Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma

Although follicular lymphoma (FL) is generally responsive to conventional-dose chemotherapy, improved survival in patients with this disease has been difficult to demonstrate. High-dose chemo/radiotherapy followed by autologous stem-cell transplantation (ASCT) can improve response rates, although its effects on survival remain controversial. Between 1990 and 2003, we transplanted 49 patients with low-grade FL at our institution. Twenty-two patients (45%) had undergone histologic transformation at the time of ASCT. In all, 44 patients (90%) had relapsed disease and five patients (10%) were resistant to chemotherapy at the time of transplantation. After ASCT, 30 patients (61%) were in complete remission (CR). The median overall survival (OS) has not been reached, while the median event-free survival (EFS) is 2.4 years. At a median follow-up of 5.5 years (longest 12.4 years), a plateau has been reached with 56% of patients remaining alive, and 35% event-free. ASCT was well tolerated except for two (4%) treatment-related deaths. In multivariable analysis, CR after ASCT and age less than 60 years are the best predictors of EFS and OS. ASCT is thus a safe therapeutic approach in FL, resulting in long-term EFS and OS for some patients, even with transformed disease.     

Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999

Primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathological entity with unclear prognostic factors and optimal treatment approach. To elucidate an optimal treatment and identify predictive factors, a retrospective analysis of 141 consecutive patients was undertaken. Patients received cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone (CHOP)-like therapy, the non-Hodgkin lymphoma (NHL)-15 regimen or upfront autologous stem cell transplantation (ASCT) on Institutional Review Board approved trials or according to the institutional guidelines. Evaluation included lactate dehydrogenase, International Prognostic Index (IPI) assessment, computed tomography scan and gallium imaging. With a median follow-up of 10.9 years, event-free survival (EFS) and overall survival (OS) was 50% and 66% respectively. EFS/OS for CHOP/CHOP-like, NHL-15 and upfront ASCT was 34/51%, 60/84% and 60/78% respectively. CHOP/CHOP-like regimens had inferior EFS and OS versus NHL-15 or upfront ASCT (P < 0.001). A total of 23% of patients received radiotherapy. Multivariate analysis revealed the following outcome predictors: for EFS, greater than or equal to two extranodal sites and initial therapy received (NHL-15 or upfront ASCT); for OS, only initial therapy with NHL-15. We conclude: (i) dose-dense chemotherapy with NHL-15 may be superior to CHOP for PMLBL; (ii) The impact of consolidative radiotherapy requires randomised controlled trials; (iii) The age-adjusted IPI did not predict survival in this analysis; (iv) high-dose chemotherapy/ASCT should be reserved for upfront anthracycline-based therapy failure or in clinical trials for high-risk patients.     

From bench to bedside: the past,present and future of therapy for systemic paediatric ALCL,ALK+

Anaplastic large cell lymphoma (ALCL) is a T cell Non-Hodgkin Lymphoma that mainly presents in paediatric and young adult patients. The majority of cases express a chimeric fusion protein resulting in hyperactivation of anaplastic lymphoma kinase (ALK) as the consequence of a chromosomal translocation. Rarer cases lack expression of ALK fusion proteins and are categorised as ALCL, ALK−. An adapted regimen of an historic chemotherapy backbone is still used to this day, yielding overall survival (OS) of over 90% but with event-free survival (EFS) at an unacceptable 70%, improving little over the past 30 years. It is clear that continued adaption of current therapies will probably not improve these statistics and, for progress to be made, integration of biology with the design and implementation of future clinical trials is required. Indeed, advances in our understanding of the biology of ALCL are outstripping our ability to clinically translate them; laboratory-based research has highlighted a plethora of potential therapeutic targets but, with high survival rates combined with a scarcity of funding and patients to implement paediatric trials of novel agents, progress is slow. However, advances must be made to reduce the side-effects of intensive chemotherapy regimens whilst maintaining, if not improving, OS and EFS.     

Primary refractory Hodgkin's lymphoma: outcome after high-dose chemotherapy and autologous SCT and impact of various prognostic factors on overall and event-free survival. A single institution result of 66 patients

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%, 92% had ESHAP as salvage. Post-ASCT evaluation showed response in 50 patients (76%); complete response (CR) 37 (56%), partial response 14 (21%), no response or stable disease 3 (5%) and progressive disease in 10 (15%). Another five patients achieved CR after radiation therapy and one after surgery, making total CR 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival (OS) 78 and 57 months, respectively. Event-free survival (EFS) and OS are 36 and 64%, respectively. In all, 47% patients are in CR. Twenty-two patients (33%) died due to disease. Multivariate analysis showed elevated lactate dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.     

Role of high-dose therapy and initial response in survival of poor-risk patients with aggressive non-Hodgkin's lymphoma: a retrospective series on 126 patients from a single center

It is now established that a subgroup of non-Hodgkin's lymphoma (NHL) patients probably benefit from high-dose therapy (HDT). We therefore retrospectively analyzed survival of 126 consecutive patients with large cell lymphoma (LCL) and high-intermediate (HI) or high-risk (H) age-adjusted international prognostic index (Aa-IPI). They received either standard chemotherapy (CT) (66 patients), or HDT (60 patients). Distribution of the Aa-IPI scores showed no statistical significant difference between the two treatment groups. Complete response (CR) rate was 51% for the whole series, with 41% and 62% for the standard CT group and HDT group, respectively. With a median follow-up of 63 months (range, 16 to 159), the 5-year overall survival (OS) and event-free survival (EFS) for all patients was 52% and 43%, respectively. There was a statistical significant difference in terms of survival towards the HDT group: OS at 76% vs 31%, EFS at 64% vs 24%. Patients who achieved CR with front-line therapy had a 5-year OS at 70%, while it was 34% for patients who were not in CR. These results are comparable to those reported in the literature, and strongly suggest that both initial CR achievement and HDT as front-line treatment are predictive factors for prolonged survival of patients with poor-risk LCL. Bone Marrow Transplantation (2000) 25, 35-40.     

PCR detection of residual Bcl-2/IgH-positive cells after high-dose therapy with autologous stem cell transplantation is a prognostic factor for event-free survival in patients with low-grade follicular non-Hodgkin's lymphoma

This study was designed to evaluate the results of high-dose therapy followed by purged autologous stem cell transplantation (ASCT) for patients with low-grade follicular non Hodgkin's lymphoma (LGFL), and the prognostic significance of PCR detection of residual Bcl-2/IgH-positive cells after ASCT. Between 1992 and 1998, 49 patients with LGFL received total body irradiation and high-dose cyclophosphamide followed by purged ASCT. PCR amplification of the Bcl-2/IgH rearrangement was performed at diagnosis, on stem cell collections before and after purging and on bone marrow and blood samples after ASCT. With a median follow-up of 76 months (37-103) 34 patients remain alive and event-free. A total of 20 patients had disease recurrence, three patients developed secondary myelodysplastic syndrome (MDS). In all, 11 patients died; 10 deaths were because of recurrent disease, one because of MDS. Kaplan-Meier estimates of event-free survival (EFS) and overall survival (OS) at 5 years were 65% (+/-7%) and 77% (+/-6%), respectively. Patients who achieved a sustained molecular complete response (CR) had a lower risk of disease recurrence and experienced significantly longer EFS (93% (+/-6%) vs 11% (+/-7%) P=0.0008) and OS (100 vs 55% (+/-12%) P=0.0057). In conclusion, myeloablative therapy followed by purged ASCT may induce long EFS in patients with LGFL. The achievement of sustained molecular CR after ASCT improves EFS and OS.     

High-dose therapy and autologous stem cell transplantation in patients with diffuse large B-cell lymphoma in first complete or partial remission

Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.     

Autologous stem cell transplantation for T and null cell CD30-positive anaplastic large cell lymphoma: analysis of 64 adult and paediatric cases reported to the European Group for Blood and Marrow Transplantation (EBMT)

Anaplastic large cell lymphoma (ALCL) is a heterogeneous family of lymphoid tumours, among which the T and null cell types were recently listed in the REAL classification as a distinct entity. Reports on autologous stem cell transplantation (ASCT) in this group are only occasional. Sixty-four patients with T and null cell ALCL from 25 European centres had been registered with the European Group for Blood and Marrow Transplantation (EBMT) at the onset of this study. The median age was 25 years (range 3.2-53.0). Thirty of the 64 patients (47%) were in complete remission (CR), 18 (28%) in partial remission (PR), and the remaining 16 (25%) had a more advanced or chemotherapy-refractory disease at transplant. Eighty-one percent of the patients were conditioned with chemotherapy alone and 75% received marrow stem cells. All the patients transplanted in first CR (15), except one, maintained the CR over time; six of 15 transplanted in CR subsequent to first, six of 18 transplanted in PR and 14 of 16 transplanted in refractory or relapsed disease progressed. Actuarial overall survival (OS) at 10 years is 70%. Multivariate analysis showed that good status at transplant, younger age, absence of B symptoms and absence of extranodal disease indicated a better prognosis. These data suggest that ASCT should be considered as a possible treatment for chemosensitive patients in CR or PR. However, definitive conclusions cannot be drawn from this study and a prospective randomised trial between ASCT and conventional chemotherapy may be indicated.     

Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin's lymphoma

To evaluate autologous stem cell transplant (ASCT) in older patients with intermediate grade non-Hodgkin's lymphoma (NHL), the Mayo Clinic Rochester BMT database was reviewed for all patients 60 years of age and older who received ASCT for NHL between September 1995 and February 2003. Factors evaluated included treatment-related mortality (TRM), event-free survival (EFS) and overall survival (OS). Ninety-three patients were identified, including twenty-four (26%) over the age of 70 years. Treatment-related mortality (5.4%) was not significantly different when compared to a younger cohort (2.2%). At a median follow-up of 14 months (0.6-87.6 months), the estimated median survival is 25 months (95% confidence interval (CI) 12-38) in the older group compared to 56 months (95% CI 37-75) (P=0.037) in the younger group. The estimated 4-year EFS was 38% for the older group compared to 42% in the younger cohort (P=0.1). By multivariate analysis, the only factor found to influence survival in the older group was age-adjusted International Prognostic Index at relapse, 0-1 better than 2-3 (P=0.03). Autologous stem-cell transplant can be safely performed in patients 60 years or older with chemotherapy sensitive relapsed or first partial remission NHL. The outcome may not be different from that of younger patients in terms of TRM and EFS.     

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.     

High-dose chemotherapy and autologous stem cell transplantation for Hodgkin's lymphoma in the kingdom of Saudi Arabia: King Faisal specialist hospital and research center experience

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients out of 113 (113 patients out of 153 had complete analysis) with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%; 92% had ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) as salvage. Post-ASCT evaluation showed response in 50 patients (76%), complete response (CR) in 37 (56%), partial response in 14 (21%), no response or stable disease in three (5%) and progressive disease in 10 (15%) patients. Six patients achieved CR after XRT (5) or surgery (1), making a total with CR of 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival 78 and 57 months, respectively. EFS and overall survival (OS) are 36 and 64%, respectively. In all 47% patients are in CR. Twenty-two (33%) patients died of the disease. Multivariate analysis showed elevated lactic dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.     

Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: a single-centre experience in 211 patients

High-dose therapy with autologous stem cell therapy (ASCT) has become the treatment of choice for eligible patients with myeloma. We analysed retrospectively the prognostic influence of pre-transplant characteristics and transplant modalities on response and survival in 211 myeloma patients who were transplanted in our centre between 1994 and 2004. All patients received peripheral blood stem cell support after conditioning with melphalan alone (183 patients), or melphalan and total blood irradiation (28 patients). We evaluated the influence of age, type of multiple myeloma, status prior and post ASCT, previous treatment regimens, time of ASCT from diagnosis, year of autograft, dose of re-infused CD34(+) cells, plasma cell infiltration and beta2-microglobulin at diagnosis on overall survival (OS) and event-free survival (EFS) to define patients with better prognosis. Median OS and EFS from transplantation were 50.9 and 20.1 months, respectively. Median OS from diagnosis was 68.8 months. Transplant-related mortality was 1.4%. Lower beta2-microglobulin levels, achievement of complete remission (CR) post transplant and lower plasma cell infiltration at diagnosis and transplant correlated with longer EFS and OS, whereas CR at transplant and low international prognostic index at transplant correlated with better EFS. Higher CD34(+) cell dose correlated with improved OS. We conclude that ASCT is safe and effective and the outcome is independent of age, time from diagnosis, previous treatment and conditioning regimen.     

Anaplastic large cell lymphoma,ALK-negative

Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-negative (ALCL-ALK?) is a provisional entity in the WHO 2008 Classification that represents 2–3% of NHL and 12% of T-cell NHL. No particular risk factor has been clearly identified for ALCL, but a recent study showed an odds ratio of 18 for ALCL associated with breast implants. Usually, the architecture of involved organs is eroded by solid, cohesive sheets of neoplastic cells, with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and classical Hodgkin lymphoma being the main differential diagnoses. In this regard, staining for PAX5 and CD30 is useful. Translocations involving ALK are absent, TCR genes are clonally rearranged. CGH and GEP studies suggest a tendency of ALCL-ALK? to differ both from PTCL-NOS and from ALCL-ALK+.Patients with ALCL-ALK? are usually adults with a median age of 54–61 years, and a male-to-female ratio of 0.9. At presentation, ALCL-ALK? is often in III–IV stage, with B symptoms, high International Prognostic Index score, high lactate dehydrogenase serum levels, and an aggressive course. ALCL-ALK? presents with lymph node involvement in ～50% of cases; extranodal spread (20%) is less common. Staging work-up for ALCL-ALK? is similar to that routinely used for nodal NHL. Overall prognosis is poor, with a 5-year OS of 30–49%, which is significantly worse when compared to OS reported in patients with ALCL-ALK+ (5-year: 70–86%). Patients with systemic ALCL exhibit a significantly better survival compared with patients with PTCL-NOS, with a 5-year OS of 51% and 32%, respectively. Age, PIT scoring system, β2-microglobulin, and bone marrow infiltration are the main prognostic factors. The expression of proteins involved in the regulation of apoptosis (caspase 3, Bcl-2, PI9) and of CD56 is related to clinical outcome.ALCL-ALK? is generally responsive to doxorubicin-containing chemotherapy, but relapses are frequent. CHOP is the most commonly used regimen to treat systemic ALCL with complete remission rates of 56%, and a 10-year DFS of 28%. Encouraging results have been reported with more intensive chemotherapy regimens. The addition of etoposide improved outcome. Alemtuxumab-CHOP regimen was associated with excellent remission rate but increased toxicity. The role of high-dose chemotherapy supported by ASCT has not been investigated in a trial of exclusively ALCL patients. When used in first remission, it was associated with a 5-year PFS of 64%. High-dose chemotherapy with ASCT is the standard therapeutic option for patients with relapsed or refractory disease. The role of allogeneic transplantation in patients with relapsed/refractory ALCL remains to be defined but there are data to support the contention that a graft-versus-lymphoma effect does exist. Myeloablative conditioning has been associated with 5-year PFS and OS of 40% and 41%, respectively, but a 5-year TRM of 33% was reported. Allo-SCT can be an option for relapsed/refractory ALCL in younger patients, preferably in the setting of a clinical trial.Pralatrexate, anti-CD30 monoclonal antibodies, brentuximab vedotin (SGN-35) in particular, ¹³¹I-anti-CD45 radioantibody, yttrium-anti-CD25 radioimmunoconjugates, histone deacetylase inhibitors, bortezomib, gemcitabine, vorinostat, lenalidomide, and their combinations represent the most appealing chemotherapy and/or targeted agents to be investigated in future trials.     

Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Osea phase II trial

Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55%[95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P = 0.00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.     

Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma

A single center, prospective clinical trial was conducted evaluating 2 cycles of induction high-dose chemotherapy for adults younger than 65 years of age with aggressive non-Hodgkin lymphoma (NHL) and 2 to 3 Age-Adjusted International Prognostic Index risk factors. Patients received one cycle of standard dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by one cycle of dose-intensive cyclophosphamide 5.25 g/m(2), etoposide 1.05 g/m(2), cisplatin 105 mg/m(2) (DICEP), then underwent autologous blood stem cell collection, followed by one cycle of high-dose carmustine (BCNU) 300 mg/m(2), etoposide 800 mg/m(2), Ara-C 1600 mg/m(2), melphalan 140 mg/m(2) (BEAM), and autologous stem cell transplantation (ASCT) and radiotherapy to prior bulk. From June 1998 to August 2004, 55 patients aged 20 to 63 years (median 44 years) were accrued, 51 (92%) of whom had diffuse large B-cell NHL. Poor prognostic factors included stage 4 (n = 46), elevated lactate dehydrogenase (LDH; n = 47), Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (n = 43), bulky mass more than 10 cm (n = 34), and marrow involvement (n = 16). Only one patient experienced nonrelapse mortality. With a median follow-up of 49 months, 4-year event-free survival (EFS) and overall survival (OS) rates for all 55 patients are 72% (95% confidence interval [CI] = 60%-84%) and 79% (95% CI = 69%-90%), respectively. In conclusion, CHOP-DICEP-BEAM is feasible and gave encouraging EFS and OS for patients with poor-prognosis aggressive NHL.     

Overweight as an adverse prognostic factor for non-Hodgkin's lymphoma patients receiving high-dose chemotherapy and autograft

Despite detailed evaluation of disease-associated prognostic factors, little is known about the impact of overweight in autograft programs for non-Hodgkin's lymphoma (NHL) patients. In order to address this issue, 121 NHL patients were retrospectively evaluated. They had been upfront (92 patients) or in relapse (29 patients) and received high-dose sequential (HDS) chemotherapy including peripheral blood progenitor cell (PBPC) autograft. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters; overweight was defined as BMI > or = 28. Univariate and multivariate analyses were used to determine the prognostic implication of overweight and other known prognostic indicators on overall (OS) and event-free (EFS) survival for the entire group and overweight and non-overweight (reference) subgroups. With a median follow-up of 3 years, the estimated 5-year OS and EFS for the entire group were 58% and 49%, respectively. Twenty-eight patients (23%) had BMI > or = 28. Their median OS and EFS were 2.2 and 1.4 years, respectively, whereas median OS and EFS for the reference group have not been reached, with a 5-year projection of 65 and 55%, respectively (P < 0.002). On multivariate analysis, the risk of death among overweight patients was 2.9 (CI, 1.3-6.2) times that of the reference group; using EFS as the end point, a similar association between overweight and survival was observed. In conclusion, in high-risk NHL patients undergoing intensive chemotherapy and PBPC autografting overweight is associated with a poorer outcome.     

High-dose therapy and autologous stem cell transplant does not result in long-term disease-free survival in patients with recurrent chemotherapy-sensitive ALK-negative anaplastic large-cell lymphoma

Primary systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) has a poor prognosis. This study sought to determine if high-dose therapy and ASCT results in long-term disease-free survival (DFS) in patients with recurrent, chemotherapy-sensitive ALK-negative ALCL. All patients with non-Hodgkin's lymphoma (NHL) who underwent ASCT at Wake Forest University and Upstate Medical University from 1 January 1990 to 12 December 2002 were reviewed to determine if they had T-, B- or null-cell NHL that was CD30+/CD15-/ALK negative. In all, 16 patients were thus identified as having ALK-negative ALCL. All 16 patients underwent ASCT at the time of first relapse and form the basis of this report. Median age of the 16 patients was 51 years. There were 11 males and five females. International prognostic index scores in 12 patients at the time of relapse were: low 3, LI 6 and HI 3. Of 15 patients, 13 relapsed after ASCT; one patient was lost to follow-up. Median progression-free survival for the 15 patients was 12 weeks (3-212+ weeks). Of 15 patients, 10 have died; nine of recurrent disease. Median overall survival for the 15 evaluable patients was 72 weeks. In our experience, high-dose therapy and ASCT does not produce long-term DFS in patients with recurrent chemotherapy-sensitive ALK-negative ALCL.     

Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome

Sj?gren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.     

Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease

Prospective randomized studies have determined that high dose therapy and autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed Hodgkin's disease (HD); however, the role of this approach in patients with primary refractory disease has been controversial. This report is an integrated analysis of 75 consecutive patients with biopsy-confirmed primary refractory HD, who were treated with high dose chemoradiotherapy (HDT) and ASCT at the Memorial Sloan Kettering Cancer Center. The patients underwent conventional dose cytoreductive chemotherapy followed by HDT and ASCT. At a median follow-up of 10 years for surviving patients, the event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) rates were 45%, 49% and 48% respectively. Only chemosensitivity to standard-dose second-line chemotherapy (SDSC) predicted for a better survival, thus responding patients had an EFS, PFS and OS of 60%, 62% and 66%, respectively, versus 19%, 23% and 17% for patients who had a poor response to SDSC (P < 0.001). While patients with chemosensitive disease have an excellent outcome with HDT and ASCT, novel approaches are needed to cure HD patients who fail front-line and second-line chemotherapy.     

FDG-PET/CT predicts outcome in patients with aggressive non-Hodgkin’s lymphoma and Hodgkin’s disease

Early therapy response assessment with metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma and, thus, can guide first-line therapy. Forty-eight patients with aggressive lymphoma [24 Hodgkin’s disease (HD); 24 non-Hodgkin’s lymphoma (NHL)] underwent fluoro-deoxyglucose positron emission tomography (FDG-PET) before chemotherapy (PET1) and at mid-treatment (PET2). Therapeutic response was evaluated using conventional methods at mid-treatment. PET2 results were related to event-free survival (EFS) and overall survival (OS) using Kaplan–Meier analyses. PET1 was positive in all patients. PET2 was negative in 38 patients (18 NHL-20 HD) and positive in 10 (6 NHL-4 HD). Of the PET-negative patients, 61 and 65% achieved complete remission, and only 50 and 25% of PET-positive patients, respectively, for NHL and HD, achieved complete remission. Significant associations were found between PET2 and EFS (p=0.0006) and OS (p=0.04) for NHL, and EFS (p<0.0001) for HD (but not for OS, because no HD patient died). FDG-PET at mid-treatment can predict the outcome of patients with aggressive lymphoma and should be a useful tool to modify an ineffective therapy.