Mini-beam as salvage chemotherapy for refractory Hodgkin's disease and non-Hodgkin's lymphoma

Long-term disease-free survival after conventional dose salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) is rare. Intensive chemotherapy and autologous bone marrow transplantation (ABMT) is regarded by many as the treatment of choice. For lymphoma, eligibility for transplant is frequently restricted to cases with chemotherapy-sensitive disease or minimal tumour bulk. We evaluated the mini-BEAM regimen as further treatment for patients unresponsive to initial salvage therapy and thus ineligible for ABMT at our centre. Carmustine 60 mg/m(2) I.V. day one, etoposide 75 mg/m(2) I.V. days 2-5, cytosine arabinoside 100 mg/m(2) I.V. q12h days 2-5 and melphalan 30 mg/m(2) day 6 (mini-BEAM) was administered to 24 patients with lymphoma, 22 of whom were refractory to at least first-line salvage chemotherapy. Eleven had HD and 13 NHL. The complete response (CR) rate was 21% and the overall response was 59%. Febrile neutropenia occurred in 48% of treatment episodes. There were two treatment-related deaths. Thirteen patients underwent bone marrow transplantation (BMT), 11 received ABMT (8 HD, 3 NHL). Six patients did not achieve remission after transplant but 7 patients remain in continuous CR, with a follow-up of 6-17 months post-transplant. Consequently, 7 of 24 (29%) patients responded to mini-BEAM and many achieve long-term disease-free survival after BMT. Further evaluation of mini-BEAM as a salvage regimen prior to BMT is indicated.     

Impact of Conditioning Regimen on Outcome of 2-Year Disease-Free Survivors of Autologous Stem Cell Transplantation for Hodgkin Lymphoma

BackgroundAutologous stem cell transplantation is the standard of care for patients with relapsed HL and the long-term outcomes for survivors 2 years after ASCT have not been well described. No prospective trials have compared the effect of different conditioning regimens on outcomes.Patients and MethodsWe searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with either CBV (cyclophosphamide, carmustine, and etoposide) or BEAM (carmustine, etoposide, cytarabine, and melphalan).ResultsAt a median follow-up of 8 (range, 2-26) years, 225 patients were alive and disease-free 2 years after ASCT. Analysis was limited to these patients. At 5 years, the progression-free survival (PFS) was 92% for BEAM and 73% for CBV (P = .002) and the overall survival (OS) was 95% for BEAM and 87% for CBV (P = .07). At 10 years, the PFS was 79% for BEAM and 59% for CBV (P = .01) and the OS was 84% for BEAM and 66% for CBV (P = .02).ConclusionPatients with HL who are disease-free and alive 2 years after ASCT have favorable outcomes. We observed lower risk of progression and longer survival associated with use of BEAM vs. CBV. Patients in the BEAM group received a transplant in more recent years so we cannot exclude the possibility that the superior outcomes seen in the BEAM group are because of better supportive care, use of peripheral blood stem cell grafts, or improvements in salvage therapies before transplantation.     

Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial.

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.     

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m²) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m²). The transplant phase consisted of mitoxantrone (60 mg/m²) and melphalan (180 mg/m²) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.     

Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation

Background: The role of intensive chemotherapy with autologous blood andmarrow transplantation (ABMT) for patients with relapsed or refractoryintermediate grade non-Hodgkins lymphoma has recently been established.However, conventional dose salvage chemotherapy is frequently used todetermine chemotherapy sensitivity and reduce tumor bulk prior to intensivetherapy. Different salvage regimens have been proposed but none appearssignificantly superior. The purpose of this study was to determine theefficacy of mini-BEAM salvage chemotherapy in patients referred for ABMT andto define prognostic factors of response.Patients and methods: One hundred four patients referred forconsideration of ABMT after failure of primary anthracycline-basedchemotherapy received BCNU 60 mg/m² day 1, etoposide 75mg/m² day 2–5, ara-C 100 mg/m² q12h day2–5, melphalan 30 mg/m² day 6 (mini-BEAM) until maximumtumor reduction. Median age was 52 (range 18–65); 57% had failedto achieve a complete response (CR) to doxorubicin-based chemotherapy atdiagnosis and only 13% had a previous CR lasting > 12 months.Seventy-six received mini-BEAM as first salvage chemotherapy.Results: The overall response rate (RR) was 37% (95%confidence interval (CI) 28–46%) with 12 patients achieving CRand 25 achieving PR. Theresponse rate among patients treated as first salvage was 43% comparedto 20% for patients who had failed to respond to a previous salvageregimen. Only 15% of patients who failed to respond to mini-BEAMresponded to another conventional dose salvage regimen. Thirty-eight of 104patients ultimately demonstrated sufficient response to proceed to ABMT.Actuarial survival at four years is 22% for all 104 patients, and36% for those who went on to ABMT. For those who were not transplanted,four-year survival was 18%. B symptoms and tumor burden at relapse weresignificant predictors of response to mini-BEAM in multivariate analysis, andidentified a poor prognosis group of patients unlikely to be cured by thisapproach.Conclusions: Mini-BEAM does not appear to be a superior salvage regimen inthis high-risk group of relapsed or refractory NHL patients for whom ABMT wasthe ultimate treatment intention. Only one-third of patients referred for ABMTultimately proceed to transplant; alternative treatment strategies should bedeveloped for those with a low likelihood of cure by this approach.     

IMVP-16/Pd followed by high-dose chemotherapy and autologous stem cell transplantation as a salvage therapy for refractory or relapsed peripheral T-cell lymphomas

The present study aimed to analyse the treatment outcome of IMVP-16/Pd (ifosfamide, methotrexate, etoposide and prednisone) followed by high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with peripheral T-cell lymphomas (PTCLs) who were previously treated with CHOP. Since 1995, 32 PTCL patients were treated with IMPV-16/Pd. Nine of 32 patients achieved a response (5 demonstrating complete response (CR) and 4 partial response), with an overall response rate of 28.1% (95% onfidence interval 0.12-0.45). Considering histopathologic subtypes, 3 of 4 relapsed natural killer (NK)/T-cell lymphoma patients (75%) achieved CR, but only 1 of 6 in non-NK/T-cell lymphoma patients (16.7%) achieved CR (P = 0.19). Six of 9 IMVP-16/Pd sensitive patients underwent HDC/ASCT. Three of them relapsed after 3, 4 and 15 months, respectively, of HDC/ASCT. Estimated 3-year overall survival and progression-free survival rates were 14.2% and 12.2%, respectively. Multivariate analysis revealed that responsiveness to first-line CHOP was a significant prognostic factor (P < 0.05). These results indicate that IMVP-16/Pd followed by HDC/ASCT appears to be an effective salvage regimen, especially for NK/T-cell lymphoma.     

Gemcitabine,Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients

BackgroundSecond line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting.Patients and MethodsForty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP.ResultsThirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 10⁶/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively.ConclusionOur results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.     

新药诱导后自体干细胞移植巩固治疗对不同危险度骨髓瘤患者的作用探讨*

目的：探讨自体造血干细胞移植（autologous hematopoietic stem cell transplantation ,ASCT）作为新药诱导后的巩固治疗对不同危险分层骨髓瘤患者的无进展生存时间（progression-freesurvival ,PFS）及总生存时间（over all survival,OS）的影响。方法：回顾性分析2006年8 月至2011年7 月在本科行自体干细胞移植巩固治疗的67例多发性骨髓瘤患者,根据ISS 分期及FISH检测结果为基础的最新IMWG 预后标准分为高危组17例,中危组24例,低危组26例。另选取同时期67例接受化疗作为巩固治疗的骨髓瘤患者进行年龄、危险分层配对,比较移植组与化疗组的PFS 和OS差异。所有患者前期均接受硼替佐米和/或沙利度胺为主的诱导治疗。结果：所有患者诱导治疗后均达到部分缓解（partial remissive disease ,PR）以上疗效,移植组与化疗组vs . 接近完全缓解率（nCR/CR）差异无统计学意义（44.8% vs. 37.3% ,P=0.380）。 巩固治疗后,高、中、低危移植组患者中位nCR/CR率分别由47.1% ,37.5% ,50.0% 增加为62.9% ,62.5% ,61.5% 。高危患者移植巩固后中位PFS（30.5 个月vs. 11.2 月,P<0.001）和OS（85.5 vs. 34个月,P=0.015）均明显延长;中危移植组和化疗组中位PFS 和OS无统计学差异（P>0.05）;低危移植组患者与化疗组相比,中位PFS 延长（34.8 vs. 17.6 个月,P=0.012）,OS差异无统计学意义（P>0.05）。 结论：在硼替佐米和/或沙利度胺为基础的新药诱导治疗后,高危骨髓瘤患者更能从自体造血干细胞移植巩固治疗中获益,进而延长生存。     

Dexamethasone, carmustine, etoposide, cytarabine, and melphalan (dexa-BEAM) followed by high-dose chemotherapy and stem cell rescue--a highly effective regimen for patients with refractory or relapsed indolent lymphoma

We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2-5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 x 10(6)/kg (range 1.6-8.2 x 10(6)/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8-42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response.     

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a therapeutic option for patients with relapsed follicular lymphoma (FL). The clinical characteristics and outcomes of FL relapse after ASCT in the rituximab era have not yet been fully elucidated. We retrospectively reviewed 414 FL patients treated with ASCT between 2000 and 2014 in four hematology departments. All patients received rituximab as a first-line treatment. We specifically analyzed the clinical characteristics, treatment strategies at relapse, and outcomes of 95 patients (23%) who relapsed after ASCT. The patients (median age, 57 y) received a median of two lines of therapy (range, 2-6) prior to ASCT, with 92% in complete response (CR) or partial response (PR) before ASCT. Histological transformation at relapse after ASCT was observed in 20% of the patients. Treatment at relapse after ASCT consisted of chemotherapy with or without rituximab (n = 45/90, 50%), targeted agents (18%), rituximab monotherapy (14%), or consolidation allogeneic transplantation after induction chemotherapy (12%) and radiotherapy (6%). After relapse, the median progression-free survival (PFS) and overall survival (OS) were 1 year (95% CI, 0.541-1.579) and 5.5 years (95% CI, 1.910-9.099), respectively. In the multivariate analysis, histological transformation (HT) was associated with OS (P = .044; HR 2.439; 95% CI, 1.025-5.806), and a high FLIPI score at relapse was associated with PFS (P = .028; HR 2.469; 95% CI, 1.104-5.521). This retrospective study showed that the period of PFS of patients who relapsed after ASCT is short. A biopsy should be performed for these patients to document the HT. Our results indicate that new treatment strategies will need to be developed for these patients.     

Characteristics associated with long-term progression-free survival following high-dose chemotherapy in metastatic breast cancer and influence of chemotherapy dose.

BACKGROUND: The purpose of this study was to characterize long-term progression-free survivors (LTPFS) of metastatic breast cancer (MBC) following high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) and to assess the influence of chemotherapy dose in order to identify patients who derive major benefit from this approach. PATIENTS AND METHODS: We compared patient and tumor characteristics of 16 LTPFS with the characteristics of 118 MBC patients who received HDCT with ASCT at our institution between 1992 and 2000. To estimate the cumulative dose of chemotherapy received, the summation dose intensity product (SDIP) of the different chemotherapy regimens was calculated as recently described by Hryniuk et al. The SDIP of the induction regimens was added to that of the HDCT regimens to yield the total SDIP of the chemotherapy received. Multivariate analysis was performed to describe the influence of the total SDIP and other prognostic factors on progression-free survival (PFS). RESULTS: LTPFS were mostly < or = 50 years of age and had limited, chemotherapy-sensitive, hormone-responsive MBC. Due to an apparent dose-survival relationship, an increase by 10 units (U) in the SDIP increased the PFS time by 3 months. Independent predictors of an improved PFS were positive estrogen receptors (P = 0.001), positive combined hormone receptors (P = 0.020), and a complete remission/no evidence of disease status after HDCT (P < 0.001). In patients who had a disease-free interval (DFI) >24 months after primary surgery, an SDIP of >55 U was independently associated with a longer PFS [hazard ratio (HR) = 2.73; 95% confidence interval 1.29-5.81; P = 0.009]. CONCLUSION: HDCT can achieve long-term PFS in young MBC patients with limited, hormone-responsive and chemotherapy-sensitive disease. After a DFI >24 months, a longer PFS is associated with a higher chemotherapy dose as measured by SDIP. These retrospective analyses suggest SDIP might be a tool for studying cumulative dose as a determinant of outcome of MBC chemotherapy. Thus far, however, we cannot clearly identify any subgroup of MBC patients in whom HDCT with ASCT is of particular benefit.     

Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma

BACKGROUND:: Patients with Hodgkin's disease (HD) and intermediate or high-gradenon-Hodgkin's lymphoma (NHL) who fail to achieve a completeremission (CR) with standard induction therapy have a poor prognosiswith conventional-dose salvage therapy alone. We examined therole of subsequent intensive therapy and autologous bone marrowtransplantation (ABMT) in patients who demonstrated a responseto conventional-dose salvage therapy. PATIENTS AND METHODS:: Sixty-six patients with either HD (n = 30) or NHL (n = 36) underwentintensive therapy with etoposide (60 mg/kg), intravenous melphalan(160–180 mg/m²) followed by infusion of unpurged autologousbone marrow and/or blood cells. All patients had advanced stageor bulky disease at diagnosis and failed to achieve a CR afteran anthracycline-containing front-line chemotherapy regimen(NHL) or ABVD or equivalent regimen (HD). Patients who achieveda CR after involved-field radiotherapy were excluded. All patientsdemonstrated sensitivity to conventionaldose salvage treatmentbefore advancing to intensive therapy and ABMT. RESULTS:: The CR, partial response (PR) and overall response rate (RR)following ABMT for HD patients was 48%, 17% and 65%, respectively.At a median follow-up of 35 months, the predicted three-yearoverall survival (OS) is 51% (95% CI: 44%–60%) and event-freesurvival (EFS) is 34% (95% CI: 26%–54%). For patientswith NHL, the CR, PR and RR were 68%, 9% and 77%, respectively.At a median follow-up of 28 months, the predicted three-yearOS is 51% (95% CI: 35%–66%) and EFS is 39%(95% CI: 21%–57%). CONCLUSIONS:: Intensive therapy with etoposide and melphalan followed by ABMTresults in prolonged survival in selected patients with lymphomawho fail to achieve a complete remission to front-line chemotherapy.Based on our previous studies of outcome to conventionaldosesalvage chemotherapy, we estimate that of all patients failinginduction therapy, 28% with HD and 15% with NHL will be eventfreeat three years after ABMT. induction failure, Hodglun's disease, non-Hodgkin's lymphoma, refractory lymphoma     

含利妥昔单抗化疗方案治疗套细胞淋巴瘤效果分析

目的探讨含利妥昔单抗化疗方案治疗套细胞淋巴瘤(MCL)患者效果及预后影响因素。方法回顾性分析2007年6月至2018年11月苏州大学附属第一医院血液科收治的56例≤65岁MCL患者临床资料,化疗方案中均包括利妥昔单抗,观察临床特征、治疗方案及生物学指标对总生存(OS)和无进展生存(PFS)的影响。结果56例患者中位发病年龄57岁,男性43例,女性13例。24例接受R-CHOP方案化疗;29例接受含阿糖胞苷方案化疗,其中15例接受R-hyper CVAD/R-MA方案化疗,14例接受R-CHOP/R-DAHP交替治疗;3例接受其他方案化疗。19例接受自体造血干细胞移植(ASCT)巩固治疗。56例患者中位OS时间74个月,2年OS率83.8%,3年OS率70.9%,2年PFS率72.0%,3年PFS率49.7%。国际预后指数(IPI)评分和治疗中是否接受ASCT是MCL患者OS和PFS的独立影响因素。含阿糖胞苷治疗组总有效率(ORR)93.1%,优于R-CHOP方案组(83.3%),差异无统计学意义(χ²=0.465,P=0.495);两组间OS及PFS差异均无统计学意义(OS:χ²=0.291,P=0.590;PFS:χ²=0.912,P=0.339)。诱导化疗达缓解的MCL患者中,ASCT巩固治疗可延长中位OS时间(72个月比124个月,χ²=3.973,P=0.040)及中位PFS时间(34个月比90个月,χ²=3.984,P=0.046)。简化MCL国际预后指数(sMIPI)评分中高危组患者中接受ASCT巩固治疗患者OS和PFS优于未接受ASCT治疗者(OS:χ²=5.037,P=0.025;PFS:χ²=6.787,P=0.009),而sMIPI评分低危组患者中,是否接受ASCT组间OS、PFS差异均无统计学意义(均P>0.05)。结论含阿糖胞苷的化疗方案对改善MCL患者的预后和生存并不理想。对于诱导化疗达缓解及sMIPI评分中高危组的MCL患者,ASCT巩固治疗可改善其预后,可作为年轻患者的一线巩固治疗方案。     

Pretransplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in aggressive B-cell non-Hodgkin lymphoma

BACKGROUND.

Limited data exist about the role of second‐line chemotherapy response assessed by positron emission tomography (PET) as a prognostic factor in patients with aggressive non‐Hodgkin Lymphoma (NHL) who undergo autologous stem cell transplantation (ASCT). The objective of this analysis was to investigate the main determinants of prognosis in patients with aggressive B‐cell NHL who undergo ASCT, focusing on the impact of pretransplantation PET, secondary age‐adjusted International Prognostic Index (sAA‐IPI) score, histology, and previous response to first‐line chemotherapy.

METHODS.

Seventy‐five patients with diffuse, large B‐cell lymphoma or grade 3 follicular lymphoma who were treated at the author' institution with second‐line chemotherapy (combined ifosfamide, etoposide, and epirubicin [IEV]) followed by ASCT between September 2002 and September 2006 were included. All patients were evaluated by PET after 1 to 3 courses of IEV chemotherapy before ASCT, and all patients received a conditioning regimen of combined carmustine, etoposide, cytosine arabinoside, and melphalan. The prognostic impact of pretransplantation PET, sAA‐IPI score, histology, and previous response to first‐line chemotherapy was evaluated by univariate and multivariate analyses.

RESULTS.

Seventy‐two of 75 patients underwent ASCT. In a univariate analysis for progression‐free survival (PFS) and overall survival (OS), a significant association was observed with pretransplantation PET (PFS, P < .00001; OS, P < .01) and previous first‐line response (PFS, P = .02; OS, P = .04). In the multivariate framework, pretransplantation PET was identified as the only independent prognostic factor (PFS, P < .001; OS, P = .01).

CONCLUSIONS.

The current data indicated that pretransplantation PET is the main prognostic predictor in patients with aggressive B‐cell NHL who are scheduled for ASCT. Cancer 2008. © 2008 American Cancer Society.     

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

Background

Immunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes.

Design and methods

Seventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group.

Results

Median age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT.

Conclusions

Despite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients.     

Vinorelbine,Paclitaxel, Etoposide,Cisplatin, and Cytarabine (VTEPA) Is an Effective Second Salvage Therapy for Relapsed/Refractory Hodgkin Lymphoma

BackgroundFor Hodgkin lymphoma (HL) patients with refractory or relapsed (R/R) disease after primary therapy, the standard of care is a salvage regimen followed by autologous stem cell transplant (ASCT). However, patients who fail to respond to a salvage regimen have limited options. Our phase I study of cytarabine combined with fixed doses of vinorelbine, paclitaxel, etoposide, and cisplatin (VTEPA) for patients with R/R lymphoma showed an overall response rate (ORR) of 33%.Patients and MethodsTo further examine the effectiveness of VTEPA, we conducted a retrospective review of 30 cases of R/R HL who received a salvage combination of VTEPA.ResultsThis population included 15 men (50%), 18 stage III/IV (60%), and 14 with an International Prognostic Score ≥3 (47%). The median number of previous regimens was 2 (range, 1-4), 19 patients (63%) received previous salvage therapy with ifosfamide, carboplatin, and etoposide. Twenty-seven patients were evaluable for response. The most common Grade 3/4 toxicities were pancytopenia (19 patients, 97%), nausea/vomiting (17, 57%), fatigue (14, 47%), and infection (6, 20%). Of the 27 patients evaluable for response, the ORR was 70% (7 complete response and 12 partial response). Twenty patients (66%) went on to ASCT and 1 patient underwent allogeneic transplant. With a median follow-up of 32 months, the median progression-free survival (PFS) and overall survival (OS) in patients who received transplantation after VTEPA were 28 and 38 months, respectively.ConclusionTreatment with VTEPA for R/R HL is feasible with manageable side effects. With a high ORR, the PFS and OS for this group of patients suggest that VTEPA is a promising regimen for HL patients in whom previous lines of therapy have failed.     

Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy?

PURPOSE: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse. PATIENTS AND METHODS: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment. RESULTS: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients' original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS). CONCLUSION: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.     

Efficacy of up-front treatment with a double stem cell transplantation in multiple myeloma

BACKGROUND: We report the outcome of 53 patients with multiple myeloma (MM), who received autologous stem cell transplantation (ASCT) from April 1996 to September 2004 at our institution and who survived for more than 3 months after the transplant. METHODS: Following the first ASCT, 36 patients underwent an up-front second SCT, which consisted of either an ASCT (n = 24) or a reduced-intensity conditioning allogeneic stem cell transplant (RIST) (n = 12). Seventeen patients were given maintenance treatment. RESULTS: Seventy-seven percent of the patients (n = 41) showed an objective response to the initial therapy prior to the first ASCT. Overall, 60.4% (32 out of 53) and 32.1% (17 out of 53) of the patients had a complete response (CR) and partial response (PR) after the first ASCT, respectively. At the time of analysis, 34 patients (64.2%) were still alive. With a median follow-up of 32 months (range 9-98), the estimated progression-free survival (PFS) and overall survival (OS) at 5 years were 17.0 and 34.9%, respectively. Multivariate analysis revealed that the second SCT, normal hemoglobin and <50% marrow plasma cells were associated with an improved PFS. A second SCT, CR to the first SCT, female gender and an absence of advanced bone lesions were associated with a better OS. CONCLUSIONS: A second SCT is the most significant factor for an improved PFS and OS after the first ASCT (P < 0.001, respectively). Up-front double SCT is needed to improve the OS and PFS in patients with MM.     

Maintenance therapy with thalidomide improves overall survival after autologous hematopoietic progenitor cell transplantation for multiple myeloma

BACKGROUND: High-dose chemotherapy with autologous hematopoietic progenitor cell (HPC) transplantation improves survival for patients with multiple myeloma (MM); however, most patients develop recurrent disease after undergoing transplantation, and new treatment approaches are needed. The objective of this retrospective review of autologous HPC transplantation for patients with MM was to evaluate the impact of conditioning regimens and posttransplantation therapy on survival. METHODS: The authors reviewed 112 patients with MM who received autologous HPC grafts at their institution. Between June 1992 and August 2001, 54 patients received busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16), and 58 patients received high-dose melphalan (MEL-200) followed by autologous HPC transplantation. After transplantation, 36 patients received thalidomide for maintenance or salvage therapy, and 76 patients received no posttransplantation thalidomide. RESULTS: At a median follow-up of 58 months, the median survival was 54 months. There was no statistically significant difference noted with regard to response to conditioning regimen, progression-free survival, or overall survival between the Bu/Cy/VP-16 and MEL-200 cohorts. Patients who received thalidomide after transplantation had improved median survival (65.5 months) compared with patients who did not receive thalidomide (44.5 months; P = .09). When they were separated according to reasons for thalidomide use, patients who received thalidomide as maintenance had improved overall survival compared with patients who received thalidomide as salvage (65 months vs. 54 months; P = .05). CONCLUSIONS: Combination chemotherapy provided no advantage over high-dose melphalan in patients with MM who underwent autologous HPC transplantation. The posttransplantation use of thalidomide seemed to improve the survival of patients compared with historical controls from the prethalidomide era. Further prospective trials are underway to confirm the benefit of thalidomide in the posttransplantation setting.     

A phase II study of dexamethasone, ifosfamide, cisplatin and etoposide (DICE) as salvage chemotherapy for patients with relapsed and refractory lymphoma

The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the < 55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.