Diffuse Large B-cell Histology Research Articles

NIMG-98. IDENTIFYING PATTERNS OF FAILURE AFTER INITIAL THERAPY IN PRIMARY CNS LYMPHOMA IN A LARGE PATIENT COHORT

Abstract INTRODUCTION Treatment of primary CNS lymphoma (PCNSL) has rapidly evolved, emphasizing improved efficacy while reducing neurotoxicity. PCNSL has historically been considered a multifocal disease and many patients relapse after first-line therapy. We evaluated relapse patterns in a large cohort of contemporarily treated patients. METHODS Consecutive PCNSL patients treated at MSKCC between 1983-2020 were analyzed. T1 post-contrast-enhancing disease on baseline MRI was characterized. Site of initial relapse was characterized as purely local (involving/adjacent to initial site) vs distant intraparenchymal, or other (e.g., both local and distant, systemic, ocular). Progression-free survival (PFS) was evaluated using Kaplan Meier methods. RESULTS Of 645 patients, 564 were eligible for analysis (diffuse large B-cell histology, sufficient data, ≥ 1 MRI response assessment). Median follow-up was 2.7 years (IQR 1.2-5.6). Median age was 63 years (range 19-90). Baseline disease was often supratentorial (420, 74%), multifocal (274, 49%), and bilateral (224, 40%). Fewer had leptomeningeal disease (94/430 CSF+, 22%; 117/559 radiographically positive, 21%). Most received methotrexate (MTX)-based induction (534, 96%), most commonly rituximab, MTX, procarbazine, vincristine (R-MVP; 257, 46%) or MVP (144, 26%). Overall, 286 (51%) patients relapsed with a median PFS of 2.1 years (95% CI 1.8-2.5). Of 275 characterizable relapses, 75 (27%) were exclusively local intraparenchymal, 91 (33%) were distant intraparenchymal, and 109 (40%) were other. Baseline unifocal disease often relapsed unifocally (66/118 baseline unifocal; 56%). Of 126 unifocal relapses, 45 (36%) were local. Of 202 patients with baseline supratentorial disease, 152 (75%) relapsed supratentorially. Unilateral relapses often remain ipsilateral (49% left- and 54% right-hemispheric lesions at baseline and relapse). CONCLUSIONS In a large PCNSL cohort, relapses often maintained baseline characteristics. For a disease historically considered multifocal, a substantial proportion of relapses were local. Future analyses will evaluate predictors of relapse, which can further efforts in informing personalization of treatment in the era of cellular therapies.

Intradural primary marginal zone lymphoma of the cervical spine 2years following a posterior cervical instrumented fusion.

Primary low grade central nervous system lymphoma is a rare entity, with the majority being intracranial marginal zone B-cell lymphoma. Primary spinal lymphoma is unusual, and commonly presents as an epidural lesion with diffuse large B-cell histology, as described in prior literature. We present a case of a 56year-old woman diagnosed with a primary intradural spinal lymphoma two years after a posterior cervical fusion at the same level. She was treated successfully with surgical resection and postoperative radiotherapy. To our knowledge, this is the first case in the literature describing an intradural primary marginal zone B-cell lymphoma of the spine.

Primary central nervous system lymphoma: a new prognostic model for patients with diffuse large B-cell histology.

BackgroundAge and performance status are important prognostic factors in primary central nervous system (CNS) lymphoma. Although several prognostic models have been proposed, there is no consensus on the optimal model for patients with diffuse large B-cell histology.MethodsSeventy-seven patients with primary CNS diffuse large B-cell lymphoma were retrospectively analyzed to determine factors affecting survival. Three Western models were applied to our eligible patients; we devised a novel model based on our findings.ResultsThe median patient age was 59 years (range, 29–77); the median event-free and overall survival (OS) durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and Memorial Sloan Kettering Cancer Center models were applicable to our cohorts. Multivariate analysis showed that advanced age, multifocal lesions, and high cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A novel model for predicting prognosis was then developed based on these variables. Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3 were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very high-risk groups (N=4), respectively. Sixty-one patients were eligible considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the low-, moderate-, high-, and very high-risk groups, respectively (P<0.01).ConclusionAdvanced age, multifocal lesions, and high CSF protein concentration were adversely related with prognosis. Our model can be helpful in pre-treatment risk stratification for patients with primary CNS lymphoma with diffuse large B-cell histology.

Central nervous system recurrence of systemic lymphoma in the era of stem cell transplantation - an International Primary Central Nervous System Lymphoma Study Group project

Autologous stem cell transplantation has greatly improved the prognosis of systemic recurrent non-Hodgkin's lymphoma. However, no prospective data are available concerning the feasibility and efficacy of this strategy for systemic lymphoma relapsing in the central nervous system. We, therefore, we performed an international multicenter retrospective study of patients with a central nervous system recurrence of systemic lymphoma to assess the outcome of these patients in the era of stem cell transplantation. We collected clinical and treatment data on patients with a first central nervous system recurrence of systemic lymphoma treated between 2000 and 2010 in one of five centers in four countries. Patient- and treatment-related factors were analyzed and compared descriptively. Primary outcome measures were overall survival and percentage of patients transplanted. We identified 92 patients, with a median age of 59 years and a median Eastern Cooperative Oncology Group/World Health Organization performance status of 2, of whom 76% had diffuse large B-cell histology. The majority (79%) of these patients were treated with systemic chemotherapy with or without intravenous rituximab. Twenty-seven patients (29%) were transplanted; age and insufficient response to induction chemotherapy were the main reasons for not being transplanted in the remaining 65 patients. The median overall survival was 7 months (95% confidence interval 2.6-11.4), being 8 months (95% confidence interval 3.8-5.2) for patients ≤ 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic Index for primary central nervous system lymphoma was prognostic for both undergoing transplantation and survival. In conclusion, despite the availability of autologous stem cell transplantation for patients with central nervous system progression or relapse of systemic lymphoma, prognosis is still poor. Long-term survival is, however, possible and more likely in patients able to undergo stem cell transplantation.

Phase I study cohort evaluating an optimized administration schedule of SAR3419, an anti-CD19 DM4-loaded antibody drug conjugate (ADC), in patients (pts) with CD19 positive relapsed/refractory b-cell non-Hodgkin’s lymphoma (NCT00796731).

8057 Background: The recommended dose (RD) of SAR3419 administered intravenously every 3 weeks (q3w) for 6 cycles is 160 mg/m2 and is 55 mg/m2 when administered weekly (q1w) for 8-12 doses. Reversible corneal deposits were dose limiting (DLT) in the q3w schedule. The q1w schedule was well tolerated and active. However, based on the occurrence of late/cumulative adverse events (AE) at the RD supported by pharmacokinetic (PK) analyses showing ADC plasma accumulation after 4 weekly doses, an optimized schedule consisting of 4 weekly doses followed by 4 bi-weekly doses at the RD was tested. Methods: The q1w study was extended to treat 25 pts with the optimized schedule for 8 to 12 doses. Results: Twenty-one pts were evaluable. Main histologies were diffuse large B-cell (DLBCL) (9; 43%) and follicular (6; 29%). Median number of prior regimens was 2 [1-8], 6 pts received prior autologous transplantation and 95% of pts were Ann Arbor stage III-IV at study entry. Median number of doses received was 8 as planned with a median relative dose intensity of 1.0 [0.8-1.0]. Most frequent AEs were asthenia (1 pt with grade 3) and gastrointestinal disorders in 7 pts each. No AE fulfilled the defined DLT criteria. Reversible grade 1 blurred vision/corneal event occurred in 1 pt. Grade 3-4 haematological toxicities were minor consisting of non complicated neutropenia in 4 pts, thrombocytopenia in 2 pts and anemia in 1 pt with no transfusion support. Six (29%) pts, among them 3 with DLBCL, achieved an objective response including 3 CRu (1 in a pt refractory to last regimen). In addition, 9 (43%) pts had stable disease. Response duration was [8-35+] weeks, 5 pts still responding at the cut-off date. Conclusions: The optimized administration schedule shows an improved safety profile compared to prior tested schedules. The clinical efficacy is preserved essentially in aggressive lymphoma. The optimized schedule is being assessed in 2 phase II studies evaluating SAR3419 either as a single agent or in combination with rituximab in pts with DLBCL histology.

Management of primary intraocular lymphoma (PIOL): Results from the prospective German PIOL registry (PIOL-R).

2054 Background: Primary intraocular lymphoma (PIOL) is a very rare disorder, and the optimal treatment is yet to be defined. Here, we report clinical characteristics and outcome of patients with PIOL enrolled in the prospective German PIOL registry (PIOL-R). Methods: Patient data in this prospective, non-interventional multicenter study were compiled by standardized questionnaires sent to Ophthalmology and Hematology/Oncology centers in Germany. All histologically or cytologically confirmed immunocompetent PIOL patients were eligible. Results: Fifteen patients (8 female, median age 66 years, median Karnofsky performance status 90%) from 4 centers were included between August 2008 and January 2012. Median follow-up was 7 months. Median time from first occurrence of symptoms to PIOL diagnosis was 5 (range, 1-11) months. All PIOL were of diffuse large B-cell histology. Eight patients had concomitant (n=3), prior (n=2) and/or subsequent (n=4) parenchymal brain involvement. First-line treatment included methotrexate (MTX)-, rituximab- and/or ifosfamide-based systemic chemotherapy in 12 (including high-dose chemotherapy [HDCT] with autologous stem cell transplantation [ASCT] in 2), intraocular (i.o.) chemotherapy with MTX (n=2) and/or rituximab (n=6) in 7, and ocular radiation in one patient(s). Two patients received prophylactic intrathecal (i.th.) treatment with MTX and none had whole-brain irradiation. The PIOL remission rate was 100% (complete remission in 11/14 evaluable patients and partial remission in 3 patients). Four patients relapsed in the brain after 5, 6, 21 and 23 months and received salvage treatment with MTX and/or ifosfamide (n=3) and HDCT with ASCT (n=1). No ocular or systemic relapses were observed. Median progression-free survival was 23 (95% confidence interval, 19-26) months. All patients are alive. Conclusions: Although the awareness of PIOL and diagnostic possibilities have improved over the past 2 decades, time from symptom presentation to diagnosis seems to remain at previously reported levels. There appears to be a shift from local ocular treatments and radiation to systemic therapy as compared to anecdotal data with promising response and survival rates.

Cytarabine and Etoposide (CYVE) as First-Line Therapy for Primary Central Nervous System Lymphoma

AbstractAbstract 4895 Background:The treatment of primary central nervous system lymphoma (PCNSL) is characterized by high rates of toxicity and intracranial relapse despite initial response. High-dose methotrexate (HD-MTX), with or without cranial irradiation, has become the standard of care; combining this with other chemotherapeutic agents has improved complete remission rates but at the expense of increased treatment-related adverse events, particularly haematologic and neurologic toxicity. Cytarabine has been used in combination with etoposide (CYVE) as a salvage therapy for patients who have been refractory to or relapsed after HD-MTX-based regimens (Soussain C et al, J. Clin. Oncol. 2001; Soussain C et al, J. Clin. Oncol. 2008). In these studies, cytarabine was given as an infusion at a dose of 50mg/m2/d over 12 hours on days 1–5, and at a dose of 2g/m2/d over 3 hours on days 2–5 with etoposide at 200mg/m2/d on days 2–5. Both responders and non-responders were eligible to proceed to autologous stem cell transplant (autoSCT) using a conditioning regimen of thiotepa 250mg/m2/d on days -9 to -7, busulfan 10mg/kg total dose po or 8mg/kg total dose iv over days -6 to -4, and cyclophosphamide 60 mg/m2/d on days -3 to -2. Median OS was 58.6 months in patients able to undergo autoSCT, but with significant neurotoxicity that may have been related in part to prior therapies. Methods and Results:Given its excellent CNS penetration, CYVE may be an effective regimen in previously untreated patients, with lower risk of neurotoxicity. We have used CYVE as a first-line therapy for patients with PCNSL who are potentially eligible for subsequent autoSCT. Between January 1, 2005 and December 31, 2009, 7 patients with a diagnosis of PCNSL were treated with first-line CYVE using the regimen described above. All were HIV negative, showed no disease outside of the CNS on bone marrow biopsy and staging CT or PET scan, and had biopsy-proven PCNSL with diffuse large B-cell histology. Median age was 55 (42-61) with 4 female and 3 male patients. Median International Extranodal Lymphoma Study Group Prognostic Index score was 2 (0-2), although in actuality may have been higher, as 4 patients were not able to undergo lumbar puncture at diagnosis. ECOG status was < 2 in 3 patients, ≥ 2 in 3 patients, and not documented in 1 case. Patients received a median of 2 cycles of CYVE (1-3), with 2 receiving concurrent rituximab and the 1 patient with intra-ocular lymphoma receiving post-adjuvant orbital radiation. No cranial radiation was administered. Five patients achieved CR and proceeded to autoSCT. Two patients had a PR but later died of progressive disease at day +48 and day +117, respectively. In both cases, however, the patients were suspected of having disease long before they were treated with CYVE. The first had presented 3 years prior to the diagnosis with a solitary brain lesion that resolved with decadron monotherapy before pathologic documentation. The second had had a brain biopsy that failed to show malignant disease 4 months before the PCNSL diagnosis was confirmed and treatment initiated. Median OS and PFS for the group have not yet been reached with mean follow-up of 657 days. Among the 5 patients who achieved CR, all patients remain alive in CR with a mean follow-up of 841 days (320-1262 days), or 28 months. Toxicities included at least 1 episode of febrile neutropenia in all 7 patients, 2 possible but unconfirmed cases of pulmonary aspergillosis, 2 cases of drug-induced hepatitis (with ALT > 3x ULN), 1 case of toxic epidermal necrolysis secondary to imipenem use during an episode of febrile neutropenia, 1 small bowel obstruction requiring surgical intervention, and 1 case of late grade 2 neurotoxicity presenting 3 years after treatment. Conclusions:In this small cohort of patients, first-line CYVE has shown to be highly effective (ORR 100%, CR 71%) with minimal long-term toxicity compared to that which is seen using it as a salvage therapy. When followed by autoSCT, long-term survival with preserved quality of life may be possible. A prospective study would be necessary to confirm these initial results in practice. Disclosures:No relevant conflicts of interest to declare.

Primary testicular non-Hodgkin lymphoma: A single institution experience from India

Primary testicular non-Hodgkin lymphoma (NHL) is an uncommon extra nodal presentation, constituting 1% of all NHL. Median age at time of presentation is 60 years. Anthracycline based chemotherapies are most frequently used. There is not enough data on use of monoclonal antibody (Rituximab) in testicular NHL. We screened approximately eight hundred and fifty NHL cases registered from January 2002 to May 2008 and found six primary testicular NHL patients. These six cases were analyzed for baseline clinical features, investigations, staging, treatment and outcome variables. Median age was 55 years (range 7-72 years) and median duration of symptoms was 3.5 months (range 1-8 months). All patients had testicular swelling and abdominal lymphadenopathy. Five patients (83%) had stage IV and one had stage IE disease. Majority had diffuse large B-cell histology (83%). All patients were treated with anthracycline based combination chemotherapy and CNS prophylaxis after local therapy except one pediatric patient who did not receive any local therapy. Four patients completed therapy and are on follow up while two patients having extensive disease with poor performance status died of neutropenic sepsis after 1-2 cycles of chemotherapy. The surviving four patients achieved complete remission and are without any recurrence with a median follow up of 26 months (1-78 months). Primary testicular NHL is an uncommon entity and with current combined modality treatment and CNS prophylaxis, the outcome may be as good as nodal NHL.

Changing Epidemiology and Risk Factors for Gastrointestinal Non-Hodgkin's Lymphoma in a North American Population: Population-Based Study

To assess the incidence, risk factors, and endoscopic presentation of gastrointestinal non-Hodgkin's lymphoma (GI NHL) in a large predominantly urban adult population sample. A comprehensive database review of all diagnoses of GI NHL in the Calgary Health Region over a 5-yr period (1999-2003) was undertaken. Longer-term data from a population-based HIV database (1985-2004) were also reviewed. A regional pathology database was used to corroborate case identification. All patients 18 yr of age or older were included. Age- and gender-adjusted incidence rates were calculated. Within the HIV-positive population, incidence rates were compared over time. Endoscopic appearances were assessed and compared. Fifty-six GI NHL cases occurred during the study period. The age- and gender-adjusted annual incidence of GI NHL was 1.73 per 100,000 in the study population. The majority were diffuse large B-cell histology (54%), followed by lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) (29%). Increasing age, history of kidney transplant, and H. pylori positivity in MALT lymphoma were identified as risk factors. Within the HIV-positive population, a highly significant drop in GI NHL was seen over time, with an incidence of 3.86 per 1,000 patient-years in 1985-1989 compared to zero cases in 2000-2004, despite a greater prevalence of HIV disease (P < 0.0001 for trend). MALT lymphoma was less likely to manifest as a mass on endoscopy versus other presentations (P < 0.05). Population-based GI NHL incidence rates in Calgary are higher than those described elsewhere in North America or in Britain. The incidence of GI NHL within the HIV population has virtually disappeared, presumably due to the advent of highly active retroviral therapy.

Adult testicular lymphoma in the United States (1985–2004): Analysis of 3,669 cases from the National Cancer Data Base (NCDB)

19503 Background: Because patients with testicular lymphoma are rare and generally excluded from clinical trials, data on clinical features,treatment and survival are limited. Methods: We retrospectively reviewed all cases of adult (age ≥18 years) testicular lymphoma registered with the NCDB from 1985–2004. Survival data were available only for patients diagnosed before 2001. The NCDB, a project of the American College of Surgeons Commission on Cancer, serves as a comprehensive clinical surveillance resource for all forms of cancer and captures approximately 75% of all cancer cases in the US. Results: We identified3669 cases of testicular lymphoma. This comprised 0.6% of all non-Hodgkin lymphoma. Major histological groups included diffuse large B-cell (DLBCL) (77.8%), other B-cell (21.1%), and T/NK/null cell (1.1%). Median age at diagnosis was 70 years (range, 20–101), with 34.9% under age 65. The right testis was as frequently involved as the left (46.4% v 44.2%). Bilateral testicular involvement occurred in 6.1%. Among those with complete staging work-up, the stage distribution was: I (59.1%), II (15.3%), III (6.0%), and IV (19.6%). Majority were cared for in the community(62.4%) and either had surgery plus additional treatment (59.9%) or surgery alone (23.8%). Median overall survival improved over time, 35.5, 37.6, and 49.5 months for those diagnosed in 1985–1989, 1990–1994, and 1995–2000, respectively (P= 0.01). Other significant predictors of better survival were age <65 years, non-black race, stages I/II at diagnosis, multi-modality treatment, and treatment at a non- Veterans Affairs facility. After multivariate analysis, only age, stage, race, and treatment modality remained independent predictors of survival. Conclusions: This is the largest reported clinical series of testicular lymphoma. Testicular lymphoma is rare and usually presents as early stage disease. Even prior to the introduction of rituximab, the prognosis of testicular lymphoma improved over time, perhaps due to the more frequent use of multimodality therapy. Notably, black race predicted for a worse outcome while DLBCL histology unexpectedly did not. No significant financial relationships to disclose.

No Role for Chemoradiotherapy When Compared with Chemotherapy Alone in Elderly Patients with Localized Low Risk Aggressive Lymphoma: Final Results of the LNH93-4 GELA Study.

Chemoradiotherapy is standard treatment for localized aggressive lymphoma (Miller et al., NEJM, 1998). Because previously published series were heterogeneous with regard to prognostic factors such as age, we aimed to determine the optimal therapy for elderly patients with low risk localized lymphoma. From March 1993 to June 2002, 576 patients (pts) over 60y of age with aggressive lymphoma (WF histology: F, G, H or Kiel anaplastic) and without any adverse factor of the age-adjusted International Pronostic Index were randomly assigned to a chemoradiotherapy arm (299 pts) consisting of 4 cycles of CHOP (doxorubicin 50 mg/m2 d1, cyclophosphamide 750 mg/m2 d1, vincristine 1.4 mg/m2 [up to 2 mg] d1, prednisone 60 mg/m2 d1-5) given every 3 weeks followed by 40 Gy involved-field radiotherapy or to a chemotherapy-alone arm (277 pts) consisting of 4 cycles of CHOP given every 3 weeks. Randomization was stratified according to center and the presence of bulky disease (≥ 10 cm). Principal characteristics were: median age, 68y; male gender, 52%; stage I, 63%; bulky disease, 8%; extranodal involvement, 56%; diffuse large B-cell histology, 80%. Complete response at the end of treatment was similar in both groups (89% and 90 % respectively). Treatment-related death occurred in 1% of pts in each group. On an intent-to-treat basis and with a median follow-up of 6.8y, event-free survival (EFS) and overall survival (OS) did not differ significantly between the two treatment groups (p= 0.7 and p = 0.6, respectively). 5y-EFS rates were 68% for pts treated with chemotherapy alone as compared to 66% for those receiving chemoradiotherapy; 5y-OS rates were 72% and 68% respectively. 66%, of deaths resulted from lymphoma progression. In the subgroup of 247 pts over 70y of age, the 5y-OS was higher in those treated by chemotherapy alone (70% as compared to 58%) but this trend did not reach significance (p=0.1). In a multivariate analysis of the 576 pts, EFS and OS were affected by stage II (p<0.0001), male gender (p=0.02), not by tumor bulk.Conclusion: mature data of the LNH93-4 trial indicate that CHOP plus radiotherapy does not provide any advantage over CHOP alone for the treatment of low risk localized aggressive lymphoma in elderly pts. To note, although the majority of patients had stage I disease, local control by irradiation did not decrease the overall relapse rate. A similar conclusion was recently reached in young adult pts treated by chemotherapy alone (Reyes et al, NEMJ 2005). Taking these results together, we consider that local irradiation following chemotherapy has no role in the treatment of pts with low risk localized aggressive lymphoma. On the basis of its previous published results (Coiffier et al, NEJM, 2002), the GELA recommends to treat such elderly pts with rituximab plus CHOP.

Primary non-Hodgkin’s lymphoma of the breast: First report of the multicentre retrospective study of the International Extranodal Lymphoma Study Group (IELSG-15)

6575 Background: Primary breast lymphoma is a rare poorly-defined condition. This large multi-centre retrospective review investigates its prognosis and patterns of relapse. Methods: Patients presenting with histologically-proven primary non-Hodgkin’s lymphoma of one or both breasts between 1980 and 2003 are included. Data was obtained retrospectively from patient medical records. Central histology review was undertaken where possible. Survival curves were estimated using the Kaplan-Meier method, and prognostic factors analysed by univariate and multivariate analysis. The major study endpoints were progression-free and overall survival. Results: A total of 276 eligible patients were identified. Of these, 202 patients had diffuse large B-cell histology, and form the basis of this analysis. Sixty-seven percent of patients had Stage IE disease, 28% were stage IIE, and 5% were stage IVE(bilateral). B-symptoms were present in 4%. International Prognostic Index (IPI) was 0,1,2 and 3 in 27,37,15 and 3%, respectively. Eighty percent of patients received chemotherapy, 64% radiotherapy, and 50% both, with 87% of patients achieving a complete response at the end of planned first-line therapy. Thirty-seven percent of patients subsequently progressed in one or more sites. The crude rates for recurrence in breast, loco-regional nodes, and central nervous system (CNS) were 15%, 6%, and 5%. Only one breast relapse occurred in an irradiated breast. The median progression-free survival was 5.9 years (95% CI: 3.7, 8.0), with a median follow-up duration of 5.5 years. Median overall survival was 8.4 years (95% CI: 6.5, 10.9). The only statistically significant prognostic factor on multifactor analysis was IPI. Conclusions: The outcome for patients presenting with primary diffuse large B-cell non-Hodgkin’s lymphoma of the breast was significantly worse than that anticipated for Stage I and II nodal lymphomas treated during a similar period. The data suggests that future prospective studies should investigate intensification of treatment, and that the addition of specific prophylactic therapy targeted at the major sites of recurrence may improve prognosis. No significant financial relationships to disclose.

The Cutaneous B-Cell Lymphoma Prognostic Index: A Novel Prognostic Index Derived From a Population-Based Registry

Three classification and prognostic systems exist for primary cutaneous B-cell lymphoma (PCBCL). Whereas the WHO classification defines its categories based on histology, both the European Organisation for Research and Treatment of Cancer classification and the conventional staging system consider skin site. We sought to incorporate both histology and skin site into a single prognostic index designed to predict survival in patients with PCBCL. The associations between histology, skin site, and survival were determined using adjusted proportional hazards analysis conducted on 926 patients with PCBCL identified in the Surveillance, Epidemiology, and End Results data, spanning 1973 to 2001. Four primary CBCL prognostic index (CBCL-PI) groups were identified. Group IA included indolent histologies involving any skin site. Group IB included diffuse large B-cell histology involving favorable skin sites (head/neck, arm). Group II included diffuse large B-cell histology involving unfavorable skin sites (trunk, legs, disseminated) or immunoblastic large B-cell histology involving favorable skin sites. Group III included immunoblastic large B-cell histology involving unfavorable skin sites. The adjusted mortality hazards ratios were 1.0, 1.3 (95% CI, 0.99 to 1.7), 2.1 (95% CI, 1.6 to 2.7), and 4.5 (95% CI, 2.8 to 7.2) for groups IA/B to III, respectively. The corresponding 5-year relative survivals were 94%, 86%, 60%, and 34%. The CBCL-PI identifies adverse combinations of histology and skin site, helping to reconcile differences in current classification and prognostic systems for PCBCL.

Lymhoma of the Oral Cavity. A Rare Entity with Favorable Prognosis. Ten-Year Experience of a Single Hematology Unit.

Lymphomas of the oral cavity consist <5% of the malignancies of the region. B-cell lymphoma of the diffuse large cell histology is the predominant type (B-DLCL). The purpose of our study was to describe the clinicopathologic characteristics of a group of patients with oral cavity lymphomas and their treatment outcome. We reviewed the records of 46 patients (21 males and 25 females) with oral lymphomas who were diagnosed and treated in our Service, between 1993 and 2003. The mean age was 57 years and the most prevalent site of involvement was the tonsil (41.3%) followed by the tongue (15.2%), while 8.7% had >1 involved sites. Thirty six patients (pts) (78.3%) had clinical stage I or II and 10 (21.7%) advanced stage disease. A monoclonal lymphocytic population was detected in the blood of 7 pts (15.2%) by PCR (IgH or TCR rearrangement), 4 of them with early stage lymphoma. 56.5% of the lesions were diagnosed as B-DLCL and only 10.8% as peripheral T-cell lymphomas.Nineteen pts with B-DLCL received CHOP or equivalent chemotherapy regimens and 11 CHOP combined with anti-CD20. Chlorambucil was administered in 4 pts with MALT lymphoma and local radiotherapy as the sole treatment in 1. The pts with T-cell lymphoma received CHOP (3) or interferon alfa-2b (2). Thirty eight pts are in complete remission. There were 3 deaths due to the disease (1 MALT, 1 predominantly small cleaved cell and 1 B-DLCL). Three additional pts relapsed and achieved complete response with a second chemotherapy course and 2 pts developed a lymphoma of different histology. In conclusion, oral lymphoma is a rare disease mainly of a diffuse large B-cell histology and a prolonged survival, when treated with chemotherapy (10-year Event Free Survival 82.5%).

Autoimmune Hemolytic Anemia with Myelodysplastic Features Followed by Bilateral Adrenal Non-Hodgkin Lymphoma: A Case Report and Review of the Literature

Primary adrenal lymphoma is a rare entity characterized mainly by bilateral involvement, presenting predominantly diffuse large B-cell histology, adrenal insufficiency and poor prognosis. Approximately 85 cases have been described in the literature. We report here a case of a 77-year-old man who presented with autoimmune hemolytic anemia (AIHA), which preceded the diagnosis of lymphoma by more than 2 years. An ultrasound guided biopsy revealed diffuse, large B-cell, lymphoma; subsequent staging revealed no other disease site, and the patient was considered to have primary adrenal lymphoma. The patient had adrenal insufficiency at diagnosis. He received hormonal replacement and chemotherapy, but he succumbed to his disease because of sepsis and multi-organ failure a few days post diagnosis. To our knowledge, this is the first case in the literature in which AIHA preceded bilateral adrenal lymphoma. We also provide a summary of the current data for the clinical features, diagnosis and treatment of primary adrenal lymphoma.

The modified International Prognostic Index can predict the outcome of localized primary intestinal lymphoma of both extranodal marginal zone B-cell and diffuse large B-cell histologies.

We have previously reported on the efficacy of a modified International Prognostic Index (MIPI) in predicting the outcome of patients with primary gastric lymphoma. This prompted the retrospective analysis of a large series of patients with primary intestinal lymphoma (PIL) of both diffuse large B-cell (DLCL) and low-grade (extranodal marginal zone B-cell lymphoma, MZL) histology. Clinical records of 122 patients with localized primary intestinal lymphoma of MZL (n=35) and DLCL (n=87) histology, confirmed by an ad hoc expert panel of pathologists, were reviewed. Forty-nine patients were treated with single therapy, while 72 received combined-modality treatment, which included surgery followed by a short-term chemotherapy. MIPI was included in a multivariate prognostic analysis for overall survival (OS) and event-free survival (EFS). Sixty-five patients (75%) with DLCL and 22 with MZL(65%) achieved complete remission. After a median follow-up of 42 months (range 6-163 months), 5-year estimates of OS and EFS were 68% and 50% for DLCL and 65% and 26% for MZL. OS varied according to MIPI, from, respectively, 86% and 87% for DLCL and MZL patients with 0-1 risk factor to 50% and 32% for patients with > 1 risk factor (P=0.01 and P=0.02). Similar results were obtained for EFS. Cox regression analysis showed an unfavourable MIPI to be the only independent predictor of shorter EFS. This retrospective study shows that stage-MIPI can be a reliable prognostic indicator for PIL of both low-grade MZL and diffuse large B-cell histology, enabling the early identification of patients at higher risk of failure.

Chemotherapy for management of localised high-grade gastric B-cell lymphoma: how much is necessary?

BackgroundRecent data suggest that chemotherapy with the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen is a highly effective treatment for localised primary gastric lymphoma of diffuse large B-cell histology (DLBCL). We have reported that the large majority of patients achieve complete remission (CR) following three cycles of treatment, and now provide an updated series with special emphasis on patients receiving only short-term chemotherapy. Patients and methodsAll patients with a histologically verified diagnosis of gastric DLBCL in stages EI and EII1 undergoing chemotherapy with the CHOP regimen were evaluated. Data analysed included clinical stage, histology [presence of an additional mucosa-associated lymphoid tissue (MALT) component], evidence of Helicobacter pylori infection, H. pylori eradication, time to CR, survival and regular restaging (i.e. after three and six cycles, respectively). ResultsA total of 37 patients with DLBCL of the stomach with localised disease were identified, five of whom also had a MALT component. Twenty-two patients presented with stage EI and 15 with stage EII1 disease. All patients were given chemotherapy as sole management of their lymphoma; 36 patients received CHOP, while one patient was given CHOP along with rituximab. Thirty-two (86%) achieved a CR after a maximum of three cycles, while only four patients had to be given six cycles for CR. In total, nine of 37 patients (24%) discontinued therapy earlier than scheduled: one patient received one cycle, two receivedtwo, six received three and one patient received four cycles. Two of these patients stopped treatment due to toxicity, i.e. protracted thrombocytopenia or chemotherapy extravasation. One additional patient died after one cycle of treatment; autopsy disclosed no signs of remaining lymphoma. Three patients have died after a median follow-up of 39 months (including the one patient who discontinued therapy after one cycle of treatment), while the remaining 34 patients are alive without evidence of disease. Twenty-four out of 37 patients (65%) had also undergone H. pylori eradication (including six of nine patients receiving only short-term treatment). ConclusionsDLBCL of the stomach appears to be a highly chemosensitive disease. Our data question the need for full-term CHOP treatment in patients achieving CR upon first follow-up. However, recent data suggest that additional H. pylori eradication might have contributed to the excellent results achieved in our series.

Stage-modified international prognostic index effectively predicts clinical outcome of localized primary gastric diffuse large B-cell lymphoma

The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stage-modified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. After a median follow-up of 66 months (range 0.6-300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with > or = 3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.