IGHV gene usage and mutational status in follicular lymphoma: Correlations with prognosis and patient age.

Follicular lymphoma (FL) is a heterogeneous disease with some patients developing progressively or transformed disease early, whereas others follow an indolent clinical course. We evaluated the prognostic value of immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in FL patients. One hundred and four IGH sequences were obtained in tumour samples from 99 patients. The IGHV3 subgroup had the highest usage frequency (57.7%) with IGHV3-23 being the most common sequence. Patients with the IGHV5 subgroup or IGHV sequences from more than one subgroup had significantly less favourable prognosis with an estimated 5-year survival of 62.5 and 50.0%, respectively, as compared with a 5-year survival of 95.1% for patients with other IGHV subgroups (P=0.013 and P<0.001, log-rank). The poor survival associated with IGHV5 or >1 IGHV subgroup usage was an independent prognostic factor in Cox multivariate analysis (P=0.005). IGHV genes were unmutated showing >98% homology in 15.2% of cases. Contrasting the situation in chronic lymphocytic leukaemia (CLL), the presence of unmutated sequences did not yield prognostic information, although unmutated sequences were associated with age at diagnosis >60 years (P=0.022, Fisher's exact). In conclusion, our results indicate that analysis of IGHV gene usage might aid in predicting prognosis for FL patients.

Prognostic value of bone marrow involvement by clonal immunoglobulin gene rearrangements in follicular lymphoma.

AIMS: We aimed to evaluate the prognostic value of routine use of PCR amplification of immunoglobulin gene rearrangements in bone marrow (BM) staging in patients with follicular lymphoma (FL). METHODS: Clonal rearrangements were assessed by immunoglobulin heavy and light-chain gene rearrangement analysis in BM aspirates from 96 patients diagnosed with FL and related to morphological detection of BM involvement in biopsies. In 71 patients, results were also compared with concurrent flow cytometry analysis. RESULTS: BM involvement was detected by PCR in 34.4% (33/96) of patients. The presence of clonal rearrangements by PCR was associated with advanced clinical stage (I-III vs IV; p<0.001), high FL International Prognostic Index (FLIPI) score (0-1, 2 vs ≥3; p=0.003), and detection of BM involvement by morphology and flow cytometry analysis (p<0.001 for both). PCR-positive patients had a significantly poorer survival than PCR-negative patients (p=0.001, log-rank test). Thirteen patients positive by PCR but without morphologically detectable BM involvement, had significantly poorer survival than patients with negative morphology and negative PCR result (p=0.002). The poor survival associated with BM involvement by PCR was independent of the FLIPI score (p=0.007, Cox regression). BM involvement by morphology or flow cytometry did not show a significant impact on survival. CONCLUSIONS: Our results showed that routine use of PCR-based clonality analysis significantly improved the prognostic impact of BM staging in patients with FL. BM involvement by PCR was also an independent adverse prognostic factor.

High-dose therapy with autologous stem cell support for lymphoma--from experimental to standard treatment.

High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.

Diagnostic yield of biopsies of cervical lymph nodes using a large (14-gauge) core biopsy needle.

The purpose of this study was to assess retrospectively complications and diagnostic yield of core needle biopsy (CNB) of cervical lymph nodes using 14-gauge as sole needle bore. During a 10-year period ultrasound (US)-guided CNB, using a 14-gauge Tru-Cut needle (non-advancing), was performed in 140 consecutive cases (135 patients, aged 8-88 years) when a detailed histological diagnosis was required to guide therapy. CNB findings were consistent with the final diagnosis in 129 of the 140 cases, comprising 36 benign lesions, 40 metastases, and 53 lymphomas (40 NHL and 13 HL) of which subclassification (WHO criteria) was partial in 5NHL, and complete in 35 (87.5%) NHL and 13 HL (100%), including all 7 lymphomatous nodes with short-axis diameter ≤1.0 cm. Two lymphomas were falsely interpreted as reactive hyperplasia. Nine samples (6.4%) were inadequate for histopathological analysis. One patient experienced pain in an arm lasting 3-4 days. No other immediate or delayed complications were diagnosed. A 14-gauge may be used safely as the sole needle bore in US-guided CNB of cervical lymph nodes, rendering samples sufficient for full subtyping in lymphoma, even in the smallest nodes.

Autologous peripheral blood progenitor cells cryopreserved with 5 and 10 percent dimethyl sulfoxide alone give comparable hematopoietic reconstitution after transplantation.

BACKGROUND: Previous in vitro studies have demonstrated decreased apoptosis and necrosis in peripheral blood progenitor cells (PBPCs) cryopreserved with 5 percent instead of 10 percent dimethyl sulfoxide (DMSO). This study was carried out to investigate whether these in vitro findings were supported by clinical data concerning hematopoietic engraftment after autologous stem cell transplantations with PBPCs cryopreserved with 5 and 10 percent DMSO. STUDY DESIGN AND METHODS: During a 6-year period, 103 consecutive patients with newly diagnosed multiple myeloma (MM; n = 58) and lymphoma (n = 45) were transplanted with autologous PBPCs. Throughout the first part of the period cells were cryopreserved with 10 percent DMSO and later with 5 percent. A retrospective comparison was carried out of the clinical results for these two groups. RESULTS: No significant difference in median time to neutrophil and platelet (PLT) engraftment was demonstrated for MM and lymphoma patients transplanted with PBPCs cryopreserved with 5 or 10 percent DMSO. Time until neutrophil counts of more than 0.5 x 10(9) per L was 10 days both for the 5 and 10 percent MM groups and 12 days for both the 5 and the 10 percent lymphoma patients. Median time until stable PLT counts of more than 20 x 10(9) per L was 11 days in all four groups. In addition, transfusion requirements and duration of days admitted to hospital did not differ between the groups. CONCLUSION: The routines for cryopreservation of autografts vary considerably between transplantation centers, and this makes it difficult to compare different clinical studies. Our results suggest that cryopreservation with 5 percent DMSO alone followed by storage in nitrogen is a simple, highly standardized, and safe procedure for cryopreservation of autologous stem cell graft.

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility.

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.