Treatment outcome of front-line systemic chemotherapy for localized extranodal NK/T cell lymphoma in nasal and upper aerodigestive tract

We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 - 45.03] and 15.27 months (95% CI = 2.92 - 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.     

Role of the molecular staging and response in the management of follicular lymphoma patients

Bcl-2/IgH rearrangement is the molecular hallmark of follicular lymphoma which is present in 70 - 90% of cases at diagnosis. The significance of the bcl-2 rearrangement at onset of disease and of its clearing after treatment (molecular response) is still controversial.

The aims of the present analysis are: to evaluate the incidence of bcl-2 rearrangement in blood and marrow in a cohort of patients systematically investigated at diagnosis, to describe the correlation between bcl-2 and presenting features, to clarify the correlation of molecular response with outcome.

Of 98 patients studied at initial staging for the presence of bcl-2 rearrangement, 64 (65%) showed bcl-2/IgH rearrangement in peripheral blood (PB) and/or bone marrow (BM) (58 at Major Breakpoint Region, MBR, and 6 at minor cluster region, mcr) while no bcl-2/IgH rearrangement was detected in the remaining 34 (35%) (germline status). No statistically significant differences were found between bcl-2 positive and bcl-2 negative cases as concerns presenting clinical features and response to first-line therapy. The median event-free survival, EFS, was not reached for the bcl-2 negative patients in PB and was 11 months for bcl-2 positive patients (statistically significant, P = 0.01) and, similarly, the median EFS was not reached for the bcl-2 negative patients in BM and was 11 months for bcl-2 positive patients (statistically significant, P = 0.04).

Of the 64 bcl-2 positive cases, patients were analysed for molecular response (48 in BM and 40 in PB): 16 were molecular responders in BM and 20 were molecular responders in PB. The median EFS was 19 months for molecular responders in PB and 9 months for non-responders; 1-year-EFS was 68% (95% CI; 49 - 88), for responders in PB and 42% (95% CI; 22 - 61) for non-responders (P = 0.05). The median EFS was 11 months both for molecular responders and non-responders in BM; 1-year-EFS was 52% for responders in BM (CI; 30 - 73), and 43% (CI 33 - 71) for non-responders (P = 0.7). No clinical feature showed significant correlation with PB and BM molecular responses.

This analysis shows that bcl-2 rearrangement in blood and bone marrow is frequently detected at staging, even in stage I disease. Absence of the bcl-2 rearrangement is related to a better EFS and the achievement of a molecular response in peripheral blood after therapy is associated with a better EFS.     

Serum levels of syndecan-1 in B-cell chronic lymphocytic leukemia: correlation with the extent of angiogenesis and disease-progression risk in early disease

Syndecan-1 is a transmembrane proteoglycan generally not expressed in mature B-cell neoplasias like chronic lymphocytic leukemia (CLL). Moreover, information dealing with the evaluation of soluble syndecan-1 in CLL are lacking. We measured syndecan-1 concentrations in serum drawn at the time of diagnosis from 67 B-cell CLL patients (Binet stage A, 46; stage B, 7; stage C, 14). For this purpose a syndecan-1 enzyme-linked immunosorbent assay (ELISA, Diaclone, Besancon, France) was used. Detectable levels of syndecan-1 were found in all patients, although serum concentrations were significantly lower in CLL patients in comparison to age- and sex-matched controls (P = 0.02; Mann-Whitney test). No correlation was found with Binet clinical stages (P = 0.796), β2-microglobulin (P = 0.923), hemoglobin level (P = 0.605), platelet count (P = 0.992) and lymphocyte doubling time (P = 0.709). Only an association with absolute peripheral blood lymphocytosis (PBL) (P = 0.01) and LDH (P = 0.05) could be detected. Serum levels of syndecan-1 did not parallel those of several angiogenic cytokines such as vascular endothelial growth factor (VEGF) (P = 0.963), basic fibroblastic growth factor (FGF-2) (P = 0.216), angiogenin (P = 0.478), metalloproteinase-9 (MMP-9) (P = 0.125) as well as bone marrow (BM) microvessel density (P = 0.110). The same applied with adhesion molecules such as CD54 (P = 0.233), CD108 (P = 0.799), CD44 (P = 0.816) and CD31 (P = 0.508). Interestingly, the inverse correlation (r = -0.4967; P = 0.03) between serum concentrations of syndecan-1 and plasma levels of stromal derived growth factor-1 (SDF-1) is in keeping with the different function, respectively, pro- and anti-apoptotic, of these molecules. In 46 Binet stage A patients, serum levels of syndecan-1 were further evaluated as a dichotomous variable with respect to progression-free survival (PFS), an end-point surrogate for overall survival in early B-cell CLL. The best separation of curves was seen with a cut-off point at the median value of syndecan-1 (i.e. 36.5 pg/ml). Median PFS was not reached in the patient group with low syndecan-1, compared to a median of 34 months observed in the remaining patients (P = 0.018; HR = 0.208; 95% CI = 0.115 - 0.816). At the multivariate analysis performed including variables significant in the univariate analysis [i.e. PBL (P = 0.03) and syndecan-1 (P = 0.01)], only syndecan-1 retained a trend of significance (P = 0.08).

Despite the pro-angiogenic activity of syndecan-1 which mediates FGF-2 binding and activity, no correlation with either angiogenic cytokines or the extent of BM angiogenesis was found in CLL. The inverse correlation with plasma levels of SDF-1 suggests an involvement in the processes leading to apoptosis. Finally, our results highlight the involvement of syndecan-1 in the mechanisms of disease-progression of early CLL.     

The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis

A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide - thalidomide - dexamethasone) and infusional CVAMP (cyclophosphamide - vincristine - doxorubicin - methylprednisolone) as induction therapy followed by autologous peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.     

The pretransplant Follicular Lymphoma International Prognostic Index is associated with survival of follicular lymphoma patients undergoing autologous hematopoietic stem cell transplantation

We retrospectively evaluated the association of the Follicular Lymphoma International Prognostic Index (FLIPI) and other characteristics with survival following high-dose therapy and autologous stem cell transplantation (ASCT) in 207 consecutive follicular lymphoma (FL) patients. The FLIPI was associated with OS both when evaluated as a categorical variable (0 - 1 vs. 2 vs. 3 vs. 4, p = 0.01, global test) and a continuous linear variable (p = 0.002). The association of FLIPI with survival appeared to be more relevant for patients who received standard conditioning regimens compared to those that were treated with high-dose radioimmunotherapy (p = 0.004). Among all patients, mortality was also associated with chemosensitive disease (HR = 0.47, p = 0.01) or untreated relapse (HR = 0.20, p = 0.0002) vs. chemoresistant disease, and ≥2 extranodal sites (HR = 2.82, p = 0.03) after adjusting for FLIPI. These data suggest that the FLIPI and select non-FLIPI factors after adjustment for the FLIPI are associated with survival in FL patients undergoing ASCT.     

Cladribine combined with cyclophosphamide and mitoxantrone is an active salvage therapy in advanced non-Hodgkin's lymphoma

The aim of this study was to determine the feasibility, efficacy and toxicity of the combined therapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in patients with refractory or relapsed non-Hodgkin's lymphoma (NHL). Thirty six patients, 14 with mantle cell lymphoma (MCL), 10 with diffuse large B-cell lymphoma (DLBCL), 5 with follicular lymphoma (FL), 3 with small lymphocytic lymphoma (SLL), and 4 with T-cell lymphoma were enrolled to the study. The CMC protocol consisted of 2-CdA at a dose of 0.12 mg/kg in a 2-hour infusion on days 1 through 3, mitoxantrone 10 mg/m² i.v. on day 1 and cyclophosphamide 650 mg/m² i.v. on day 1. The CMC courses were repeated at intervals of 4 weeks. Thirty three patients were available for evaluation of response. Overall response rate (OR) was 58% (95% CI, 41 - 75%). Seven patients (21%; 95% CI, 7 - 35%) achieved a complete response (CR) and 12 patients (36%; 95% CI, 20 - 52%) achieved a partial response (PR). Seven of 19 patients with CR/PR are still in remission with a median follow-up of 3 months (range, 2 - 17 months). The median failure-free survival (FFS) was 5 months (range, 2 - 17 months). The median overall survival (OS) for the entire group was 9 months (range, 0.1 - 77 months). There was a significant difference in OS between responders and nonresponders after CMC therapy (log rank test, P = 0.015). When different disease status before CMC treatment was considered, a trend toward longer survival of recurrent patients was observed (log rank test, P = 0.08). Grade 3 - 4 neutropenia developed in 14 (39%) patients, and 16 episodes (15%) of grade 3 - 4 infections were observed. Grade 3 - 4 thrombocytopenia or anemia was seen in 9 patients (25%) and 10 patients (28%), respectively. The results of our study show that the CMC regimen is effective salvage therapy with acceptable toxicity in heavily pretreated patients with NHL including MCL and DLBCL.     

Aggressive non-Hodgkin's lymphoma: concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome

The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.     

Role of anemia in survival of patients with elderly aggressive non-Hodgkin's lymphoma after chemotherapy

Baseline anemia is a relevant prognostic factor in the overall population of non-Hodgkin's lymphoma (NHL) patients, and studies focusing on elderly NHL are awaited. We conducted a pooled analysis of a cohort of comparable patients enrolled (1993 - 2001) in three multicenter clinical trials on use of a MACOP-B-like regimen (VNCOP-B) for front-line treatment of elderly aggressive NHL. Models of Cox's proportional hazards regression analysis of prognostic value of pre-/post-treatment hemoglobin values in terms of 5-year overall survival included age, sex, initial tumor staging and response to treatment. Of the 168 patients screened, 16 were excluded due to missing data or lack of 5-year follow-up. In addition to achievement of complete/partial remission (adjusted relative risk [RR], 0.215; p = 0.0001) and advanced stage (II-IV vs. I - II; adjusted RR, 1.55; p = 0.0023), post-treatment hemoglobin values were an independent predictor of survival (adjusted RR per 1-g/dL increment, 0.76; p = 0.0041). In the present analysis, pretreatment hemoglobin values were associated with only marginal risk reduction (adjusted RR per 1-g/dL increment, 0.985; p = 0.049). Post-treatment hemoglobin values appear to provide a strong independent predictor of 5-year survival in elderly aggressive NHL, supporting the potential role of anemia correction in this group of patients.     

Distribution and clinicopathologic characteristics of non-Hodgkin's lymphoma in India: a study of 935 cases using WHO classification of lymphoid neoplasms (2000)

The frequency of various subtypes of non-Hodgkin's lymphoma (NHL) differs in various regions worldwide. We studied distribution of various subtypes of NHL by using WHO classification of lymphoid neoplasms (2000), immunophenotyping and clinicopathologic characteristics of various histologic subtypes in 935 cases. B- and T-cell NHL constituted 79.3% and 18.8% of cases. Diffuse large B-cell lymphoma (DLBL) was the most common subtype (50.2%). A lower frequency of follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma (MCL) was noted compared to that observed in the developed countries, whereas a lower frequency of peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS) and extranodal NK/T-cell lymphoma was seen compared to that in the other Asian countries. A higher frequency of DLBL and precursor T-lymphoblastic leukemia/lymphoma was noted. Extranodal and bone marrow involvement in MCL and PTCL-NOS was less frequent. Anaplastic variant of DLBL was noted in 21.5% of all DLBLs. Null/T-cell anaplastic large cell lymphoma presented in the older age.     

HFE gene mutations in patients with acute leukemia

An increased incidence of HFE gene mutations has been described in hematologic malignancies. In the present study, we investigated the allelic frequency of HFE gene mutations in 154 adult patients with acute leukemia (AL) [107 acute myeloid leukemia (AML), 20 acute promyelocytic leukemia (APL) and 27 acute lymphoblastic leukemia (ALL)]. The allelic frequency of the H63D mutation was 29% in AL patients and 25% in the healthy controls [P = 0.41; odds ratio (OR) = 1.20; 95% confidence interval (CI) = 0.77 - 1.93]. No difference was found between controls and AML or APL patients, whereas the H63D mutation was significantly more frequent in ALL than controls (44% vs. 25%, P = 0.04; OR = 2.37; 95% CI = 1.05 - 5.36). The overall comparison of the mutation among the three subtypes of AL demonstrated a higher allelic frequency in ALL (P = 0.02). In conclusion, our data demonstrate a correlation between the presence of the H63D mutation and the occurrence of ALL in adult patients.     

Clinical features and outcome in HCV-positive aggressive non-Hodgkin's lymphoma

The clinical features and outcome of 25 previously untreated aggressive non-Hodgkin's lymphoma (NHL) patients with hepatitis C virus (HCV) infection were evaluated retrospectively. The patients included 18 males and 7 females with a median age of 66 years. The median observation period for survivors was 32 months. Although there were no patients with hepatocellular carcinoma during the follow-up period, 7 patients had cirrhosis (LC) at the initiation of therapy for NHL. Seventeen patients (68%) had initial extranodal involvement including 2 cases with liver involvement. The 5-year overall survival (OS) rate in the whole group was 46%, and the 5-year relapse-free survival (RFS) rate of patients with complete response (CR) was 48%. Patients with non-cirrhosis (n=18) showed better OS (P=0.04) compared with patients with LC (n=7) and 5-year OS rates were 55 and 21%, respectively. Fourteen patients died in the whole group; 4 of NHL and 2 of liver failure in the LC group and 8 of NHL in the non-cirrhotic group. Among the latter 8 patients, cumulative dose (CD) of doxorubicin (ADR) and cyclophosphamide (CPA) were significantly lower than those of survivors with non-cirrhosis. In conclusion, patients with HCV-positive aggressive NHL have a similar prognosis as HCV-negative aggressive NHL. In non-cirrhotic patients, attention should be paid to the CD of drugs required to cure the aggressive NHL.     

Morbidity and transplant-related mortality of CBV and BEAM preparative regimens for patients with lymphoid malignancies undergoing autologous stem-cell transplantation

CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and transplant-related mortality (TRM) in 113 patients with non-Hodgkin's lymphoma (69) and Hodgkin's disease (44) undergoing ASCT between 1990 - 2004. CBV (cyclophosphamide, 6000 mg m^-2; VP-16, 750 mg m^-2; and high-dose BCNU, 800 mg m^-2) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m^-2; VP-16, 800 mg m^-2; cytarabine, 800 mg m^-2; melphalan, 140 mg m^-2). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.     

Rituximab-related viral infections in lymphoma patients

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.     

Clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma in patients diagnosed at the Mayo Clinic (1986-2000)

There are few data on the clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma (NHL). Using the NHL registry at the Mayo Clinic, we compared age of diagnosis, gender, tumor site and histologic subtype between patients with sporadic and familial NHL. In 2001, we identified all new cases of adult NHL diagnosed between 1986 and 2000 in the Mayo Clinic NHL database (n = 2,289) and mailed out a family history questionnaire to all living patients with a current address (n = 1,043). Each NHL patient was categorized according to their self-report of leukemia or lymphoma in first-degree (1°) relatives. We received complete FH information on 740 patients (71%). Age at diagnosis of NHL ranged from 18 - 88 years (mean = 59 years) and 53% of our cases were male. First-degree FH of lymphoma was reported by 43 patients (6%), 1° FH of leukemia by 27 patients (4%) and 1° FH of both in 4 (1%). There was a nonstatistically significant later age at diagnosis for cases with any family history of lymphoma or leukemia (mean age = 61.3 and 61.7 years, respectively) vs. no family history (59.0 years) (P = 0.58). The male to female ratio for those with a FH of leukemia (ratio = 2.9) was higher compared to those with FH lymphoma (0.95) or no FH (1.1) (P = 0.08). No differences were apparent between 1° FH and site of NHL (nodal vs. extranodal) (P = 0.53). Among recently diagnosed cases (since 1995), there was some suggestion of a greater proportion of aggressive tumors for those with any family history (69% and 55%) vs. none (50%) (P = 0.20). We found little evidence of large differences between familial and sporadic NHL with regard to age, gender, site or histologic subtype.     

Primary gastrointestinal non-Hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG)

The aim of this retrospective study was to illustrate the clinicopathologic data and the treatment results in patients with primary gastrointestinal tract non-Hodgkin's lymphoma (GI NHL). Among 810 patients with NHL, 128 cases (15.8%) were diagnosed as primary GI tract NHL. There were 79 males and 49 females with median age of 62 years. The most common primary site was the stomach (68%). Overall, 67.2% of the patients were in stages I - II, and 32.8% in stages III - IV. Simultaneous involvement of the GI tract and other extranodal sites was observed in 26 patients (20%). Extranodal marginal zone B-cell lymphoma (MZBL) (i.e., low-grade lymphoma of mucosa-associated lymphoid tissue type) accounted for 48.4% of lymphomas. Aggressive lymphomas (diffuse large B-cell lymphoma [DLBL]) accounted for 44.5%. Eighty-three patients (67.5%) achieved complete response (CR), either by surgery (43/43 patients, 17 with DLBL and 25 with MZBL) or by primary chemotherapy (40/64 patients, 22 with DLBL and 17 with MZBL). Sixty-two patients remain in CR; 33/43 after surgical resection (13/17 with DLBL and 20/25 patients with MZBL), and 29/40 after only chemotherapy (18/22 with DLBL and 10/17 with MZBL). The major prognostic factor for outcome in the present study was the stage of the disease. Patients with localized lymphoma (stage I and II) had significantly longer DFS and OS (DFS and OS at 3-year: 83% and 87%, respectively) than patients with extended disease (stage III and IV) (DFS and OS at 3-year: 46% and 60%, respectively) (P < 0.0001). The International Prognostic Index (IPI) for patients with aggressive lymphomas was prognostic only for DFS (79% for low-risk patients [IPI score 0 - 1] vs 49% for higher risk groups [IPI score >1] at 3-year, P = 0.0131).     

Autoimmune hemolytic anemias, Evans' syndromes, and pure red cell aplasia in non-Hodgkin lymphomas

We analyzed 108 cases of non-CLL non-Hodgkin lymphoma (NHL) associated with autoimmune hemolytic anemia (AIHA) (+/- pure red cell aplasia (PRCA)) or Evans' syndrome. The analysis was based on cases reported in the literature, which were retrieved by means of Pubmed and Medline searches and of an original series of 121 patients with NHL as well as reference lists of papers in the field. The number of cases in various NHL subtypes was small (n = 6 - 25). Nevertheless, interesting and sometimes unexpected differences in sex prevalence, temporal relationship between onset of lymphoma and AIHA, stage of lymphoma, relative frequency of warm antibody-AIHA (WA-AIHA) and cold antibody (CA-AIHA), association with PRCA and response of AIHA to treatments were noted for various lymphoma entities. WA-AIHA was more frequent in B-cell lymphomas, while CA-AIHA and PRCA predominantly occurred in T-cell lymphomas. Anti-lymphoma treatment seemed to be more effective against AIHA than conventional therapy with steroids or immunoglobulin. Although generated by a literature survey, this compilation of data indicates a complex relation of lymphoma and AIHA and warrants more attention and specific studies.     

Prognostic value of early 18 fluorodeoxyglucose positron emission tomography and gallium-67 scintigraphy in aggressive lymphoma: a prospective comparative study

The prognostic value of fluorodeoxyglucose positron emission tomography (FDG-PET) and gallium-67 scan (GS) performed early after chemotherapy was assessed in 40 patients with newly diagnosed aggressive lymphoma. FDG-PET and GS were performed before and after three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or two cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone), with or without rituximab. Thirty-five patients had diffuse large B-cell lymphoma (DLBCL), two had mantle-cell lymphoma and three had T-cell lymphoma. Four patients relapsed despite early negative FDG-PET and GS including all three patients with T-cell lymphoma. Nine patients stayed in remission despite positive FDG-PET and/or GS of whom five showed moderate intensity residual bone uptake. Seven of these nine early false positives had a negative exam at the end of treatment. In patients with DLBCL, the 2-year event-free survival was 85% for negative versus 30% for positive FDG-PET patients (P = 0.003) whereas it was 78% for negative versus 33% for positive GS patients (P = 0.018). Sensitivity, specificity and diagnostic accuracy of FDG-PET and GS were not significantly different: 90% versus 70%, 76 versus 80% and 80 versus 77%, respectively. We conclude that both FDG-PET and GS are valuable tools to early predict outcome in patients with DLBCL.     

Dexa-BEAM as salvage therapy in patients with primary refractory aggressive non-Hodgkin lymphoma

Although aggressive NHL in relapse after remission can still be cured by second-line treatment followed by high-dose therapy and autologous stem cell transplantation, the long-term prognosis of patients who fail to obtain remission after first-line therapy remains extremely poor. We retrospectively evaluated a series of 29 consecutive patients with primary refractory high-grade NHL who were treated with Dexa-BEAM (DB) as uniform salvage therapy at a single institution. Twenty-nine patients with aggressive NHL primary refractory to CHOP or CHOP-like induction therapy with a median age of 47 (range, 22 - 64) years received 1 - 2 cycles of DB and were candidates for subsequent autologous stem cell (PBSC) mobilization and transplantation (PBSCT). Follow-up of all patients was updated in March 2004. Eight of 29 patients (28%) responded to one cycle of DB (1 complete/7 partial remissions); 2 of whom are alive after PBSCT (1 autologous/1 matched unrelated donor), 1 patient died after autologous PBSCT. Reasons for failure to proceed to high-dose therapy in spite of response to DB were recurrent progressive disease (n = 2), septicemia (n = 1), and allogeneic transplant-related mortality after mobilization failure to DB (n = 2). Twenty-one patients failed to respond to DB and died of progressive disease. Overall survival was 7% after 41 months. We conclude that Dexa-BEAM salvage therapy is not effective in patients with truly primary refractory high-grade NHL. The efficiency of rituximab combined with Dexa-BEAM or novel chemotherapeutic strategies needs to be established.     

Epstein-Barr virus infection is not the sole cause of high prevalence for Hodgkin's lymphoma in Saudi Arabia

The age-adjusted incidence of Hodgkin's lymphoma (HL) is markedly higher in Saudi Arabia than in the USA, and accounts for 10.5% of all neoplasias in children aged 15 years or older in Saudi Arabia. Epstein - Barr virus (EBV) infection has been suspected to cause high HL incidence in developing countries. To investigate the role of EBV for the high frequency of HL in Saudi Arabia, we analysed 169 HLs from Saudi Arabia and 30 HLs from Europe for EBV infection by in situ hybridization with fluoresence in-conjugated EBV on tissue microarray sections. All Saudi Arabian and European HLs were analysed in one experiment under identical conditions. Unexpectedly, our data show only minor, insignificant differences in EBV infection rates between Saudi Arabian (42 out of 147 informative cases 28.6%) and European HL (nine out of 30 informative cases; 30%; P = 0.8752). Within the Saudi Arabian population, EBV infection was most frequently seen in mixed cellularity HL (52.4%). This was significantly more frequent than in nodular sclerosing HL (26.1%; P = 0.0236). EBV positivity was unrelated to patient prognosis. In conclusion, our data strongly suggest that EBV is not the main cause for the high prevalence of HL in Saudi Arabia. This would be consistent with a major role of genetic susceptibility genes for HL in these populations. The Saudi Arabian population, with high consanguinity and large families, would prove ideal for identifying HL susceptibility genes.     

Long-term follow-up of Asian patients younger than 46 years with acute myeloid leukemia in first complete remission: comparison of allogeneic vs. autologous hematopoietic stem cell transplantation

Optimal therapy for patients with acute myeloid leukemia (AML) in first complete remission (CR-1) remains the subject of debate: with the possibilities of chemotherapy alone, autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT). We undertook a retrospective analysis of AML patients aged below 46 years and in CR-1, who had undergone auto- or allo-HSCT in our institution, to determine the factors associated with a better outcome. Between September 1985 and April 2003, 81 patients underwent autologous (n = 29) or allogeneic (n = 52) HSCT in CR-1. With a median follow-up of 10 years, the probability of 15-year overall survival (OS) was 51%[95% confidence interval (CI) = 32 - 70%] for auto-HSCT vs. 55% (95% CI = 42 - 69) for allo-HSCT, respectively (P = 0.92). The cumulative incidence of relapse at 3 years was 49% (95% CI = 30 - 67) (auto) vs. 21% (95% CI = 10 - 30) (allo), respectively. Non-relapse-related mortality at 3 years was 5% (95% CI = 0 - 14) (auto) vs. 17% (95% CI = 7 - 28) (allo), respectively. This retrospective analysis confirmed that auto- and allo-HSCT led to similar OS. The significantly lower incidence of relapse amongst allograft recipients was balanced by an increased incidence of death in CR.