Utility of subsequent conventional dose chemotherapy in relapsed/refractory transplant-eligible patients with diffuse large B-cell lymphoma failing platinum-based salvage chemotherapy

Up to 60% of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) do not respond to second-line (salvage) chemotherapy and hence are not offered autologous hematopoietic cell transplantation (AHCT). The utility of further salvage chemotherapy in an attempt to proceed with AHCT remains undefined. The authors reviewed 201 patients with DLBCL relapsed/refractory to anthracycline-based chemotherapy who received first-line salvage chemotherapy containing cis-platinum. Of the 120 non-responders to first-line platinum-based salvage chemotherapy, 73 received second-line salvage chemotherapy. The response rate to second-line salvage chemotherapy was 14%. Factors predicting lack of response were progression on primary therapy (p = 0.007), abnormal lactate dehydrogenase findings (p = 0.0027) and tumor bulk (p = 0.013) at second progression. Eight patients who responded received AHCT and appeared to have comparable survival to those transplanted after one salvage regimen. The authors conclude that the utility of second-line salvage chemotherapy is low, and that it is best reserved for patients demonstrating initial anthracycline sensitivity and low tumor burden.     

Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre‐transplant FDG‐PET scan following salvage chemotherapy

The utility of ^[18F]fluoro‐2‐deoxy‐ d ‐glucose positron‐emission tomography (FDG‐PET) for predicting outcome after autologous stem cell transplantation (ASCT) for diffuse large B cell lymphoma (DLBCL) is uncertain – existing studies include a range of histological subtypes or have a limited duration of follow‐up. Thirty‐nine patients with primary‐refractory or relapsed DLBCL with pre‐ASCT PET scans were analysed. The median follow‐up was 3 years. The 3‐year progression‐free survival (PFS) for patients with positive PET scans pre‐ASCT was 35% vs. 81% for those who had negative PET scans (P = 0·003). The overall survival (OS) in these groups was 39% and 81% (P = 0·01), respectively. In a multivariate analysis, PET result, number of salvage cycles and the presence of relapsed or refractory disease were shown to predict a longer PFS; PET negativity (P = 0·04) was predictive of a longer OS. PET is useful for defining those with an excellent prognosis post‐ASCT. Although those with positive scans can still be salvaged with current treatments, PET may useful for selecting patients eligible for novel consolidation strategies after salvage therapies.     

Mini-BEAM is effective as a bridge to transplantation in patients with refractory or relapsed Hodgkin lymphoma who have failed to respond to previous lines of salvage chemotherapy but not in patients with salvage-refractory DLBCL

Patients with relapsed or refractory lymphoma can be cured with stem cell transplantation if they are shown to have disease that is responsive to salvage chemotherapy. Patients who fail to respond to first-line salvage chemotherapy tend to do very poorly. Here we report on 39 such patients who received mini-BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy as second or subsequent-line salvage chemotherapy. Fifty-six percent of these patients had primary refractory disease and a further 28% had responses to first-line therapy that lasted <12 months. Seventy-two percent had progressive disease following the salvage chemotherapy administered immediately prior to mini-BEAM and the remaining 28% had stable disease. Overall there was a 38% response to mini-BEAM (complete response = 28%, partial response = 10%). Patients with Hodgkin lymphoma (HL) had a higher response rate compared to those with diffuse large B cell lymphoma (DLBCL) (63% vs. 20%). Seventy-four percent of HL patients were able to proceed to transplantation compared with 30% of patients with DLBCL. Mini-BEAM is a very effective bridge to transplantation in very poor risk patients with HL who have failed to respond to first-line salvage chemotherapy. Its efficacy in non-Hodgkin lymphoma is more modest.     

Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin's lymphoma resistant to platinum-containing first-line salvage chemotherapy

Background

The management of patients with relapsed or refractory Hodgkin’s lymphoma who achieve less than a partial response to first-line salvage chemotherapy is unclear. The objective of this study was to evaluate response and outcomes to second-line salvage and autologous stem cell transplantation in patients not achieving a complete or partial response to platinum-containing first-line salvage chemotherapy.

Design and Methods

Consecutively referred transplant-eligible patients with relapsed/refractory Hodgkin’s lymphoma after primary chemotherapy received gemcitabine, dexamethasone, and cisplatin as first salvage chemotherapy. Those achieving a complete or partial response, and those with a negative gallium scan and stable disease with bulk <5 cm proceeded to high-dose chemotherapy and autologous stem cell transplantation. Patients with progressive disease or stable disease with a positive gallium scan or bulk ≥5 cm were given second salvage chemotherapy with mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Patients who responded (according to the same definition) proceeded to autologous stem cell transplantation.

Results

One hundred and thirty-one patients with relapsed/refractory Hodgkin’s lymphoma received first-line salvage gemcitabine, dexamethasone, and cisplatin; of these patients 99 had at least a partial response (overall response rate 76%). One hundred and twelve (85.5%) patients proceeded to autologous stem cell transplantation, while the remaining 19 (14.5%) patients received mini-BEAM. Among these 19 patients, six had at least a partial response (overall response rate 32%), and nine proceeded to autologous stem cell transplantation. The remaining ten patients received palliative care. Seven of the nine patients transplanted after mini-BEAM had a subsequent relapse. Patients receiving second salvage mini-BEAM had poor outcomes, with a 5-year progression-free survival rate of 11% and a 5-year overall survival rate of 20%.

Conclusions

Patients who require a second salvage regimen to achieve disease control prior to autologous stem cell transplantation have a relatively poor outcome and should be considered for alternative treatment strategies.     

F‐18 FDG‐PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem‐cell transplantation for relapsed and refractory Hodgkin lymphoma

Total lymphoid irradiation (TLI) followed by high‐dose chemotherapy and autologous haematopoietic stem cell transplant (aHSCT) is an effective strategy for patients with relapsed/refractory classical Hodgkin lymphoma (HL). We report outcomes for patients with relapsed/refractory HL who received TLI followed by high‐dose chemotherapy and aHSCT. Pre‐transplant fludeoxyglucose positron emission tomography (FDG‐PET) studies were scored on the 5‐point Deauville scale. Of 51 patients treated with TLI and aHSCT, 59% had primary refractory disease and 63% had active disease at aHSCT. The 10‐year progression‐free survival (PFS) and overall survival (OS) for all patients was 56% and 54%, respectively. Patients with complete response (CR) by PET prior to aHSCT had a 5‐year PFS and OS of 85% and 100% compared to 52% and 48% for those without CR (P = 0·09 and P = 0·007, respectively). TLI and aHSCT yields excellent disease control and long‐term survival rates for patients with relapsed/refractory HL, including those with high‐risk disease features. Achievement of CR with salvage therapy is a powerful predictor of outcome.     

Combination of PD-1 inhibitor with GVD (gemcitabine,vinorelbine, liposomal doxorubicin) versus GVD regimen as second-line therapy for relapsed/refractory classical Hodgkin lymphoma

Patients with classical Hodgkin lymphoma (cHL) who do not achieve complete remission (CR) after second-line chemotherapy have poor clinical outcomes. Besides, conventional salvage chemotherapy regimens have an unsatisfactory CR rate. The present retrospective study reports the efficacy and toxicity of the GVD (gemcitabine, vinorelbine, liposomal doxorubicin) regimen with or without programmed cell death 1 (PD-1) inhibitor for patients with cHL who failed first-line treatment. A total of 103 patients with cHL (GVD+PD-1 group, n = 27; GVD group, n = 76) with response assessment based on positron emission tomography were included. The GVD+PD-1 group tended to have a higher CR rate than GVD group (85·2% vs. 65·8%, P = 0·057) and had a better event-free survival (EFS) (P = 0·034). Subgroup analysis showed that patients with low-risk second-line International Prognostic Score might benefit from the addition of PD-1 inhibitor (GVD+PD-1 vs. GVD, 100·0% vs. 64·7%, P = 0·028) and had better EFS than GVD alone (P = 0·016). Further analysis demonstrated that PD-1 consolidation therapy might provide an EFS benefit (P = 0·007). The toxicity of the GVD+PD-1 regimen was comparable to the GVD regimen, except for higher rates of hypothyroidism and autoimmune pneumonitis, which were manageable. In conclusion, combining a PD-1 inhibitor with a GVD regimen could be a potentially effective second-line therapy for patients with cHL.     

Crucial microscopic features leading to diagnosis of cobalamin C deficiency in a new‐born

In the positron emission tomography (PET) era, traditional prognostic factors may not apply for patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT). Moreover, little is known about prognostic factors in patients transplanted for transformed indolent lymphoma (TIL). We conducted a retrospective study of 143 patients with R/R DLBCL and TIL who were transplanted in the last decade and had a post‐salvage PET scan. We examined prognostic factors in both groups, and constructed a prognostic score for DLBCL patients. For patients with DLBCL, post‐salvage PET response was an important prognostic factor. Advanced age and symptomatic relapse were also significantly associated with outcome. A simple score could stratify patients into three risk groups with 4‐year post‐ASCT overall survival of 84%, 59%, and 10%, and 4‐year progression‐free survival of 67%, 41% and 0% (P < 0·0001 for both). However, none of those factors (including PET response to salvage) appeared relevant for patients with TIL, despite their comparable overall outcome. Our prognostic score for DLBCL patients undergoing ASCT may be useful for prognostication, for stratification in clinical trials, and to motivate the design of new strategies for patients in the high‐risk group, who may not derive benefit from standard ASCT.     

GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma

Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m² day (D)1, D8 and D15; methylprednisolone 1,000 mg D1–5; and cisplatin 100 mg/m² D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1–6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30–62 %) and 5-year overall survival was 59 % (95 % CI, 43–74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.     

Outcomes of patients with relapsed/refractory diffuse large B‐cell lymphoma with progression of lymphoma after autologous stem cell transplantation in the rituximab era

Salvage chemotherapy followed by autologous stem cell transplant (ASCT) remains the current standard of care for patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) with chemosensitive disease. The addition of rituximab results in improved overall survival (OS) after first‐line treatment, but cure rates of salvage therapy with ASCT are inferior when compared to historical controls. Historically, patients with DLBCL with disease progression following ASCT have had an extremely poor prognosis with a median OS of 3 months. However, there are little data regarding outcomes in the rituximab era. We performed a retrospective study of 56 patients with relapsed or refractory DLBCL with prior exposure to rituximab who had disease progression following ASCT. The median OS from progression following ASCT for the cohort was 9.9 months (95% CI: 5.3–13.1 months). Patients who progressed less than 1 year from ASCT had a significantly shorter OS than those who progressed at 1 year or greater from ASCT (8.2 vs. 26.7 months, P = 0.01). Patients with at least stable disease following ASCT had a longer OS than those who progressed immediately after ASCT (12.3 vs. 5.3 months, P = 0.01). Other factors associated with OS were International Prognostic Index (IPI) (P = 0.01) and LDH level (P = 0.0003) at the time of progression following ASCT. In the rituximab era, the prognosis for patients with disease progression following ASCT remains poor, but is improved when compared with historical controls. Ultimately, more work needs to be done to develop novel therapeutic strategies tailored to individual patients in this heterogeneous population. Am. J. Hematol. 88:890–894, 2013. © 2013 Wiley Periodicals, Inc.     

A phase II,single‐arm,multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B‐cell lymphoma

In this phase II, multicentre, single‐arm study, 52 patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) received the anti‐CD19 antibody–drug conjugate coltuximab ravtansine (55 mg/m²) and rituximab (375 mg/m²) weekly for 4 weeks, then every 2 weeks for 8 weeks. The primary endpoint was objective response rate (ORR) by International Working Group Criteria. The primary objective was to reject the null hypothesis of an ORR of ≤40%. Among 45 evaluable patients, the ORR was 31·1% (80% confidence interval [CI]: 22·0–41·6%) and the primary objective was not met. The ORR appeared higher in patients with relapsed disease (58·3% [80% CI: 36·2–78·1%]) versus those refractory to their last (42·9% [80% CI: 17·0–72·1%]) or first‐line therapy (15·4% [80% CI: 6·9–28·4%]). Median progression‐free survival, overall survival and duration of response were 3·9 [80% CI: 3·22–3·98], 9·0 [80% CI: 6·47–13·67] and 8·6 (range: 0–18) months, respectively. The pharmacokinetics of both drugs were unaffected by co‐administration. Common adverse events included gastrointestinal disorders (52%) and asthenia (25%). No patients discontinued due to adverse events. In conclusion, coltuximab ravtansine with rituximab was well tolerated and yielded clinical responses in a subset of patients with relapsed/refractory DLBCL.     

Outcomes of primary refractory diffuse large B‐cell lymphoma (DLBCL) treated with salvage chemotherapy and intention to transplant in the rituximab era

Rituximab‐containing salvage chemotherapy followed by high‐dose therapy and autologous stem cell transplant (ASCT ) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B‐cell lymphoma (DLBCL ). However, its role in those patients achieving less than a complete response to first‐line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant‐eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high‐dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3‐year overall and progression‐free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long‐term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and <20% of patients with stable or progression of disease following initial therapy. These results suggest that salvage chemotherapy with the intent of subsequent high‐dose therapy and ASCT remains a feasible strategy in certain patients with primary refractory DLBCL , particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population.     

Gemcitabine,cisplatin and methylprednisolone (GEM-P) with or without Rituximab in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL)

This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/V disease. The overall response rate (ORR) was 59% (95% CI 42.1–74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1–4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45–84%) compared to 47% (95% CI 21–73%) in GEM-P alone. one-year progression-free survival was 51% (95% CI 28–69%) in GEM-PR group compared to 27% (95% CI 8–49%) in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients with relapsed or refractory DLBCL and the addition of Rituximab appears to further improve outcomes.     

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.     

Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma – results of the UK HD3 relapse treatment strategy

The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005 , 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4–6 cycles of EPIC [etoposide, prednisolone, ifosfa3mide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5‐year overall survival [OS] and progression‐free survival from relapse was 75·8% [64·8–83·9] and 59·9% [48·3–69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19–1·18] for those with a time from end of treatment to relapse of 3–12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04–0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse . Survival outcome in children with primary refractory HL is poor.     

Results of a multicentre UK‐wide retrospective study evaluating the efficacy of pixantrone in relapsed,refractory diffuse large B cell lymphoma

Relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) in those unfit or ineligible for autologous stem cell transplantation is associated with a poor outcome and new treatment approaches are needed. Pixantrone is a novel aza‐anthracenedione which is structurally similar to anthracyclines and is licenced in R/R DLBCL and National Institute for Health and Care Excellence (NICE)‐approved following the PIX301 trial. No data exist post‐NICE approval. We performed a UK‐wide retrospective multi‐centre study of 92 R/R DLBCL who received pixantrone. Eighty‐five per cent had refractory disease and 72% had an international prognostic index (IPI) 3–5 at commencement of pixantrone. The median progression‐free survival (PFS) was 2·0 months (95% confidence interval (CI) 1·5–2·4) and the median overall survival was 3·4 months (95% CI 2·7–4·5). The overall response rate was 24% (complete response 10%; partial response 14%). We demonstrate that pixantrone has limited activity in a cohort of high risk, predominantly refractory DLBCL. Multivariate Cox regression revealed that patients who relapsed >12 months after first line treatment, those with fewer prior lines of therapy and relapsed (non‐refractory) DLBCL had improved PFS. The major population of unmet need are those with refractory DLBCL who are poorly represented within trials and in whom pixantrone appears less efficacious compared to relapsed DLBCL.     

Rituximab retherapy in patients with relapsed aggressive B cell and mantle cell lymphoma

Neither effective salvage regimens nor the outcome and response to retherapy with rituximab containing chemotherapy have been defined for rituximab pre-treated patients with relapsing aggressive lymphoma. We report here a single-centre retrospective outcome analysis of second-line immunochemotherapy with rituximab. In 28 patients with relapsed or refractory diffuse large B cell lymphomas, first-line immunochemotherapy had induced objective responses in 18 patients. Nine of 28 patients responded to rituximab containing salvage therapy, leading to a median overall survival of 243 days after start of second immunochemotherapy. Long-term disease free survivors (1,260 and 949 days) were restricted to the group of twelve patients that had received allogeneic stem cell transplantation as consolidation therapy. In 21 patients with relapsed mantle cell lymphomas (MCL), 19 patients had reached remissions with first-line therapy. Of those, 16 patients experienced responses to salvage therapy with a median overall survival of 226 days. Noteworthy, none of patients with initial non-responding disease reached a remission with second immunochemotherapy. Seven patients with MCL stayed free from progression after high-dose therapy with autologous or allogeneic stem cell transplantation in two and five cases, respectively. In summary, responses to repeated immunotherapy with rituximab were observed in approximately one third and two thirds of initially responding patients with aggressive B cell lymphoma and mantle cell lymphoma, respectively, but not in primarily refractory disease. Lasting remissions were achieved only by high-dose chemotherapy with stem cell transplantation.     

Prognostic utility of pre-transplantation [18F] fluorodeoxyglucose positron emission tomography/computed tomography in patients with diffuse large B-cell lymphoma who underwent rituximab,dexamethasone, high-dose cytarabine,carboplatin salvage chemotherapy

We analysed the outcomes of 62 patients with refractory/relapsed diffuse large B-cell lymphoma (rrDLBCL) who had pre-transplantation fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after R-DHAC (rituximab, dexamethasone, high-dose cytarabine, carboplatin) salvage chemotherapy, and were evaluated using Deauville criteria and total lesion glycolysis (TLG). A positive pre-transplantation PET/CT with Deauville score of 5 was associated with shorter progression-free survival (PFS) (P = 0·01), while a Deauville score of 4 was not predictive of outcome. Only pre-transplant TLG was significantly associated with both PFS (P = 0·005) and overall survival (P = 0·03). TLG deserves to be further investigated in prospective studies.     

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.     

Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma

We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m²) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.     

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.