scholarly journals Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Secondary Central Nervous System Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4911-4911
Author(s):  
Daria Gaut ◽  
Caspian Oliai ◽  
Monica Mead
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Primary Graft Failure ◽  
Secondary Central Nervous System

Abstract Introduction: Aggressive non-Hodgkin's lymphoma (aNHL) with secondary central nervous system (sCNS) involvement has a poor prognosis. Studies have reported a response to induction treatment as low as 35%, leaving less than half of patients eligible for autologous stem cell transplant (ASCT). Outcomes of patients in these clinical scenarios are dismal and treatment is ill-defined. Small case series suggest chimeric antigen receptor (CAR)-T cell therapy may play a role in the management of relapsed/refractory (R/R) B-cell lymphoma (BCL) with sCNS involvement, but follow-up is limited and response duration is uncertain. Allogeneic hematopoietic stem cell transplant (alloHCT) offers a durable remission for a subset of patients with R/R systemic aNHL primarily mediated through a graft versus lymphoma (GVL) effect, but it is unclear if GVL properties include the immune-privileged CNS. The present study aims to describe outcomes of a cohort of patients with R/R aggressive B- and T-cell NHL with sCNS involvement who underwent alloHCT at a single academic institution. Methods: This is a retrospective analysis that includes all patients with R/R aNHL with sCNS involvement who underwent alloHCT at the University of California, Los Angeles from 2005-2020. The UCLA Institutional Board Review approved this study. Relevant clinical data was extracted from medical records. Hematopoietic cell transplantation comorbidity index (HCT-CI) and time to neutrophil and platelet engraftment were measured according to Center for International Blood and Marrow Transplant Research criteria. Results: Ten patients were included (3 females, 7 males). Histologic subtypes included anaplastic BCL (1), mantle cell lymphoma (1), blastic natural killer-cell lymphoma (1), peripheral T-cell lymphoma, not otherwise specified (1), primary mediastinal BCL (1), and diffuse large B-cell lymphoma (DLBCL) (non-germinal center=3, germinal center-like=2). Two DLBCL patients had histologic transformed lymphoma (follicular lymphoma =1, chronic lymphocytic lymphoma = 1). Four patients had sCNS involvement at the time of initial diagnosis or during frontline treatment; the remaining 6 patients developed sCNS lymphoma at relapse. sCNS lymphoma was identified in the parenchymal (n=4), leptomeningeal (n=3), or both (n=3) compartments. The median age at the time of alloHCT was 49.5 (range 28-68), and 1 patient was ˃ 60. At the time of alloHCT, 1 patient had residual disease in the CNS and the remaining 9 patients were in a complete remission. Eight patients received ˃ 3 prior lines of therapy, and 3 patients failed prior ASCT. HCT-CI scores were 0 (n=1), 1 (n=2), 2 (n=3), 3 (n=1), and unknown (n = 3). Donor types included 10/10 matched related (3), 10/10 matched unrelated (4), 9/10 mismatched related (1), and double umbilical cord blood (2). Graft source was peripheral blood in 8 patients and cord blood in 2 patients. Conditioning regimens included myeloablative, reduced intensity and non-myeloablative in 6, 3 and 1 patient(s), respectively. Six patients received total body irradiation-containing conditioning. The average time to neutrophil engraftment was 18 days (range 11-29), and the average time to platelet engraftment was 26.5 days (range 18-59). One patient had primary graft failure. Of the 6 patients with day 100 disease reassessment (CR at time of alloHCT=5, PR in CNS at time of alloHCT=1), all were in CR. With a median follow-up of 341 days, 2 patients relapsed (CNS=1 and systemic = 1), and 6 patients died. Cause of death included infection (n=3), lymphoma (n=1), primary graft failure (n=1), and organizing pneumonia (n=1). Six patients developed acute graft versus host disease (GVHD) (grade 1-2, n=1; grade 3, n=5), and 4 patients developed chronic GVHD (score 1-2, n= 2; score 3, n=2). The median overall and progression-free survival for the entire cohort was 341 days (range 23-4825) and 268.5 days (range 23-4825), respectively. Conclusions: AlloHCT in patients with R/R aNHL with sCNS involvement is feasible and may provide a durable response in a subset of patients. Four patients remained alive and free of disease one year post-alloHCT and one patient converted from a PR to a CR in the CNS 100 days post-alloHCT, suggesting effective donor immune surveillance within the CNS. Transplant-related morbidity and mortality limits the widespread application of this therapeutic modality and less toxic approaches are urgently needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Update of a phase II, multicenter study of high-dose chemotherapy with autologous stem cell transplant followed by maintenance romidepsin for T-cell lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7533-7533
Author(s):  
Niloufer Khan ◽  
Farhad Khimani ◽  
Andrei R. Shustov ◽  
Mazyar Shadman ◽  
Jia Ruan ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Multicenter Study ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem

7533 Background: Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes with conventional chemotherapy. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first complete or partial remission (CR1 or PR1), with median progression-free survival (PFS) after AHCT of 36-48% by intent to treat (d’Amore et al JCO 2012, Reimer et al JCO 2009). Romidepsin (romi) is a histone deacetylase inhibitor approved for treatment of relapsed/refractory T-cell lymphoma. We present updated data of the first multicenter study to evaluate PFS of patients (pts) receiving maintenance therapy with romi after AHCT. Methods: This was a phase 2, open-label, investigator-initiated study (expected PFS 45%, desired PFS 70%; success achieved if 15 or more pts out of 25 were progression-free at 2 years post-AHCT). 26 pts transplanted in CR1 or PR1 were evaluable for the primary endpoint of 2-year PFS (Cohort 1, Table). An exploratory cohort (Cohort 2, n=7) enrolled pts either transplanted ≥ CR/PR2 (n=5) or with high risk histologies (n=2). Pts underwent AHCT with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. Maintenance romi 14 mg/m2 started days 42-80 post AHCT; every other week through 6 mon, every 3 weeks through 1 year and every 4 weeks through 2 years post AHCT. PFS was estimated by Kaplan-Meier. Results: 47 pts consented; 13 did not receive romi (no AHCT, n=2; relapse before romi, n=3; cardiac comorbidity, n=3, patient declined, n=5). 1 consented pt did not have PTCL. 15 out of the first 25 pts in Cohort 1 were progression free after 2 years; median follow up of 31 mon (21 - 36 mon). Estimated 2-year PFS was 62% (45-83%, 95% CI); median PFS 30 mon (12.0- NA, 95% CI). In Cohort 2, estimated 2-year PFS was 43% (18 – 100, 95% CI); median follow up of 30 mon (range, 24 – 37 mon); median PFS 14 mon (5 – NA, 95% CI). Across cohorts, 5 pts required dose reduction. The most common toxicities (≥10% of pts, all grades) were fatigue (n=24, 73%), decreased platelets (n=16, 48%) and anemia (n=16, 48%). Conclusions: While the study did not meet its desired primary efficacy endpoint, maintenance romi was well-tolerated with an estimated 2-year PFS of 62%, greater than historical data. A larger, randomized study would be needed to determine the superiority of this approach. Clinical trial information: NCT01908777. [Table: see text]

Relapsed subcutaneous panniculitis-like T cell lymphoma: role of haploidentical hematopoietic stem cell transplant

2017 ◽  
Vol 96 (12) ◽  
pp. 2125-2126 ◽  
Author(s):  
Bhagirathbhai Dholaria ◽  
Raj J. Patel ◽  
Jason C. Sluzevich ◽  
Sikander Ailawadhi ◽  
Vivek Roy
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Hematopoietic Stem

Outcomes of Patients with Refractory/Relapsed Diffuse Large B-Cell Lymphoma Who Progress After Autologous Stem Cell Transplantation in the Rituximab Era.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2689-2689
Author(s):  
Sarah J. Nagle ◽  
Kaitlin Woo ◽  
Rosemarie Mick ◽  
Stephen J. Schuster ◽  
Sunita D. Nasta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Transplant ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Historical Controls ◽  
First Line Treatment

Abstract Abstract 2689 Salvage chemotherapy and autologous stem cell transplant (ASCT) remain the current standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who have primary refractory disease or relapse after initial therapy. The addition of rituximab results in improved overall survival (OS) after first line treatment, but cure rates of salvage therapy and ASCT are inferior when compared to historical controls (Gisselbrecht et al, JCO 2010). In the pre-rituximab era, patients with DLBCL who progressed after ASCT had an extremely poor prognosis, with a median OS of 3 months from the time of progression (Vose et al, Blood 1992). There is a paucity of data regarding outcomes and clinical patterns following progression after ASCT in the rituximab era. We conducted a retrospective analysis using our institutional database of DLBCL patients who underwent ASCT for primary refractory or relapsed disease. For those who progressed after ASCT, we evaluated OS defined as time from date of progression after ASCT to date of death from any cause or last follow-up. We also analyzed OS for various subgroups based on their clinical characteristics and post-progression therapy. The impact of post-progression therapy on outcome was assessed by calculating OS from the time of exposure to a particular treatment to date of death from any cause or last follow-up. Median OS was estimated by the Kaplan-Meier method and subgroup comparisons were performed using the log rank test. We identified 215 patients with primary refractory or relapsed DLBCL who underwent ASCT between January 1, 2005 and December 31, 2011. All patients received rituximab as part of their first line treatment. Fifty-six patients (26% of total) were found to have progression after ASCT. Eight patients were excluded from the analysis because they were not re-biopsied at relapse (n=5) or they had indolent disease at relapse (n=3). Data on the remaining 48 patients (median age 57 years; range 20–74) were further analyzed. The median OS from progression after ASCT for the entire cohort was 10.7 months (95% CI: 6.8–18.0 months). Patients who progressed < 1 year from ASCT (n=39) had a significantly shorter OS than those who progressed ≥ 1 year from ASCT (n=9): 9.5 vs. 26.7 months (p=0.02). Patients with at least stable disease as first assessment after ASCT (n=29) had a significantly longer OS than those who progressed immediately after ASCT (n=19): 18 vs. 6 months (p=0.01). Patients who were exposed to at least one novel agent (lenalidomide, radioimmunotherapy, non-rituximab monoclonal antibodies or tyrosine kinase inhibitors) as part of their post-progression therapy after ASCT (n=20) had a median OS of 11.2 months from treatment initiation. In contrast, patients who were treated with conventional cytotoxic chemotherapy but not novel agents (n=20) had a median OS of 6.7 months. In particular, patients who underwent radioimmunotherapy at some point after progression post-ASCT (n=9) had a median OS of 17.5 months (95% CI: 2.6-n/a months) with one patient in complete response > 48 months after the treatment. Patients who underwent allogeneic stem cell transplant following progression after ASCT (n=6) had a median OS of only 7.1 months (95% CI: 0.8-n/a months). In the rituximab era, the median OS of DLBCL patients who progress after ASCT appears improved when compared to historical controls, especially in those who progress > 1 year from ASCT. Patients with DLBCL progressing after ASCT should be considered for therapy with novel agents, which may result in long term survival. Disclosures: No relevant conflicts of interest to declare.

Stem Cell Transplant (SCT) and Pralatrexate Therapy: Outcome of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma Who Received SCT Prior to or Following Pralatrexate Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3420-3420
Author(s):  
Leslie Popplewell ◽  
Barbara Pro ◽  
Eric Jacobsen ◽  
Steven M. Horwitz ◽  
Adam Boyd ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Additional Therapy

Abstract Abstract 3420 Poster Board III-308 Background Stem cell transplant (SCT) may be offered as a curative approach in patients with chemotherapy-sensitive peripheral T-cell lymphoma (PTCL). Thus, new agents with the ability to induce a response for relapsed or refractory patients are important to identify. This analysis evaluated SCT use before or after pralatrexate, a new anti-folate, as monotherapy in the PROPEL study. Methods Patients with relapsed or refractory PTCL received pralatrexate 30 mg/m2 by IV push once weekly for 6 weeks in 7-week cycles with vitamin B12 and folic acid supplementation in PROPEL. Eligibility criteria included histologic confirmation of PTCL by central review, disease progression after ≥ 1 prior treatment, and ECOG performance status £ 2. Response was assessed centrally using the International Workshop Criteria. Patients who had received prior allogeneic SCT were not permitted to enroll. Patients with prior autologous SCT were eligible if they had not relapsed within 75 days of SCT. There were no restrictions on SCT after completing study treatment. Subsequent post-pralatrexate therapies were recorded during follow up until patient death, loss to follow-up, or data cutoff. Results One-hundred and nine patients in the PROPEL trial were evaluable for response. Eighteen (16%) had received autologous SCT previously, including 8 (7%) patients for whom SCT was the most recent therapy prior to study enrollment. The overall response rate (ORR: complete response [CR/CRu] or partial response [PR]) was 33% (6/18), including 2 CRs, for patients with a prior autologous SCT at any time prior to receiving pralatrexate and 63% (5/8), including 2 CRs, for those patients whose most recent therapy was autologous SCT. Patients were followed from initiation of pralatrexate for a median of 10.5 months (range, 1.0-24.0). Of the 109 patients who were evaluable for response, 6 (6%) patients went on to SCT (2 autologous SCT, 4 allogeneic SCT) as their initial subsequent therapy after responding to pralatrexate according to investigator assessment of response. Four of these patients were still in response by central review at the time they started SCT. At the time of data cutoff, no additional therapy was administered to any of these 4 patients post SCT. The other 2 patients had PRs by investigator review and progressive disease by central review at the time SCT was started; neither of these patients had additional therapy documented after SCT. All 6 patients were alive at the time of last contact. Conclusions The PROPEL trial showed that pralatrexate as a single agent had activity, including CRs, in patients who relapsed following an autologous SCT. The PROPEL trial also demonstrated that patients with relapsed or refractory PTCL can proceed to subsequent SCT after achieving a response with pralatrexate, permitting these patients a transplant option and potential cure. Disclosures Pro: Allos Therapeutics, Inc.: Research Funding. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Boyd:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment.

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