Biweekly THP‐COP therapy for newly diagnosed peripheral T‐cell lymphoma patients

Pirarubicin tetrahydropyranyl adriamycin (THP‐ADR) is an analogue of doxorubicin. This agent exhibits activity against some doxorubicin‐resistant cell lines. We performed a phase II study of biweekly THP‐COP [50 mg/m² pirarubicin, 750 mg/m² cyclophosphamide, 1.4 mg/m² vincristine (2.0 mg maximum) on day 1, and 100 mg/body predonisolone on days 1–5] in patients with peripheral T‐cell lymphoma (PTCL). Seventeen patients with newly diagnosed PTCL were enrolled. Histological diagnoses were of PTCL, not otherwise specified (n = 5), or angioimmunoblastic T‐cell lymphoma (n = 12). All diagnostic specimens including those of the historical control group were centrally reviewed by hematological pathologists. All patients received six cycles of biweekly THP‐COP. The patient group included 13 male and 4 female patients, with a median age of 62 years. The median follow‐up time in surviving patients was 30 months. Overall response rate was 94% with 15 cases of complete remission (88%). The 3‐year progression‐free survival and overall survival rates were 57% and 75%, respectively. The most frequent adverse events associated with biweekly THP‐COP were leukocytopenia (100%), neutropenia (100%), and lymphopenia (100%), followed by alopecia (92%) and anaemia (88%). All of these occurred only transiently, and the patients subsequently recovered. Biweekly THP‐COP is a safe and promising therapy for patients with newly diagnosed PTCL. This study is registered in a public database (UMIN000010485). Copyright © 2014 John Wiley & Sons, Ltd.     

Evaluation of clinical trial eligibility and prognostic indices in a population‐based cohort of systemic peripheral T‐cell lymphomas from the Danish Lymphoma Registry

Clinical trials (CTs) are needed to improve the outcome for peripheral T‐cell lymphomas (PTCL), and accrual into CTs is one of the main recommendations in international treatment guidelines. The use of risk‐adapted strategies has been suggested as a way to optimize treatment outcome in PTCL. The aim of the present study was to evaluate CT eligibility and selected prognostic indices in a population‐based PTCL cohort of 481 PTCL patients identified from the Danish Lymphoma Registry in the period 2000–2010. According to five predefined parameters (age, performance status, P‐creatinine, P‐ALAT and measurable tumour lesion), patients were subdivided into four groups: ‘younger fit’, ‘elderly fit’, ‘frail’ and ‘not CT eligible’. International prognostic index (IPI), prognostic index for T‐cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein expression were tested at subtype‐specific level. Overall, 41% of the patients were considered eligible for interventional CTs implicating curatively intended multiagent chemotherapy, including, if considered appropriate, consolidating stem cell transplantation (SCT), as part of the upfront management strategy. Moreover, 28% was elderly fit and eligible for interventional CT, including those with SCT as part of the trial design. Approximately 7% were defined as ‘too frail’ for aggressive treatment schedules, whereas 24% were deemed not to be eligible for any CT. Both overall and progression‐free survivals were effectively predicted by IPI and PIT (p < 0.001). ALK‐positive anaplastic large cell lymphoma patients were significantly younger (median age 40 vs. 62, p < 0.001) and had a better outcome than their ALK‐negative counterparts (p < 0.001). However, ALK expression lost its prognostic significance when adjusting for age. In a population‐based cohort of adult Caucasian PTCL patients, approximately half were eligible for multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are useful prognostic indices in all ‘primary nodal’ PTCL entities. The prognostic value of ALK protein expression in anaplastic large cell lymphoma is significantly downsized when adjusting for age. Copyright © 2014 John Wiley & Sons, Ltd.     

Clinico-pathologic features and outcome of Japanese patients with peripheral T-cell lymphomas

We studied the clinico-pathologic features and treatment outcome of patients with peripheral T-cell lymphoma (PTCL). This study included 215 patients with T/natural killer (NK)-cell lymphoma, including 59 with PTCL-unspecified (PTCL-U), 42 with angioimmunoblastic T-cell lymphoma (AILT) and 20 with anaplastic large-cell lymphoma (ALCL). Most of the analyses were performed on patients with AILD, ALCL and PTCL-U. The patients with AILT and PTCL-U tended to be older than those with ALCL. Stage III/IV disease was seen in 90.5% of the AILT cases, 55% of the ALCL cases and 67.8% of the PTCL-U cases. In addition, 61.9% of the AILT cases had an international prognostic index (IPI) of H-I or H risk. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 72.2 and 76.1% among the ALCL cases, 40.7 and 42.2% among the PTCL-U cases and 31.2 and 49.3% among the AILT cases, respectively. Among the patients with PTCL-U, the 5-year PFS and OS rates in group low (L), low-intermediate (L-I), high-intermediate (H-I) or high (H) risk group of IPI were: 47.6 and 56.1%, 55.6 and 53.8%, 42.4 and 40.1% and 9.1 and 9.1%, respectively. The 5-year PFS and OS rates in group 1, 2, 3 or 4 by prognostic index of PTCL-U (PIT) were: 88.9 and 85.7%, 57.1 and 54.9%, 33.5 and 28.8% or 13.3 and 13.3%, respectively. The 5-year PFS and OS rates among patients who received CHOP therapy, CyclOBEAP [cyclophosphamide (CPA), vincristine (VCR), bleomycine, etoposide, doxorubicin (DXR), prednisone (PDN)] therapy or autologous stem cell transplantation were: 22 and 25.7%, 59 and 61.7% or 33.3 and 60%, respectively. Multivariate analysis revealed that the PIT score was associated with OS and PFS. These results indicate that the presence of bone marrow (BM) involvement is an independent prognostic factor which may predict both OS and PFS. PTCL-U is a heterogeneous disease with regard to histological type and pathological state. Because PTCL-U is generally not responsive to CHOP therapy, new treatment strategies need to be developed.     

Serum albumin level at diagnosis of diffuse large B‐cell lymphoma: an important simple prognostic factor

This study compared the value of several simple laboratory parameters with known prognostic models for predicting survival in patients with diffuse large B‐cell lymphoma (DLBCL). The data of 157 adult patients with DLBCL diagnosed at Rabin Medical Center in 2004–2008 and treated with R‐CHOP immunochemotherapy were retrospectively reviewed. Main clinical features of the cohort were as follows: mean age 63.0 years, 43% male, 63% stage III/IV disease, 28% ECOG performance status > 2, 60% elevated lactate dehydrogenase level. Median duration of follow‐up was 6.6 years. The NCCN‐International Prognostic Index (IPI) was found to be a more powerful prognosticator than the IPI. Five‐year overall survival (OS) was 69.6; 73.6% for patients with intermediate NCCN‐IPI and 38.4% for patients with poor NCCN‐IPI. On univariate analysis, pretreatment hemoglobin and albumin levels were significantly associated with survival. By albumin level, 5‐year OS was 77.6 + 4% in patients with >3.5 g/dl and 53 + 7% in patients with < 3.5 g/dl (p < 0.001); 5‐year progression‐free survival (PFS) was 69.9% and 50.9%, respectively (p = 0.002). By hemoglobin level, 5‐year OS was 82.9 + 4.5% in patients with >12 g/dl and 58.8 + 5% in patients with < 12 g/dl (p = 0.007); 5‐year PFS was 75.5% and 54.1%, respectively (p = 0.008). On multivariate analysis with Cox regression, pretreatment albumin level was a significant independent predictor of OS. Furthermore, 5‐year OS of patients with a high NCCN‐IPI and albumin < 3.5 g/dl was 29.2% compared with 60% in patients with albumin > 3.5 g/dl (p = 0.022). In conclusion, pretreatment albumin level is a strong prognostic factor for OS in patients with DLBCL and can discriminate high‐risk patients for good and poor prognosis. Copyright © 2015 John Wiley & Sons, Ltd.     

Phase 2 trial of combined cisplatin,etoposide, gemcitabine,and methylprednisolone (PEGS) in peripheral T‐cell non‐Hodgkin lymphoma

BACKGROUND:

Patients with peripheral T‐cell lymphomas (PTCLs) have inferior progression‐free survival (PFS) and overall survival (OS) compared with patients who have aggressive B‐cell non‐Hodgkin lymphoma. Because PTCLs over express multidrug resistance gene 1/P‐glycoprotein (MDR‐1/P‐gp), we devised platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) with agents that are not substrates of the efflux pump. Gemcitabine was included because of its excellent single‐agent activity in PTCL.

METHODS:

Patients who had PTCL with stage II bulky disease, stage III or IV disease with extra‐nodal, nodal, and transformed cutaneous presentations were eligible. Patients received intravenous cisplatin 25 mg/m² on days 1 through 4, etoposide 40 mg/m² on days 1 through 4, gemcitabine 1000 mg/m² on day 1, and methylprednisolone 250 mg on days 1 through 4 of a 21‐day cycle for 6 cycles.

RESULTS:

In total, 34 patients were enrolled, 33 were eligible, and 79% were newly diagnosed. Histologic types were PTCL not otherwise specified (n = 15), anaplastic lymphoma kinase (ALK)‐negative anaplastic large cell lymphoma (n = 4), angioimmunoblastic T‐cell lymphoma (n = 6), or other T‐cell non‐Hodgkin lymphomas (n = 8). Adverse events included 1 grade 5 infection with grade 3 or 4 neutropenia and 9 grade 4 hematologic toxicities. The overall response rate was 39% (47% in PTCL not otherwise specified, 33% in angioimmunoblastic T‐cell lymphoma, 25% in ALK‐negative and 38% in other T‐cell non‐Hodgkin lymphomas). The PFS rate at 2 years was 12% (95% confidence interval, 0.1%‐31%), and the median PFS was 7 months. The OS rate at 2 years was 30% (95% confidence interval, 8%‐54%), and the median OS was 17 months. Immunohistochemical analysis of P‐gp expression revealed strong positivity in a subset of lymphoma cells (n = 6) and tumor endothelium (n = 25).

CONCLUSIONS:

Overall, PEGS was well tolerated, but OS was not considered promising given the design‐specified targets. These results may serve as a benchmark for future comparisons for non‐CHOP regimens. Cancer 2013. © 2012 American Cancer Society.     

Mean platelet volume predicts prognosis in patients with diffuse large B‐cell lymphoma

To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B‐cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R‐CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut‐off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. * Patients with MPV ≤ 9.1 fl experienced a shorter progression‐free survival (PFS) (2‐year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2‐year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL.     

Multicentre phase II study of CyclOBEAP plus rituximab in patients with diffuse large B‐cell lymphoma

The R‐CHOP regimen has been found to improve the outcome of diffuse large B‐cell lymphoma (DLBCL). However, it does not provide a satisfactory treatment outcome in the high‐risk group. We previously administered the CyclOBEAP regimen to patients with DLBCL, and reported its safety and efficacy. The R‐CyclOBEAP regimen was administered over a total period of 12 weeks, and rituximab 375 mg/m² was given every 2 weeks. There were 101 eligible patients. CR was achieved in 96 patients (95%). The 5‐year overall survival (OS) rate was 85% and progression‐free survival (PFS) rate was 76%. When the patients were divided according to the IPI, the 5‐year OS and PFS rates did not significantly differ among the risk groups. The 5‐year PFS of the germinal centre B‐cell group was 80% and that of the non‐GCB group was 74% (NS). Univariate analysis showed that the presence of B symptoms, extranodal lesions ≧2, and sIL‐2R were significant poor prognostic factors. Grade 4 neutropenia was observed in 91 patients and thrombocytopenia in 9 patients. The addition of rituximab to CyclOBEAP therapy may enhance the effect of CyclOBEAP therapy for DLBCL. Copyright © 2010 John Wiley & Sons, Ltd.     

R‐High‐CHOP/CHASER/LEED with autologous stem cell transplantation in newly diagnosed mantle cell lymphoma: JCOG0406 STUDY

Although induction immunochemotherapy including high‐dose cytarabine and rituximab followed by high‐dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) is recommended for younger patients (≤65 years old) with untreated mantle cell lymphoma (MCL), no standard induction and HDC regimen has been established. We conducted a phase II study of induction immunochemotherapy of R‐High‐CHOP/CHASER followed by HDC of LEED with ASCT in younger patients with untreated advanced MCL. Eligibility criteria included untreated MCL, stage II bulky to IV, and age 20‐65 years. Patients received 1 cycle of R‐High‐CHOP followed by 3 cycles of CHASER every 3 weeks. Peripheral blood stem cells (PBSC) were harvested during CHASER. LEED with ASCT was delivered to patients who responded to R‐High‐CHOP/CHASER. Primary endpoint was 2‐year progression‐free survival (PFS). From June 2008 to June 2012, 45 patients (median age 59 years; range 38‐65 years) were enrolled. PBSC were successfully harvested from 36 of 43 patients. Thirty‐five patients completed ASCT. Two‐year PFS was 77% (80% CI 68‐84), which met the primary endpoint. Five‐year PFS and overall survival were 52% (95% CI 34‐68%) and 71% (95% CI 51‐84%), respectively. Overall response and complete response rates after induction immunochemotherapy were 96% and 82%, respectively. The most common grade 4 toxicities were hematological. In younger patients with untreated MCL, R‐High‐CHOP/CHASER/LEED with ASCT showed high efficacy and acceptable toxicity, and it can now be considered a standard treatment option.     

Diffuse large B‐cell lymphoma

BACKGROUND:

The objective of this study was to compare the clinical features and prognosis of patients with diffuse large B‐cell lymphoma (DLBCL) of Waldeyer ring (WR‐DLBCL) and patients with lymph node DLBCL (N‐DLBCL).

METHODS:

One hundred eighty‐one patients with WR‐DLBCL and N‐DLBCL were reviewed. There were 57 patients with stage I disease, 83 patients with stage II disease, 26 patients with stage III disease, and 15 patients with stage IV disease. Among them, 101 patients had primary N‐DLBCL, and 80 patients had primary WR‐DLBCL.

RESULTS:

Patients with WR‐DLBCL and N‐DLBCL usually presented at an older age and had localized disease, a low frequency of B symptoms, a good performance status, and a low‐risk International Prognostic Index (IPI) score. Compared with patients who had N‐DLBCL, patients who had WR‐DLBCL presented with more stage II disease and lower tumor burdens. The overall response rate after treatment was similar in both groups. The 5‐year overall survival (OS) and progression‐free survival (PFS) rates were 76% and 61% in patients with WR‐DLBCL, respectively, and 56% and 50% in patients with N‐DLBCL, respectively (P = .119 for OS; P = .052 for PFS). IPI scores and elevated β2‐microglobulin and LDH levels were associated with a poor prognosis for patients who had WR‐DLBCL; whereas bulky tumor, elevated β2‐microglobulin levels, and IPI scores were associated with poor OS for patients who had N‐DLBCL.

CONCLUSIONS:

The current results supported the continued inclusion of WR‐DLBCL as a lymph node group in the staging of DLBCL. Patients with WR‐DLBCL had clinical features and prognosis similar to those of patients with N‐DLBCL. Cancer 2009. © 2009 American Cancer Society.     

A Retrospective Analysis of Peripheral T-Cell Lymphoma Treated With the Intention to Transplant in the First Remission

BackgroundPeripheral T-cell lymphomas are aggressive lymphomas that have no standard treatment. Studies suggest that HD-ASCT in the first CR improves outcome. Few data exist regarding allo-HSCT in the first CR.Patients and MethodsWe retrospectively identified patients (2001-2011) with PTCL-not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, initially treated with CHOP, CHOP-ICE (ifosfamide, carboplatin, etoposide), or other therapy with the intention to transplant in the first CR. Disease characteristics, therapy, progression-free survival (PFS), and OS were evaluated.ResultsSixty-five patients were identified. PFS and OS were 38% and 52%, respectively, at 4 years. CHOP and CHOP-ICE regimens had similar outcomes. Treatment with allo-HSCT and HD-ASCT had OS at 4 years of 66% and 67%, respectively. Patients who did not proceed to transplant had OS of 27%. IPI score ≤ 2 and Prognostic Index for T-cell Lymphomas scores ≤ 1 predicted improved outcome. Combined analysis of interim response to CHOP and IPI score also predicted PFS and OS.ConclusionOur results support consolidation of first CR with transplantation. The addition of etoposide did not improve outcomes. Baseline IPI and interim response to CHOP can predict outcomes and guide decisions about transplantation in first CR in PTCL. Randomized trials are necessary to confirm the efficacy of this approach.     

Immunophenotype and intermediate‐high international prognostic index score are prognostic factors for therapy in diffuse large B‐cell lymphoma patients

BACKGROUND.

The development of gene expression profiling and tissue microarray techniques have provided more information about the heterogeneity of diffuse large B‐cell lymphoma (DLBCL), enabling categorization of DLBCL patients into 3 prognostic groups according to cell origin (but independently from the International Prognostic Index [IPI] score): germinal center (GCB), activated B‐cell (ABC), and not classified (NC) diffuse large B‐cell lymphoma. This study investigated the role of immunohistochemical discrimination between GCB and ABC&NC‐DLBCL subtypes in identifying those high‐risk patients who may benefit from a more aggressive first‐line therapeutic approach.

METHODS.

From February 2003 to August 2006, 45 newly diagnosed DLBCL patients, with IPI≥2, were considered eligible for this study: 13 had a GCB, 8 an ABC, and 24 a NC‐DLBCL. GCB patients received 6 courses of rituximab, cyclophophosphamide, doxorubicin, vinicristine, and prednisone (R‐CHOP) chemotherapy, with a subsequent, autologous stem cell transplantation in case of partial response. All ABC and NC‐DLBCL patients received 6 R‐CHOP cycles and autologous stem cell transplantation.

RESULTS.

Complete response rate for each treatment arm was 84.6% for GCB and 89.7% for ABC&NC‐DLBCL (P = .50), with a continuous complete response rate of 81.8% and 84.6%, respectively (P = .59). Projected 4‐year overall survival is 100% for GCB and 82% for ABC&NC patients (P = .12). Progression‐free survival is 77% and 79% (P = .7), respectively.

CONCLUSIONS.

The autologous stem cell transplantation consolidation in the ABC&NC‐DLBCL subtypes induced the same rate of complete response (and similar progression‐free survival rate) compared with GCB‐DLBCL. In ABC&NC‐DLBCL patients the authors observed a complete response rate of 89.7% vs. 84.6% in the GCB‐DLBCL subset, without any significant difference in progression‐free survival rate. Cancer 2010. © 2010 American Cancer Society.     

How to predict the outcome in mature T and NK cell lymphoma by currently used prognostic models?

To select an appropriate prognostic model in the treatment of mature T- and natural killer (NK) -cell lymphoma (peripheral T-cell lymphoma (PTCL) and NK-/T-cell lymphoma (NKTCL)) is crucial. This study investigated the usefulness of Ann Arbor staging classification International prognostic index (IPI), prognostic index for T-cell lymphoma (PIT) and International peripheral T-cell lymphoma Project score (IPTCLP). Between 2000 and 2009, 176 patients (122 males) with PTCL and NKTCL were diagnosed and treated from a single institute in Taiwan. The correlation between complete response (CR) rate, 3-year overall survival (OS), early mortality rate and four prognostic models was analyzed. Thirty-one patients received hematopoietic stem cell transplantation (HSCT) and were analyzed separately. Three-year OS rate was 34.7%, and anaplastic large-cell lymphoma harbored better outcome than others. IPI score had the lowest Akaike information criterion value (1081.197) and was the best score in predicting OS and early mortality (P=0.009). Ann Arbor stage classification can predict CR rate more precisely (P=0.006). OS was significantly better in patients who received HSCT, even in patients with unfavorable features compared with chemotherapy alone. All prognostic models were useful to evaluate the outcome of patients with PTCL and NKTCL but IPI score did best in predicting OS in PTCL and PIT score in NKTCL. This study also supported the role of HSCT in patients with high-risk or refractory PTCL or NKTCL.     

Impact on survival of addition of etoposide to primary chemotherapy in diffuse large B‐cell lymphoma: a Swedish Lymphoma Registry study

No randomised study in the rituximab era has been performed specifically to evaluate addition of etoposide to treatment of diffuse large B‐cell lymphoma (DLBCL). The aim of this study was to compare the outcome with three chemotherapy regimens (R‐CHOP‐21, R‐CHOP‐14 and R‐CHOEP‐14) in a population‐based cohort in terms of overall survival, adjusted for clinical prognostic factors. Through the Swedish Lymphoma Registry, 3443 patients with DLBCL were identified 2007–2012. Among all patients, there was no evidence of a difference between the regimens, after adjustment for prognostic factors. However, when restricted to patients aged up to 65, R‐CHOEP‐14 was associated with superior outcome compared to both R‐CHOP‐21 (hazard ratio: 0.49, 95% confidence interval: 0.3–0.9, p = 0.028) and R‐CHOP‐14 (hazard ratio: 0.64, 95% confidence interval: 0.4–1.0, p = 0.06), when adjusted for prognostic factors. Results were consistent in an additional stratified analysis with patients grouped according to age and IPI‐score. In conclusion, we could show that R‐CHOEP‐14 was associated with superior overall survival in patients with DLBCL aged up to 65 years, indicating that this may be a valid treatment option for this patient population. To further investigate which patient groups that may benefit the most from treatment intensification, R‐CHOEP‐14 should be compared to R‐CHOP‐21 in a randomised setting. Copyright © 2015 John Wiley & Sons, Ltd.     

Independent prognostic impact of tumour‐infiltrating macrophages in early‐stage Hodgkin's lymphoma

Although patients with early‐stage Hodgkin's lymphoma have a high rate of cure, a portion of these are resistant to or relapse after standard treatment. Current prognostic criteria based on clinical and laboratory parameters at diagnosis do not allow to accurately identify the subset of patients with less favourable clinical outcome. An increased number of tumour‐infiltrating macrophages was found to be associated with shortened survival in patients with classic Hodgkin's Lymphoma. The aim of this study was to assess the clinical significance of the proportion of CD68‐positive infiltrating macrophages in patients with early‐stage classic Hodgkin's lymphoma. By using immunohistochemistry technique, we evaluated for CD68 expression diagnostic biopsies of 106 patients affected by supradiaphragmatic early‐stage classic Hodgkin's lymphoma treated at our institution since 2000 to 2010. All patients were treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by radiotherapy in the majority. The 2‐year overall survival and progression‐free survival (PFS) in the entire cohort were 97% and 83% respectively. The 2‐year PFS was statistically different between patients with favourable and those with unfavourable prognosis according to the European Organisation for Research and Treatment of Cancer (EORTC) risk criteria (96% vs 79%, p = 0.039) and between patients having less than 25% of CD68‐positive infiltrating macrophages and those with more than 25% (85% vs 67%, p = 0.012). All patients with favourable EORTC criteria had CD68 expression lower than 25%. Within those with unfavourable EORTC criteria, patients with a CD68+ count greater than 25% had a worse 2‐year PFS than patients having values lower than 25% (64% vs 82%, p = 0.03). Moreover, in multivariate analysis, after adjusting for CD68+ macrophages count and EORTC score, only CD68+ macrophages count higher than 25% retained a prognostic effect on PFS (hazard ratio = 2.8, 95%CI: 1.1–7.6, p = 0.038). Our data show that a proportion of tumour‐infiltrating macrophages greater than 25% is associated with unfavourable clinical outcome in patients with early‐stage Hodgkin's lymphoma Copyright © 2016 John Wiley & Sons, Ltd.     

Total lesion glycolysis in positron emission tomography is a better predictor of outcome than the International Prognostic Index for patients with diffuse large B cell lymphoma

BACKGROUND:

This study was undertaken to evaluate the prognostic value of quantitative metabolic parameters in [¹⁸F]2‐fluoro‐2‐deoxyglucose (FDG)‐positron emission tomography (PET) for diffuse large B cell lymphoma (DLBCL).

METHODS:

A total of 140 DLBCL patients underwent FDG‐PET scans before rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R‐CHOP) chemotherapy. The maximal standardized uptake value (SUV_max) and total lesion glycolysis (TLG) were calculated, with the margin thresholds as 25%, 50%, and 75% of SUV_max of all lesions. Treatment outcomes were compared between groups according to metabolic parameters and the International Prognostic Index (IPI).

RESULTS:

After a median follow‐up of 28.5 months (range, 5‐81 months), the 2‐year progression‐free survival (PFS) and overall survival (OS) were 83% and 87%, respectively. Among metabolic parameters, TLG at the threshold of 50% (TLG₅₀) was significantly associated with treatment outcomes. High TLG₅₀ values (>415.5) were associated with reduced survivals compared with low TLG₅₀ values (≤415.5) (2‐year PFS of 73% versus 92%, P = .007; and 2‐year OS of 81% versus 93%, P = .031). High IPI score (≥3) significantly reduced OS (2‐year OS of 79% versus 90%, P = .049). Ann Arbor stage III/IV adversely affected PFS (P = .013). However, high IPI score and Ann Arbor stage of III/V did not significantly shorten PFS (P = .200) and OS (P = .921), respectively. High TLG₅₀ values independently predicted survivals by multivariate analysis (hazard ratio = 4.4; 95% confidence interval = 1.5‐13.1; P = .008 for PFS and hazard ratio = 3.1; 95% confidence interval = 1.0‐9.6; P = .049 for OS).

CONCLUSIONS:

Combined assessment of volume and metabolism (ie, TLG) is predictive of survivals in DLBCL patients who are treated with R‐CHOP. Cancer 2013. © 2012 American Cancer Society.     

Serum concentrations of l‐kynurenine predict clinical outcomes of patients with peripheral T‐cell lymphoma,not otherwise specified

Indoleamine 2,3‐dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l ‐tryptophan. The activity of indoleamine 2,3‐dioxygenase can be estimated by measuring serum l ‐kynurenine concentrations. Here, we aimed to determine the role of l ‐kynurenine as a prognostic factor for peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) in a retrospective analysis of data derived from 31 consecutive patients between June 2000 and March 2013 who were histologically diagnosed with PTCL‐NOS according to the World Health Organization classification and treated with 6?8 cycles of cyclophosphamide, doxorubicin or pirarubicin, vincristine, and prednisolone. l ‐kynurenine concentrations in serum samples collected at admission were measured using high‐performance liquid chromatography. The median serum concentration of l ‐kynurenine was 3.28 (range 0.92–8.16) μM. The l ‐kynurenine cutoff was set at 3.07 μM using receiver operating characteristics curves. The complete remission rates of patients with l ‐kynurenine <3.07 and ≥3.07 μM were 69% and 51%, respectively. The 5‐year overall survival (OS) rates for patients with l ‐kynurenine <3.07 and ≥3.07 μM were 80.2% and 23.4%, respectively (p < 0.001). More advanced age, poor performance status, elevated lactate dehydrogenase, an unfavorable International Prognostic Index, and a poor prognostic index for T‐cell lymphoma were significantly worse factors for OS. Multivariate analyses revealed only l ‐kynurenine as an independent prognostic factor for OS. In conclusion, serum concentrations of l ‐kynurenine might comprise a novel prognostic factor with which to determine the outcomes of treatment for PTCL‐NOS. Copyright © 2016 John Wiley & Sons, Ltd.     

Impact of the introduction of rituximab in first‐line follicular lymphoma: a retrospective study of 247 unselected patients referred to a single institution with a long‐term follow‐up

Rituximab was approved in France in 2004, following randomized trials that demonstrated efficacy in newly diagnosed high tumour burden follicular lymphoma (FL). This retrospective study compared the management and outcome of FL in unselected patients treated in a single institution before and after rituximab approval. Two hundred and forty‐seven adult patients were referred with first‐line FL between 1996 and 2010 and are included in this study. The 103 pre‐rituximab patients comprising cohort 1 were diagnosed between January 1996 and December 2003; cohort 2 includes the 144 patients diagnosed after the approval of rituximab between January 2004 and December 2010. Baseline clinical and biological data, type of therapy, treatment response, progression‐free survival (PFS) and overall survival (OS) rates were compared. There were no statistically significant differences between the two cohorts with respect to baseline clinical and disease characteristics, including FL International Prognostic Index score. The major difference between the two cohorts is the use of rituximab in first line. Seventy‐one per cent of patients in cohort 2 received rituximab (19% alone, 52% with chemotherapy) versus 10% in cohort 1 (2% alone, 8% with chemotherapy; p < 0.0001). The objective response rate (ORR) was significantly higher for cohort 2 (ORR 84% compared with 72% for cohort 1; p = 0.03). The PFS and OS rates were also significantly better: 3‐year PFS 72% [95% confidence interval (CI) 64–80%] versus 55% (95% CI 45–64%), p = 0.0039 and 3‐year OS 98% (95% CI 94–99%) versus 83% (95% CI 74–90%), p = 0.0007. Effect of period of study is significant when using multivariate analysis on PFS and OS and lactate dehydrogenase level (PFS and OS) and age (OS). These data from everyday practice confirm the benefit for patients with FL treated in the last decade through availability of rituximab in first line used alone or in association with various chemotherapy regimens. Copyright © 2014 John Wiley & Sons, Ltd.     

Bcl‐2, Bcl‐6, and the International Prognostic Index are prognostic indicators in patients with diffuse large B‐cell lymphoma treated with rituximab‐containing chemotherapy

This study aimed to clarify the clinicopathological prognostic parameters of de novo diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. We examined the correlation of 22 clinicopathological parameters with progression‐free survival (PFS), overall survival (OS), and primary refractory disease in 285 DLBCL patients treated with rituximab‐containing chemotherapy. Complete response rate was 87%, overall response rate was 91%, 5‐year PFS rate was 72%, and 5‐year OS rate was 91%. By log–rank test, higher International Prognostic Index (IPI) (P < 0.0001), Bcl‐2 positivity (P = 0.0013), Bcl‐6 negativity (P = 0.0112), and no irradiation (P = 0.0371) were significantly correlated with shorter PFS; higher IPI (P = 0.0107), starry sky pattern (P = 0.0466), and no irradiation (P = 0.0264) correlated with shorter OS. In multivariate analyses, higher IPI (P = 0.0006), Bcl‐2 positivity (P = 0.0015), and Bcl‐6 negativity (P = 0.04) were significantly correlated with shorter PFS; higher IPI (P = 0.0045) correlated with shorter OS. Bcl‐2 (P = 0.0029), Bcl‐6 (P = 0.002), and IPI (P < 0.0001) were significantly correlated with primary refractory disease. In conclusion, Bcl‐2 positivity, Bcl‐6 negativity, and higher IPI were indicators of shorter PFS and OS plus primary refractory disease in patients with DLBCL in the rituximab era.     

Comparison of four prognostic scores in peripheral T-cell lymphoma

BackgroundTo compare the usefulness of four prognostic scores in patients with peripheral T-cell lymphoma (PTCL) from a single institution.Patients and methodsOne hundred twenty-one patients (77 male/36 female, median age 53 years) with PTCL [anaplastic large-cell lymphoma (ALCL) 21, PTCL not otherwise specified 56 and other 44)]. Complete response (CR) rate and 5-year overall survival (OS) were 41% and 31%, respectively. International Prognostic Index (IPI), Prognostic Index for T-cell lymphoma (PIT), International peripheral T-cell lymphoma Project score (IPTCLP) and modified Prognostic Index for T-cell lymphoma (mPIT) were calculated as in the original references. mPIT was only assembled to 41 patients in whom Ki-67 immunostaining was available. ALCL patients were analyzed separately.ResultsConcordance among IPI, PIT and IPTCLP was 52% for low-risk group, 27% for low/intermediate-risk group, 20% for high/intermediate-risk group and 14% for high-risk group. IPI, PIT and IPTCLP predicted CR, with IPI being the best score in logistic regression. Neither Ki-67 immunostaining nor mPIT predicted CR. Five-year OS (low-risk versus intermediate- or high-risk categories) according to IPI, PIT, IPTCLP and mPIT were 52% versus 45%, 75% versus 49%, 58% versus 20% and 39% versus 0%, respectively. IPTCLP was the best score for OS in multivariate analysis.ConclusionAll the scores demonstrated their usefulness to assess the outcome of patients with PTCL, with IPTCLP being the most significant to predict OS.     

Isolated central nervous system relapses in primary mediastinal large B‐cell lymphoma after CHOP‐like chemotherapy with or without Rituximab

Central nervous system (CNS) involvement in patients with primary mediastinal large B‐cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R‐CHOP ± RT in comparison to patients treated with CHOP ± RT (n = 45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R‐CHOP treated patients and a 2‐year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2‐year actuarial incidence of 7.5% (p = 0.29). Again, both patients had isolated CNS relapses. Parenchymal‐only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age‐adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R‐CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high‐dose therapy and autologous stem cell transplantation: They are both alive and disease‐free 18 and 23 months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long‐term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL. Copyright © 2012 John Wiley & Sons, Ltd.