scholarly journals Predictors of Central Nervous System (CNS) Involvement in North American Adult T-Cell Leukemia Lymphoma (ATLL) and Their Survival Pattern

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1400-1400
Author(s):  
Riya Patel ◽  
Shafia Rahman ◽  
Nishi Shah ◽  
Astha Thakkar ◽  
Ana Acuna-Villaorduna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
North American ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
The United States ◽  
Publicly Traded ◽  
Cns Involvement

Abstract Introduction: North American-ATLL (NA-ATLL) is a distinct genomic and clinical entity when compared with Japanese ATLL. Despite the frequent CNS involvement by this entity there are no prognostication tools to identify variables associated with higher risk. We studied one of the largest NA-ATLL cohorts in the United States at a minority rich ethnically diverse New York City based tertiary care center to identify discrete variables that may be associated with CNS involvement. Additionally, we examined the predictive power of the previously validated International Prognostic Index (IPI) developed for Diffuse Large B-cell Lymphoma (DLBCL) in terms of CNS involvement as well as overall survival in our cohort. In our previous work, we assigned CNS involvement of ATLL if: 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive; 2) CNS imaging was positive for disease involvement or 3) physical exam was compatible with neurologic involvement. Methods and results: Of 65 NA-ATLL patients (pts), 20 (30.77%) had CNS involvement by ATLL meeting above mentioned criteria. The median age of all pts in our dataset was 59 years. Pts were divided into non- CNS involved NA-ATLL (non-CNS NA-ATLL) and CNS involved NA-ATLL (CNS NA-ATLL) groups. Parameters to predict CNS involvement were outlined as leukocytosis (>11000 per microliter [μL]), elevated acute lymphocytic count (>4000/ μL), elevated lactate dehydrogenase (LDH) (>190 units/liter [u/l]), generalized lymphadenopathy (LAD) defined as involvement of 2 or more non-contiguous nodal sites, elevated corrected serum calcium levels (>10.5 mg/deciliter), bone marrow (bm) involvement and serosal involvement defined as pleural or peritoneal involvement. These variables were chosen given our prior work identifying them as critical to predict OS in our general NA-ATLL population. We then performed the Fisher test of proportions to determine if the variables above mentioned were different between the CNS NA-ATLL and the non-CNS NA-ATLL. We did not find significant associations when analyzing gender (p=0.0535), leukocytosis (p= 0.4001), lymphocytosis (p =0.57), hypercalcemia (p= 0.7661), elevated LDH (p= 0.4898), generalized LAD (p=0.271), serosal involvement (p= 0.05088) or bone marrow involvement (p=1). We only found a strong association when examining ATLL subtypes, being the acute/lymphomatous variant strongly associated with CNS involvement (p=2.226e10 -5). To identify variables that can have an impact in OS in CNS NA-ATLL vs non-CNS NA-ATLL we calculated Kaplan Meier survival curves. We did not find any difference based on age (p=0.23), gender (p=0.95), leukocytosis (p= 0.074), lymphocytosis (p =0.21), hypercalcemia (p= 0.094), elevated LDH (p= 0.37), generalized LAD (p=0.28), and serosal involvement (p= 0.1) in the overall survival. The only significant association we found was bone marrow involvement in predicting poor OS in CNS NA-ATLL group (p= 0.038). Next, we determined IPI scores (age>60, ECOG performance status>2, Ann Arbor stage III/IV, serum LDH score >190 u/L and more than 1 extra-nodal site) in our CNS NA ATLL and non-CNS NA ATLL cohorts. We sought to determine if: 1) this prognostication tool is predictive in NA-ATLL and 2) if these variables can be used to identify CNS involvement in our cohort. CNS pts with a higher IPI score (>3) showed tendency towards a lower survival rate (p=0.089) than non-CNS pts (p=0.3). IPI score of 3 or more was not predictive of CNS involvement in our sample (p=1). Conclusions: NA-ATLL is a rare and protean disease with poor prognosis and CNS involvement is prevalent. With the variables used we did not find clear predictors of CNS associated disease other than patients presented with the lymphomatous and acute subtypes. We also observed than bone marrow involvement portends a dismal prognosis for individuals with CNS involvement. Future studies with a larger cohort could provider further insight on discovering predictors for CNS involvement in NA ATLL. Figure 1 Figure 1. Disclosures Shah: Celgene/BMS: Research Funding; Janssen: Research Funding. Gritsman: iOnctura: Research Funding. Shastri: GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy; Onclive: Honoraria. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company. Janakiram: Amgen: Honoraria.

Risk Factors for CNS Relapse Among Patients with DLBCL Treated with EPOCH-R

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1500-1500 ◽  
Author(s):  
Mary Kathryn Malecek ◽  
Shaina Rozell ◽  
Benjamin A. Chu ◽  
Trifilio Steve ◽  
Natalie Galanina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Cns Prophylaxis ◽  
Upper Limit ◽  
Cns Relapse ◽  
Increased Risk ◽  
Ecog Ps

Abstract Background: Central nervous system (CNS) relapse in pts with aggressive non-Hodgkin lymphoma (NHL) is a generally fatal complication, with median overall survival (OS) of less than six months (Abramson et al., 2010). Several studies have identified features associated with increased risk of CNS relapse, such as extranodal (EN) sites of disease, elevated lactate dehydrogenase (LDH), presence of B symptoms, and bone marrow involvement (Bernstein et al., 2009; van Besien et al., 1998). Moreover, multivariate analyses have suggested that LDH greater than 3x upper limit of normal (ULN) is strongly associated with increased risk of death or progression among patients with aggressive NHL (Zhou et al., 2014). Despite little evidence on its true efficacy, prophylaxis (ppx) intrathecal (IT) chemotherapy, most frequently with methotrexate (MTX), is often used to among pts thought to be at high risk for CNS relapse. Data on efficacy or need for CNS prophylaxis in patients receiving infusional therapy with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (R-EPOCH) is not available. As R-EPOCH, is being increasingly used in pts with lymphoma, we sought to evaluate the role of IT chemotherapy when used with this regimen. Methods: We conducted a retrospective chart review analysis of patients with diffuse large B-cell lymphoma (DLBCL) who received R-EPOCH as frontline therapy, between 2005 and 2014. Use of IT ppx was at the discretion of the treating physician. We excluded patients under the age of 18, those receiving fewer than two cycles of R-EPOCH, those with CNS involvement at time of diagnosis, and those who received high-dose intravenous CNS ppx. Two-tailed Fisher's exact test was used to determine whether any of the following baseline features was associated with risk of CNS relapse: age>60, ECOG PS>1, LDH>normal and/or >3x ULN, presence of B symptoms, two or more EN sites, anatomic location of EN sites, international prognostic index (IPI) score > 1, bone marrow involvement, and HIV infection. In order to determine whether IT ppx was associated with any improvement in CNS and/or systemic control of disease, we compared, using Kaplan-Meier survival curves with log-rank analyses, the patterns of overall survival (OS), progression-free survival (PFS), and freedom from CNS progression (FFCP, in which death is not counted as an event) between patients receiving IT ppx and those not receiving it. Results: We identified 117 patients for analysis. Median age was 53 (range 19-80). 26% had ECOG PS>1; 76% had LDH above upper limit of normal (ULN). 38% had two or more EN sites of disease, and 68% had stage III-IV disease. 62 patients received IT ppx, and 55 did not. Of those receiving IT ppx, 95% received MTX, with the remainder receiving cytarabine. Those receiving IT ppx were more likely to have >1 EN site of disease, and IPI score >1 (Table 1). A total of seven had observed CNS relapse, occurring at a median of 6 months from time of NHL diagnosis (range 2-24 months). At a median follow up of 18 months, the 24-month PFS and OS were 80% and 83%, respectively. Median PFS and OS were not reached. The only factors associated with increased risk of CNS relapse were genitourinary EN disease and LDH >3x ULN (Table 2). There were no significant differences in OS, PFS, or FFCP among patients who did and did not receive CNS prophylaxis (Figure 1, panels A-C). Conclusions: The risk of CNS progression among DLBCL patients receiving R-EPOCH was similar to previous reports with R-CHOP, at 6%. GU location of EN disease and LDH >3xULN were associated with increased risk of CNS relapse. IT ppx was not associated with improved outcomes. Despite the common use of IT PPX in pts treated with R-EPOCH, our data suggest that this practice might not impact CNS progression and/or relapse, though randomized studies would be needed to answer this. Such studies are warranted in order to better determine what factors are associated with CNS progression, and whom, if anyone, may benefit from IT ppx. Figure 2. Figure 2. Disclosures Nabhan: Celgene Corporation: Honoraria, Research Funding. Petrich:Seattle Genetics: Consultancy, Honoraria, Research Funding.

Prognostic impact of concordant and discordant cytomorphology of bone marrow involvement in patients with diffuse, large, B-cell lymphoma treated with R-CHOP

2013 ◽  
Vol 66 (5) ◽  
pp. 420-425 ◽  
Author(s):  
Hyoeun Shim ◽  
Jae-Il Oh ◽  
Sang Hyuk Park ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
International Prognostic Index Score ◽  
Large B Cell Lymphoma

BackgroundBone marrow involvement confers a poor prognosis in patients with diffuse, large, B-cell lymphoma (DLBCL). However, the prognostic significance of concordant and discordant bone marrow involvement in these cases differs. We analysed this further in patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) at a single institute.Design and MethodsThe cytomorphology of bone marrow involvement was evaluated in 632 patients who were diagnosed with DLBCL in primary tissues and had received R-CHOP therapy. Bone marrow trephine biopsies and clot sections were analysed, along with the immunohistochemical analysis of CD20, CD79a and CD3.ResultsBone marrow involvement was identified in 80 of our DLBCL patient subjects (12.7%). Of these, 32 (40%) showed discordant bone marrow involvement, and 48 (60%) showed concordant involvement. Kaplan–Meier survival analysis showed that progression-free survival and overall survival was poorer in the concordant group (p<0.001). Multivariate analysis, adjusted for the International Prognostic Index score, showed that concordant involvement was an independent predictor of progression-free survival (p<0.001) and overall survival (p=0.011). Discordant involvement was not a negative prognostic factor independent of the International Prognostic Index.ConclusionsPrognostication based on bone marrow involvement cytomorphology is a useful indicator of progression-free survival and overall survival, independent of the International Prognostic Index score, in DLBCL patients. Accurate staging based on morphology should thus be included in bone marrow examinations of such cases.

90Y-Ibritumomab Tiuxetan Followed by Rituximab Is a Safe Treatment Option for Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin s Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2866-2866
Author(s):  
Katarina Luptakova ◽  
Michelle Kim ◽  
Pamela Ely ◽  
Barbara Grant ◽  
John Anthony Parker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Baseline Platelet Count ◽  
Large B Cell

Abstract Abstract 2866 Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy and is generally responsive to anthracycline-containing chemotherapy. However, 60% of patients (pts) will relapse after their first line treatment. At the time of relapse the only curative approach includes the use of a stem cell transplant (SCT). The incidence of DLBCL increases with age which creates a subset of pts who are not candidates for first line anthracycline-based chemotherapy, and a large subset of pts who are not candidates for SCT due to advanced age and/or co-morbidities. Thus, there is a significant unmet need for therapies with a low toxicity profile in elderly or medically unfit pts with DLBCL. 90Y-ibritumomab tiuxetan (90Y-IT) is an anti-CD20 murine antibody linked with a beta-emitting isotope approved for use in indolent lymphoma. Maintenance rituximab (R) has been reported to increase response rates and prolong remission duration in some lymphomas. We performed a phase II multicenter clinical trial to examine the efficacy of 90Y-IT induction followed by maintenance R in pts with DLBCL. Patients and Methods: Eligible pts were either intolerant of anthracycline-based chemotherapy or had relapsed or refractory CD20+ DLBCL with measurable disease. Pts had to be ineligible for SCT for reasons other than failure to harvest stem cells. Bone marrow involvement by lymphoma of less than 25% based on bilateral bone marrow aspirate and biopsy was required. R 250 mg/m2 was administered IV immediately followed by 111In-ibritumomab tiuxetan. Nuclear scans were performed at 24 and 48 hours to insure there was no altered biodistribution. On day 8 a second infusion of R 250 mg/m2 followed by 0.4 mCi/kg (for pts with a baseline platelet count >150,000/mm3) or 0.3 mCi/kg 90Y-IT (for pts with a baseline platelet count 100,000-149,000/mm3) was given. Pts with multiple extranodal sites or prior bone marrow involvement received CNS prophylaxis with intrathecal methotrexate or cytarabine. Maintenance R 375 mg/m2 was given on weeks 3–6, then weekly × 4 every 6 months × 4 cycles or until progression. Results: Between 10/2003 and 9/2009, 25 pts have been treated. During the course of the study, the ownership of the therapeutic agent changed three times and therefore enrollment was interrupted on two occasions. The median age of pts was 79 (range 45–91), 36% pts had a sIPI score 3 or more. The median number of prior regimens is 2 [0-5]. The 90Y-IT treatment regimen produced an overall response rate of 36% [9 pts] with 28% CR [7 pts]. To date, the mean OS is 18 months (median 8.1 months) with a median follow-up of 11.2 months. Among responding pts, the median OS has not been reached with a median follow-up of over 26.2 [0.1-71.4] months. Thirteen pts died within the first year, 6 patients (24%) continue to be in remission greater than 18 months, and 4 patients (16%) remain in long-term remission [39.9-71.4 months]. The most frequently observed toxicity was hematologic. Eleven percent of pts had grade 4 neutropenia with only one patient experiencing febrile neutropenia, and 16% of pts experienced grade 4 thrombocytopenia. There were no unexpected non-hematologic toxicities except for 1 patient that experienced extravasation. One late-occurring case of MDS/AML was reported that is possibly related to the study regimen, and one case of adenocarcinoma of the GI tract that is likely unrelated. Of note, none of the pts that progressed on the chemotherapy preceding this study achieved a response to the study regimen. Conclusions: The 90Y-IT treatment regimen has an acceptable toxicity profile in elderly or heavily pretreated pts with DLBCL. The two week outpatient 90Y-IT infusion produces response rates and durations similar to that of more prolonged cytotoxic chemotherapy regimens. Progression on previous chemotherapy predicts for poor response to 90Y-IT. Treatment with 90Y-IT can provide durable remission to a select subset of pts who are not candidates for SCT, or intensive anthracycline based chemotherapy. Disclosures: Off Label Use: We are describing a phase II study of the use of 90Y-Ibritumomab Tiuxetan for treatment of diffuse large B-cell lymphoma. Current FDA approved use of 90Y-Ibritumomab Tiuxetan includes relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) or previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy. Joyce:Spectrum Pharmaceuticals, Inc.: Research Funding; Cell Therapeutics Inc: Research Funding; Biogen Idec: Research Funding.

Ixazomib, Dexamethasone and Rituximab in Previously Untreated Patients with Waldenström Macroglobulinemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2956-2956 ◽  
Author(s):  
Jorge J. Castillo ◽  
Joshua Gustine ◽  
Kirsten Meid ◽  
Toni Dubeau ◽  
Guang Yang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Induction Phase ◽  
Primary Therapy ◽  
Wild Type ◽  
Median Serum

Abstract Introduction: Waldenström's macroglobulinemia (WM) is an incurable B-cell lymphoma characterized by the accumulation of IgM-secreting lymphoplasmacytic cells in the bone marrow and other organs. Bortezomib in combination with rituximab and dexamethasone (BDR) is highly active as primary therapy in WM, though treatment-related neuropathy is common with BDR in WM, and often leads to premature treatment discontinuation. Ixazomib is an orally administered proteasome inhibitor with limited neuropathy that is active in myeloma, but has not been previously evaluated in WM Methods: Symptomatic, previously untreated patients with a clinicopathological diagnosis of WM were included in this prospective, single-arm phase II study evaluating ixazomib 4 mg PO on days 1, 8 and 15 + dexamethasone 20 mg PO/IV on days 1, 8 and 15 + rituximab 375 mg/m2 IV on day 1 (IDR) were administered for six 4-week cycles (induction) followed by six 8-week cycles (maintenance). Rituximab was held for the first two cycles of therapy to minimize risk of IgM flare. Zoster prophylaxis and proton pump inhibitors were administered throughout IDR therapy. The study was approved by the institutional review board at the Dana-Farber Cancer Institute, and registered under Clinicaltrials.gov ID NCT02400437. Results: Twenty-six WM patients were enrolled and were exposed to IDR therapy. The median age at WM diagnosis was 63 years (range 46-81 years) and the median age at initiation of therapy was 65 years (range 46-82 years). Baseline median hemoglobin was 10.2 g/dl (range 6.9-13.2 g/dL), median serum IgM level was 5,068 mg/dl (range 653-7,650 mg/dL), 46% of patients had lymphadenopathy and 12% had splenomegaly. The median bone marrow involvement was 55% (range 5-95%). The MYD88 L265P gene mutation was identified in all cases. CXCR4 gene mutations were identified in 15 patients (58%), of whom 10 (67%) had nonsense, and 5 (33%) frameshift mutations. Sixteen patients have completed the induction phase of therapy at this time. Following induction therapy, the median serum IgM level decreased to 2,316 mg/dl (range 287-5,820 mg/dL), median hemoglobin increased to 13.1 mg/dl (range 10.4-14.6 g/dL), and median bone marrow involvement decreased to 23% (range 0-76%). P-value <0.001 for all comparisons against baseline. Using consensus response criteria, the overall response rate was 88% (VGPR 6%, PR 44%, MR 38%) with a major response rate of 50%. Major responses (VGPR + PR) were observed in 47% of patients with CXCR4 mutations versus 64% in those who were wild-type CXCR4 (p=0.32). The median time to response was 8 weeks. The median time to response in CXCR4 mutant patients was 12 weeks versus 8 weeks in wild-type CXCR4 patients (log-rank p=0.03). Four patients have been taken off study; 2 for lack of response, 1 due to lack of clinical benefit with persistent failure to thrive while in PR, and 1 for progressive neuropathy while in PR although in part due to worsening of diabetic neuropathy. No other grade 3 or 4 adverse events were reported. Conclusion: These preliminary data suggest that the combination of IDR is an active and well-tolerated, neuropathy-sparing regimen in symptomatic untreated WM patients. Disclosures Castillo: Biogen: Consultancy; Otsuka: Consultancy; Abbvie: Research Funding; Pharmacyclics: Honoraria; Millennium: Research Funding; Janssen: Honoraria.

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.

scholarly journals Baseline Suvmax Did Not Predict Histological Transformation from Follicular Lymphoma to Aggressive Lymphoma in the Phase III GALLIUM Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4160-4160 ◽  
Author(s):  
Farheen Mir ◽  
Sally F Barrington ◽  
Michel Meignan ◽  
Helen Brown ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Aggressive Lymphoma ◽  
Histological Transformation

Abstract Introduction: Follicular lymphoma (FL) generally has an indolent clinical course, but there is a 1-2% annual rate of histological transformation (HT) into aggressive lymphoma. Nodal HT sites have a higher maximum standardized uptake value (SUVmax) than non-transformed sites, and patients with HT typically show greater variation in SUVmax between sites. Upfront identification of patients at high risk of HT would allow physicians to consider treatment intensification. The objective of this analysis was to assess the relationship between baseline SUVmax (bSUVmax) and HT in the GALLIUM study (NCT01332968). Methods In the randomized, phase III GALLIUM study, 1202 previously untreated patients with grade 1-3a FL were randomized to receive induction with either obinutuzumab (GA101; G)- or rituximab (R)-based immunochemotherapy. Patients who responded received maintenance therapy with the same antibody. The primary endpoint of investigator-assessed progression-free survival was significantly improved in the G arm relative to the R arm (hazard ratio 0.66; p=0.001). As an exploratory endpoint, the degree of 18-fluorodeoxyglucose (FDG)-avidity expressed by SUVmax was assessed in patients with baseline FDG positron emission tomography (FDG-PET) scans by an independent review committee. Results: Among 522 patients with available bSUVmax data, 13 (2.5%) experienced biopsy-confirmed HT to diffuse large B-cell lymphoma or Grade 3b FL after a median follow-up of 59 months. Patients with HT were older (median age 61 vs 56 years), and were more likely to have a poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status 2: 15.4% vs 2.6%), present with high-risk Follicular Lymphoma International Prognostic Index (FLIPI; 61.5% vs 40.3%), and have bone marrow involvement (76.9% vs 52.9%) than those without. More than 65% of patients showed bSUVmax >10, but only a minority of these experienced HT. Median (range) bSUVmax in patients with versus without HT was 12.4 (8.14, 27.95) versus 11.8 (3.05, 64.43), respectively. Median (range) baseline SUVrange (bSUVrange), defined as the difference between bSUVmax of the most and least FDG-avid lymphoma sites, was 6.6 (1.08, 23.91) versus 7.14 (0.00, 59.81), respectively (Figure). Conclusions: bSUVmax >10 is common in patients with previously untreated FL and is rarely associated with early HT. Neither bSUVmax nor bSUVrange predicted HT in GALLIUM, suggesting there may be little benefit in re-biopsy of lesions to exclude HT before commencing therapy. Better markers for identification of FL patients at risk of transformation are needed. Disclosures Mir: F. Hoffmann-La Roche: Employment. Barrington:F.Hoffmann-La Roche: Membership on an entity's Board of Directors or advisory committees; Department of Health (England): Research Funding; MRC: Research Funding; CRUK: Research Funding; EPSRC: Research Funding; National Institute of Health Research: Research Funding. Meignan:F. Hoffman-La Roche Ltd: Honoraria. Brown:PAREXEL, external business partner with Roche Products Ltd, Welwyn, UK: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Sahin:F. Hoffman-La Roche Ltd: Other: Ownership interests PLC. Trotman:F. Hoffman-La Roche: Other: Travel to meeting, Unremunerated member of Ad Board, Research Funding; Janssen: Other: Unremunerated member of Ad Board, Research Funding; Beigene: Research Funding; Takeda: Other: Unremunerated member of Ad Board; Celgene: Other: Unremunerated member of Ad Board, Research Funding; PCYC: Research Funding.

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.

Survival after Autologous Transplantation to Treat Diffuse Large B-Cell Lymphoma with a History of CNS Involvement, Bone Marrow Involvement, or Histologic Transformation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5237-5237
Author(s):  
Brandon Hayes-Lattin ◽  
Pritesh Mehta ◽  
Adam Dunn ◽  
Nan Subbiah ◽  
Jose F. Leis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
History Of ◽  
Large B Cell

Abstract Background: Patients with diffuse large B-cell lymphoma (DLBCL) who present with extra-nodal involvement or histologic transformation from low-grade disease have lower rates of survival after conventional-dose therapy. The impact of these features on outcomes after high-dose therapy with autologous transplantation was investigated. Methods: We retrospectively reviewed the outcomes of 64 consecutive patients receiving autologous transplantation from 1995 to 2003 for the treatment of DLBCL. Variables considered were age, gender, histologic transformation, history of bone marrow involvement, history of central nervous system (CNS) involvement, time from diagnosis to transplant, number of pre-transplant regimens, chemosensitivity prior to transplant, conditioning regimen, year of transplant, and the use of peripheral blood or bone marrow stem cells. Survivals were estimated by the Kaplan-Meier method. The Cox proportional hazards regression model was used to test the significance of factors on survival. Univariate association between variables and survival were tested by the log-rank test. Correlation between variables was tested with Spearman’s rank coefficient. Results: The median age at transplant among 64 patients was 53.5 years (17–74). The median overall survival was 3.3 years. Among these patients, 12 had a history of CNS involvement, 10 had a history of bone marrow involvement, and 12 had transformed from low-grade lymphoma. A Cox regression model suggested age <50 (log-rank, p=0.093), <2 regimens prior to transplant (log-rank, p=0.052), and the lack of BEAM as conditioning regimen (log-rank, p=0.019) as multivariate factors for survival. However, the use of BEAM was highly associated with older age (R²= 0.42, p=0.001) and more prior chemotherapy regimens (R²=0.24, p=0.054). A history of extranodal involvement, including prior CNS involvement (p=0.842) or bone marrow involvement (p=0.518), was not associated with lower survival by univariate analysis. No significant association was found between survival and a history of transformation (p=0.484). Conclusions: A history of CNS involvement, bone marrow involvement, or histologic transformation is not associated with lower rates of survival among patients undergoing autologous transplantation for diffuse large B-cell lymphoma at our institution. Patients who present with such histories remain candidates for autologous transplantation.

Prognostic Utility of Extranodal Disease Involvement in Diffuse Large B-Cell Lymphoma in Patients Treated with R-CHOP.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1563-1563
Author(s):  
David Hui ◽  
Jane Donaldson ◽  
Paul Hoskins ◽  
Richard Klasa ◽  
Kerry J. Savage ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Significant Prognostic Factor ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Prognostic Utility ◽  
Extranodal Disease

Abstract Background: Extranodal status is one of the five key factors in the International Prognostic Index (IPI) for diffuse large B-cell lymphoma (DLBCL). We have re-examined the prognostic utility of extranodal involvement in DLBCL patients by determining whether the number and location of extranodal sites correlate with survival, particularly in the post-rituximab era. Methods: Using the Lymphoid Cancer Database of the British Columbia Cancer Agency, all patients with a diagnosis of DLBCL were included between January 1979 and May 2006 except those who were less than age 18 at diagnosis, HIV positive, presented with disease in the testicular or central nervous system, had discordant indolent lymphoma at or before diagnosis, or did not receive any chemotherapy. Any degree of extranodal involvement was recorded as positive for extranodal disease and all sites of involvement were documented. Results: 1803 patients were identified with the following characteristics: median age 62 (range 19–93), male 58%, stage III/IV 49%, elevated LDH 51% and performance status ≥2 34%. Of the 1268 patients treated without rituximab, 358 (28%) had only nodal disease, 532 (42%) had 1 extranodal site and 378 (30%) had ≥2 extranodal sites. Among 535 patients who received rituximab, 163 (30%), 217 (41%) and 155 (29%) had 0, 1 and ≥2 extranodal sites, respectively. Of the 37 coded extranodal sites, the most commonly involved sites included soft tissue (16.2%), bone (11.3%), bone marrow (9.1%), pleura (9.1%), head and neck soft tissue (8.2%), stomach (8.7%), intestine (8.2%), lung (7.8%) and liver (5.8%). In multivariate analysis that included other IPI variables, extranodal involvement as defined in the IPI (≥2 sites) was not a significant prognostic factor in our cohort (with or without rituximab, see Table 1). However, the presence of any extranodal disease was found to correlate with a poorer overall survival in patients treated with rituximab (p=0.03). When specific extranodal sites were examined in the rituximab group, bone marrow (p&lt;0.001), liver (p=0.03) and pleura (p=0.05) involvement correlated with inferior overall survival in univariate analysis, but only bone marrow involvement (HR=1.9, p=0.02) remained significant in multivariate analysis. Conclusions: In the post-rituximab era, extranodal involvement remains a significant prognostic factor, although not as traditionally defined in the IPI, but rather refined as the presence of any extranodal disease involvement. Furthermore, bone marrow involvement represents the only extranodal site associated with a poorer overall survival independent of the IPI. Table 1: Prognostic Significance of Extranodal Disease Involvement for Overall Survival

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