Impact of Central Nervous System International Prognostic Index on the treatment of Diffuse Large B Cell Lymphoma

2020 ◽  
Author(s):  
Mohammad Ma'koseh ◽  
Mohammad Ma’koseh ◽  
Faris Tamimi ◽  
Alaa Abufara ◽  
Lana Abusalem ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intrathecal Chemotherapy ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Selection Of

Abstract Background The central nervous system international prognostic index [CNS-IPI]is being usedwidely for the identification of patients with diffuse large B cell lymphoma [DLBCL]with highrisk of CNS relapse. The aim of our study is to confirm the value of the CNS-IPI in predicting CNS relapse in our young study population and to evaluate the impact on selection of patients for CNS prophylaxis. Methods We retrospectively reviewed patients with pathological diagnosis of DLBCL who were treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] regimen from January 2004 till December 2016 with no evidence of CNS involvement on diagnosis. Different demographic, disease characteristics and treatment given including the use of intrathecal chemotherapy prophylaxis were collected. Correlation between CNS-IPI and CNS relapse was examined through chi square test. Median time to CNS relapse and median overall survival [OS] after CNS relapse were estimated using the Kaplan-Meier plots. Results 354 patients were included. Median age was 46 years. 52 [15%] patients were given intrathecal chemotherapy [ITC] prophylaxis, of whom CNS-IPI was high in 7[13%]. Overall, 5% of the patients [n = 17] developed CNS relapse.The median survival after CNS relapse was 7 months. The rate of CNS relapse in patients with low, intermediate and high risk CNS-IPI was 0.6%, 3% and 22% respectively [p = < 0.001].On multivariate analysis, involvement of bone marrow [p = 0.039]and renal or adrenal glands[p = 0.023]significantly correlated with CNS relapse. Considering theCNS-IPI and high risk anatomical sites [breast, uterus, testis and epidural space], 26% of our patients with DLBCLwould have needed prophylaxis. Conclusion Although CNS-IPI helps in better selection of DLBCL patients for CNS prophylaxis, it will significantly and possibly unnecessarily increase the number of patients exposed to prophylaxis. More investigational biomarkers and methods are necessary to better refining high risk patients.

scholarly journals S5-KL-1 CURRENT TREATMENT FOR DLBCL AND PROPHYLAXIS AND TREATMENT FOR SECONDARY CNS LYMPHOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii4-ii4
Author(s):  
Koji Izutsu
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, comprising 30% of all lymphoma cases. More than 60% of patients can be cured with current standard treatment, R-CHOP. On the other hand, prognosis of patients with relapsed or refractory DLBCL is disappointing with less than 10% being cured with salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation. Prognosis of patients with central nervous system (CNS) relapse is especially poor because of a limited treatment option. Thus, evaluating risks of CNS relapse at diagnosis and administering prophylaxis including intrathecal methotrexate (MTX) or systemic high-dose MTX concurrently with R-CHOP or as consolidation therapy in high-risk patients are often-used approach. Clinically, higher risk according to the International Prognostic Index and extranodal involvement in organs such as kidney, adrenal gland, breast, testis, or bone marrow are considered to be high-risk for CNS relapse. Recently, CNS-International Prognostic Index has been proposed to integrate aforementioned risk factors. Moreover, patients with intravascular large B-cell lymphoma, CD5+ DLBCL, double hit lymphoma are reported as high-risk for CNS relapse. Further, the MYD88 L265P mutation, a common mutation in primary CNS DLBCL (PCNSL) is also common in DLBCL of testis or breast, which are the sites associated with CNS relapse. Strategies for CNS prophylaxis have not established yet, and it is still unclear whether intrathecal MTX or high-dose MTX can prevent CNS relapse. Moreover, treatment for secondary CNS relapse have not been established. In particular, for those with both CNS and extra-CNS lesions, effective treatment options are very limited. The role of novel agents such as BTK inhibitors, lenalidomide, and immune check point inhibitors, whose efficacy have been shown for PCNSL, should be investigated further in the management of secondary CNS lymphoma.

Central Nervous System (CNS) Prophylaxis Does Not Decrease the Rates of CNS Relapse From Diffuse Large B-Cell Lymphoma In the Era of R-CHOP

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4161-4161
Author(s):  
Hany R.Y. Guirguis ◽  
Mervat Mahrous ◽  
Matthew Cheung ◽  
Liying Zhang ◽  
Rena Buckstein
Keyword(s):  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Testicular Lymphoma ◽  
Large B Cell

Abstract Abstract 4161 Background: While some clinical characteristics/sites of diffuse large B-cell lymphoma (DLBCL) are associated with increased rates of central nervous system (CNS) relapse, the role/benefits of CNS prophylaxis are controversial, particularly in the era of better disease control with R-CHOP chemotherapy. We evaluated the benefits of high dose methotrexate (HDMTX 3 g/m2) and intrathecal (IT) chemotherapy (MTX 12 mg) as primary CNS prophylaxis (CNSPr) in patients with DLBCL (de novo or transformed) treated with curative intent R-CHOP chemotherapy between the years of January 2002-December 2008. During this period, we adopted a local ‘informal' clinical practice recommendation for CNS prophylaxis for patients with testicular involvement, increased lactate dehydrogenase enzyme (LDH) and greater than 1 extranodal (EN) site, epidural disease, invasive sinus or skull involvement. Compliance with and efficacy of this treatment recommendation was the catalyst for this retrospective audit. Methods: Using the cancer pharmacy database, we retrospectively identified 214 patients who received 1–8 cycles of R-CHOP chemotherapy (median 6) for DLBCL. Patients with transformed histologies were included if they had not yet received R-CHOP chemotherapy. Patients with HIV or CNS involvement at diagnosis were excluded. Results: The median age was 64 with 54% male patients. 71% had stage III-IV disease, 49% had an elevated LDH, 57% EN disease (35% >1 EN site), 49% had high or high-intermediate international prognostic index scores (IPI), 14% had transformed disease, 8 patients had testicular lymphoma, 11% had increased LDH + > 1 EN site. 27 patients (12.6%) received some form of CNS prophylaxis (37% IT MTX alone (median 1.5 times (1-3)); 7% with HDMTX 3g/m2 alone (median 1.5 times (1-3)) and 56% with both HDMTX and IT chemotherapy (median 2 HDMTX (1-6) and 3 IT chemotherapy (1-9)). Compared with patients that did not receive CNSPr, patients that did had higher stage disease (p=.0061), more EN disease (P <0.0001), more testicular involvement (p<0.0001), higher IPI (p=.029), age adjusted IPI (aaIPI) (p=.048) and revised international prognostic index (R-IPI) (p=.016). Of those deemed to be at higher risk of CNS relapse defined by high IPI (20%; Haioun et al. 2000), high-intermediate and high aaIPI (52%; Feugier et al. 2004), or increased LDH and > 1 EN site (11%; Van Besien et al. 1998), 23%, 18% and 29% received CNSPr respectively, demonstrating imperfect compliance with local practice guidelines. 75% of patients with testicular lymphoma received CNSPr, 83% inclusive of both HDMTX (median 2) and IT chemotherapy (median 3). Eight patients (3.7% of all patients) relapsed in the CNS at a median time of 17 months (6-35 months range). Five patients developed parenchymal CNS relapse, 2 had leptomeningeal disease and 1 had both parenchymal and leptomeningeal involvement. The relapse rates in those that received or did not receive prophylaxis were 7.4% (2/27) and 3.2% (6/187) respectively. Six out of the 8 relapses were isolated relapses in the CNS and 4/8 were in testicular lymphoma patients. If the 8 testicular lymphoma patients were excluded, the overall rate of CNS relapse was 1.9% (0% in the 21 with prophylaxis and 2% in the 185 that did not). 62% (5/8) of those with CNS relapse have died with a median survival post CNS relapse of 2 months (range 0.5–16). Of the 4/8 patients with testicular involvement that relapsed, 3 had received CNS prophylaxis with HDMTX and IT chemotherapy (median 2 (range 1–5)). By multivariate analysis, testicular involvement was the only negative risk factor for CNS relapse (HR 33.5, p<.0001 (95% CI 8.3–135). Conclusion: R-CHOP chemotherapy may negate the need for CNS prophylaxis in patients with DLBCL, even those formerly identified as higher risk using standard prognostic scoring systems with the exception of testicular lymphoma. Better forms of CNS prophylaxis are needed in these patients. CNS relapses appear to occur later as isolated parenchymal events compared with the pre rituximab era, but survival post CNS relapse remains short. Disclosures: No relevant conflicts of interest to declare.

Lack of Influence of Rituximab and CNS Directed Prophylactic Therapy on CNS Relapse in High-Risk Diffuse Large B Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1711-1711
Author(s):  
Mahender Yellu ◽  
Ehsan Malek ◽  
Berry Thavalathil ◽  
Tahir Latif
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
Risk Group ◽  
B Cell Lymphoma ◽  
High Risk Group ◽  
Intrathecal Methotrexate ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Standard Risk

Abstract Background/method: Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) although uncommon, can be devastating. Conflicting reports have been published regarding the reduction in incidence of CNS relapse in post-rituximabera.We retrospectively identified all the patients with DLBCL who has received rituximab-based chemotherapy at initial presentation in our institute between 2004 and 2014. Patients were divided into two groups, ‘high risk’ group and ‘standard risk’ group, based on following definition. High risk group will have at least one of the following risk factors 1) LDH ≥ 650 U/L 2) Age adjusted International Prognostic Index (IPI) of ≥ 4 3) Involvement of > 1 extra nodal site 4) Involvement of testis 5) Breast 6) Bones 7) Kidneys 8) Adrenal glands 9) Retroperitoneal lymph nodes 10) Para-meninges or 11) Bone marrow. Patients without any of these risk factors were deemed standard risk. Descriptive statistics were used to analyze the incidence of CNS relapse, patient and disease characteristics. Historically reported incidence rates were used for comparison. Results:One hundred and forty two consecutive patients with DLBCL were included in our study. One hundred and twenty two patients received rituximab-based therapy at the initial diagnosis. Forty-nine patients (40%) met the criteria for ‘high risk’ based on the above definition. Seventy-three patients (60%) qualified for standard risk group. Standard risk group received no CNS directed prophylaxis and none of these patients had CNS relapses. Thirty-one of 49 ‘high risk’ patients received CNS prophylaxis, mainly intrathecal methotrexate. Total 5 patients (4.09%) developed CNS relapse. CNS relapse in high-risk group was 10.2% (5/49). Median age at diagnosis in patients with CNS relapse was 53 years. Median time to relapse was 8.76 months. Median survival after the CNS relapse was 9.16 months. Four out of 5 patients received CNS prophylaxis with intrathecal methotrexate or systemic methotrexate or systemic cytarabine or a combination of them. Average number of doses of prophylaxis received by each patient was 3.2 (range 1-7). Only one patient who developed CNS relapse did not receive any CNS directed therapy as prophylaxis. Conclusion:No significant reduction in the incidence of CNS relapse was noted with upfront use of rituximab. Our study confirms that majority of the DLBCL patients do not need CNS directed therapy. For high risk DLBCL patients, we not only need to develop better predictive markers for CNS relapse but also need better CNS directed therapies to prevent this fatal complication of highly curable disease. Disclosures No relevant conflicts of interest to declare.

Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 1989-1996 ◽  
Author(s):  
Paul A. Hamlin ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Jing Qin ◽  
Jaya M. Satagopan ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intermediate Risk ◽  
Second Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P &lt; .001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P &lt; .001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens.

Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

2007 ◽  
Vol 25 (17) ◽  
pp. 2426-2433 ◽  
Author(s):  
Silvia Montoto ◽  
Andrew John Davies ◽  
Janet Matthews ◽  
Maria Calaminici ◽  
Andrew J. Norton ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL). Patients and Methods From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%. Results The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed. Conclusion Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.

The t(14;18) Is Associated with Germinal Center Phenotype Subset of the Diffuse Large B-Cell Lymphoma Patients in Egypt.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4124-4124
Author(s):  
Hasan A. Abdel-Ghaffar ◽  
Sherin M. Abdel-Aziz ◽  
Doaa A. Shahin ◽  
Ezzat S. Sobki Board ◽  
Nadia I. Attwan ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Biological Variables ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a generic term for clinically and biologically heterogeneous group of tumors. Identification of high risk patients at presentation will allow effective trials of treatment. Therefore, t(14;18) detection using interphase Florescence in Situ Hybridization (FISH) and Biomed multiplex polymerase chain reaction (PCR) was done on formalin fixed paraffin embedded lymph node archives from pathology department, National Cancer Institute, Cairo, Egypt. Diagnosis were confirmed by pathological review using the diagnostic criteria defined in the revised European-American Classification of Lymphoid Neoplasm / WHO classification. The study was carried out on 26 patients with lymph screen CD 19 +/ CD 5 - / CD 10 ± correlating t(14;18) with the immunophenotypic biological variables, Immunohistochemistry, and the standardized international prognostic index (IPI) with a median follow up for 5 years. Comparison of FISH and PCR techniques showed identical specificity with advantageous sensitivity of FISH over the PCR. Nine patients out of eleven with t(14;18) were associated with Germinal Center (GC) phenotype (CD10+ /Bcl-6 +). However, Only two out of fifteen with non GC phenotype(CD10- /Bcl-6 -) were associated t(14;18). The mean 5 years survival time of patients with t(14;18) was significantly lower (31.18 ± 3.06 month) compared to those without translocation (54.32 ± 2.54 month) (P=0.001). Interestingly, patients with t(14;18) showed Bcl-2 positive (100%) compared to 46.6% in patient without t(14;18) (P=0.004). There is a significant correlation between t(14;18) and the clinicopathological risk criteria of IPI(P=0.01). In our study we demonstrated a detection of t(14;18) by FISH was found to be superior to PCR. The high risk group of GC phenotype together with Bcl-2 expression were associated with t(14;18) and could be used to tailor treatment.

scholarly journals An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era

Blood ◽  
2014 ◽  
Vol 123 (6) ◽  
pp. 837-842 ◽  
Author(s):  
Zheng Zhou ◽  
Laurie H. Sehn ◽  
Alfred W. Rademaker ◽  
Leo I. Gordon ◽  
Ann S. LaCasce ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Tool ◽  
Large B Cell Lymphoma ◽  
Key Points ◽  
Large B Cell

Key Points The clinically based NCCN-IPI is a robust prognostic tool for the rituximab era that better discriminates low- and high-risk DLBCL patients compared with the IPI. The NCCN-IPI outperforms the IPI by refined categorization of age and LDH, and the identification of disease involvement at specific extranodal sites.

scholarly journals The clinical features and prognosis of 31 HIV-infected diffuse large B-cell lymphoma cases

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110225
Author(s):  
Yun Lian ◽  
Jiayu Huang ◽  
Huihui Zhao
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Standard Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

This retrospective study was designed to describe the clinical characteristics and prognosis of human immunodeficiency virus (HIV)-infected diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively enrolled 31 patients newly diagnosed with HIV-infected DLBCL from 2009 to 2019 in our institution. The median age of patients was 47 years, and most patients were male ( n = 27, 87.1%). Baseline mean CD4+ count was 150.72 ± 146.57/μl. Eighteen (58.1%) patients had B symptoms. Categorized by international prognostic index (IPI) score, 7 cases (22.6%) were in low-risk group (IPI 0-1) and 24 cases (77.4%) were in medium-high risk group (IPI 2-5). Twenty-five (80.6%) patients received highly active antiretroviral therapy (HAART) and 16 (51.6%) underwent standard chemotherapy. The mortality rate was 58.1% (18/31). Univariate survival analysis revealed that HCV infection ( p = 0.032), standard chemotherapy treatments ( p = 0.038) were associated with overall survival (OS). Our results showed that HIV-infected DLBCL patients had high-risk stratification and high mortality. HCV-coinfection might be associated with poor OS. Early diagnosis and standardized treatments might be beneficial for promoting the survival of HIV-infected DLBCL patients.

Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1136-1143 ◽  
Author(s):  
Sharon L. Barrans ◽  
Ian Carter ◽  
Roger G. Owen ◽  
Faith E. Davies ◽  
Russell D. Patmore ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P &lt; .0001) and bcl-2 (R = 0.14, P = .0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = −0.025, P = .02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2− group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

Blood ◽  
2021 ◽  
Author(s):  
Victor Manuel Orellana-Noia ◽  
Daniel Reed ◽  
Ashley Alesia McCook ◽  
Jeremy Michael Sen ◽  
Christian M Barlow ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Significant Difference ◽  
Relapse Rates

Prophylaxis is commonly used to prevent central nervous system (CNS) relapse in diffuse large B cell lymphoma, with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013-2019. Prophylaxis was administered intrathecally (IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7 %) had CNS relapse, after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4 vs 6.8%, p=0.4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected versus observed CNS relapse rates were nearly identical (5.8 vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated and reconsideration of prophylaxis strategies in DLBCL is of critical need.

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