High-dose therapy with autologous stem cell transplantation in patients with peripheral T cell lymphomas

Peripheral T cell lymphomas (PTCL) have a poorer prognosis after conventional treatment than do high-grade B cell lymphomas. The place for high-dose therapy (HDT) with autologous stem cell support in these patients is still not clear. Forty patients, 10 women and 30 men, median age 41.5 years (range 16-61) with PTCL were treated with HDT and autologous stem cell support at The Norwegian Radium Hospital, Oslo, Norway and The University Hospital, Uppsala, Sweden, between February 1990 and September 1999. The histologic subtypes were: PTCL unspecified, 20 patients; intestinal, two patients; angioimmunoblastic (AILD), two patients; angiocentric, two patients and anaplastic large cell lymphoma (ALCL), 14 patients. All patients had chemosensitive disease and had received anthracycline-containing regimens prior to transplantation. At the time of HDT, 17 patients were in first PR or CR and 23 were in second or third PR or CR. Conditioning regimens were BEAM in 15 patients, BEAC in 14 patients, cyclophosphamide and total body irradiation (TBI) in eight patients, BEAC, without etoposide and TBI in one patient and mitoxantrone and melphalan in two patients. There were three (7.5%) treatment-related deaths. The estimated overall survival (OS) at 3 years was 58%, the event-free survival (EFS) 48% and the relapse-free survival (RFS) 56%, with a median follow-up of 36 months (range 7-100) for surviving patients. The patients with ALCL tended to have a better prognosis compared to those with other PTCL subtypes, OS 79% vs 44%, respectively. In conclusion, patients with chemosensitive PTCL who are failing to achieve CR with first-line chemotherapy or are in relapse can successfully be treated with HDT and autologous stem cell support.     

Infused CD34 cell dose, but not tumour cell content of peripheral blood progenitor cell grafts, predicts clinical outcome in patients with diffuse large B-cell lymphoma and follicular lymphoma grade 3 treated with high-dose therapy

Previously, we have shown that patients with diffuse large B-cell lymphoma (DLBCL) transplanted with contaminated bone marrow (BM) generally have a poor outcome. Whether this is also the case when peripheral blood progenitor cell (PBPC) grafts are used is not known. Forty-three patients with chemosensitive DLBCL or follicular lymphoma grade 3 (FLgr3) were treated with high-dose therapy (HDT) and autologous stem cell support. Nine patients received purged grafts. Quantitative real-time polymerase chain reaction (QRT-PCR) for either the BCL2/IgH translocation or allele specific oligonucleotide (ASO) QRT-PCR for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 were used. Nine of 25 (36%) PBPC grafts contained tumour cells as tested by QRT-PCR, including two grafts purged by CD34(+) cell enrichment combined with B-cell depletion. The level of contamination of the PBPC/CD34(+) cells ranged from 0 to 8.28%. No relationship could be shown between the total number of tumour cells infused and relapse. Patients receiving PCR-positive or PCR-negative PBPC grafts had similar progression-free survival (PFS) (P = 0.49). However, a significant difference was seen in PFS and overall survival (OS) for the patients given >/=6.1 x 10(6) CD34(+) cells/kg compared with those given <6.1 x 10(6) CD34(+) cells/kg (P = 0.01 and P < 0.05 respectively).     

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.     

Testicular microlithiasis: The importance of self‐examination

Aim: To explore the issue of appropriate management of testicular microlithiasis. We report the third ever case of tumour arising from a testis previously known to have microlithiasis in childhood and review the literature to provide an evidence‐based approach to management of testicular microlithiasis. Methods: Case report and review of previous literature. Results and Conclusions: Although there is a strong association between testicular microlithiasis and testicular malignancy at diagnosis, there are only three reported cases of subsequent tumour development in childhood. Testicular microlithiasis is an increasingly recognised entity. There is insufficient evidence in the current literature to support any regime of clinical surveillance. Self‐examination is the most important factor in the early detection of testicular malignancy.     

Low levels of monoclonal small B cells in the bone marrow of patients with diffuse large B-cell lymphoma of activated B-cell type but not of germinal center B-cell type

Background

Multiparameter flow cytometry allows the detection of minor monoclonal B-cell populations. Using this technique combined with morphology, we were struck by the presence of minor populations of small monoclonal B cells in bone marrows of patients with diffuse large B-cell lymphoma in routine diagnostic samples and performed a systematic retrospective study.

Design and Methods

Bone marrows of 165 patients with primary diffuse large B-cell lymphoma without histological evidence of concurrent non-Hodgkin’s lymphoma were studied by routine microscopy of trephines and smears, immunohistochemistry and multiparameter flow cytometry.

Results

Diffuse large B-cell lymphoma infiltration in marrows was documented in 11 of 165 patients. Morphological examination consistently revealed a higher tumor load than evidenced by flow cytometry. Of interest, only 3 of 119 patients with diffuse large B-cell lymphoma not otherwise specified, the largest subtype, showed marrow infiltration. By contrast, flow cytometry revealed a minor monoclonal B-cell population in 24 of 165 patients, none of whom showed diffuse large B-cell lymphoma infiltration by morphology. Of interest, morphological examination revealed the presence of small B cells in the marrows of those patients. Moreover, 11 of 39 (28.2%) of patients with diffuse large B-cell lymphoma not otherwise specified of ABC subtype and only 3 of 80 (3.7%) with the GCB subtype showed these monoclonal small B cells (P=0.0002). In addition 4 of 8 (50%), 4 of 15 (26.7%) and 2 of 3 (66.7%) patients with primary testicular, primary central nervous system and leg-type diffuse large B-cell lymphoma, respectively, showed monoclonal small B cells.

Conclusions

Bone marrow infiltration with diffuse large B-cell lymphoma in patients with diffuse large B-cell lymphoma not otherwise specified is rare at diagnosis. By contrast, a high number of diffuse large B-cell lymphoma not otherwise specified of the ABC subtype but not of GCB subtype is associated with monoclonal small B cells in the marrow. Whether these monoclonal small B cells are precursors of diffuse large B-cell lymphoma of the ABC type or arise in a common background that favors clonal B-cell expansion remains to be demonstrated.     

A national study on conditional survival,excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non‐Hodgkin lymphoma

This national population‐based study aimed to investigate conditional survival and standardized mortality ratios (SMR) after high‐dose therapy with autologous stem‐cell transplantation (HDT‐ASCT) for non‐Hodgkin lymphoma (NHL), and to analyse cause of death, relapses and second malignancies. All patients ≥18 years treated with HDT‐ASCT for NHL in Norway between 1987 and 2008 were included (n = 578). Information from the Cause of Death Registry and Cancer Registry of Norway were linked with clinical data. The 5‐, 10‐ and 20‐year overall survival was 61% (95% confidence interval [CI] 56–64%), 52% (95%CI 48–56%) and 45% (95%CI 40–50%), respectively. The 5‐year survival conditional on having survived 2, 5 and 10 years after HDT‐ASCT was 81%, 86% and 93%. SMRs were 12·3 (95%CI 11·0–13·9), 4·9 (95%CI 4·1–5·9), 2·4 (95%CI 1·8–3·2) and 1·0 (95%CI 0·6–1·8) for the entire cohort and for patients having survived 2, 5 and 10 years after HDT‐ASCT respectively. Of the 281 deaths observed, 77% were relapse‐related. Treatment‐related mortality was 3·6%. The 10‐year cumulative incidence of second malignancies was 7·9% and standardized incidence ratio was 2·0 (95%CI 1·5–2·6). NHL patients treated with HDT‐ASCT were at increased risk of second cancer and premature death. The mortality was still elevated at 5 years, but after 10 years mortality equalled that of the general population.     

Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times

The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10·0years (range, 4·6-16·0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 1-2, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 1-2 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 1-3A and independently of clinical factors, grade 3B correlated with higher mortality (P=0·008), but outcome was improved after upfront anthracycline-containing therapy (P=0·015). In contrast to grade 1-3A patients, grade 3B patients experienced no relapses or deaths beyond 5years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 1-3A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease.     

Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study

Abstract Objective. Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. Material and methods. In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. Results. Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0-50) years at the time of Ltx and follow-up after Ltx was 5 (0-20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3-2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. Conclusion. The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated.     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.