scholarly journals Prognostic Factors for Patients with Diffuse Large B Cell Lymphoma and Transformed Indolent Lymphoma Undergoing Autologous Stem Cell Transplantation in Denmark 2000-2012

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1983-1983
Author(s):  
Bente Arboe ◽  
Kristina Fruerlund Nielsen ◽  
Charlotte Madsen ◽  
Rasmus Heje Thomsen ◽  
Soeren Ramme Nielsen ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Refractory Disease ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is the largest subgroup of malignant lymphoma. Today more than 80% of the patients will achieve partial or complete remission. However more than 20 % will either relapse or present with refractory disease. The standard approach for patients without major comorbidity is salvage treatment followed by high dose therapy with autologous stem cell transplant (HDT). This potentially curative treatment is toxic with many side effects and procedure related mortality, and therefore identification of patients eligible for HDT is a difficult challenge. Objectives: Patients with relapse of de novo DLBCL and transformed indolent lymphoma (TIL) were included. The aim was to identify clinical prognostic markers that can identify patients who will not benefit from HDT. Methods: From the national lymphoma registry patients with relapse of B-cell lymphoma in Denmark in the period 2000-2012, who underwent HDT, were extracted. Medical records were reviewed for clinical, pathological, and treatment information, and outcome. Patients were followed until death or emigration or until February 1, 2015. The Kaplan-Meier method was used to estimate overall survival (OS) and progression free survival (PFS). Cox regression models were used to assess prognostic factors. Results: A total of 370 patients were included, 174 with de novo DLBCL, and 196 with TIL, 143 of the 196 had histologically confirmed transformation. Median age was 58 (22-73), and 59% of the patients were male. With a median follow-up of 82 months from HDT, the 5-year OS was 52% and the 5-year PFS was 44% (median PFS 3.2 years). For the DLBCL patients the 5-year OS was 43% and the 5-year PFS was 38%. For TIL patients the OS was 62% and the PFS 49% (figure 1). During the first 100 days, 29 patients (8%) were admitted to the intensive care unit (14 DLBCL), and only four of these patients were alive at six months. The non-relapse mortality (NRM) at day 100 was 6 % for both groups, after five years 25% for DLBCL and 15% for TIL. No significant difference in 5-year PFS was seen between sexes or age, but patients younger than 58 had better 5-year OS compared to patients aged 58 or above (p=0.047). There was no difference in relapse treatment (DHAP vs ICE). Smoking (ever vs. never) caused a significantly worse OS (p=0.034). All IPI-factors, except Ann Arbor stage, was of prognostic importance (PFS). Primary refractory disease was of poor prognostic importance (p=0.001), and in patients, for whom the time from last salvage treatment to reinfusion of stem cells was more than 2 months, had a worse outcome (p=0.006). Patients, with less than 20 days of hospital admission in the period from the date of relapse to start of HDT, had a significantly higher survival (OS and PFS) (p>0.001). In a multivariate analysis (PFS), LDH above upper normal reference, HR 1.4 (95% CI: 1.0;2.1), involvement of more than one extranodal site, HR 1.6 (1.1;2.3) primary refractory disease, HR 1.6 (1.1;2.3) and more than two earlier relapses, HR 1.9 (1.1;3.5) were all factors associated with adverse outcome. For OS, the multivariate analysis showed, that patients with TIL had a better outcome, HR 0.7 (0.5;0.9), compared to DLBCL. Age above 58, HR 1.5 (1.1;2.1), involvement of more than one extranodal site, HR 1.9 (1.4;2.8), and primary refractory disease, HR 1.6 (1.1;2.3) were factors associated with adverse outcome. Discussion: In this population based study we find a 5-year OS of 52% after HDT and a 5-year PFS of 44%. Patients with TIL have a significantly higher 5-year PS (49%) than patients with de novo DLBCL (38%) whereas NRM is identical for the two groups at day 100 (6%). However, NRM increases subsequently more for DLBCL than for TIL over time to 25% and 15 % respectively after five years. Furthermore we show that hospitalization days less than 20 and postponement of stem cell infusion beyond 2 month after harvest may be useful parameters that can identify patients that have better or worse outcome after HDT. This nationwide study cohort with the long follow-up period is applicable to a general population of patients, and this may explain the somewhat lower outcome compared to other published HDT cohorts. Figure 1. Progression Free Survival (PFS) curves for Diffuse Large B-Cell Lymphomas (DLBCL) and Transformed Indolent Lymphomas (TIL) after high dose therapy with autologous stem cell transplant Figure 1. Progression Free Survival (PFS) curves for Diffuse Large B-Cell Lymphomas (DLBCL) and Transformed Indolent Lymphomas (TIL) after high dose therapy with autologous stem cell transplant Disclosures Brown: Bayer: Consultancy; Roche: Consultancy, Speakers Bureau.

High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem-Cell Transplantation for Adults ≥ 60 Years Old With Relapsed or Refractory B-Cell Lymphoma

2007 ◽  
Vol 25 (11) ◽  
pp. 1396-1402 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Ted A. Gooley ◽  
John M. Pagel ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Older Adults ◽  
Stem Cell ◽  
B Cell ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
Dose Therapy ◽  
Anti Cd20

Purpose The majority of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) are older than 60 years, yet they are often denied potentially curative high-dose therapy and autologous stem-cell transplantations (ASCT) because of the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Patients and Methods Patients older than 60 years with relapsed B-cell NHL (B-NHL) received infusions of tositumomab anti-CD20 antibody labeled with 185 to 370 Mbq (5 to 10 mCi) [131I]-tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of [131I]tositumomab (median, 19.4 Gbq [525 mCi]; range, 12.1 to 42.7 Gbq [328 to 1,154 mCi]) to deliver 25 to 27 Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results Twenty-four patients with a median age of 64 years (range, 60 to 76 years), who had received a median of four prior regimens (range, two to 14 regimens), were treated. Thirteen patients (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survival rates were 59% and 51%, respectively, with a median follow-up of 2.9 years (range, 1 to 6 years). All patients experienced expected myeloablation with engraftment of platelets (≥ 20 K/μL) and neutrophils (≥ 500/μL), occurring at a median of 9 and 15 days after ASCT, respectively. There were no treatment-related deaths, and only two patients experienced grade 4 nonhematologic toxicity. Conclusion Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

High-Dose Therapy and Autologous Stem Cell Transplantation for Chemoresistant Diffuse Large B Cell Lymphoma: The Seattle Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5097-5097
Author(s):  
Jonathan A. Gutman ◽  
Ted A. Gooley ◽  
Jacob Nourigat ◽  
John M. Pagel ◽  
Oliver W. Press ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Large B Cell Lymphoma ◽  
One Year ◽  
Large B Cell

Abstract High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed or refractory diffuse large B cell lymphoma (DLBCL). Unfortunately, there are few established options for DLBCL patients with chemoresistant disease and data regarding the efficacy of ASCT in this setting are limited. We conducted a retrospective review of patients with chemoresistant DLCBL undergoing ASCT at our Center with the goal of identifying variables associated with better outcomes. Between March 1990 and September 2004, 40 pts underwent ASCT for chemoresistant DLBCL, defined as < 50% reduction in the size of the tumor with the chemotherapy regimen immediately preceding ASCT. The median age of these pts was 44 years (range 17–69). The number of prior chemotherapies was 2 (n=21), 3 (n=15), or 4 (n=4). Twenty-two (55%) patients had progressive disease (PD) following their pre-transplant salvage therapy and 18 (45%) patients had stable disease (SD). Sixteen patients (40%) had never achieved at least a partial response (PR) to any previous chemotherapy. Median time from diagnosis to ASCT was 13 months (range 6–98). The international prognostic index (IPI) at time of ASCT was available for 33 patients and was 0–1 for 10 patients and 2–4 for 23 patients. Twenty-four patients (60%) underwent conditioning with combined chemotherapy and radiation and 16 patients (40%) received chemotherapy only. All patients received mobilized peripheral blood stem cells. Thirty-three patients have died as of last contact, with an estimated 3-year overall survival (OS) of 21% and a median follow-up of 4.0 years among the 7 survivors. Among 34 patients who did not have refractory disease following transplant, estimated 3-year progression free survival (PFS) was 12%. Causes of death include PD (n=24), ASCT toxicity (n=3), and late infection (n=2). After adjusting for year of transplant, patients with a remission duration of less than one year following initial treatment and patients whose remission duration exceeded one year had a reduced, but not statistically significant, hazard of mortality compared to patients that never responded (remission <1 year: HR=0.28, p=0.21; > 1 year: HR=0.14, p=0.08) (Figure 1). The hazard of death decreased with transplants performed more recently (p=0.03). There was no statistically significant association between outcomes and age at transplant, number of prior chemotherapy regimens, conditioning regimen (radiation vs non-radiation based), disease status at ASCT (progressive vs stable), or pre-ASCT IPI (available for 33 patients). Though outcomes following ASCT for chemoresistant DLBCL are poor, a minority of patients with prolonged remission prior to initial relapse may achieve long term survival following HDT. Additional strategies are needed to treat this disease. Figure Figure

High-Dose Therapy and Autologous Stem Cell Transplant (HD-ASCT) for Transformed Non-Hodgkin Lymphoma (NHL) In the Rituximab Era

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2393-2393
Author(s):  
Makiko Ban-Hoefen ◽  
Jonathan W. Friedberg ◽  
Jennifer L. Kelly ◽  
Steven H. Bernstein ◽  
Jane L. Liesveld ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Indolent Lymphoma ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
Indolent Disease

Abstract Abstract 2393 Background: The transformation of indolent non-Hodgkin's lymphoma (NHL) to a more aggressive histology remains a therapeutic challenge. For younger patients with a favorable performance status, high-dose therapy and autologous stem cell transplantation (HD-ASCT) results in a prolonged progression-free survival (PFS) in a substantial subset, based upon retrospective single and multi-institutional experiences. Rituximab improves PFS and overall survival (OS) in both follicular and aggressive NHL when combined with chemotherapy. However, the impact of prior rituximab on outcome of HD-ASCT for transformed NHL has not been elucidated. Methods: We therefore analyzed consecutive patients with indolent NHL (including follicular lymphoma and marginal zone lymphoma) who developed histologically confirmed transformation to diffuse large B-cell lymphoma (DLBCL) and subsequently underwent HD-ASCT at the University of Rochester Medical Center between 1998 – 2009. Patients who transformed within 6 months of the diagnosis of indolent lymphoma were excluded from the study. Progression free survival (PFS) was defined as time from HD-ASCT to date of disease relapse, progression, or death due to any cause. Kaplan-Meier survival curves were estimated, and differences in PFS between those who received rituximab prior to transformation versus those who were rituximab-naïve at transformation were assessed using the log-rank test. Results: 19 patients were identified, (10 female) who received rituximab-containing therapy at transformation. The median age at HD-ASCT was 59 years (range 40–66). Patients were treated with a median of 3 (range 1–9) chemotherapy regimens prior to HD-ASCT. Median time from the diagnosis of indolent lymphoma to transformation was 55 months (range 8–276). Conditioning regimens at HD-ASCT were BEAM (N=15), BEAC (N=1) and Cy/TBI (N=3). With a median follow-up of 47 months, the 2-year PFS was 58% and the 2-year OS was 84%. There were no treatment-related mortalities. Seven patients relapsed after HD-ASCT (2 with indolent histologies and 5 with DLBCL); 3 of these patients have died. Two additional patients have died of myelodysplastic syndrome-acute myeloid leukemia after HD-ASCT. Eight patients did not receive rituximab for indolent disease prior to transformation; this group had a significantly better PFS at 2 years (86% vs 36%, p = 0.049) compared to 11 patients who were treated with rituximab for indolent disease prior to ASCT. The patients who did not receive rituxmiab prior to ASCT had similar characteristics to patients who received rituximab, except that the time from indolent diagnosis to transformation was longer in the rituximab-naïve group (90 months vs 39 months). Conclusions: HD-ASCT remains an effective therapeutic option for transformed NHL in the rituximab era. However, transformed patients exposed to rituximab prior to HD-ASCT appear to have inferior outcomes, similar to the experience of patients with de novo NHL treated with rituximab prior to HD-ASCT in the recently reported CORAL study (JCO, published online ahead of print July 26, 2010). Patients who transform after rituximab-containing therapy may represent a higher risk group of patients with a unique biology, who may benefit from novel conditioning and maintenance regimens in the setting of HD-ASCT. Disclosures: No relevant conflicts of interest to declare.

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