Radioimmunotherapy with 131-I tositumomab enhanced survival in good prognosis relapsed and high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving high-dose chemotherapy and autologous stem cell transplantation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8013-8013 ◽  
Author(s):  
J. Vose ◽  
P. Bierman ◽  
G. Bociek ◽  
F. Loberiza ◽  
C. Enke ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplant ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Good Prognosis ◽  
Phase Iii ◽  
Cell Transplant ◽  
Outpatient Basis

8013 Background: The 5-year overall survival (OS) for pts with relapsed chemosensitive DLBCL with standard transplantation is approximately 40–50%. We previously piloted the addition of standard outpatient radioimmunotherapy (RIT) with 131-I tositumomab to the transplant regimen for patients with relapsed chemoresistant NHL. This phase I study demonstrated a 3 yr OS of 55% in these poor prognosis patients (JCO 23: 461–467, 2005). The current study is a follow-up phase II study in good prognosis relapsed and high risk DLBCL patients using 131-I tositumomab with BEAM (BCNU, etoposide, cytarabine, and melphalan) followed by an autologous stem cell transplant. Methods: Forty patients were accrued to the study between 2000–2005. The patients had a median age of 54 yrs (26–75) and all had a diagnosis of DLBCL. The patients had a median of two prior chemotherapies before transplant and 88% had received prior Rituximab. All patients had chemotherapy sensitive disease at the time of stem cell transplant. Following stem cell collection, all patients received a stem cell preparative regimen of 75 cGy total body dose of 131-I tositumomab (dosimetric dose day -19 and therapeutic day -12) followed by a standard BEAM transplant regimen. Autologous unpurged stem cells were infused on day 0. The median time of follow-up of the survivors is 28 months (3–68). Results: Seventy eight percent of the patients had a complete remission following the transplant. The 3 year progression free survival (PFS) is 70% (95% CI - 48 - 84%) and the 3 year OS is 81% (95% CI - 61 - 91%). The entire transplant can be delivered on an outpatient basis. No increased toxicity compared to a similar cohort receiving BEAM alone could be detected. Conclusions: The addition of 131-I tositumomab to BEAM and autologous stem cell transplant for relapsed or high-risk chemosensitive DLBCL produces a 3-yr OS of 81% without excess toxicity. This compares favorably to historical controls. This regimen is currently being tested in a phase III trial in the BMT/CTN of Rituximab/BEAM vs. 131-I tositumomab/BEAM in patients with relapsed chemosensitive DLBCL. No significant financial relationships to disclose.

Maintenance Rituximab after Autologous Stem Cell Transplant for High-Risk B-Cell Lymphoma Induces Prolonged and Severe Hypogammaglobulinemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1408-1408
Author(s):  
Seah H. Lim ◽  
Yana Zhang ◽  
Zhiqing Wang ◽  
William V. Esler ◽  
David Beggs ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Cell Recovery

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 < 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.

Improved Survival for Patients Undergoing Autologous Stem Cell Transplant for Primary CNS Lymphoma in First or Later Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1222-1222 ◽  
Author(s):  
Patrick B Johnston ◽  
Ivana N Micallef ◽  
Stephen M Ansell ◽  
David J Inwards ◽  
Luis F. Porrata ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
Cell Transplant ◽  
Additional Therapy

Abstract Abstract 1222 Poster Board I-244 Background Survival for patients with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now update on outcomes of patients who have had at least 100 day follow up post ASCT. Baseline characteristics Between June, 2000 and January, 2009, 22 patients underwent ASCT for PCNSL. Median age at transplant was 50 years old (range 26-67). Median number of prior treatments 1 (range 1-3). Median time from diagnosis to transplant was 7.2 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0-3). Disease status at transplant: First CR 10 patients, later CR or PR 12 patients. Results Twenty-two patients underwent ASCT for PCNSL and have a minimum of 100 days follow-up. All patients received BEAM conditioning. Median follow up post-transplant was 30 months (range 3-107 months). Eight patients have relapsed at a median of 217 days (range 40-1349). Of the patients who relapsed, four have died of disease progression and the remaining four are alive after additional therapy. Median overall survival from diagnosis or transplant has not been reached. Median progression free survival from transplant was 70 months. Conclusions Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2-3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline secondary to radiation therapy in patients who are appropriate candidates. Disclosures No relevant conflicts of interest to declare.

Tandem Autologous Stem Cell Transplants (auto-auto) with or without Maintenance Therapy Versus Single Autologous Transplant Followed by HLA-Matched Sibling Non- Myeloablative Allogeneic Stem Cell Transplant (auto-allo) for Patients (pts) with High Risk (HR) Multiple Myeloma (MM): Results From the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0102 Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 526-526 ◽  
Author(s):  
Edward A Stadtmauer ◽  
Amrita Krishnan ◽  
Marcelo C Pasquini ◽  
Marian Ewell ◽  
Edwin P Alyea ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Cell Transplant ◽  
Primary Analysis ◽  
Hematopoietic Stem

Abstract Abstract 526 The prognosis of patients with high-risk myeloma (HR MM) continues to be dismal, despite the early incorporation of novel agents. Early phase trials of allogeneic hematopoietic stem cell transplant (alloHCT) suggest the possibility of an immunologic graft-versus-myeloma effect that might favorably affect survival. Less toxic reduced-intensity HCT preparative regimens now allow more widespread use of alloHCT in the MM population. BMT CTN 0102 is a phase III multicenter clinical trial that biologically assigned patients to either melphalan 200mg/m2 (MEL 200) auto-auto without (obs) or with 1 year of thalidomide and dexamethosone (ThalDex), or an auto-allo approach using MEL 200 followed by alloHCT using 2 Gy total body irradiation. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine and mycophenolate mofetil. Patients were stratified by biological prognostic factors that were considered to be high risk at the time of the trial design: chromosome 13 deletions by metaphase karyotype and beta-2 microglobulin ≥4 mg/dl. The primary endpoint was 3-year progression free survival (PFS). Between December 2003 and March 2007, 710 patients from 43 US centers were enrolled, and 85 fulfilled the criteria of HR MM. Among them, 48 were assigned to auto-auto (24 Thal-Dex and 24 obs) and 37 to auto-allo. Groups differed in age (median 57 y and 51y, p=0.02) but were otherwise balanced. Compliance with second transplant was 65% for auto-auto and 78% for auto-allo. Compliance with ThalDex was poor, so the two auto-auto arms were pooled for the primary analysis. Three-year PFS was 33% (95% Confidence Interval (CI), 22–50%) and 40% (95% CI, 27–60%, p=0.74) and 3-year OS was 67% (95% CI, 54–82%) and 59% (95% CI, 49–78%, p=0.46) for auto-auto and auto-allo, respectively. Corresponding probabilities for 3-year progression/relapse was 53% and 33% (p=0.09), and 3 year treatment-related mortality was 8% and 20% (p=0.3). Among auto-allo patients, probabilities of grade 3–4 acute and chronic GVHD were 9% and 48%, respectively. Among the 59 (31 auto-auto, 28 auto-allo) patients who received second transplant, 3 year PFS was 35% and 46% (p=0.6). Disease response at day 56 after second transplant was 57% for very good partial response (VGPR) or better and 37% for complete response (CR) and near CR (nCR) in the auto-auto group; and 48% (VGPR or better) and 41% (CR+nCR) in the auto-allo group. In conclusion, this planned secondary analysis of a cohort of HR MM patients demonstrated equivalent 3-year PFS and OS for auto-auto and auto-allo in both intention-to-treat and as-treated analyses. However, trends in late PFS and time to progression/relapse suggest further follow-up is needed before final conclusions regarding the utility of auto-allo in this HR cohort can be made. Finally, this study shows the feasibility of an alloHCT approach for HR MM patients and may serve as a platform for future studies seeking to enhance graft-versus-myeloma effects. Disclosures: Stadtmauer: Celgene: Speakers Bureau. Krishnan:Celgene: Speakers Bureau. Qazilbash:Celgene: Speakers Bureau. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

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