Autologous stem cell transplantation for large B-cell lymphoma with secondary central nervous system involvement.

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P ≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P = .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P = .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P = .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes.

Impact of Donor Type and Melphalan Dose on Allogeneic Transplantation Outcomes for Patients with Lymphoma.

We analyzed 186 patients with lymphoma who underwent allogeneic stem cell transplantation (ASCT) with fludarabine-melphalan (FM) conditioning and different types of donors (25 haploidentical [HD], 98 matched unrelated [MUD], and 63 matched related [MRD]) at our institution between September 2009 and January 2018. Patients received fludarabine 160 mg/m2 (40 mg/m2/day for 4 days) in combination with 1 dose of melphalan 140 mg/m2 (FM140) or 100 mg/m2 (FM100). Engraftment was similar among the 3 groups (92%, 89%, and 98%, respectively; P = .7). The 6-month cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 4% in the HD group, 14% in the MUD group, and 8% in the MRD group (P not significant), and the respective 3-year cumulative incidence of chronic GVHD was 5%, 16%, and 26% (P not significant). The respective 3-year nonrelapse mortality and relapse rates were 31%, 32%, and 10% (HD versus MUD, P = .9; HD versus MRD, P = .02) and 15%, 21%, and 39% (HD versus MUD, P = .4; HD versus MRD, P = .04). At 3 years, progression-free survival (PFS) was 59%, 44%, and 46% (P not significant); overall survival (OS) was 52%, 54%, and 67% (P not significant); and GVHD-free, relapse-free survival was 39%, 31%, and 24% (P not significant). No differences in the 3-year PFS (57% versus 43%; P = .3) and OS (64% versus 58%; P = .7) were seen between patients receiving FM100 and those receiving FM140. Our data demonstrate that in patients with lymphoma, ASCT with HD transplants have similar outcomes as ASCT with HLA-matched transplants, and the FM100 conditioning regimen appears to be at least as effective as the FM140 regimen.

Patient age and number of apheresis days may predict development of secondary myelodysplastic syndrome and acute myelogenous leukemia after high-dose chemotherapy and autologous stem cell transplantation for lymphoma.

BACKGROUND: The goal of our study was to find predictors for the development of secondary myelodysplastic syndrome or acute myelogenous leukemia (s-MDS/AML) in patients with relapsed or refractory lymphoma who received high-dose chemotherapy and autologous stem cell transplantation (ASCT). STUDY DESIGN AND METHODS: We conducted a retrospective review of 295 patients with relapsed or refractory lymphoma who had undergone their first stem cell collection and ASCT. Patient, disease, and treatment characteristics were collected. The primary goal of this study was to analyze the association between the number of apheresis days needed to collect the requisite stem cell dose in addition to the previously described factors such as age, sex, number and type of prior chemotherapeutic regimens, disease type and status, and the risk of developing s-MDS/AML. RESULTS: Twenty-two patients of 295 were diagnosed with s-MDS/AML after a median follow-up of 62 months. Multivariate analysis using a classification and regression tree showed that the incidence of s-MDS/AML was lowest in patients who were not more than 55 years old at transplantation and in whom the target cell dose was collected in fewer than two apheresis sessions (5-year cumulative incidence, 1%), whereas incidence was highest in patients who were more than 55 years old at transplantation and who received a transplant more than 21 months after their initial lymphoma diagnosis (5-year cumulative incidence, 20%). CONCLUSION: Our study defines a subset of relapsed or refractory lymphoma patients who should be closely monitored for development of s-MDS/AML after high-dose chemotherapy and ASCT.

Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin's lymphomas.

PURPOSE: We investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m(2) and 7 days after chemotherapy at 1,000 mg/m(2)), together with granulocyte colony-stimulating factor 10 mug/kg and granulocyte-macrophage colony-stimulating factor 250 microg/m(2) administered subcutaneously daily. HD-R of 1,000 mg/m(2) was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab. RESULTS: With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to >/= 500 cells/microL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab. CONCLUSION: The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation.

PURPOSE: Allogeneic transplantation for patients with lymphoma who experience a recurrence after an autologous transplantation has been considered a hazardous therapeutic choice. We investigated the safety and efficacy of nonmyeloablative stem-cell transplantation in these patients. PATIENTS AND METHODS: Patients were required to have chemosensitive or stable disease. Twenty consecutive patients were treated in two sequential trials. Fifteen patients underwent a preparative regimen of fludarabine (30 mg/m(2) daily for 3 days), intravenous cyclophosphamide (750 mg/m(2) daily for 3 days), and rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m(2) continuous infusion daily for 4 days), fludarabine (30 mg/m(2) daily for 2 days), and cytarabine (1,000 mg/m(2) daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. RESULTS: All patients experienced engraftment of donor cells. One patient (5%) experienced grade 2 acute graft-versus-host disease, and no patients experienced a higher grade. One patient experienced disease progression at 115 days post-transplantation and responded to donor lymphocyte infusion. The remaining patients remained disease-free. One patient died at 10.5 months from a fungal infection. With a median follow-up time of 25 months, the estimated 3-year current progression-free survival rate was 95%. CONCLUSION: These data suggest that nonmyeloablative allogeneic stem-cell transplantation is an effective option in lymphoma patients with chemosensitive or stable disease who experience disease recurrence following autologous transplantation.