Autologous Stem Cell Transplant in Recurrent Diffuse Large B- Cell Lymphoma: Prior Rituximab Therapy Has No Impact On Early Lymphocyte Recovery and Transplant Outcome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3407-3407
Author(s):  
Daniel G Stover ◽  
Vishruth K Reddy ◽  
John P. Greer ◽  
Madan Jagasia ◽  
David Morgan ◽  
...  

Abstract Abstract 3407 Poster Board III-295 Background: Diffuse Large B Cell (DLBCL) is the most common histological subtype of lymphoma diagnosed in the United States. Following failure with standard Rituximab- CHOP chemotherapy, salvage therapy followed by autologous stem cell transplant is the standard treatment for those who are transplant eligible. Previous data suggest that early lymphocyte recovery is associated with superior survival after autologous stem cell transplantation (ASCT) in lymphoma. However, there are no consistent data on whether prior rituximab therapy affects lymphocyte recovery early post- transplantation. In this study we present our transplant outcome experience regarding early lymphocyte recovery in patients exposed to prior rituximab therapy. Methods: One hundred fifteen patients undergoing autologous stem cell transplant for relapsed DLBCL at a single institution between January 2000 and December 2008 were included in our analysis after obtaining IRB approval. Descriptive statistics, Wilcoxon signed rank sum test and Kaplan-Meier analysis were performed as required using SPSS software. Results: Median age of patients undergoing ASCT was 50 years (range: 24-69 years). Nine patients who underwent ASCT for transformed DLBCL and 7 patients with T-cell rich B cell lymphoma were also included in the final analysis. Six patients had stage I disease, 29 patients with stage II, 33 patients with stage III and 36 patients were diagnosed with stage IV. Thirteen patients had bulky retroperitoneal adenopathy at the time of original diagnosis. Seventy one (66.3%) patients received one salvage therapy prior to transplant. Thirty six (33.7%) patients received two or more salvage therapies prior to transplant. Mobilization data was available on 89 patients. Of those, 82 patients were mobilized with chemotherapy and 5 patients underwent mobilization with GCSF alone. High dose cytclophosphamide (7200 mg/sq.m), etoposide (2000 mg/sq.m) and BCNU (400 mg/sq.m) [CBV] was the conditioning regimen in 88 (77.2%) patients. Sixty eight (59.6%) patients received pretransplant rituximab therapy. Sixty one (61.6%) patients were in radiographic complete response (CR) following salvage therapy at the time of transplant. Sixty nine (78.4%) patients continued to be in CR at day 100 evaluation. Nineteen (21.6%) patients had persistent disease requiring further therapy. The median survival of all patients was 38.7 months (range: 3 months- 186 months). At the time of the analysis, 69 (60.5%) patients were still alive. Prior rituximab therapy did not affect lymphocyte recovery on day 14 (p=0.95) or day 28 (p=0.27). Lymphocyte recovery on day 14 and day 28 (continuous and categorical variables) had no impact on transplant outcome. Other factors such as age, disease stage at presentation, presence of bulky retroperitoneal nodal disease, number of regimens, mobilization procedure, type of conditioning regimen, pre-transplant radiation therapy, pre-transplant disease status (CR vs. PR in chemo sensitive disease) had no impact on survival. Conclusions: our data demonstrate that prior rituximab therapy has no impact on lymphocyte recovery on day 14 or day 28. In this group of patients, lymphocyte recovery did not impact on autologous stem cell transplant outcome. The survival benefit with early lymphocyte recovery as mentioned in prior reports may be lost with longer follow up. Prior rituximab therapy may mitigate the effect of the number of treatment regimens or disease status (CR vs. PR) on transplant outcome. Disclosures: No relevant conflicts of interest to declare.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19501-e19501
Author(s):  
Aung M. Tun ◽  
Yucai Wang ◽  
Seth Maliske ◽  
Umar Farooq ◽  
Ivana N. M. Micallef ◽  
...  

e19501 Background: The current standard of care for patients with relapsed or refractory (RR) diffuse large B-cell lymphoma (DLBCL) following frontline immunochemotherapy (IC) is salvage therapy, followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) rescue in patients responding to salvage therapy. Time to first relapse (or refractory status) and response to salvage therapy in patients with RR DLBCL may reflect the chemosensitivity of the underlying disease. The aim of this study is to determine whether these factors impact post-ASCT outcomes. Methods: Patients with DLBCL that relapsed after R-CHOP or R-CHOP-like frontline therapy who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma and transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using Kaplan-Meier method and Cox proportional hazards models. Results: A total of 437 patients with RR DLBCL who underwent salvage therapy and ASCT were identified. 280 (64%) were male. Median time from initial diagnosis to 1st relapse/salvage was 1.0 years (range 0.1-16.4). A median of 1 line (range 1-3) of salvage therapy was required. Response prior to ASCT was complete response (CR) in 211 (48%), partial response in 199 (46%), stable disease in 24 (5%), and unknown in 3 (1%) patients. Median age at ASCT was 61 years (range 19-78), and median follow up after ASCT was 8.0 years (95% CI 7.2-8.7). Median PFS and OS was 2.7 (95% CI 1.5-4.3) and 5.4 (4.2-7.4) years, respectively. Time to 1st relapse/salvage (≤1 vs 1-2 vs > 2 years) was not associated with PFS (median 0.8 vs 2.4 vs 4.9 years, p = 0.170) but was associated with OS (2.4 vs 7.4 vs 6.8 years, p = 0.013). Patients who required > 1 line of salvage therapy had significantly inferior PFS (median 0.3 vs 4.5 years, p < 0.001) and OS (0.9 vs 7.4 years, p < 0.001). In addition, patients who failed to achieve a CR prior to ASCT had significantly worse PFS (median 0.8 vs 5.3 years, p < 0.001) and OS (2.7 vs 9.2 years, p < 0.001). In multivariate Cox regression models adjusted for age and sex, time to 1st relapse/salvage was not associated with PFS (p = 0.313) or OS (p = 0.081); however, lines of salvage and response prior to ASCT remain significantly prognostic for PFS ( > 1 line of salvage: HR 2.14, 95% CI 1.59-2.87, p < 0.001; non-CR: HR 1.61, 95% CI 1.26-2.05, p < 0.001) and OS ( > 1 line of salvage: HR 2.25, 95% CI 1.66-3.05, p < 0.001; non-CR: HR 1.63, 95% CI 1.26-2.12, p < 0.001). Conclusions: In patients with RR DLBCL following frontline IC, requiring more than 1 line of salvage therapy and failure to achieve CR are strong independent risk factors for poor PFS and OS after ASCT. Novel therapies such as CAR-T cell therapy should be studied in this population.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3993-3993 ◽  
Author(s):  
Andy I Chen ◽  
Craig Okada ◽  
Nate Gay ◽  
Phil Reiss ◽  
Stephen Spurgeon ◽  
...  

Abstract Double hit lymphoma (DHL), defined as B cell lymphoma with a c-MYC rearrangement plus a IGH/BCL2 rearrangement, confers a poor prognosis. Outcomes with R-CHOP are dismal with reported 2 year EFS <30% in multiple series. To improve upon these results, Burkitt type regimens such as R-HyperCVAD and dose adjusted (DA) R-EPOCH have been attempted, but 2 year EFS remains < 50% in early reports. In addition, the SWOG-9704 study found a benefit for consolidative autologous stem cell transplant (autoSCT) in high risk DLBCL, likely including some DHL, although this reported benefit has not been confirmed in three other randomized European studies. Since 2010 the treatment algorithm at Oregon Health & Science University for fit patients with DHL has been DA-R-EPOCH followed by consolidative autoSCT in responding patients. Here we report the first 16 patients treated with consolidative autoSCT. At diagnosis, the median age was 58, and the median IPI was 3. All patients had rearrangements of c-MYC and IGH/BCL2. One of the c-MYC rearrangements was a classical t(8;14); the translocation partners in the other cases were unknown. Three patients also had a ‘triple hit’ with an additional BCL6 rearrangement. Fourteen patients received DA-R-EPOCH with intrathecal prophylaxis for induction. One received R-CHOP at another institution, and one received R-HyperCVAD. 15 of 16 patients were in CR after induction. Stem cell mobilization was performed with G-CSF +/- plerixafor, and BEAM was utilized as the high dose conditioning regimen. With a median follow-up of 18 months, the estimated 2 year PFS is 91 %, and the 2 year OS is 91 % in the 16 patients who underwent consolidative autoSCT. There were no deaths from non-relapse mortality, and the only relapse was 6 months post-transplant. All other patients undergoing autoSCT remain alive and in remission. An additional 15 patients also underwent induction with DA-R-EPOCH but did not proceed to autoSCT. Four patients who had intended to undergo autoSCT were refractory to induction. Of the remaining 11 patients, 9 did not pursue autoSCT because of age and/or comorbidities, and 1 each declined out of personal preference or insurance denial. Four of these 11 have relapsed or died. Our results suggest that consolidative autoSCT, especially after DA-R-EPOCH induction, is an effective treatment strategy for DHL in fit patients and should be explored in prospective studies. Disclosures No relevant conflicts of interest to declare.


2011 ◽  
Vol 35 (6) ◽  
pp. e59-e60 ◽  
Author(s):  
Seah H. Lim ◽  
Joseph M. Guileyardo ◽  
Robbie Graham ◽  
Lorna R. Strong ◽  
William V. Esler

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1408-1408
Author(s):  
Seah H. Lim ◽  
Yana Zhang ◽  
Zhiqing Wang ◽  
William V. Esler ◽  
David Beggs ◽  
...  

Abstract Rituximab, a chimeric CD20 antibody, has been incorporated in various chemotherapy regimen for B-cell lymphoma. It has also been used as maintenance therapy in some of these patients. However, the effects of its long-term use on the immune system has not been previously documented. Here, we present our preliminary analysis of the effect of maintenance rituximab therapy on the B-cell immune repertoire in nine consecutive patients with B-cell lymphoma who were treated with maintenance rituximab after autologous stem cell transplant (ASCT) for high-risk disease. Nine patients (seven men and two women) with high-risk B-cell lymphoma were treated. Their diagnosis were: advanced mantle cell lymphoma in first CR (6), Stage IV DLCL in CR1 (1) and high grade NHL in CR2 (2). Median age was 66 years (range 38–72 years). CR was achieved using R-CHOP (8) or R-DHAP (1). Autologous stem cells were harvested during hematopoietic recovery from the last course of chemo-immunotherapy and G-CSF. Within two weeks after stem cell harvest, each patient received intravenous melphalan (200 mg/m2) following by the infusion of at least 2 x 106/kg CD34+ cells. All patients received a rituximab infusion (375 mg/m2) every three months starting D+100 after ASCT for a total of 2 years or until disease relapse. Unlike patients who underwent ASCT without rituximab, in whom B-cell recovery occured between 3–6 months, we observed severe delays in the immunoglobulin recoveries in these patients. At 9 months after transplant, all patients were IgM and IgG deficient, with only 1/9 patient acheived a normal IgA level. Even at 24 months after transplant, all patients were still IgM deficient and only 20% achieved normal IgA and IgG levels. The severity of immuno-deficiencies was next examined. We observed severe immunoglobulin deficiency (defined by &lt; 50% normal levels) in IgM in all patients and in IgG and IgA in more than 20% patients at 24 months, suggesting that the immunoglobulin recovery was both delayed and severely affected. The severe immunoglobulin deficiencies may be clinically relevant. One patient developed two episodes (follow-up of 12+ months), one seven episodes (follow-up 28+ months) and another two episodes of chest infection and a vancomycin-sensitive chronic diarrhea (follow-up 18+ months). All three patient had severe and prolonged immunoglobulin deficiencies. With a median follow-up of 27 months (range 12–31 months), all patients have remained lymphoma-free. These preliminary results, therefore, suggest that rituximab administration every three months after autologous transplant for high-risk B-cell NHL delays immunoglobulin recovery and may be associated with increased risks of infection. Although this approach may reduce lymphoma relapse, careful monitoring of the immunoglobulin recovery and interventional as appropriate should be done routinely in these patients.


2019 ◽  
Vol 25 (3) ◽  
pp. S394-S395
Author(s):  
Neeraj Saini ◽  
Rima M. Saliba ◽  
Romil D. Patel ◽  
Mustafa Nooruldeen Abdulrazzaq ◽  
Chitra M. Hosing ◽  
...  

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