Treatment outcome of relapsed/refractory primary central nervous system diffuse large B-cell lymphoma: a single-center experience of autologous stem cell transplantation

No salvage treatment strategy has been established for relapsed or refractory primary central nervous system lymphoma (PCNSL). We compared treatment outcomes of patients who underwent salvage chemotherapy with or without autologous stem cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were histologically diagnosed with diffuse large B-cell lymphoma. All patients relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were refractory to high-dose MTX. Patients were treated with salvage chemotherapy, such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high-dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by ASCT was performed if patients were eligible for ASCT after salvage treatment. Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose MTX. Despite the important difference that ICE/D was used predominantly for early relapsed or refractory patients, the two salvage treatments produced similar overall response rates [84.4 % (38/45) for ICE/D and 81.3 % (13/16) for high-dose MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received salvage chemotherapy alone. The median progression-free survival of patients who underwent ASCT (19.5 months) was significantly better than that of patients who did not receive ASCT (6.7 months, P = 0.023). Multivariate analysis showed that refractoriness to initial treatment and no ASCT were significantly associated with poor survival outcome. Our study suggested that the combination of ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible salvage treatment option for relapsed or refractory PCNSL, and that high-dose chemotherapy containing thiotepa and busulfan followed by ASCT may be effective for patients with a favorable toxicity profile.     

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.     

Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B‐cell lymphoma: mature results of a phase II multicentre study

Salvage therapy followed by high‐dose therapy (HDT) remains a mainstay for patients with relapsed lymphoma, however no optimal regimen has been defined. Here we report on the results of R‐DexaBEAM (rituximab, dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by HDT. Patients aged 18–65 years, Eastern Cooperative Oncology Group performance score 0–2, with relapsed/refractory B‐cell non‐Hodgkin lymphoma (NHL) were eligible. R‐Dexa‐BEAM was given for two cycles followed by stem cell mobilization and HDT. Primary endpoint of the trial was progression‐free‐survival (PFS). One hundred and three patients were included: aggressive NHL (aNHL): diffuse large B‐cell lymphoma 55, mantle cell lymphoma 7, follicular lymphoma (FL) grade 3: 5, indolent Lymphoma (iNHL): FL grade 1–2: 29, marginal zone lymphoma 6, Immunocytoma 1. The overall response rate after salvage therapy was 62% for aNHL and 78% for iNHL patients. 66% of patients with aNHL and 86% with iNHL underwent HDT. Treatment‐related mortality for HDT was 1·3%. For aNHL patients, the median PFS was 0·83 years with 44% alive at the median follow‐up of 7·3 years. Corresponding figures for iNHL were: median PFS 3·7 years and 72% alive after 8 years. The combination of rituximab with DexaBEAM followed by HDT resulted in high response rates and sustained remissions in responders. R‐DexaBEAM followed by HDT can be considered a valid salvage option for NHL.     

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis

High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.     

Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma

Patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) who achieve complete response (CR) before autologous stem cell transplantation (ASCT) generally have better outcomes than those who achieve only partial response (PR). We investigated whether adding rituximab to the ifosfamide-carboplatin-etoposide (ICE) chemotherapy regimen (RICE) could increase the CR rate of patients with DLBCL under consideration for ASCT. Thirty-six eligible patients were treated with RICE, and 34 received all 3 planned cycles. The CR rate was 53%, significantly better than the 27% CR rate (P =.01) achieved among 147 similar consecutive historical control patients with DLBCL treated with ICE; the PR rate was 25%. Febrile neutropenia was the most frequent grade 3 or 4 nonhematologic toxicity; it occurred in 7.5% of delivered cycles. No patient had RICE-related toxicity that precluded ASCT. The median number of CD34(+) cells per kilogram mobilized was 6.3 x 10(6). Progression-free survival rates of patients who underwent transplantation after RICE were marginally better than those of 95 consecutive historical control patients who underwent transplantation after ICE (54% vs 43% at 2 years; P =.25). RICE appears to induce very high CR rates in patients with relapsed and refractory DLBCL; however, further studies are necessary to determine whether this treatment regimen will improve outcomes after ASCT.     

High-dose therapy and autologous stem cell transplantation in peripheral T-cell lymphoma: treatment outcome and prognostic factor analysis

Peripheral T-cell lymphoma (PTCL) carries a poor prognosis with conventional treatment. We retrospectively analyzed data from 45 patients with PTCL who received high-dose therapy and autologous stem cell transplantation (HDT/ASCT) from 1990 to 2008 in our center. Eighteen patients underwent HDT/ASCT in complete remission to induction chemotherapy (CR1), and 27 patients underwent HDT/ASCT in other disease statuses. The median follow-up was 113.5 months (range 52.6–261.0) for surviving patients. The 5-year overall survival (OS) and progression-free survival (PFS) were 64 and 60 %, respectively. The 5-year OS for patients in CR1 and in other disease statuses was 89 and 47 %, respectively (P = 0.002), and 5-year PFS was 83 and 43 % (P = 0.007). In the subgroup excluding anaplastic large cell lymphoma, patients transplanted in CR1 also had significantly better 5-year OS (82 vs. 37 %, P = 0.009) and PFS (82 vs. 33 %, P = 0.008) than those transplanted in other disease statuses. Multivariate analysis showed that CR1 status was the only significant prognostic factor for OS (P = 0.040) and PFS (P = 0.040). These results support the use of HDT/ASCT consolidation in CR1 for PTCL patients. Prospective randomized trials are necessary to confirm the efficacy of this approach.     

High-dose chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: complete response at transplant predicts survival

Although the role of high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established in several large prospective studies, its effectiveness in patients with peripheral T cell lymphoma (PTCL) has not been defined. We aimed to evaluate the efficacy of HDT and ASCT and prognostic factors for survival in patients with PTCL. We retrospectively analyzed the results of 40 PTCL patients treated with HDT and ASCT at Asan Medical Center between January 1995 and December 2005. Twenty patients had PTCL-U (peripheral T cell lymphoma, unspecified), 10 had extranodal natural killer/T cell lymphoma, 5 had anaplastic large cell lymphoma, 3 had angioimmunoblastic T cell lymphoma, 1 had hepatosplenic γσ T cell lymphoma, and 1 had disseminated mycosis fungoides. Disease status at transplant was complete response (CR)1 in 3 patients, CR2 or greater in 8, partial remission in 25, and refractory in 4. At a median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 46.1%. The median event free survival (EFS) was 3.6 months (95% confidence interval, 2.5 to 4.8 months). Ten patients (25%) remain alive without evidence of disease. The median OS of 11 patients with CR at ASCT was not reached; of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR at ASCT was a prognostic factor for EFS (P = 0.025) and OS (P = 0.027) and normal lactate dehydrogenase (LDH) at ASCT was a prognostic factor for improved OS (P = 0.025). Chemosensitive patients with PTCL who achieved CR before ASCT seem to benefit from HDT and ASCT. Pretransplant values of LDH had potential to predict the survival.     

Gemcitabine,dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma—not otherwise specified

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma—not otherwise specified (PTCL—NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL—NOS. We retrospectively reviewed patients with relapsed or refractory PTCL—NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2–8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p < .01). In addition, the low International Prognostic Index, low Prognostic Index for T cell lymphoma, or normal level of LDH in serum was associated with favorable prognosis. Grade 3/4 adverse effect was observed in 10 of 25 patients treated with GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL—NOS.     

Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma

We previously reported that remission duration < 1 year, extranodal disease, and B symptoms before salvage chemotherapy (SLT) can stratify relapsed or refractory Hodgkin lymphoma (HL) patients into favorable and unfavorable cohorts. In addition, pre-autologous stem cell transplant (ASCT) (18)FDG-PET response to SLT predicts outcome. This phase 2 study uses both pre-SLT prognostic factors and post-SLT FDG-PET response in a risk-adapted approach to improve PFS after high-dose radio-chemotherapy (HDT) and ASCT. The first SLT uses 2 cycles of ICE in a standard or augmented dose (ICE/aICE), followed by restaging FDG-PET scan. Patients with a negative scan received a transplant. If the FDG-PET scan remained positive, patients received 4 biweekly doses of gemcitabine, vinorelbine, and liposomal doxorubicin. Patients without evidence of disease progression proceeded to HDT/ASCT; those with progressive disease were study failures. At a median follow-up of 51 months, EFS analyzed by intent to treat as well as for transplanted patients is 70% and 79%, respectively. Patients transplanted with negative FDG-PET, pre-HDT/ASCT after 1 or 2 SLT programs, had an EFS of > 80%, versus 28.6% for patients with a positive scan (P < .001). This prospective study provides evidence that the goal of SLT in patients with Hodgkin lymphoma should be a negative FDG-PET scan before HDT/ASCT.     

Brentuximab vedotin for the treatment of patients with relapsed or refractory Hodgkin lymphoma after autologous stem cell transplantation

Brentuximab vedotin (BV) is the first approved novel agent for salvage treatment of relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after autologous stem cell transplantation (ASCT). In this study, a literature-based analysis was undertaken to assess, via an indirect treatment comparison, the comparative efficacy of BV to salvage chemotherapy as treatment for R/R cHL patients following ASCT. This comparative effectiveness research was undertaken to support a reimbursement submission for BV to the Australian Pharmaceutical Benefits Advisory Committee. Retrospective analysis of individual patient data from four data sources demonstrated that the use of BV as first salvage treatment in cHL patients relapsing or progressing post-ASCT achieved improvements in both clinical response and overall survival. More specifically, BV was associated with an incremental improvement of 22% in overall response rate compared to salvage chemotherapy. Five-year overall survival and progression-free survival rates were 92·2% [95% confidence interval (CI): 85·5–99·3%] and 32·2% (95% CI: 19·1–54·6%) respectively for BV, compared to 30·5% (95% CI: 22·2–42·0%) and 3·2% (95% CI: 1·1–8·9%) respectively for salvage chemotherapy. The encouraging results from this conservative analysis have the potential to support informed clinical management and funding decisions for the first salvage of cHL patients demonstrating recurrence after ASCT.     

High-dose chemotherapy and autologous stem-cell transplantation in Korean patients with relapsed or refractory Hodgkin lymphoma

High-dose chemotherapy and autologous stem-cell transplantation (HDCT–ASCT) is a standard therapy for patients with relapsed or refractory Hodgkin lymphoma (HL). However, its efficacy in Asian patients has not been well investigated. A retrospective analysis of outcomes in 10 consecutive patients who underwent ASCT for HL in a single Korean centre from August 2005 to September 2010 was conducted. The median age was 34.5 years (range 17–64 years) and seven patients were male. Six patients were of stage III–IV at presentation. B symptoms were present in six patients. International Prognostic Score (IPS) was as follows: IPS = 1 (n = 5), IPS = 2 (n = 1), IPS = 4 (n = 2), and IPS = 5 (n = 2). The analysis included nine patients with relapsed HL and one primary refractory case. Four patients were in second complete response and the others were in partial response after salvage chemotherapy. With a median follow-up duration of 58.0 months, 3-year progression-free survival rate and overall survival rate from ASCT were 40 and 76 %, respectively. The results suggest that the efficacy of high-dose chemotherapy followed by ASCT in Korean patients with refractory or relapsed HL is comparable to that in Western patients.     

Autologous stem cell transplantation as consolidation therapy for patients with peripheral T cell lymphoma in first remission: long-term outcome and risk factors analysis

This report is a retrospective analysis of 65 patients with peripheral T cell lymphoma (PTCL), who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (autoHCT) as a consolidation of first response achieved with either induction or salvage chemotherapy. We intended to determine the prognostic factors that influenced outcome after autoHCT and to define the predictive value of the scoring systems most often applied for transplant outcomes. Nineteen patients in either complete or partial remission underwent autoHCT after induction chemotherapy. Forty-six patients received second-line chemotherapy as a consolidation of partial response after induction chemotherapy (n?=?34) or as a salvage therapy after primary induction failure (n?=?12), and thereafter proceeded to autoHCT. Finally, the 36 patients were in complete remission, and 29 in partial remission at autoHCT. The median follow-up of survivors was 53 months (range 7–157 months). The 5-year overall survival and progression-free survival for all patients were 61.5 % (95 % CI 47.0–74.2 %) and 59.4 % (95 % CI 46.1–71.5 %), respectively. In multivariate analysis, bone marrow involvement at diagnosis and less than partial remission after induction chemotherapy were factors independently predictive for overall survival and progression-free survival. The prognostic index for PTCL could reliably stratify the prognosis of PTCL in this analysis.     

Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group

OBJECTIVE: Retrospective data shows that peripheral T-cell lymphoma (PTCL) patients sensitive to conventional chemotherapy for aggressive lymphomas may respond better if this treatment is consolidated with frontline autologous stem cell transplantation (ASCT). Here, we present data from a prospective phase II trial of high-dose chemotherapy and ASCT as a frontline consolidation therapy for aggressive nodal PTCL. METHODS: This study involved 26 gallium-scan-positive patients with high-risk nodal PTCL [excluding anaplastic lymphoma kinase (ALK) positive]. Patients received three courses of MegaCHOP before they were evaluated, and those that were gallium-scan-negative at this stage then received another course of MegaCHOP and ASCT. Patients who remained gallium-scan-positive received two courses of an IFE regimen (ifosfamide 10 g/m(2), etoposide 150 mg/m(2)/12 h on days 1-3) and if they at least achieved PR, they then received the transplant. RESULTS: Complete response (CR) was achieved by 12 patients (46%) after three courses of MegaCHOP and 12 patients received IFE as a salvage therapy. After the ASCT (n = 19), 89% of patients achieved CR. In contrast, six patients (23%) did not receive the transplant because of the progression of the disease (n = 5) or lethal toxicity (n = 1). One patient in first-line CR refused ASCT. After a median follow-up of 35 months, the overall survival (OS) and progression-free survival (PFS) at 3 yr was 73% and 53%, respectively. Moreover, the OS, PFS and disease-free survival (DFS) were 84%, 56% and 63%, respectively 2 yr after transplant in patients who received ASCT consolidation (n = 19). CONCLUSIONS: Early salvage therapy for patients with high-risk aggressive nodal PTCL that do not achieve CR after three courses of chemotherapy and ASCT frontline consolidation for chemosensitive patients may improve treatment outcome.     

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P <.001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.     

Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine‐based high‐dose chemotherapy regimen

High‐dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third‐generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR‐HL accrued into a prospective registry‐based study. Application of FEAM resulted in a 2‐year progression‐free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64–0·81] with median PFS, overall survival and time to progression yet to be reached. The 2‐year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12–0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose (^18FFDG)‐uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had ^18FFDG‐positrin emission tomography‐positive lesions before HDT, the 2‐year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12–0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR‐HL patients typically pre‐exposed to lung‐damaging treatments.     

Autologous stem cell transplantation in adult patients with peripheral T-cell lymphoma: a nation-wide survey

Limited experience is available on the feasibility and efficacy of high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL). Therefore, a nation-wide survey was conducted in adult patients transplanted for PTCL in Finland during 1990-2001. After histopathology review, 37 patients were identified. The median age was 46 years (16-68) at the time of ASCT. Histology included PTCL not otherwise specified in 14 patients, anaplastic large cell lymphoma (ALCL) in 14 patients, and other in nine patients. Disease status at the time of ASCT was CR/PR1 in 18 patients; CR/PR2 in 14 patients, and other in five patients. HDT consisted of either BEAC (N=22) or BEAM (N=15), supported by blood stem cells in 34 patients (92%). Early transplant-related mortality was 11%. With a median follow-up of 24 months from HDT, 16 patients (43%) have relapsed or progressed. The estimated 5-year overall survival (OS) was 54%. Patients with ALCL had superior OS when compared with other subtypes (85 vs 35%, P=0.007). OS at 5 years was 63% in patients transplanted in CR/PR1 vs 45% in those transplanted in other disease status (P=NS). Prospective studies are needed to define the role of ASCT in this lymphoma type.     

Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma

Autologous transplantation (ASCT) is the standard of care for chemosensitive relapsed or primary refractory aggressive lymphoma, but little is known about its efficacy in the subset of patients with peripheral T-cell lymphoma (PTCL). We undertook a retrospective review of patients with PTCL who underwent ASCT for relapsed or refractory disease after responding to second-line therapy, excluding patients with indolent histologies and those with anaplastic lymphoma kinase (ALK) expressing anaplastic large cell lymphoma. The results of 24 patients with PTCL were compared with those of 86 consecutive patients with chemosensitive relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL). With a median follow-up time of 6 years for surviving patients with PTCL and DLBCL, the 5-year progression-free survival (PFS) rates for PTCL and DLBCL patients were 24% and 34% respectively (P = 0.14); the corresponding overall survival (OS) rates were 33% and 39% respectively. There were no significant differences between the two groups with respect to time to disease progression or survival after progression. The second-line age-adjusted international prognostic index was the only variable prognostic for PFS and OS in a multivariate analysis. The outcome of ASCT for patients with chemosensitive relapsed or primary refractory PTCL is similar to that for patients with DLBCL.     

Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL

A number of prognostic factors affect outcome in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory disease and the second-line age-adjusted international prognostic index. In de novo DLBCL, the cell of orgin, as determined by expression microarray analysis or immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the cell of origin, as well as other pathologic markers of outcome, on the repeat biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide, carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they prognostic in the salvage setting. Pretreatment clinical factors were well balanced between the cohorts. There was no significant difference in response to SLT, HDT, event-free or overall survival based on the cell of origin or any of the common pathologic markers examined. The cell of origin as determined by IHC does not predict outcome in transplantation-eligible patients with relapsed or primary refractory DLBCL.     

Combined ifosfamide, etoposide and oxalipatin chemotherapy, a low-toxicity regimen for first-relapsed or refractory Hodgkin lymphoma after ABVD/EBVP: a prospective monocentre study on 34 patients

Around 20% of Hodgkin lymphoma (HL) patients are refractory to first‐line therapy with ABVD (adriamycin–bleomycin–vinblastine–dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose‐reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide–etoposide–oxaliplatin) salvage regimen in terms of response rate, toxicity and stem‐cell mobilization. Thirty‐four patients with relapsed/refractory HL after anthracycline‐containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m² days 1–3), etoposide (150 mg/m² days 1–3) and oxaliplatin (130 mg/m² day 1). Patients <65 years old received high‐dose therapy followed by autologous stem‐cell transplantation (HDT–ASCT). Response was assessed by computed and positron‐emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose‐reductions. Twenty‐six patients underwent HDT–ASCT. With median follow‐up at 5 years, the 5‐year overall and event‐free survival rates were 74% and 63%, respectively. IVOx is a well‐tolerated outpatient regimen for relapsed HL, that does not hamper stem‐cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens.     

Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan

High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17–110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting.