients had a preponderance of males, whereas females prevailed among lacrimal gland lymphoma patients. The orbit was the most common site of involvement in DLBCL and MCL. Most DLBCL patients had unilateral involvement, while MCL patients had a high frequency of bilateral involvement. Similarly, localized lymphoma was relatively frequently seen in DLBCL patients in contrast to the predominance of disseminated lymphoma in the MCL group. The majority of lacrimal gland lymphomas were low grade, and the distribution of subtypes was as follows: extranodal marginal zone lymphoma, 10 (37%); follicular lymphoma, 5 (19%); DLBCL, 4 (15%); MCL, 3 (11%); chronic lymphocytic leukaemia/small lymphatic lymphoma, 2 (7%); and unclassified B-cell lymphoma, 3 (11%). The overall survival rates at 3 and 5 years for the entire study group of DLBCL were 42% and 20%, whereas 58% and 22% of MCL patients were alive 3 and 5 years after the time of diagnosis. The 5-year overall survival rate of lacrimal gland lymphoma patients was 70%. Concordant bone marrow involvement and the International Prognostic Index score were predictive factors for the overall survival in the DLBCL group in Cox regression analysis. Rituximab-containing chemotherapy was associated with an improved survival rate in MCL patients. Diffuse large B-cell lymphoma and MCL involving the ocular adnexal region and lymphoma of the lacrimal gland are prevalent among elderly patients. The overall prognosis in DLBCL and MCL was poor, whereas the prognosis for lacrimal gland lymphoma patients was relatively good. Concordant bone marrow involvement and the International Prognostic Index score were independent predictive factors for mortality in the DLBCL group. Chemotherapy containing rituximab significantly improved survival in the MCL group.

Unusual CD5+ large B-cell lymphoma: Possible follicular variant of diffuse large B-cell lymphoma

We report the unusual case of a CD5+ large B-cell involving lymph node, peripheral blood and the bone marrow of a 63-year-old female. Lymph node findings included an exclusive population of large neoplastic cells against a background of well-formed follicular dendritic cell meshworks. Immunophenotypic findings were reminiscent of those seen in small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), including CD5 and CD23 expression. There were no immunophenotypic or genotypic findings to suggest mantle cell or conventional follicular lymphoma. There was a remote history of a CD5+ large B-cell lymphoma from biopsy of an abdominal mass, with an involved bone marrow, monotypic for the same light chain as the more recent specimen. This lesion displayed a virtually identical histology, and was also found to be CD23 positive. Concordant bone marrow involvement was documented in both 1993 and 2004. A relationship to SLL/CLL was never documented at any point in the patients' clinical course, but is difficult to exclude. Alternatively, findings may be more consistent with a follicular variant of diffuse large B-cell lymphoma, CD5 + .

Diffuse large B‐cell lymphoma of the ocular adnexal region: A nation‐based study

To characterize the clinicopathological features of diffuse large B-cell lymphoma (DLBCL) of the ocular adnexal region. The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re-evaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed DLBCL were collected. A total of 34 patients with DLBCL of the ocular adnexal region were identified. Eighteen of the patients were men. The patients had a median age of 78 years (range 35-97 years). Ninety-seven per cent of the patients had unilateral ocular adnexal region involvement, and the orbit (76%) was the most frequently affected site. Nineteen patients (56%) presented with Stage I lymphoma. Of these, 18 were diagnosed with primary lymphoma. Four patients (12%) had Stage II, one patient (3%) had Stage III and ten patients (29%) presented with Stage IV lymphoma. The 5-year overall survival (OS) rate for the whole study group was 20%. The patients with Stage I lymphoma had a significantly better 5-year OS rate (28%) than patients in Stage II-IV (5-year OS rate, 9%). In Cox regression analysis, concordant bone marrow involvement and the International Prognostic Index (IPI) score were prognostic factors for OS. Diffuse large B-cell lymphoma of the ocular adnexal region is mainly prevalent in elderly patients. Most patients had unilateral orbital involvement. The overall prognosis is poor. Concordant bone marrow involvement and the IPI score were independent prognostic factors for mortality.

Concordant and Discordant Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma: Are They Understudied Phenomena?

TO THE EDITOR: The article by Sehn et al analyzed the prognostic significance of the concordant versus discordant bone marrow involvement (BMI) in a cohort of 795 patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. On the basis of this large series, the authors found that both types of BMI produced a negative impact in terms of progression-free survival, whereas only the concordant involvement was a negative prognostic factor for overall survival that was also independent of the International Prognostic Index score at multivariate analysis. With this report, the first step toward the understanding of this topic seemed to be completed, and it is time to look further. Nevertheless, other important clues could have been retrieved from this representative series with relatively small additional effort. For example, among the group of patients with concordant BMI, a subset analysis of outcomes according to the cell of origin (COO) (ie, the germinal center B-cell v non–germinal center B-cell categories) could potentially further discriminate variables with prognostic relevance. Because categorization according to the COO could be performed retrospectively by means of the algorithm of Hans et al or other similar algorithms that are based on conventional immunohistochemistry, it still could be explored in a follow-up report of this series. Ideally, gene-expression profiling should also be analyzed in future prospective or retrospective studies to determine whether the different COO signatures are associated with different risk of BMI or different outcomes within the category of concordant BMI, but thus far, this has been limited by the availability of frozen tissue. Concerning the group of patients with discordant BMI, it still remains to be determined whether those low-grade infiltrates that are clonally related with the diffuse large B-cell lymphoma (which define a possible transformation from a low-grade to a higher-grade histology) lead to similar biologic effects in terms of progression-free survival and overall survival compared with clonally unrelated cases (which define the presence of two different lymphomas in the same patient). This delineation could be also explored in a retrospective series by determining B-cell receptor rearrangements by polymerase chain reaction– based methods applied on paraffin-embedded tissue samples. As a result of the difficulties in gathering sufficiently large series of patients with BMI and adequate tissue availability, it would be of major interest for the clinical community to maximize the analysis of all variables that could bear a potential predictive or prognostic impact and are assessable by widely available techniques or tools.

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

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. 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. 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. 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.

Diffuse large B‐cell lymphoma with concordant bone marrow involvement has peculiar genomic profile and poor clinical outcome

Bone marrow (BM) involvement in diffuse large B-cell lymphoma (DLBCL) can be morphologically discordant from the primary tumor. Concordant BM infiltration has been shown associated with a poorer outcome in patients treated with CHOP. In order to evaluate tumor-related factors leading to BM involvement in DLBCL, we performed an integrated analysis of i) genomic profiles obtained with a high-density genome wide SNP-based arrays ii) immunomorphological and iii) clinical data from 133 patients uniformly treated with R-CHOP. BM infiltration was found in 27 of 133 (20%) cases; and it was concordant in 18/27 (67%) cases. Concordant infiltration, but not discordant, influenced negatively OS, PFS and DFS and was associated with higher serum LDH, lower CR and higher PD rates. No association with cell of origin was found between BM+ and BM- DLBCL. As compared with BM- cases, BM+ DLBCL showed absence of 7q gain.

Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement.

Both Discordant and Concordant Bone Marrow (BM) Involvement Predict for a Poorer Outcome Independent of the IPI in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP.

Recently, it has been suggested that concordant but not discordant BM involvement is a negative predictor of outcome in DLBCL patients treated with CHOP (Chung et al, Blood 2007). The significance of BM involvement in pts treated in the current era of therapy including rituximab has not been fully examined. We evaluated the prognostic impact of BM involvement in DLBCL patients treated with the current standard of care, R-CHOP.Patients: We identified 282 patients with biopsy proven de novo DLBCL treated in British Columbia (BC) with an R-CHOP regimen between 01/01/2001 and 01/01/2005 with complete clinical information and staging bone marrows available for review. Cases were identified using the Lymphoid Cancer Database of the BC Cancer Agency. Median follow-up is 44 mos (range 1–77).Results: 234/282 (83%) had a negative staging BM, 27 pts (10%) had a positive BM with concordant histology (Con-BM) and 21 (7%) had a positive BM with discordant histology (Dis-BM) with predominantly small B-cells present. Clinical characteristics for the entire cohort were as follows: median age 64 y (range 18–88); 66% male; 65% stage III/IV; 39% PS>1; 51% elevated LDH; 31% >1 extranodal site. IPI risk factors: 10% 0; 42% 1–2; 48% 3–5. In addition to higher stage and greater extranodal involvement, pts with a positive BM were more likely to have a higher LDH and a poorer PS than pts with a negative BM. Compared to pts with Con-BM, pts with Dis-BM were more likely to be elderly, but otherwise exhibited a similar distribution of clinical prognostic factors. The Kaplan-Meier 4-year PFS was significantly worse for pts with both Dis-BM (32%) and Con-BM (46%) involvement compared to pts with a negative BM (75%) (p<0.0001) (see Figure). Similarly, 4-year overall survival was significantly worse for pts with Dis-BM and Con-BM involvement (53% and 54%) compared to pts with a negative BM (74%) (p=0.005). All patients with Dis-BM involvement who developed progressive or relapsed disease were believed to have progression of their aggressive lymphoma based on clinical behavior or biopsy proof. In a multivariate analysis controlling for the IPI, BM involvement (Dis-BM and Con-BM) remained an independent predictor of PFS (p=0.03).Conclusions: In DLBCL pts treated with R-CHOP, both discordant and concordant BM involvement predict for a poorer outcome independent of the IPI. It is possible that pts with DLBCL and discordant BM involvement represent a subset of pts with transformed disease which is inherently less treatment-sensitive. [Display omitted]

Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index

AbstractIn diffuse large B-cell lymphoma (DLBCL), previous studies have suggested that, while concordant bone marrow (BM) involvement confers a poor prognosis, discordant BM involvement does not. Whether this correlation is independent of the non-Hodgkin lymphoma International Prognostic Index (IPI) was previously unknown. We reviewed all DLBCL case histories from 1986 to 1997 at our center with complete staging, IPI data, and follow-up. A total of 55 (11.2%) of 489 patients had BM involvement, including 29 with concordant involvement and 26 with discordant involvement. The 55 patients with BM involvement had a poor prognosis compared with the uninvolved BM group (5-year overall survival [OS], 34.5% versus 46.9%; log-rank P = .019). However, concordant involvement portended a very poor prognosis (5-year OS, 10.3%; P < .001), whereas discordant involvement did not (5-year OS, 61.5%, P value nonsignificant). Compared with the discordant subset, the concordant subset patients were older, had a higher serum lactate dehydrogenase level, and a significantly higher IPI. However, the poor survival associated with concordant BM involvement was independent of the IPI score (P = .002, Cox regression). We conclude that in patients with DLBCL, concordant but not discordant BM involvement confers a very poor clinical outcome. Furthermore, concordant BM involvement is an independent adverse prognostic factor.