J L Binet

Survivals of two series of CLL patients (99 from a retrospective series and 196 from a prospective series) were studied separately. The three main staging systems (Rai, Binet, Rundles) agreed well, but as far as survival is concerned, too many stages are defined. The authors performed a Cox multivariate analysis of survival in order to isolate important prognostic factors at diagnosis and to use them to build a simple three-stage classification. Thrombopenia and anemia appeared as the most important risk factors. Among the nonanemic and nonthrombopenic patients, the number of involved areas was clearly related to prognosis in the authors' two series. This study allowed the authors to propose a new classification in three prognostic groups. Group C: anemia (Hb less than 10 g) and/or thrombopenia (platelets less than 100,000/mm3); about 15% of the patients; median of 2 years. Group B: no anemia, no thrombopenia, three or more involved areas (counting as one each of the following: axillary, cervical, inguinal, lymph nodes, whether unilateral or bilateral, spleen and liver); about 30% of patients; median of 7 years. Group A: no anemia, no thrombopenia, less than three involved areas; about 55% of patients; the survival of this group does not seem different from that of the French population of the same age and sex distribution. This three-stage classification only requires clinical examination and routine hemogram, has a good prognostic value which was confirmed on the series of Montserrat and Rozman (146 patients), and should therefore be helpful in planning new clinical trials.

One hundred and twenty-nine patients with chronic lymphocytic leukemia (CLL) followed in our outpatient department for periods ranging from 6 months to 13 years were divided into five anatomico-clinical stages: stage O (peripheral and bone marrow lymphocytosis); stage I (stage O + lymph node enlargement); stage II (stage O + palpable spleen); stage III (stage I + II); and stage IV (anemia or thrombocytopenia). Analysis of actuarial survival curves revealed the following: 1) median survival of the entire population exceeded 114 months; 2) there was no difference between the curves of stage O and stage I patients, 3) there was a significant difference between survival for stage III and IV patients as compared with stages O, I and II (p < 0.01); and 4) median survival for stage III and stage IV was 70 months; and 23 months, respectively. Age did not appear to be a prognostic factor. Prognosis was poorer in male patients and in those with a high initial lymphocyte count (50,000/mm3), but this was due to the higher incidence of stages III and IV in this population (p < 0.01). It was not possible, from this study, to draw any conclusions as to the beneficial effect of chlorambucil in the treatment of this disease. However, in patients treated with chlorambucil the response to therapy appeared to be a factor of prognostic significance. Patients who showed clinical and hematologic remission had a better prognostic outlook than those who showed only a partial response, while the worst prognosis was encountered in patients who did not respond at all. The five-stage anatomico-clinical classification system suggested appears to be the dominant prognostic factor and may thus serve as a guideline for therapeutic strategy. Cancer 40:855–864, 1977.

PURPOSE: Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. PATIENTS AND METHODS: There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. RESULTS: The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). CONCLUSION: EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.

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