scholarly journals Satu tahun kesintasan penderita limfoma non-hodgkin berdasarkan klasifikasi histopatologi working formulation

2018 ◽  
Vol 2 (2) ◽  
pp. 28-31
Author(s):  
Evan Pratama Ludirdja ◽  
Ni Made Renny Anggreni Rena ◽  
Ketut Suega ◽  
Made Bakta

Latar belakang: Limfoma Non-Hodgkin (LNH) memiliki manifestasi dan gambaran histologi yang heterogen. Berdasarkan klasifikasi Working Formulation, LNH dibagi menjadi 3, yaitu derajat keganasan rendah, menengah, dan tinggi, yang mencerminkan derajat agresifitas LNH berdasarkan gambaran histopatologiknya. Pada beberapa studi dikatakan LNH tipe indolen cenderung tumbuh lambat dan memiliki kesintasan lebih panjang dibanding tipe yang lebih agresif Tujuan: Membandingkan median kesintasan penderita LNH dari jenis sel B berdasarkan derajat keganasannya sesuai dengan klasifikasi Working Formulation Metode: Penelitian ini menggunakan desain kohort retrospektif, antara bulan Januari 2013 sampai Juli 2017 di RSUP Sanglah Denpasar. Analisis menggunakan Kaplan meier dan seluruh data dianalisis menggunakan SPSS. Hasil: Dari 88 penderita LNH, diambil 38 subyek yang eligible. Dari data didapatkan sebanyak 21 penderita (55,3%) berjenis kelamin laki-laki, dengan gambaran histopatologi terbanyak berupa Diffuse Large Cell (36,8%). Sebanyak 3 penderita (7,9%) termasuk dalam derajat keganasan rendah, 25 penderita (65,8%) termasuk dalam derajat keganasan menengah, dan 10 penderita (26,3%) dengan derajat keganasan tinggi. Median kesintasan pada LNH derajat keganasan rendah di atas 1 tahun (IK 95%), derajat keganasan menengah 271 hari (IK 95%), dan derajat keganasan tinggi 31 hari (0-72,837, IK 95%), dengan nilai p=0,133, namun kelompok dengan derajat keganasan tinggi cenderung memiliki kesintasan yang lebih rendah dibanding 2 kelompok yang lain. Simpulan: Tidak terdapat perbedaan yang signifikan kesintasan penderita LNH dengan derajat keganasan rendah, sedang, dan tinggi.

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 422-426 ◽  
Author(s):  
HJ Weinstein ◽  
EE Lack ◽  
JR Cassady

Abstract Twenty-nine patients with biopsy-proven malignant lymphoma of large- cell “histiocytic” type were treated with the APO protocol (vincristine, adriamycin, and prednisone). Treatment consisted of two years of therapy with a modified adriamycin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and regional radiotherapy (for patients with clinically localized lymphoma). The median age was 13 years (range, two to 20 years). Thirteen patients had localized disease (stage I, II), and 16 had disseminated disease (stage III, IV). The median follow-up is four years (range, seven months to nine years), and Kaplan-Meier estimates of overall and relapse-free survival are 83% and 76%, respectively. No recurrences have been observed in primary or bulk sites of lymphoma in the group of children treated with chemotherapy only. We conclude that the APO protocol, which was modeled after an acute lymphoblastic leukemia regimen, combined with regional radiotherapy can produce long- term remissions for children with malignant lymphoma of large cell “histiocytic” type.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4568-4568
Author(s):  
Sunil A. Reddy ◽  
Howard Liu ◽  
Sabine Kohler ◽  
Richard T. Hoppe ◽  
Youn H. Kim

Abstract Primary cutaneous CD30+ anaplastic large cell lymphoma (PCALCL) represents the malignant end of the spectrum of CD30+ lymphoproliferative disorders. The management of PCALCL is markedly different than that of its primary nodal counterpart. The basis of this difference is due to the less aggressive nature of PCALCL. There is no evidence that chemotherapy is necessary or superior to the excellent results of local therapies such as radiation and/or excision for unilesional or local disease. Even patients with generalized disease have done well in some series. Here we review the characteristics and management of 40 cases of this rare cutaneous lymphoma. We have excluded Lymphomatoid Papulosis (LyP), the benign counterpart of PCALCL. In our series PCALCL was defined as CD30+ ALCL with disease limited to the skin as defined by a negative CT scan. Bone marrow biopsy was not necessary although it was always negative when done. Unilesional, local and extensive regional patients were generally treated with radiotherapy and/or excision, while chemotherapy and biologics were reserved for extensive regional and multifocal patients. The study included 30 men and 10 women with a mean age of 57.5 years (range 24–86). The estimated Kaplan-Meier disease specific survival (DSS) at 4 years for the entire group is 75.6%, with a median follow-up of 27.5 months (1–213). Twenty-six patients presented with unilesional or local disease, while there were 8 multifocal and 6 extensive regional patients (defined as 2 or more lesions beyond a 15 cm2 area apart but limited to 1 or 2 contiguous body regions). The unilesional/local patients had an estimated 4 year DSS of 93%. All but 2 of these patients are alive. The estimated Kaplan-Meier 4 year DSS of patients with either multifocal or extensive regional disease is 30%. Estimated 4 year Kaplan-Meir survival of PCALCL by extent of skin involvement unilesional/local 93% multifocal/extensive regional 30% P-value<0.001 Seven deaths occurred in this series of which 6 were either directly or indirectly attributable to PCALCL. Of the deaths 3 were among the 6 patients with extensive regional disease and 2 were among the 8 patients with multifocal disease. Furthermore, 4 multifocal and 2 extensive regional patients have active disease at the time of last follow-up. Further followup will determine their eventual outcome. The 2 patients with unilesional disease who died, both developed rapid progression to extensive regional disease. Although most patients with PCALCL present with local disease and do quite well with local therapy, it appears that some PCALCL patients with multifocal disease, extensive regional disease, and rapidly progressive unilesional disease behave as high grade lymphomas refractory to standard chemotherapy.


Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1046-1051 ◽  
Author(s):  
ME Hill ◽  
KA MacLennan ◽  
DC Cunningham ◽  
B Vaughan Hudson ◽  
M Burke ◽  
...  

The Bcl-2 protein is capable of preventing apoptosis, and in vitro evidence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's lymphoma (NHL), but the clinical significance of these findings is controversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrangement in a large cohort of prospectively accrued patients with intermediate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in British National Lymphoma investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin blocks were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain reaction-based method, and for Bcl-2 expression using immunohistochemistry. Failure to achieve complete remission (CR), relapse, death from NHL, and deaths from all causes were used as end points to measure CR rate, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identified and tested for the bcl-2 MBR translocation, with 27 (17%) found to be positive; 153 of these patients were tested with immunocytochemistry, and 84 (55%) showed evidence of Bcl-2 expression. For patients who achieved CR from the initial treatment, the relapse rate was significantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the only factor significantly related to relapse rate in the subjects measured. The cause-specific survival for NHL in the series as a whole was significantly lower in patients with Bcl-2 expression than in those without. MBR status had no significant influence on any of the outcome measures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse.


1994 ◽  
Vol 12 (5) ◽  
pp. 895-898 ◽  
Author(s):  
J T Sandlund ◽  
C H Pui ◽  
V M Santana ◽  
H Mahmoud ◽  
W M Roberts ◽  
...  

PURPOSE To determine the frequency of CD30 expression and its relationship to clinical features, immunophenotype, histotype, and outcome in childhood large-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS We reviewed 45 cases of large-cell NHL in children treated at St Jude Children's Research Hospital from 1975 to 1990 for whom there was sufficient tissue to perform immunophenotypic studies. All 45 were screened with a panel of antibodies to detect the presence of CD30 and T-cell and B-cell antigens. Cases were classified according to the National Cancer Institute (NCI) Working Formulation and the Kiel classification system. Clinical features, immunophenotype, pathologic classification, and treatment outcome were compared for CD30+ and CD30- cases. RESULTS CD30 expression was documented in 18 cases (40%). These 13 boys and five girls had a median age of 13 years at diagnosis. Most (n = 14) had advanced-stage (III and IV) disease. Nodal disease was equally common in CD30+ and CD30- cases, whereas skin involvement was significantly more frequent in CD30+ cases (P = .007). There was no significant association of CD30 expression with histologic subtype according to the NCI Working Formulation, but CD30+ cases were more likely to be anaplastic by the Kiel classification (P < .001). All CD30+ cases had either T-cell or null-cell phenotype, while the majority of CD30- cases were B-cell phenotype (P < .001). Among patients with limited-stage disease, the mean +/- SE estimated 5-year event-free survival (EFS) was 75% +/- 22% for CD30+ cases and 92% +/- 9% for CD30- cases (P = .10); estimates for advanced-stage disease were 57% +/- 17% and 29% +/- 17%, respectively (P = .096). For patients with advanced-stage disease, CD30 expression was associated with a significantly better overall 5-year survival probability (84% +/- 12% v 27% +/- 16%, P = .0016). CONCLUSION CD30 is frequently expressed in pediatric large-cell NHL and is significantly associated with T-cell or null-cell phenotype, anaplastic morphology, skin involvement, and better overall survival among advanced-stage patients.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Deepa Jagadeesh ◽  
Robert B. Sims ◽  
Steven M. Horwitz

Background In the ECHELON-2 phase 3 clinical trial, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed clinically meaningful and statistically significant efficacy in patients with peripheral T-cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by IHC. In addition to the ECHELON-2 study, response data are available from an additional 344 subjects with CD30-expressing PTCL and other large-cell lymphomas (including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma-NOS) who had been treated in studies with brentuximab vedotin as a single agent or in combination with chemotherapy, in both frontline and relapsed/refractory settings. Among these 344 subjects, 184 had tumors with CD30 expression &lt;10% by local assessment, including 83/184 with undetectable CD30 by immunohistochemistry (CD30=0). Responses to brentuximab vedotin have been observed at all levels of CD30 expression, including in tumors with undetectable CD30 levels (Advani 2019; Horwitz 2019). It is hypothesized that A+CHP will demonstrate efficacy in subjects with PTCL and CD30 expression &lt;10% because: i) brentuximab vedotin has shown activity in lymphomas with low CD30 expression; and ii) the activity of CHP chemotherapy in PTCL is unrelated to CD30 expression. This study will include subjects with PTCL subtypes other than systemic anaplastic large cell lymphoma (sALCL). Study Design and Methods This is a dual-cohort, open-label, multicenter, phase 2 clinical trial designed to evaluate the efficacy and safety of A+CHP in subjects with non-sALCL PTCL and CD30 expression &lt;10% on tumor cells. Enrollment will be based on CD30 expression per local lab assessment. Subjects will be assigned to 1 of 2 cohorts based on CD30 expression; up to approximately 40 subjects will be enrolled in the CD30 negative (expression &lt;1%) cohort and approximately 40 subjects will be enrolled in the CD30 positive (expression ≥1% to &lt;10%) cohort. An archived tumor biopsy specimen will be submitted to a central pathology lab for confirmation of CD30 expression. Only subjects with CD30 expression &lt;10% per central confirmation will be analyzed for the primary and secondary endpoints. Subjects will receive 21-day cycles of A+CHP for a target of 6-8 cycles. The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR). Key secondary endpoints include CR and PFS per BICR and overall survival. Key inclusion criteria include the following: subjects aged 18 years and older with newly diagnosed PTCL, excluding sALCL, per the WHO 2016 classification; CD30 expression &lt;10% by local assessment; and fluorodeoxyglucose-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist. Lymphoma response and progression will be assessed by BICR using Revised Response Criteria for Malignant Lymphoma and modified Lugano criteria. A CT scan will be performed at the time of suspected clinical progression. Subsequent restage assessments (CT scans only) will be performed according to the calendar, relative to the first dose of study treatment, to ensure that tumor progression is uniformly assessed between the treatment arms. Efficacy and safety endpoints will be summarized with descriptive statistics by cohort, with the CD30 negative cohort and the CD30 positive cohort. The summary of overall (CD30 negative and positive cohort combined) may be presented as appropriate. Descriptive statistics (mean, median, standard deviation, minimum, and maximum) will be used to describe continuous variables. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier methodology and Kaplan-Meier plots will be presented. Medians for time-to-event analyses (eg, median PFS), will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method. The trial will have sites open in the US and multiple countries in Europe, with enrollment planning to begin in September 2020. Disclosures Jagadeesh: Verastem: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Research Funding; Debiopharm Group: Research Funding; Regeneron: Research Funding. Sims:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Travel expenses. Horwitz:ASTEX: Consultancy; Millenium/Takeda: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Celgene: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Aileron: Consultancy, Research Funding; ADCT Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Myeloid Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Vividion Therapeutics: Consultancy; Affirmed: Consultancy; Kura Oncology: Consultancy; Miragen: Consultancy; Kyowa Hakka Kirin: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; Portola: Consultancy, Research Funding.


2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S49-S49
Author(s):  
P Q Deb ◽  
H J Hurley ◽  
C Bhate ◽  
D Cai

Abstract Introduction/Objective Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is the second most type of cutaneous lymphoma of T cell origin. Although PC-ALCL is considered clinically indolent with an excellent overall survival rate, very few studies have examined the epidemiology and survival of this disease in significant depth. Here we have used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database to identify the cases of PC-ALCL with immunohistologic or molecular confirmation and analyzed disease-specific survival across various epidemiological factors. Methods/Case Report We identified patients with PC-ALCL from the SEER database from 1975 - 2017. Cases with only histological and immunohistochemical or molecular evidence of diagnosis were included in the study. Age, sex, and race-standardized incidence rates (IR) were calculated. Survival was assessed using Kaplan-Meier curves and Cox proportional hazards models. Results (if a Case Study enter NA) 93 individuals were identified with a diagnosis of PC-ALCL. Increased age correlated significantly with the total number of cases within age groups, suggesting an associated risk. Males were significantly overrepresented in the disease population at 62%. The racial distribution of patients with PC-ALCL did not significantly differ from the racial distribution in the US. Kaplan-Meier DSS analysis was performed to assess possible influence of race, sex, age, or primary site location on the prognosis in patients with PC-ALCL. Age appears to be one of the greatest factors influencing survival, and while this trended strongly, it was not a statistically significant observation. Although males were disproportionately represented among PC-ALCL patients, sex did not affect survival. Similarly, the patient’s race had no significant effect on the length of survival. The location of the primary tumor trends towards affecting survival, and while this is quantitatively the most impressive observation, it does not reach the threshold of statistical significance. Conclusion We performed a comprehensive review of the clinical and epidemiological features present in PC-ALCL. We found age to be the most significant factor in the risk of development of PC-ALCL, and while our study lacks the statistical power to demonstrate it, age may also be the most significant factor in survival.


1992 ◽  
Vol 29 (3) ◽  
pp. 183-195 ◽  
Author(s):  
W. Vernau ◽  
V. E. O. Valli ◽  
T. W. Dukes ◽  
R. M. Jacobs ◽  
M. Shoukri ◽  
...  

A retrospective histologic study was made of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphoma. This classification scheme was found to be readily applicable to bovine lymphoma. Most of the cell types described in the National Cancer Institute Working Formulation occurred in this series of bovine lymphomas, but the distribution of cell types varied markedly compared to that of human beings. Eighty-nine percent (1,067/1,198) of bovine lymphomas were high-grade tumors. The diffuse large cell type and its cleaved variant comprised 65.9% of all bovine lymphomas. Similar to the dog, but in marked contrast to human beings where at least 34% of non-Hodgkin's lymphomas were follicular, follicular tumors were found to be extremely rare in cattle (0.3% or 4/1,198). The prevalence of cell types varied significantly between the enzootic and sporadic lymphomas. The cleaved variant of the diffuse large cell type constituted 38% (406/1,072) of enzootic lymphomas versus 14% (18/126) of sporadic lymphomas. The mitotic index (100 × oil immersion field, 175 μm in diameter) of enzootic lymphomas (3.72 ± 0.06, mean ± standard error) was significantly greater than the mitotic index of sporadic lymphomas (2.82 ± 0.17). We concluded that the cleaved variant of the diffuse large cell type with high mitotic index is characteristic of enzootic lymphoma. This characteristic high-grade cell type may be a consequence of the viral etiology of the enzootic form of bovine lymphoma.


Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1046-1051 ◽  
Author(s):  
ME Hill ◽  
KA MacLennan ◽  
DC Cunningham ◽  
B Vaughan Hudson ◽  
M Burke ◽  
...  

Abstract The Bcl-2 protein is capable of preventing apoptosis, and in vitro evidence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's lymphoma (NHL), but the clinical significance of these findings is controversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrangement in a large cohort of prospectively accrued patients with intermediate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in British National Lymphoma investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin blocks were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain reaction-based method, and for Bcl-2 expression using immunohistochemistry. Failure to achieve complete remission (CR), relapse, death from NHL, and deaths from all causes were used as end points to measure CR rate, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identified and tested for the bcl-2 MBR translocation, with 27 (17%) found to be positive; 153 of these patients were tested with immunocytochemistry, and 84 (55%) showed evidence of Bcl-2 expression. For patients who achieved CR from the initial treatment, the relapse rate was significantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the only factor significantly related to relapse rate in the subjects measured. The cause-specific survival for NHL in the series as a whole was significantly lower in patients with Bcl-2 expression than in those without. MBR status had no significant influence on any of the outcome measures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse.


Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1178-1184 ◽  
Author(s):  
Koen van Besien ◽  
Chul S. Ha ◽  
Sandy Murphy ◽  
Peter McLaughlin ◽  
Alma Rodriguez ◽  
...  

Abstract To evaluate the incidence, risk factors, and outcome of central nervous system (CNS) recurrence in adult patients with non-Hodgkin's lymphoma, we evaluated 605 newly diagnosed patients with large-cell and immunoblastic lymphoma who participated in prospective chemotherapy studies. The Kaplan-Meier estimate of probability of CNS recurrence at 1 year after diagnosis was 4.5% (95% confidence interval [CI], 4.4 to 4.6). Twenty-four patients developed CNS recurrence after a median of 6 months from diagnosis (range, 0 to 44 months). In univariate analysis, an increased risk for CNS recurrence was associated with an advanced disease stage (P = .0014), an increased LDH (P = .0000), the presence of B-symptoms (P = .0037), involvement of more than one extranodal site (P = .0000), poor performance status (P = .0005), and B-cell phenotype (P = .008). Bone marrow involvement (P = .005), involvement of parenchymal organs (P = .03), and involvement of skin, subcutaneous tissue, and muscle (P = .002) were also associated with an increased risk for CNS disease. Multivariate logistic regression analysis identified only involvement of more than one extranodal site (P = .0005) and an increased LDH (P = .0008) as independent predictors of CNS recurrence. Established CNS recurrence had a poor prognosis. Only 1 of 24 patients remains alive and the Kaplan-Meier estimate of probability of survival at 1 year after the diagnosis of CNS recurrence is only 25.3% (95% CI, 6.9 to 43.7). Intrathecal treatment provided symptomatic benefit in only 1 of 6 patients. Radiation treatment provided symptomatic improvement in 6 of 9 patients treated. However, remissions were short and followed by systemic or CNS recurrence. Serum LDH and involvement of more than one extranodal site are independent risk factors for CNS recurrence in patients with large-cell lymphoma. The presence of both risk factors identifies a patient group at high risk for CNS recurrence. Established CNS recurrence can be rapidly fatal. Transient responses occur after radiation treatment.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3783-3783 ◽  
Author(s):  
Shahrzad Abdollahi ◽  
Elise A Chong ◽  
Rebecca L. Olin ◽  
Sunita D. Nasta ◽  
Charalambos Andreadis ◽  
...  

Abstract Background: Recent studies have prospectively established that concurrent or sequential addition of rituximab (R) to conventional therapies improves the overall survival rate (OS) for patients with low-grade follicular lymphoma (FL). However, there is little information regarding the prognosis of patients considered R-resistant. Subjects/Methods: We examined the records of 305 subjects with a diagnosis of FL seen at our institution between 1995 and 2007. To better define the prognosis for R-resistant subjects, we identified 133 subjects (grade 1, N=75; grade 2, N=41; grade 1 or 2, N=17) who completed an R-containing treatment (R alone, N=61; R combination, N=72) and had at least six months of follow-up from start of R-containing therapy. For the purposes of our study, we define R-resistance as progression of lymphoma within 6 months of the first R dose (i.e., the dose defining R-resistance) of the R-containing regimen followed by progression. Overall survival rates were evaluated for all subjects from first dose of R to last follow-up or death and, for R-resistant subjects, from the dose defining R-resistance to last follow-up or death. R-resistant subjects (N=62 [47%]) were subdivided into primary refractory (R-resistant after first R-containing treatment; N=30) or acquired resistant (R-resistant after at least one prior R-containing treatment without progression within 6 months; N=32). Median age at first treatment with R was 55 years (range: 21–87) for all subjects and 54 years (range: 21–87) for R-resistant subjects (for primary refractory, median=54 years [range: 28–87]; for acquired resistant, median=55 years [range 30–81]). The median number of prior non-R-containing treatment regimens was 1 (range: 0–4) for resistant subjects, and 0 (range: 0–3) for non resistant subjects. The median number of R-containing regimens for subjects with acquired resistance was 2 (range: 2–4). The frequency of large cell transformation did not differ between R-resistant and non R-resistant cohorts (N=7/71 [10%] and N=8/62 [13%], respectively). Results: Of 20 deaths observed for all subjects with FL receiving R or R containing regimens, 19 deaths occurred after R-resistance. At a median follow-up of 56 months (range 6–115) for all subjects receiving R, the median OS was not reached with 5-year Kaplan-Meier OS estimate = 81%. For R-resistant subjects, median OS from first dose of R defining R-resistance was 64 months (range: 6–100) with 5-year Kaplan-Meier OS estimate = 58%. Median rates of OS from R dose defining R-resistance were not significantly different between primary refractory and acquired resistant subjects. For subjects with acquired R-resistance, median time from first dose of R to first dose of R defining R-resistance was 10.4 months (range: 9–83). Conclusion: The OS estimate for subjects with R-resistant FL (5-year estimate OS = 58%) appears worse than survival estimates reported for unselected subjects with FL (5 year estimate OS = 80% for grade 1; 76% for grade 2 [SEER Survival Monograph, Non-Hodgkin Lymphoma]). This inferior prognosis seems unrelated to large cell transformation. Survival is similar for subjects with primary refractory and acquired resistance when survival is measured from the R dose used to define R-resistance.


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