Busulfan, Cyclophosphamide, And Etoposide Research Articles

Evaluation of busulfan, cyclophosphamide, and etoposide as a preparation regimen for autologous stem cell transplantation in Hodgkin’s lymphoma patients

Abstract: BACKGROUND: Hodgkin’s lymphoma (HL) exhibits a cure rate of 90% in patients diagnosed at an early stage and a cure rate ranging from 70% to 90% in patients diagnosed at an advanced stage. In the case of patients with relapsed/refractory HL (r/rHL), it is recommended to provide salvage chemotherapy initially, followed by autologous stem cell transplantation (ASCT). The ideal conditioning regimen for the transplantation process is still being investigated. OBJECTIVES: For individuals with r/rHL, high-dose chemotherapy combined with ASCT (HD-ASCT) is thought to be the most effective method of treatment. The purpose of this research was to evaluate the effectiveness and safety of the busulfan, cyclophosphamide, and etoposide (BuCyE) preparation regimen in r/rHL patients. MATERIALS AND METHODS: Retrospective analysis was conducted on the data of 67 lymphoma patients older than 18 years who had HD-ASCT with the BuCyE conditioning regimen between September 2014 and November 2021 (86 months). The research consisted of 34 r/r HL patients among them. A parenteral regimen of 0.8 mg/kg of busulfan every 6 h from day −7 to day −5, 50 mg/kg of cyclophosphamide on days −3 and −2, and 400 mg/m2 of etoposide on days −5 and −4 comprised the patient preparation regimen before ASCT. All data were collected from inpatient files and the Inonu University Turgut Ozal Medical Center Hospital Information System. RESULTS: The median age of the patients was 43 years, and 67.6% were males. The most common type of HL was nodular sclerosis, which was followed by mixed cellularity. The median time for platelet and neutrophil engraftment was 14 and 11 days, respectively. 5.0 × 106/kg was the median transplanted dose of CD34+ cells (2.1–13.55). Liver toxicity was observed in 6 (17.6%) patients. Eight patients suffered from pulmonary side effects. The median number of previous chemotherapies was 2 (2–4). In all lymphoma patients, the complete response rate was 61.8% (n = 21), whereas the disease progression rate was 32.3% (n = 11). Transplantation-related mortality on the 100th day was 8.8% (n = 3). Three-year overall survival was 57.17%. CONCLUSION: When the literature was reviewed, the studies with the BuCyE preparation regimen in patients with r/rHL were limited. This conditioning regimen was found to have fewer side effects and a lower cost. It can be preferable when compared to carmustine (BCNU), etoposide, cytarabine (ARA-C), and melphalan (known as BEAM) in r/rHL.

524 - Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) As Conditioning Therapy for Autologous Transplantation in Patients with Relapsed or High Risk Non-Hodgkin Lymphoma: A Multicenter Randomized Phase II Study By the Consortium for Improving Survival of Lymphoma (CISL)

524 - Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) As Conditioning Therapy for Autologous Transplantation in Patients with Relapsed or High Risk Non-Hodgkin Lymphoma: A Multicenter Randomized Phase II Study By the Consortium for Improving Survival of Lymphoma (CISL)

Prior anti-PD-1 therapy as a risk factor for life-threatening peri-engraftment respiratory distress syndrome in patients undergoing autologous stem cell transplantation.

Peri-engraftment respiratory distress syndrome (PERDS) is a kind of potentially life-threatening complication of autologous stem cell transplantation (ASCT). PERDS is characterized by fever, dyspnea, and hypoxemia during neutrophil engraftment. In order to identify the high-risk factors for PERDS, we retrospectively analyzed 260 patients with lymphoma undergoing ASCT in recent five years. The conditioning regimen was BuCyE (busulfan, cyclophosphamide, and etoposide). There were 16 patients (6.1%) diagnosed as PERDS. In multivariate analysis, prior anti-programmed death-1 (PD-1) therapy (hazard ratio [HR] = 8.852, 95% confidence interval [CI]: 2.954-26.527, P < 0.001) and history of pulmonary disease (HR = 3.718, 95% CI: 1.197-11.545, P = 0.023) were independent risk factors for PERDS. Patients with prior anti-PD-1 therapy (n = 31) had higher incidence of engraftment syndrome (77.4% vs. 33.4%, P < 0.001), PERDS (25.8% vs. 3.5%, P < 0.001), and transplant-related mortality (9.7% vs. 0.4%, P < 0.001), compared with those without prior anti-PD-1 therapy (n = 229). Subgroup analysis showed that sintilimab seemed to be associated with higher incidence of PERDS (42.9% vs. 11.8%, P = 0.06) compared with non-sintilimab group (pembrolizumab or toripalimab). C-reactive protein might be a feasible early predictor for PERDS. In conclusion, our study suggests that prior anti-PD-1 therapy may be a strong risk factor for life-threatening PERDS in patients with lymphoma undergoing ASCT.

BUCYE can Safely Replace BEAM as Conditioning Regimen for Autologous Stem Cell Transplantation for Relapsed Lymphomas

<h3>Introduction</h3> Hodgkin's (HL) and non-Hodgkin's (NHL) lymphomas are the most frequent hematological neoplasms and have a marked variability in their behavior. Although they usually are chemosensitive and attend with high cure rates, a small portion of the patients will relapse or be refractory to the initial treatment. In this context, high-dose chemotherapy followed by consolidation with autologous stem cell transplantation (AHSCT) is still the standard of care. Carmustine-based conditioning regimens, which includes the combination of Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) are mostly used. However, due to the shortage of carmustine and melphalan, replacing BEAM by Busulfan, Cyclophosphamide and Etoposide (BUCYE), another regimen with apparently similar tolerance and response, has been needed. <h3>Objectives</h3> The main objective of this study was to compare the overall survival (OS) and progression-free survival (PFS) of patients with relapsed or recurrent HL and NHL treated with BEAM or BUCYE as conditioning regimens and undergoing AHSCT. In addition, OS and PFS according to the lymphoma's type, related to each regimen, was evaluated. <h3>Methods</h3> We retrospectively reviewed 122 medical records of patients with refractory or relapsed HL and NHL submitted to AHSCT with BEAM or BUCYE conditioning regimens, treated at A.C.Camargo Cancer Center from January of 2009 to May of 2017. OS and PFS between the groups, were calculated using the Kaplan-Meier method and compared by the log rank test. Toxicity and engraftment data were evaluated with Mann-Whitney and chi-square tests. <h3>Results</h3> The cohort was divided in two groups, those undergoing BEAM conditioning (n = 77) and those submitted to BUCYE conditioning (n = 45). The median age was 42 years. Most clinical characteristics were similar in both groups. Regarding the toxicity profile, we observed, a longer in-hospital stay (<i>p</i>=0,004) and a higher frequency of mucositis grade ≥2 (<i>p</i>=0,01) in the BUCYE group. The median time for neutrophils engraftment in the BEAM and BUCYE groups was 10 and 9 days (<i>p</i>=0,40) respectively. For platelets engraftment, the median time was 10 days for both groups (<i>p</i>=0,35). No significant difference in overall survival or progression-free survival was observed among patients treated with BEAM or BUCYE, regardless of diagnosis. <h3>Conclusion</h3> BEAM and BUCYE are well tolerated and have similar toxicity profile, as well as similar engraftment time and survival, except for a higher rate of mucositis and a longer in-hospital stay associated with BUCYE. Therefore, BUCYE conditioning regimen can be considered as an alternative to BEAM.

Thiotepa, busulfan, and cyclophosphamide or busulfan, cyclophosphamide, and etoposide high-dose chemotherapy followed by autologous stem cell transplantation for consolidation of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCT were included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen. No median OS or PFS was reached in the TBC group, while the BuCyE group reached a median OS of 4.9years (p = 0.02) and median PFS of 1.1years (p = 0.007). The incidence of oral mucositis, nausea, and vomiting was higher with TBC than BuCyE. The median admission duration and days to engraftment were similar between the two groups. Despite the greater incidence of adverse events, TBC showed better outcomes than BuCyE in terms of survival.

High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation As a Salvage Treatment in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

Introduction Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. There are only limited treatment options for patients with refractory disease to induction chemotherapy and patients with relapsed PCNSL. In this study, we evaluate high-dose chemotherapy followed by ASCT as a salvage treatment for patients with refractory or relapsed PCNSL to induction treatment.Methods The PCNSL registry data prospectively collected from March 1993 to May 2017 at a single institute, Asan Medical Center, was retrospectively reviewed. Relapsed or refractory PCNSL patients who received high-dose chemotherapy followed by ASCT as salvage modality were included in this analyses. Overall survival (OS) was defined as the time from the day of stem cell infusion to death by any cause, and progression-free survival as the time from the day of stem cell infusion to disease progression or death by any cause.Results Total 241 patients with diagnosis of PCNSL were identified and 18 patients were included in this study. Nine patients (50%) had refractory disease, 4 patients (22.2%) relapsed without consolidation, and 5 patients (27.8%) relapsed after whole-brain radiotherapy consolidation. Median follow-up period of the survivors was 2.2 years (range, 0.1-15.0). Median age was 57 years (range, 29-64) and 12 patients were male. Sixteen patients received methotrexate (MTX) based combination chemotherapy as induction treatment and 12 patients showed complete response (CR) or partial response (PR) as the best response to induction treatment. All patients received systemic chemotherapy as second-line treatment. Ten patients received ifosfamide, carboplatin, etoposide, and dexamethasone (ICE/D), 5 patients received cytarabine and etoposide (CYVE), 2 patients received high-dose MTX, and 1 patient received etoposide, dexamethasone, cytarabine, and cisplatin (EDAP). Four patients showed CR and 12 patients showed PR as the best response to second-line treatment. Twelve patients received thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimen for ASCT, 4 patients received BCNU, etoposide, cytarabine, and cyclophosphamide (BEAC), 1 patient received busulfan, cyclophosphamide, and etoposide (BuCyE), and 1 patient received BCNU, etoposide, cytarabine, and melphalan (BEAM). Median OS and PFS was 1.5 years (95% CI not applicable), and 0.9 years (95% CI 0.6-1.2), respectively. The 2-years OS and PFS rate was 49.5% and 36.7%, respectively. Median hospitalization duration was 19 days (range, 4-51) and median dose of CD34+ cells infused was 7.57 × 106 cells/kg (range, 4.77-70.50). Seventeen patients (94.4%) had complete recovery of granulopoiesis and 15 patients (83.3%) had complete recovery of thrombopoiesis. Ten patients (55.6%) showed grade 3-4 diarrhea and 4 patients (22.2%) showed grade 3-4 mucositis.Conclusion High-dose chemotherapy followed by ASCT could be a treatment option in patients with refractory or relapsed PCNSL to induction chemotherapy. Further prospective studies are warranted. DisclosuresNo relevant conflicts of interest to declare.

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

Thiotepa Containing Regimen As Conditioning Chemotherapy for Lymphoma Involving Central Nervous System Compared with BuCyE (Busulfan, Cyclophosphamide and Etoposide)

AimsPrimary or secondary central nervous system (CNS) lymphoma is a rare entity which often leads to unsatisfactory outcome. Autologous stem cell transplantation (ASCT) using thiotepa containing regimen as conditioning chemotherapy showed improved outcomes in patients with CNS lymphoma. However, there are insufficient data on response to treatments and safety profile of thiotepa containing regimen in Asian population. We, therefore, aimed to evaluate clinical outcomes including safety profile and response to thiotepa, busulfan and cyclophosphamide (TBC) chemotherapy compared with busulfan, cyclophosphamide and etoposide (BuCyE) as conditioning regimens in patients with CNS lymphoma.MethodsFrom November 2005 to April 2014, patients with primary and secondary CNS lymphoma who underwent one of the two conditioning regimens (TBC or BuCyE) followed by ASCT were included in this retrospective analysis. All patients were less than 66 years of age at the time of ASCT. TBC consists of thiotepa 250 mg/ m2 on day -9 to day -7, busulfan 3.2 mg/kg on day -6 to day-4 and cyclophosphamide 60 mg/kg on day -3 to day -2. BuCyE consists of busulfan 3.2 mg/kg on day -7 to day -5, etoposide 200 mg/m2 twice a day on day -5 to day-4 and cyclophosphamide 50 mg/kg on day -3 and day -2. Patient demographics, ECOG performance status, baseline and follow-up CBC profile, adverse events and radiologic response for 2 years after ASCT were retrospectively reviewed. Response to treatment was assessed by IELSG criteria. Event free survival (EFS), overall survival (OS) and date of engraftment were calculated by Kaplan-Meier method and compared by log-rank test. Adverse events were scored according to National Cancer Institute Common Terminology Criteria of Adverse Event version 4.0. Engraftment was defined as absolute neutrophil count (ANC) > 500 /mm3, and platelet count > 20,000 /mm3.ResultsSixty one patients with primary or secondary CNS lymphoma underwent with TBC (n=26) or BuCyE (n=35) as conditioning regimen followed by ASCT. In TBC group, 17 patients (diffuse large B cell lymphoma: 17) had primary CNS lymphoma and 9 patients (diffuse large B cell lymphoma: 7, angioimmunoblastic lymphoma: 1 and T-lymphoblastic lymphoma: 1) had secondary CNS lymphoma. In BuCyE group, 28 patients (diffuse large B cell lymphoma: 27 and peripheral T-cell lymphoma: 1) had primary CNS lymphoma and 7 patients (diffuse large B cell lymphoma: 5, NK-T cell lymphoma: 1 and mantle cell lymphoma: 1) had secondary CNS lymphoma. Median age of TBC group and BuCyE group at ASCT was 52.5 years (range, 18-64 years) and 54 years (range, 26-64 years), respectively. Median ECOG performance status of TBC group and BuCyE group was 1 (range 0-2) and 1 (range 0-1), respectively. After the induction chemotherapy, 11 patients (42.3%) in TBC group and 21 patients (60%) in BuCyE group had already achieved complete remission (CR). In TBC and BuCyE group, CR had been induced in 9 (64.2%) and 11 (78.5%) among patients in partial remission (PR) after ASCT, respectively. With a median follow up period of 8.6 months (range, 0.2 to 18.5 months), 1-year OS rate did not significantly differ between two arms (76.4% in TBC group and 68.6% in BuCyE group, p=0.634). However, 1-year EFS rate was higher in TBC group (72.8%) compared with BuCyE group (45.7%, p=0.034). TBC group achieved ANC engraftment one day earlier compared to BuCyE group (day 8, range 7-12 days vs. day 9, range 7-12 days) (p= 0.011). However, there was no difference in time to engraftment of platelet between TBC group (median 8 days, range 6 to 34 days) and BuCyE group (median 8 days, range 6 to 22 days, p=0.582). Toxicity profiles are summarized in Table 1.Table 1Toxicity above grade 2TBCBuCyEp-valueMucositis92%14.3%<0.001Nausea72%34.3%0.004Vomiting24%2.9%0.017Diarrhea84%25.7%<0.001AST,ALT elevation15.4%2.9%0.154Bilirubin elevation30.8%5.7%0.014Creatinine elevation7.7%0%0.178Veno-occlusive disease7.7%5.7%1Bleeding3.8%0%0.426ConclusionsTBC seems to be a feasible conditioning chemotherapy for Korean patients with acceptable toxicity and efficacy. DisclosuresNo relevant conflicts of interest to declare.

Autologous stem cell transplantation with busulfan, cyclophosphamide, and etoposide as an intensifying frontline treatment in patients with peripheral T cell lymphomas: a multicenter retrospective trial

The effectiveness of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) as a frontline treatment in peripheral T cell lymphomas (PTCLs) is still unclear. We retrospectively investigated the clinical outcomes of HDT/ASCT as an intensifying frontline treatment in 31 patients with newly diagnosed PTCLs. The conditioning regimen of HDT/ASCT consisted of busulfan, cyclophosphamide, and etoposide (BuCyE). At diagnosis, five (16.1 %) patients were classified as high risk according to the prognostic index for PTCL (PIT). The disease status of the patients before HDT/ASCT consisted of 23 patients (74.2 %) with complete response (CR) and eight patients (25.8 %) with partial response (PR). Six (75 %) out of eight patients with PR at pretransplantation were improved in terms of the response to CR after HDT/ASCT. At a median follow-up of 32.4 months, the 3-year probability of overall survival (OS) and progression-free survival (PFS) was 64.5 ± 8.6 %. Transplant-related mortality occurred in three patients (9.7 %), due to septic shock, hemorrhage, and delayed pneumonia, respectively. Bone marrow involvement of PTCL at diagnosis was a poor prognostic factor for OS. In conclusion, frontline HDT/ASCT with a conditioning regimen of BuCyE may be an effective and tolerable intensifying therapeutic option to improve outcomes in patients with PTCLs.

Yttrium-90 ibritumomab tiuxetan plus busulfan, cyclophosphamide, and etoposide (BuCyE) versus BuCyE alone as a conditioning regimen for non-Hodgkin lymphoma

BackgroundRadioimmunotherapy agents have a highly significant role in autologous stem cell transplantation as they improve tolerability and increase the efficacy of the conditioning regimen.MethodsWe retrospectively analyzed the efficacy and toxicity of yttrium-90 ibritumomab tiuxetan (Zevalin) combined with intravenous busulfan, cyclophosphamide, and etoposide (Z-BuCyE) compared with those of BuCyE alone followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The efficacy, toxicity, and engraftment characteristics were compared between 19 patients who received Z-BuCyE and 19 historical controls who received BuCyE.ResultsThe 2 treatment groups shared similar baseline characteristics. The median time to platelet engraftment (>20×109/L) and neutrophil engraftment (>0.5×109/L) did not significantly differ between the Z-BuCyE group (12 days and 10 days, respectively) and the BuCyE group (12 days and 10 days, respectively). No significant differences were observed between the groups with respect to toxicities and treatment-related mortality. The median follow-up period was 30.4 months, and median event-free survival was generally better in the Z-BuCyE group (12.5 months) vs. the BuCyE group (6.2 months, P=0.236). No significant difference in overall survival between the groups was noted.ConclusionAdding ibritumomab tiuxetan to BuCyE high-dose chemotherapy may benefit patients with relapsed or refractory B-cell NHL with no risk of additional toxicity.

Is radioimmunotherapy a 'magic bullet'?

Radioimmunotherapy (RIT) uses monoclonal antibodies directed against specific tumor antigens that are labeled with a particle-emitting radioisotope to deliver radiation directly to tumors (Fig. 1). Lymphoma is a good model for elucidating the effect of RIT because more than 90% of lymphoma B-cells express the cell-surface antigen CD-20. The 2 therapeutic agents for the management of lymphoma currently approved by the United States Food and Drug Administration (FDA) are 90Y ibritumomab tiuxetan and 131I tositumomab. FDA-labeled indications for RIT are the treatment of relapsed or refractory CD20+ follicular B-cell non-Hodgkin's lymphoma (NHL) and consolidation therapy in patients with follicular NHL who have shown a partial or complete response to first-line chemotherapy [1]. Fig. 1 Radioimmunotherapy (RIT) using monoclonal antibodies labeled with a radioisotope emitting gamma- or beta- rays. High-dose chemotherapy (HDC) conditioning administered in association with autologous stem cell transplantation (ASCT) or reduced-intensity conditioning with allogeneic stem cell transplantation are established treatment approaches for patients with chemotherapy-sensitive, relapsed, aggressive, or low-grade NHL. These approaches have been shown to be the only curative options for patients with relapsed NHL. Despite significant advances in ASCT, relapses occur in many patients receiving HDC in conjunction with ASCT because of contaminated grafts or cancer cells remaining in the patient after ablative chemotherapy. The role of RIT in conditioning therapy with stem cell transplantation for NHL is not yet established [2]. The current issue of the Korean Journal of Hematology includes a comparative study of this controversial issue. Jo et al. report that the use of ibritumomab tiuxetan in combination with busulfan, cyclophosphamide, and etoposide (BuCyE) as a conditioning regimen elicited similar hematologic side effects and was associated with a potential benefit in efficacy when compared to treatment with BuCyE alone [3]. Although this study was not designed to evaluate the effect of the conditioning regimen on patient survival, the findings of this study indicate shorter event-free survival and overall survival than those reported by previous studies conducted in Western countries. As the authors point out, most patients in this study had heavily pretreated aggressive lymphomas, and poorer risk factors, which may have contributed to these results. Han et al. previously reported that tandem consolidation therapy using 90Y ibritumomab tiuxetan followed by HDC with ASCT was not feasible for the treatment of high-risk patients with diffuse large B-cell lymphoma in remission after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), because of poor efficacy [4]. Further studies are needed to determine whether ethnic differences in tumor biology affect survival. Well-designed randomized controlled trials for evaluating RIT as a conditioning regimen are also warranted. This study could have important implications for Korean medicine and may suggest that RIT can be safely adopted as a conditioning regimen for malignant lymphomas.

Yttrium-90-Ibritumomab Tiuxetan and BuCyE High-Dose Chemotherapy Compared with BuCyE Alone As Conditioning Regimen in Patients with B-Cell Non-Hodgkin Lymphoma: IPI Matched Case Control Study At a Single Center,

Abstract 3703 Background:Currently, there are accumulating data on the role of radioimmunotherapy in autologous stem cell transplantation (ASCT) with promising results. We compared the efficacy and safety of yttrium-90-ibritumomab tiuxetan (90Y-ibritumomab) combined with intravenous busulfan, cyclophosphamide, and etoposide (BuCyE) with those of BuCyE alone followed by ASCT in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).Patients and Methods: From October 2005 to May 2011, 71 NHL patients underwent high-dose chemotherapy with BuCyE (n=52) or 90Y-ibritumomab plus BuCyE (n=19) followed by ASCT at the Asan Medical Center. Of 52 patients receiving BuCyE, we found 19 patients who had B-cell NHL and they comprised control group of BuCyE alone (n=19). Retrospective comparison matched by the same IPI was performed for the efficacy and safety between two groups. Results:The patient cohort consisted of 38 individuals (19 males), of median age 52 years (range, 27–65 years). The baseline characteristics were well balanced between the two groups. The median time to platelet engraftment (>20,000/mm3) and the median time to neutrophil engraftment (>500/mm3) did not differ between 90Y-ibritumomab plus BuCyE (12 days [range, 3–103 days] and 10 days [range, 8–12 days], respectively) and BuCyE alone (12 days [range, 8–35 days] and 10 days [range, 9–12 days], respectively). The objective overall response rate was 89.5% (17/19): continued CR, 42.1% (8/19); induced CR, 36.8% (7/19); PR, 10.5% (2/19) in 90Y-ibritumomab plus BuCyE group, and 78.9% (15/19): continued CR, 26.3% (5/19); induced CR, 47.4% (9/19); PR, 5.3% (1/19) in BuCyE group, respectively (p =0.649). Median follow-up duration for survivors was 30 months. Event-free survival tended to be better in 90Y-ibritumomab plus BuCyE group with a median event-free survival duration of 12.5 months in 90Y-ibritumomab plus BuCyE group and 6.2 months in BuCyE group (p =0.236) (figure 1-a).There seemed to be no significant difference in overall survival between the two groups (p =0.767, figure 1-b). The toxicities including the incidence of grade 3 or higher stomatitis, nausea, vomiting, diarrhea, hyperbilirubinemia were similar in the two groups. [Display omitted] Conclusion:Addition of 90Y-ibritumomab to BuCyE high-dose chemotherapy may potentially benefit patients with relapsed or refractory B-cell NHL at no cost of additional toxicity, which warrants further investigation. Disclosures:No relevant conflicts of interest to declare.

BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: A single center comparative analysis of efficacy and toxicity

We compared the efficacy and toxicity of BEAM (BCNU, etoposide, cytarabine and melphalan) and BuCyE (busulfan, cyclophosphamide and etoposide), given prior to autologous stem cell transplantation (ASCT), in 65 patients with non-Hodgkin's lymphoma. Of these 65 patients, 43 received BEAM and 22 received BuCyE. Their age, gender distribution, International Prognostic Index, status of disease at ASCT and median number of infused CD34 + cells/kg were similar. Neutrophil and platelet engraftment were significantly faster in the BuCyE group. Rates of mucositis, nausea/vomiting, diarrhea, bleeding and infections were similar in the two groups. Median overall survival and event-free survival did not differ significantly between the two groups. These findings indicate that BuCyE is an effective conditioning regimen, showing similar survival outcomes and toxicity profiles as BEAM. Furthermore, hematologic recovery is significantly faster in patients given the BuCyE conditioning regimen.

AUTOLOGOUS STEM CELL TRANSPLANTATION with INTRAVENOUS BUSULFAN, CYCLOPHOSPHAMIDE, and ETOPOSIDE as First-LINE TREATMENT of PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA in a SINGLE CENTER.

Abstract 1219Poster Board I-241 BackgroundHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been evaluated in several trials and has shown feasibility as first-line treatment of primary central nervous system lymphoma (PCNSL). However, the best conditioning regimen is still to be identified and high-dose chemotherapy of busulfan, cyclophosphamide, and etoposide (BuCyE) has not been tried although the regimen was shown to be effective for leukemia and systemic non-Hodgkin's lymphoma. MethodsBetween May 2005 and November 2008, 12 consecutive patients of PCNSL with pathologic diagnosis of diffuse large-B cell lymphoma were treated with the intent of upfront ASCT at Asan Medical Center, Seoul, Korea. We retrospectively analyzed the results of these patients. The treatment included induction chemotherapy of high-dose methotrexate/cytarabine (Abrey et al., JCO 21:4151, 2003), followed by BuCyE chemotherapy consisting of iv busulfan (3.2mg/kg from day -7 to day -5), iv cyclophosphamide (50mg/kg from day -3 to day -2), and etoposide (200mg/m2 every 12 hours from day -5 to day -4), and ASCT. Whole brain radiotherapy (WBRT) was reserved for patients who failed to achieve complete response (CR) after ASCT. ResultsMedian age was 50 years (range, 33-65) and 9 were male. The test of cerebrospinal fluid (CSF) cytology came out to be positive for 3 patients. Eight patients achieved CR and 4 gained partial response (PR) after induction chemotherapy. All 12 patients managed to complete ASCT. Following ASCT, additional 2 patients gained CR, resulting in total number of 10 patients (83.3%). Patients who failed to reach CR were further treated with WBRT and 2 more patients achieved CR. Median duration of first CR was 12.8 months (95% confidence interval [CI], 4.6-20.9) at a median follow-up of 23.8 months (range, 8.8-50.7). Relapse of disease occurred in 7 patients (58.3%) and 5 of them were given salvage treatment (Table 1). Two patients could regain CR and sustained remission for more than 2 years. Two patients had died of disease at the time of analysis. Median event-free survival (EFS) from the first day of induction chemotherapy was 15.0 months (95% CI, 8.3-21.8) and median overall survival (OS) was not reached. The 2-year OS probability was 78.8% and 2-year EFS was 25.7%. No patient experienced veno-occlusive disease or treatment-related mortality (TRM). Three patients among those who were treated with WBRT or intrathecal chemotherapy developed leukoencephalopathy. ConclusionBuCyE chemotherapy might be an option of conditioning regimen for ASCT considering high CR rate of 83.3% and favorable toxicity profile in the treatment of PCNSL. However, high relapse rate of 58.3% suggests that more optimization of induction and conditioning chemotherapy is still required.Table 1Patient dataSex/AgeExtent of diseasePre-ASCTPost-ASCTBrain RT (Gy)Overall Resp.1st CR Duration (Mo)Relapse siteSalvage TreatmentResponse to salvage TxEFS (Mo)OS (Mo)StatusNeuro-toxicityM/65BrainPRPR48CR41.6---50.750.7AWoDLeg weaknessF/55BrainCRCR451)CR13.2Brain & eyeChemotherapy2)PR15.048.2AWDLEPM/53BrainCRCR-CR33.1---34.834.8AWoDNDF/52BrainPRCR-CR1.6BrainWBRTCR6.834.7AWoDNDM/33Brain & CSFCRCR-CR4.1CSFIT-chemoCR6.031.2AWoDLEPM/43BrainCRCR-CR8.1BrainWBRTNE9.725.0Alive3)NDM/62BrainCRCR-CR12.8BrainWBRTPR18.922.7AWDNDM/63Brain & CSFCRCR-CR6.2Brainnone-7.89.9DODNDM/48Brain, CSF & maxillary sinusPRPR44CR4.0Brainnone-13.013.2DODLEPF/47BrainPRCR-CR6.4---12.912.9AWoDNDM/45BrainCRCR-CR6.4---9.59.5AWoDNDM/48BrainCRCR-CR6.3---8.88.8AWoDNDAbbreviations: AWoD, alive without disease; AWD, alive with disease; DOD, dead of disease; IT-chemo, intrathecal chemotherapy composed of hydrocortisone, methotrexate, and cytarabine; LEP, leukoencephalopathy; ND, not definite; NE, not evaluated1)The patient was given WBRT after ASCT as she was assessed as PR at that time. However, the residual non-enhancing lesion by MRI did not change during follow-up and showed no hypermetabolism on PET. The lesion was concluded as post-biopsy change later.2)Chemotherapy of high-dose methotrexate/cytarabine and intravitreal methotrexate injection was done.3)The patient was lost to follow-up after WBRT but he is presumed to be alive according to the data of National Health Insurance Corporation. DisclosuresNo relevant conflicts of interest to declare.

Yttrium-90-ibritumomab tiuxetan in combination with intravenous busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma

Radiolabelled immunotherapy agents have an increasingly significant role in autologous stem cell transplantation (ASCT) by improving the tolerability and increasing the efficacy of the conditioning regimen, thereby reducing the relapse risk. We evaluated the efficacy and safety of yttrium-90-ibritumomab tiuxetan ((90)Y-ibritumomab) combined with intravenous busulfan, cyclophosphamide, and etoposide (Bu/Cy/E) followed by ASCT in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Each patient received a single dose of (90)Y-ibritumomab (0.4 mCi/kg on day -14) with Bu/Cy/E as a conditioning regimen. The patient cohort consisted of 19 individuals (ten males), of median age 51 years (range, 25-63 years). Sixteen patients had received two or more chemotherapy regimens before transplantation. Histologies were diffuse large B-cell (n = 14), follicular (n = 2), mantle cell (n = 2), and Burkitt lymphoma (n = 1). All patients engrafted. The median time to neutrophil engraftment was 10 days and time to platelet engraftment was 10 days. Nineteen patients were evaluable for response. The objective overall response rate was 84.2% (16/19): continued CR, 36.8% (7/19); induced CR, 36.8% (7/19); and PR, 10.5% (2/19). With a median follow-up of 29.4 months (13.4-36.6), the estimated 3-year overall survival and event-free survival rates were 52.6% (95% confidence interval [CI] 45.8-59.4) and 26.3% (95% CI 19.8-32.8), respectively. Adverse events were similar to those seen historically with Bu/Cy/E alone, and there were no treatment related deaths. In conclusion, (90)Y-ibritumomab with Bu/Cy/E and ASCT is feasible in patients with relapsed or refractory B-cell NHL, without increased toxicity.

BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients

7097 Background: The objective of this study was to compare the efficacy and toxicity of two high-dose regimens for autologous stem cell transplantation (ASCT) in patients with non-Hodgkin's lymphoma (NHL): BEAM (BCNU, etoposide, cytarabine, and melphalan) and BuCyE (busulfan, cyclophosphamide, and etoposide). Methods: We analysed 65 NHL patients, who underwent high-dose chemotherapy with BEAM (N=43) or BuCyE (N=22), followed by ASCT, at the Asan Medical Center. BEAM was used from February 2002 to October 2005, and BuCyE was used from November 2005 to April 2008. Results: Median age was 46 years (range: 15–68), and baseline characteristics, such as gender, International Prognostic Index (IPI), age adjusted IPI, stage and status of disease at ASCT, and median number of infused CD 34+cells/kg were well balanced between groups. The incidence of mucositis, nausea/vomiting, diarrhea and bleeding, and the number of events clinically important infections during ASCT did not differ between groups. Median follow-up for survivors was 49.3 months in the BEAM group and 21.5 months in the BuCyE group. Median overall survival (OS) was 30.6 months (95% confidence interval [CI], 8.19–53.0 months) and 22.6 months (95% CI, 12.1–33.1 months) and median event-free survival (EFS) was 16.1 months (95% CI, 0.0–53.6 months) and 11.2 months (95% CI, 0.0–22.5 months) in the BEAM and BuCyE group, respectively. There were no significant differences in OS (p=0.636) and EFS (p=0.575) between the two groups. Conclusions: In our analysis, BuCyE appeared to be not inferior to BEAM for survival. And we found that regimen-related toxicities did not differ significantly between the two groups. No significant financial relationships to disclose.