Pretransplant Rituximab Research Articles

Pre-Transplant Rituximab Is Associated with Reduced Rate of Acute GvHD After RIC-Allosct In Lymphoma Patients: Results From A Retrospective Monocenter Analysis.

AbstractAbstract 1319 Introduction:both B and T cells are implicated in the pathophysiology of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (AlloSCT). Anti-thymocyte globulin (ATG) administered during conditioning has been shown to reduce both acute and chronic GvHD, while rituximab has been claimed to reduce incidence of GvHD: previous studies indicated a reduced incidence of acute and/or chronic GvHD, but sometimes with controversial results. Here we present results from a retrospective, monocenter analysis on a selected population of lymphoma patients undergoing reduced-intensity (RIC) AlloSCT, with or without ATG in the conditioning regimen. Methods:adult patients receiving RIC-AlloSCT from a HLA-identical sibling donor for relapsed CD20+ lymphoproliferative disease at our Institution were included in the analysis. Data on patients and donors, conditioning regimen, use of rituximab and cumulative dose during the six and three months before AlloSCT were collected. Rituximab was administered in association or not with chemotherapy, according to each patient's treatment strategy. Analysis was conducted separately on patients receiving ATG (ATG cohort) or not (non-ATG cohort). Correlation analysis between ATG, rituximab cumulative dose before AlloSCT and grade 2–4, grade 3–4 acute GvHD (aGvHD), or limited/extensive chronic GvHD (cGvHD) was performed. Results:a total of 57 patients transplanted between Avril 1999 and November 2009 were included in the study, 18 and 39 in the non-ATG and ATG group respectively. Of these 57 patients, 32 were treated with rituximab for a median (range) cumulative dose within 6 months before AlloSCT of 1500 (375-3375) mg/mq, ending at a median (range) of 43 (5-177) days prior to transplant. Details are shown in table 1. Median follow-up was 749 days (146-4051). No significant differences existed between patients receiving rituximab vs. those without rituximab, with the exception of a different number of patients with CLL or FCL. Among the 18 non-ATG patients, we observed a slightly reduced rate of severe (grade 3 or 4) aGvHD in those patients who received >= 375 mg/mq rituximab within three months before AlloSCT (n=13) compared to those receiving < 375 mg/mq or no rituximab (n=5): 2/13 vs. 2/5 (p=ns). In the ATG cohort, rituximab use at a dose >= 375 mg/mq (n=10) within three months was associated with a reduced rate of severe aGvHD compared with < 375 mg/mq or no rituximab (n=29): 0/10 vs. 7/29 (p=0.08). Reduction of grade 2–4 aGvHD rate was also observed: 1/10 vs. 14/29 (p=0.03). No effect on cGvHD appeared in the two cohorts. Discussion:present data suggest a role of rituximab administered before AlloSCT in reducing the incidence of aGvHD. This effect was more pronounced when concomitant administration of ATG was performed during conditioning regimen, indicating a possibly sinergistic effect of both T- and B-cell depletion in preventing GvHD. Although retrospective and small-sized, the present analysis, conducted on a quite homogeneous population of patients, confirms previous findings and enhances further investigations on larger number of patients.VariableMedianRangeRituximab cohortNo–rituximab cohortN. patients3225Median age (range)5227–6851 (34–68)52 (27–68)DiagnosisDLBCL75Folliculaire113Manteau77Foll transf20L prolymphocytaire B10LLC49Waldenstrom01Disease status at HSCTCR137PR1514SD11REFR33 Disclosures:Off Label Use: Zevalin is off-label use in conditioning regimen in France.

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

Abstract 3407Poster 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.

Impact of Pre-transplant Rituximab on Survival after Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy before AuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P < .001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM.

Pre-Transplant Rituximab Therapy Is Associated with Improved Progression-Free and Overall Survival in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma (DLBCL).

Outcomes following first-line therapy for patients (pts) with DLBCL have improved significantly with the availability of the chimeric anti-CD20 monoclonal antibody rituximab (R). Despite this progress, many pts develop refractory or recurrent DLBCL and are considered candidates for autologous hematopoietic stem cell transplantation (AuHCT). For such pts, it is possible that R given pre-transplant and/or during conditioning therapy affects the natural history of DLBCL, such that traditional methods of risk assessment and patient selection for AuHCT may need revision. We therefore studied the outcomes of 1,006 pts who underwent peripheral blood AuHCT for DLBCL between 1996 and 2003 reported to the CIBMTR, analyzed according to whether R was (n=188, “+R” group) or was not (n=818, “-R” group) administered prior to AuHCT. Using the chi-square statistic for categorical and the Kruskal-Wallis for continuous variables, there were no significant differences between the +R and -R groups with regard to gender, pre-transplant performance status, disease status at transplant, pre-transplant chemosensitivity, second-line aa-IPI score distribution, Ann Arbor stage at transplant, interval from diagnosis to transplant, bulky disease, bone marrow involvement, post-transplant radiation therapy, or post-transplant myeloid growth factor therapy. The +R group had a higher proportion of pts age 61 or older (40% vs. 23%, p<0.001). AuHCT occurred between 1999–2003 in 96% of pts in the +R group, and between 1996–2001 in 93% of the -R pts (p<0.001). For the +R pts, 94% received R only with pretransplant chemotherapy, 3% only with conditioning therapy, and 3% with both pretransplant chemotherapy and conditioning therapy. Conditioning regimens were similar in the +R and -R groups, with the majority receiving the BEAM regimen. In univariate analysis, platelet and neutrophil engraftment were not affected by use of R. Treatment-related mortality (TRM) at 1, 3, or 5 years did not differ significantly between the +R and -R groups. Progression-free survival (PFS) at 1 and 3 years was superior in the +R group (62% vs. 49% at 1 year, p=0.002; 49% vs. 38% at 3 years, p=0.010). Overall survival (OS) was superior in the +R group (68% vs. 60% at 1 year, p=0.032; 57% vs. 45% at 3 years, p=0.003). In multivariate analysis, later year of transplant (2000–2003) and age <55 were associated with lower TRM, but pre-transplant R was not. Conversely, pre-transplant R, age <55, and fewer than 3 lines of chemotherapy were associated with improved PFS, while year of transplant was not. Finally, pre-transplant R, age <55, fewer than 3 lines of chemotherapy, and year of transplant 2000–2003, were all associated with improved OS. We conclude that pre-transplant rituximab is associated with improved PFS and OS following AuHCT for DLBCL, with no evidence of impaired engraftment or increased TRM.

Prognostic significance of early lymphocyte recovery after post-autografting administration of GM-CSF in non-Hodgkin's lymphoma

The purpose of this study was to analyze the prognostic significance of early lymphocyte recovery after autologous SCT (ASCT) in the setting of routine post transplant administration of GM-CSF in patients with non-Hodgkin's lymphoma (NHL). This is a single institution retrospective comparative outcome analysis in a cohort of 268 relapsed chemosensitive NHL patients divided into two groups (early and late lymphocyte recovery) based on absolute lymphocyte counts (ALC) obtained on post transplant day +15 (ALC > or = 500, n=151 (56%) and ALC < 500, n=117 (44%)). Patient's characteristics were well-balanced between the two groups with regard to age, sex, preparative regimen, prior therapy, time from diagnosis to transplant and number of CD34+ cells infused. Post transplant complications were comparable in the two groups. Late lymphocyte recovery (ALC < 500 on day +15) was independently associated with a delay in platelet recovery (29 vs 21 days, P=0.0003) in patients who have not received pre-transplant rituximab. With a median follow-up of 22 months, no associations between early lymphocyte recovery and improvement of disease-free and overall survival were observed for either low- or intermediate-grade NHL. In conclusion, in this large single-centered retrospective analysis, where patients received routine post transplant GM-CSF, early lymphocyte recovery was not associated with favorable outcomes.

Favorable Influence of Pretransplant Rituximab but Not of High-Dose Ara-C in Upfront Autologous Stem Cell Transplantation (SCT) for Mantle Cell Lymphoma (MCL).

Recent data suggests that the prognosis of MCL might be improved by administration of rituximab and high-dose ara-C (HA) prior to upfront SCT. In order to investigate the relative contributions of rituximab and HA, respectively, we retrospectively analyzed 98 patients who received SCT as part of 1st-line treatment of advanced-stage MCL. Patients (median age 55 (29–67)) with stage II–IV MCL were treated with a sequential therapy comprising 2–8 cycles of CHOP or CHOP-like regimens +/− rituximab for remission induction, DexaBEAM (49%) or HA-containing chemotherapy (39%) for further consolidation and mobilization of stem cells, and high-dose therapy with SCT. 22% were mobilized with CHOP alone. High-dose regimens were TBI/CY (38%), TBI/CY + rituximab (R-TBI/CY; 35%), or BEAM (27%).Results: With a median follow-up of 35 (1–135) months, estimated median progression-free survival (PFS) of all 98 patients was 95 months from diagnosis and 82 months from SCT(median overall survival not reached). Pretransplant rituximab was given to 40 patients and improved PFS (3-year PFS from SCT 93% (95%CI 83–100%) vs 67% (54–79%) although this was still not statistically significant (hazard ratio (HR) .37; p .07). In contrast, pretransplant HA had no impact on PFS even after adjusting for rituximab (HR 1.9; p .61). PFS after R-TBI/CY tended to be superior to that after TBI/CY only if the 58 patients without pretransplant rituximab were considered (HR .39; p .07). Age, sex, time from diagnosis, and remission status after cytoreduction or immediately prior to SCT did not affect PFS.Conclusions: Pretransplant rituximab but not high-dose ara-C seems to improve the outcome of early SCT for MCL. Addition of rituximab to myeloablative treatment with TBI/CY might be beneficial only in the absence of pretransplant rituximab. Pretransplant rituximab with upfront SCT provides long-term disease control in a large proportion of patients with MCL.