Role of image-guided core-needle biopsy in the management of patients with lymphoma.

PURPOSE: The results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success. PATIENTS AND METHODS: Biopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight. RESULTS: The biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-grade and low-grade NHL as in nonlymphoproliferative disorders. The procedure was equally successful at diagnosis as at suspected recurrence or progression. In 33 of 80 cases in which the biopsy was performed at the time of recurrence or progression, the histology had changed; in 31 of 33, this influenced treatment. The technique was efficient at diagnosing transformation of follicular NHL in 16 of 18 patients, which allowed early adjustment of treatment at recurrence. CONCLUSION: At St Bartholomew's Hospital (SBH), image-guided core-needle biopsy has proven to be a quick, safe, and efficient alternative to excisional biopsy in the evaluation of lymphoproliferative disorders at presentation, recurrence, or progression. It should become the procedure of choice for histologic sampling in the absence of peripheral lymphadenopathy.

High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up.

PURPOSE: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements. PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement. RESULTS: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. CONCLUSION: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.

Use of the polymerase chain reaction and direct sequencing analysis to detect cells with the t(14;18) in autologous bone marrow from patients with follicular lymphoma, before and after in vitro treatment.

Between August 1993 and February 1994, 25 patients with follicular or transformed follicular lymphoma had bone marrow harvested at St Bartholomew's Hospital (SBH) with a view to proceeding to high-dose treatment comprising: cyclophosphamide 60 mg/kg x 2 and total body irradiation, 200 cGy x 6, supported by autologous bone marrow transplantation (ABMT). The marrow mononuclear cell fraction was treated in vitro with four anti-B cell antibodies and baby rabbit complement. The aim of this study was to determine whether in vitro treatment of the marrow could remove morphologically undetectable lymphoma cells. PCR analysis for the t(14;18) was used to determine the presence or absence of lymphoma. At the time of the bone marrow harvest, 21/25 bone marrow samples were positive for the t(14;18), in 15/22 patients, the rearrangement could also be demonstrated in peripheral blood. After in vitro treatment, 18/21 samples (86%) remained 'PCR positive'. Sequence analysis of the t(14;18) PCR products was performed on the latter and on lymph node biopsy material taken at diagnosis from 12 patients. The same t(14;18) sequences were found in the bone marrow harvest samples as in the patients' original biopsies. These results suggest that this form of in vitro treatment does not completely eradicate the t(14;18) bearing clone. New and better methods need to be developed.

Nodular type of lymphocyte predominant Hodgkin's disease. A clinical study of 50 cases.

BACKGROUND: Lymphocyte predominant Hodgkin's disease (LP-HD), particularly that with a nodular pattern has been suggested to constitute a distinct disorder within the spectrum of Hodgkin's disease, this issue being based on clinical, morphological and immunological observations. Furthermore, the nodular LP-HD (N-LP-HD) has been considered to differ from the diffuse subtype (D-LP-HD), although the data are conflicting. The question addressed in this study was whether the clinical course of N-LP-HD differs from that of the D-LP-HD as well as the other subtypes of Hodgkin's disease. PATIENTS AND METHODS: 90 cases diagnosed as LP-HD at St. Bartholomew's Hospital (SBH) were reviewed. The histopathological classification was based on the original Lukes and Butler criteria for classical N-LP-HD. Clinical data were retrieved from case notes and a computer database. Stage was determined by the Ann Arbor criteria. Survival and remission duration analyses were performed for the group of patients with N-LP-HD and compared with an histological control group of patients with the other subtypes of Hodgkin's disease and the cases of LP-HD that have been reclassified. RESULTS: 1. 50/90 cases (56%) originally diagnosed as N-LP-HD qualified as N-LP-HD. No case with the diffuse subtype, could be identified. Twenty-three percent of the cases were reclassified as Mixed Cellularity and 11% as Nodular Sclerosis HD, whilst 10% as non-Hodgkin's lymphomas. 2. The majority of cases (78%) presented with early stage (I + II). Bone marrow and liver involvement were rare. 3. 92% of cases achieved complete remission. Recurrence developed in only 6/46 patients within 5-12 years. A second complete remission was achieved in 5/6 (83%) cases. Further recurrences have not yet occurred. 4. The overall survival of the 50 cases with N-LP-HD was 92% at 4 years and did not differ significantly from the 40 cases that have been reclassified. Remission duration however, was significantly better for the group of N-LP-HD being 81% at 12 years. 5. Second malignancies were common and developed in 6/50 cases (12%) with N-LP-HD within 10-15 years. These included: ALL (1 case), high grade B-NHL (2 cases), squamous cell carcinoma (1 case), glioma (1 case), lung carcinoma (1 case). 6. 12/50 patients died within a period of follow-up, up to 21 years. 1/3 of the deaths was attributed to the development of second malignancy. CONCLUSIONS: The diffuse variant of LP-HD is rare, having not been seen at St. Bartholomew's Hospital during this time period. The 50 cases with N-LP-HD showed a favourable course with presentation at an early stage, good response to treatment, late recurrences and remission duration other than the other subtypes of HD. The latter could be attributable to the early stage at presentation of N-LP-HD, since the remission duration on a matching on stage analysis was superficially better in favour of N-LP-HD (p = 0.06). The indolent course of the disease in combination with the risk of second malignancy cases raises the question whether histology should be taken into consideration in the development of new protocols for HD.