Autologous Stem Cell Transplant in Fit Patients With Late Relapsed Diffuse Large B-Cell Lymphoma That Responded to Salvage Chemotherapy.

The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. 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 the Kaplan-Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1-3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 yr (range 19-78), and 36 (24%) patients were of ≥70 yr. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70-78 yr), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 versus 124.7 months, P = .045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 versus 61.4 months, P < .0001) and OS (17.8 versus 111.7 months, P = .0004). There was no statistically significant difference in survival in patients who achieved PR versus CR, though numerically inferior in the former, with median PFS of 38.9 versus 59.3 months (P = .23) and median OS of 78.3 versus 111.7 months (P = .62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70 to 78 yr at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.

Autologous stem cell transplant in fit patients with refractory or early relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy.

Chimeric antigen receptor T-cell therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (e.g., lack of resources for chimeric antigen receptor T-cell therapy, chemosensitive relapses). We retrospectively studied 230 patients with refractory or early relapsed DLBCL who underwent ST and ASCT. The median line of ST was one (range, 1-3). Best response before ASCT was complete response in 106 (46%) and partial response in 124 (54%) patients. The median follow-up after ASCT was 89.4 months. The median progression-free (PFS) and overall survival (OS) were 16.1 and 43.3 months, respectively. Patients relapsing between 6 to 12 months after frontline therapy had a numerically better median PFS (29.6 months) and OS (88.5 months). Patients who required one line of ST, compared to those requiring more than one line, had a better median PFS (37.9 vs. 3.9 months; P=0.0005) and OS (68.3 vs. 12.0 months; P=0.0005). Patients who achieved complete response had a better median PFS (71.1 vs. 6.3 months; P<0.0001) and OS (110.3 vs. 18.9 months; P<0.0001) than those in partial response. Patients who achieved complete response after one line of ST had the most favorable median PFS (88.5 months) and OS (117.2 months). Post-ASCT survival outcomes of patients with refractory or early relapsed DLBCL appeared reasonable and were particularly favorable in those who required only one line of ST to achieve complete response before ASCT, highlighting the role of this procedure in select patients with chemosensitive disease.

Day 100 Natural Killer Cell/CD14+HLA-DRDIM ratio and survival in lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

INTRODUCTION: The infusion of autograft Natural Killer Cells (NKC)/CD14+ HLA-DRDIM ratio is a predictor of survival in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). This study evaluated if the Day 100 NKC/CD14+ HLA-DRDIM ratio still functions as a prognostic immune-biomarker. METHODS: This was a retrospective, single-institution, cohort analysis including 107 patients in this study that had clinical assessment at Day 100 post-APBHSCT from our prior phase III trial. We evaluated the prognostic ability of the Day 100 NKC/CD14+ HLA-DRDIM ratio to predict overall survival (OS) and progression-free survival (PFS) using Cox regression model for outcome analysis and survival by Kaplan-Meier method. RESULTS: The median follow-up from day 100 was 94.7 months (range 4.83-158.1 months) for the entire cohort. Patients with a Day 100 NKC/CD14+ HLA-DRDIM ratio ≥1.67 experienced better OS and PFS versus those with a Day 100 NKC/CD14+ HLA-DRDIM ratio <1.67: median OS was not reached versus 49.7 months, the 5-year OS rates were 91% (95% CI, 81%-96%) versus 40% (95% CI, 27%-55%), p < .0001, respectively; and median PFS was not reached versus 23.5 months, the 5-year PFS rates were 66% (95% CI, 55%-81%) versus 21% (95% CI, 15%-40%), p < .0001, respectively. Day 100 NKC/CD14+ HLA-DRDIM ratio was an independent predictor for OS and PFS in the multivariate analysis. CONCLUSIONS: Day 100 NKC/CD14+ HLA-DRDIM ratio is a prognostic immune-biomarker in lymphoma patients post- APBHSCT.

Outcomes of Patients With Classic Hodgkin Lymphoma Who Relapsed After Autologous Stem Cell Transplant.

Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1-12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.

Outcomes of Older Adults with Non-Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation: A Mayo Clinic Cohort Analysis.

Autologous stem cell transplantation (ASCT) is an important treatment that can offer a cure for patients with lymphoma. However, advanced age is an important factor that determines eligibility and outcomes after ASCT. Over the past decade, attributed to improved supportive care, ASCT for older patients has become more feasible. In this study, we report the single-center outcomes of older patients with lymphoma undergoing ASCT at Mayo Clinic Rochester to highlight its interval improvement over time and to help redefine the implications of ASCT in the chimeric antigen receptor T cell therapy era. This single-center retrospective study evaluated the characteristics and outcomes of older patients with lymphoma who underwent ASCT between 2000 and 2021. We report various relevant transplantation-related outcomes, including progression-free survival, overall survival (OS), relapse incidence, and nonrelapse mortality (NRM) in older patients with various lymphoma histologic subtypes. The main outcome was NRM, defined as the time from ASCT to non-lymphoma-related death, with relapse as a competing event. Of 492 patients age ≥65 years were analyzed. The median age at ASCT was 68.8 years. The most common indication for ASCT was diffuse large B cell lymphoma, accounting for 59.3% of cases. In multivariate analyses, patients undergoing ASCT in 2009 to 2021, an Eastern Cooperative Oncology Group Performance Status of 0, and low Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) (0 to 3) had a significantly lower NRM. Factors associated with OS included age, lactate dehydrogenase level, and HCT-CI. The 1-year NRM in older patients was low at 6.0%, in concordance with previous reports. Age should not be the sole factor determining a patient's ASCT eligibility. With the proper patient selection, ASCT remains a reasonable option for older patients with lymphoma.

Central nervous system involvement by mantle cell lymphoma.

Involvement of the central nervous system (CNS) is a rare complication of mantle cell lymphoma (MCL) with limited treatment options. We report the outcomes of 36 patients with CNS involvement compared to 72 matched control MCL patients without CNS involvement. Four patients (11%) with CNS MCL were diagnosed with CNS involvement at time of MCL diagnosis. Median OS from MCL diagnosis was 50.3 months (95% CI: 22.8-79.6) for the CNS MCL group compared to 97.1 months (95% CI: 82.8-NR; p= <0.001) for the control group. Median OS from CNS involvement was 4.7 months (95% CI: 2.3-6.7). CNS involvement by MCL has dismal outcomes as evident by a short median OS and PFS after CNS involvement. Advanced stage, blastoid variant, elevated LDH, and elevated Ki67 at MCL diagnosis were features more commonly seen in the CNS MCL cohort.

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation.

The infusion of autograft immune effector cells directly impacts the clinical outcomes of patients treated with autologous peripheral blood hematopoietic stem cell transplantation, suggesting the possibility of an autologous graft-versus tumor cells. Furthermore, the early recovery of immune effector cells also affects survival post-autologous peripheral blood hematopoietic stem cell transplantation. Natural killer cells are among the immune effector cells reported to be collected, infused, and recovered early post-autologous peripheral blood hematopoietic stem cell transplantation. In this review, I attempt to give an update on the role of natural killer cells regarding improving survival outcomes on patients treated with autologous peripheral blood hematopoietic stem cell transplantation.

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course.

PURPOSE: High-dose methotrexate (HDMTX; > 500 mg/m2) is an important component of lymphoma therapy. Serum MTX monitoring at 48 hours is the standard approach to identify those at increased risk of developing MTX toxicity. Our aim was to characterize the incidence of complications and their association with MTX levels. METHODS: A retrospective review of our institutional electronic medical record was conducted to identify patients with lymphoma who received HDMTX between January 1, 2002, and December 31, 2018. We characterized the incidence of acute kidney injury (AKI), intensive care unit (ICU) admission, length of hospital stay (LOS), and 30-day mortality across 48-hour MTX levels. To establish an association between 48-hour MTX levels and the complications listed, we performed chi-square analysis for dichotomous variables and Kruskal-Wallis for nonparametric data. Receiver operator characteristic curve analysis was performed to identify the MTX level where AKI grade ≥ 2 was more likely. Multivariate logistic regression analysis was performed to identify risk factors for this MTX level. RESULTS: We identified 642 patients with 2,804 cycles of HDMTX. The incidence of AKI was 19.1% with AKI grade ≥ 2 making up 21% of cases. Rates of AKI, ICU admission, and 30-day mortality are associated with elevated 48-hour MTX levels. There was a significant increase in median LOS with elevated MTX levels (P < .001). Receiver operator characteristic curve analysis for AKI grade ≥ 2 demonstrated a 48-hour MTX level threshold of 1.28 µmol/L. Multivariate logistic regression analysis revealed age, male sex, elevated body surface area, higher MTX dose, monotherapy, and first cycle as independent factors. CONCLUSION: Elevated MTX levels are associated with a significant increased rate of AKI, ICU admission, prolonged LOS, and 30-day mortality. Elevated 48-hour MTX levels, particularly > 1.28 µmol/L, should alert clinicians for complications and to initiate measures to reduce MTX levels.

Long-term outcome of immunologic autograft engineering.

Our phase III trial reported that autograft-absolute lymphocyte count (A-ALC) improved survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) for a short-term follow-up of 2 years. We evaluated retrospectively in our phase III trial patients that the A-ALC still confers survival benefit with a longer follow-up. With a median follow-up of 127.6 months, patients infused with an A-ALC ≥ 0.5 × 109 cells/kg experienced better overall survival (HR = 0.392, 95% confidence of interval [CI]: 0.224-0.687, p < 0.001) and progression-free survival (HR = 0.413, 95% CI: 0.253-0.677), p < 0.0004). This study supports that A-ALC provides long-term survival benefit post APBHSCT.

The Impact of Infused Autograft Absolute Numbers of Immune Effector Cells on Survival Post-Autologous Stem Cell Transplantation.

Autologous stem cell transplantation treatment has been viewed as a therapeutic modality to enable the infusion of higher doses of chemotherapy to eradicate tumor cells. Nevertheless, recent reports have shown that, in addition to stem cells, infusion of autograft immune effector cells produces an autologous graft-versus-tumor effect, similar to the graft-versus-tumor effect observed in allogeneic-stem cell transplantation, but without the clinical complications of graft-versus-host disease. In this review, I assess the impact on clinical outcomes following infusions of autograft-antigen presenting cells, autograft innate and adaptive immune effector cells, and autograft immunosuppressive cells during autologous stem cell transplantation. This article is intended to provide a platform to change the current paradigmatic view of autologous stem cell transplantation, from a high-dose chemotherapy-based treatment to an adoptive immunotherapeutic intervention.

Progression-Free Survival at 24 Months as A Landmark After Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B-cell Lymphoma.

Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who achieve progression-free survival (PFS) at 24 months (PFS24) after immunochemotherapy (IC) have excellent overall survival (OS) comparable to that of the age- and sex-matched general population. However, a similar landmark has not been established for patients with relapsed or refractory (RR) DLBCL following frontline IC who are subsequently treated with salvage therapy followed by autologous stem cell transplantation (ASCT). To evaluate the role of PFS24 as a landmark after ASCT in patients with RR DLBCL, we identified patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic between July 2000 and December 2017 and University of Iowa between April 2003 and April 2020 from institutional lymphoma and transplantation databases. Clinical characteristics, treatment information, and outcome data were abstracted. PFS, OS, and post-ASCT relapse survival (PRS) were analyzed using Kaplan-Meier method, and cumulative incidences of relapse versus nonrelapse mortality and different causes of death were compared accounting for competing events. A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow-up of 8.0 years (95% confidence interval [CI], 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, the post-ASCT relapse rate was much higher than the nonrelapse mortality rate (48.1% versus 9.1% at 5 years). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and nonrelapse mortality were similar (14.8% and 12.3% at 5 years). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma-related and -unrelated death rates were similar after achieving PFS24. For all patients who had a post-ASCT relapse, median PRS was 0.7 (95% CI, 0.5-0.9) year, and late relapse (>2 versus ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] versus 0.5 [0.3-0.7] years, P< .001). The study establishes PFS24 as an important landmark associated with post-ASCT outcomes in patients with RR DLBCL after frontline IC.

PET2 response associated with survival in newly diagnosed diffuse large B-cell lymphoma: results of two independent prospective cohorts.

Studies evaluating Positron Emission Tomography scan after 2 cycles of chemotherapy (PET2) in newly diagnosed diffuse large B cell lymphoma (DLBCL) are heterogeneous in patient characteristics, treatments and have conflicting results. Here we report association of PET2 with outcomes in two large independent prospective cohorts of newly diagnosed DLBCL pts treated with two RCHOP-based regimens. The discovery cohort consisted of pts enrolled in single arm phase 2 MC078E study of lenalidomide with RCHOP (R2CHOP). The validation cohort consisted of RCHOP-treated pts from the Molecular Epidemiology Resource (MER) cohort. Pts who received 3-6 cycles of therapy and had PET2 were included in the study. Patients who progressed on PET2 were excluded. Revised response criteria 2007 were used to define PET2 response PET2 positive (PET2 + ) pts had inferior EFS [24-month EFS 45.5% vs 87.9%, HR 4.0, CI95 (2.1-7.9), p < 0.0001) with a trend towards lower OS [24-months OS 77% vs 94.8%, HR 2.0, CI95 (0.9-4.8), P = 0.1] than PET2 negative (PET2-) pts in MC078E cohort. PET2 + pts had an inferior EFS (24 month EFS 48.7% vs 81.6%, HR 2.9, CI95 2.0-4.2, p < 0.0001) and OS (24-month OS 68.6% vs 88.1%, HR 2.3, CI95: 1.5-3.5, p < 0.0001) in the MER cohort. These results were consistent regardless of age, sex and in the subgroup of advanced stage and high-risk international prognostic index (IPI). For MER, PET2 + pts also had higher odds of positive end of treatment PET (OR: 17.3 (CI95 7.9-37.7), p < 0.001). PET2 is an early predictor DLBCL pts at high risk of progression and death in two independent prospective cohorts. PET2-guided risk-adapted strategies may improve outcomes, and should be explored in clinical trials.

Impact of autograft-absolute lymphocyte count on survival in double/triple hit lymphomas post-autologous stem cell transplantation.

The autograft absolute lymphocyte count (A-ALC) ≥0.5 × 109 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, the A-ALC has not be tested as prognostic factor against double hit/triple hit lymphomas (DHL/THL). Thus, we set up to investigate if A-ALC is a prognostic factor for overall survival (OS) and progression-free survival (PFS) for DHL/THL post-APBHSCT. From January 2012 until December 2020, we identified 77 DHL/THL patients treated with APBHSCT. All patients required to have the diagnosis of DHL/THL by FISH for rearrangements of MYC, BCL2, and BCL6. With a median follow-up of 20.4 months (range, 0.4-94.5 months), DHL/THL patients infused with A-ALC ≥0.5 x 109 cells/kg experienced superior OS (HR = 0.251, 95%CI 0.117-0.539, p < 0.0004) and PFS (HR = 0.347, 95%CI 0.160-0.753, p < 0.007). Multivariate analysis showed that A-ALC was an independent predictor for OS (HR =0.119, 95%CI 0.030-0.473, p < 0.003) and PFS (HR = 0.400, 95%CI 0.189-0.850, p < 0.02). Our study showed that A-ALC is a prognostic factor for survival in DHL/THL. Our current practice for lymphoma patients is to collect enough stem cell but also A-ALC to improve clinical outcomes post-APBHSCT.

Impact of Cell of Origin on Outcomes After Autologous Hematopoietic Cell Transplant in Diffuse Large B-Cell Lymphoma.

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study.

Diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1-10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24-80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2-94.7%), 84.5% (CI95: 72.9-98%), and 97.0% (CI95: 91.3-100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.

Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities. Immunochemotherapy with or without involved-site radiation therapy (ISRT) is considered standard front-line therapy. Over-expression of PD-L1/PD-L2 is seen in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from 1 January 2000 to 31 December 2020. Using the Kaplan-Meier method, we calculated progression-free survival, duration of response, and overall survival in patients who received front-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with and without ISRT, and salvage ICI therapy for relapsed/refractory disease. A total of 28 patients with PCDLBCL, LT were identified. The median PFS in patients treated with R-CHOP plus ISRT was 58 months (95% CI: 18-112) compared to 14 months (95% CI: 5-not reached; p = 0.04) in those treated with R-CHOP without ISRT. The median PFS from salvage ICI therapy was 10 months (95% CI: 4-not reached), and median DOR from salvage ICI therapy was 23 months [95% CI: 4-26]. R-CHOP with ISRT had a significantly longer median PFS compared to R-CHOP without ISRT as front-line therapy for PCDLBCL, LT. ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients was observed in this study.

Infused Autograft Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched Case-Control Study.

Our group published a double phase III trial showing that patients infused with an autograft absolute lymphocyte count (A-ALC) ≥0.5 × 109 cells/kg experienced superior survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). Based on the results from our phase III study, as well as published retrospective studies, on April 1, 2017, our Bone Marrow Transplant Program changed our standard practice to collect an A-ALC ≥0.5 × 109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. The primary objective of the present study was to continue to assess the prognostic ability of A-ALC by evaluating overall survival (OS) and progression-free survival (PFS) of diffuse large B cell lymphoma (DLBCL) patients who underwent APBHSCT after April 1, 2017, compared with matched control groups at a 1:1:1 ratio with DLBCL patients infused with an A-ALC <0.5 × 109 cells/kg and A-ALC ≥0.5 × 109 cells/kg before April 1, 2017. Using the GREEDY algorithm, 85 DLBCL patients (cases) infused with an A-ALC ≥0.5 × 109 cells/kg after April 1, 2017, were matched at a 1:1:1 ratio with control groups of DLBCL patients who underwent transplantation before April 1, 2017: patients infused with an A-ALC <0.5 × 109 cells/kg (control 1) and patients infused with an A-ALC ≥0.5 × 109 cells/kg (control 2) before April 1, 2017. Groups were matched in terms of sex, age, stage, lactate dehydrogenase (LDH) level, performance status, extranodal disease, International Prognostic Index (IPI), and disease status before APBHSCT (complete or partial response). Survival follow-up was truncated at 3 years from the date of transplantation. Cases, control 1, and control 2 were balanced as to age (P = .8), sex (P = .9), LDH (P = .6), performance status (P = .5), extranodal disease (P = .2), IPI (P = .6), and disease status before APBHSCT (P = .2). Cases and control 2 showed superior OS and PFS compared with control 1. Multivariate analysis including all patients continued to show A-ALC ≥0.5 × 109 cells/kg as an independent predictor for OS (hazard ratio [HR], 0.382; 95% confidence interval [CI], 0.241 to 0.605; P < .0001) and PFS (HR, 0.437; 95% CI, 0.279 to 0.629; P < .0001). Our matched case-control study supports the results of previously published retrospective studies and our phase III study showing that the infusion of A-ALC is a prognostic factor for survival in DLBCL patients undergoing APBHSCT. Our findings support the practice of collecting not only enough stem cells for hematologic engraftment, but also enough immune effector cells (ie, A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT.

Hypomagnesemia at the time of autologous stem cell transplantation for patients with diffuse large B-cell lymphoma is associated with an increased risk of failure.

Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63-8.98 years) versus 6.29 years (95% CI: 4.73-8.95 years) with HR 1.63 (95% CI: 1.09-2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91-upper limit not estimable) versus 9.7 years (95% CI: 6.92-12.3 years) with HR 1.90 (95% CI: 1.22-2.96, p = 0.005) for OS months 0-12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT.

Outcomes of Autologous Stem Cell Transplant Consolidation in Primary Central Nervous System Lymphoma: A Mayo Clinic Experience.

A paucity of randomized phase III clinical trials in primary central nervous system lymphoma (PCNSL) has resulted in no uniform consensus on the optimal strategy for consolidation and conditioning regimens for autologous stem cell transplant (ASCT). The past 2 decades have witnessed a preference for thiotepa (TT)-based conditioning regimens due to superior central nervous system penetration. We retrospectively evaluated outcomes of patients with PCNSL who underwent ASCT at Mayo Clinic, Rochester over the past 2 decades, and the impact of TT-based conditioning regimens. Fifty-six patients underwent transplant for PCNSL, with 25 and 31 patients receiving BEAM (non-thiotepa) and carmustine (BCNU)/TT-based conditioning, respectively. All patients received high-dose methotrexate-based induction therapy. While the BCNU/TT group had higher risk disease features such as high International Extranodal Lymphoma Study Group prognostic score, elevated cerebrospinal fluid protein, and older patient population, there was no significant difference at 2 years post-transplant in progression-free survival (BEAM 68.0% [46.1% to 82.5%] versus BCNU/TT, 65.5% [45.2% to 79.8%], P = .99) or overall survival (OS) (84.0% [62.8% to 93.7%] in the BEAM group versus 81.6% [61.3% to 91.9%] in the BCNU/TT group, P = .95). Disease response status before transplant significantly affected the outcomes as those in complete remission had an OS at 2 years post-transplant of 94.7% (68.1% to 99.2%) in the BEAM group and 90.5% (67.0% to 97.5%) in the BCNU/TT group compared with those in partial response, 57.1% (17.2% to 83.7%) in BCNU/TT group and 50.0% (11.1% to 80.4%) in the BEAM group, respectively (P < .0001). Our retrospective cohort adds to the currently available literature and identifies the disease status before transplant as a significant factor affecting survival.