J. Lim

Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center.

PURPOSE To examine outcome of treatment for patients with recurrent follicular lymphoma. PATIENTS AND METHODS Two hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued. RESULTS The overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor being quality of remission. Multivariate analysis showed only age at recurrence and number of prior treatments to correlate with survival after first recurrence. Survival after second remission was only correlated with age and quality of response: Kaplan-Meier estimates gave 53% of patients reaching second complete remission alive 10 years later, compared with 28% in partial remission. CONCLUSION Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.

Apparent removal of graft-versus-leukaemia effect by the use of leucocyte-poor blood components in patients with acute myeloblastic leukaemia.

We read with interest the recent debate regarding CD23 expression in chronic lymphocytic leukaemia and its correlation to clinical stage. Dadmarz & Cawley (1988). in a study of 35 patients, reported low levels of CD23 on peripheral blood lymphocytes of patients with advanced Rai stage disease and suggested that high levels of ‘non-activated’ cells was an unfavourable prognostic sign. In contrast, Gibson et a2 (1989) found no correlation between CD23 antigen expression and clinical stage in 37 patients with B-CLL. although cases requiring chemotherapy had significantly higher expression. It was concluded that clinical disease progression from an indolent form to an active chemotherapy requiring form is manifested by transformation from a nonactivated (CD23 low) to an activated (CD23 high) phenotype. We have evaluated 47 patients with B-CLL (using flow cytometry (FACScan)) correlating Rai stage with the activation markers CD23. CD25. CD71 together with FMC-7 expression and surface membrane immunoglobulin density (SmIg). The mean CD23 antigen expression of all patients was 5 7 f 2 5% similar to the values reported by Gibson et a1 (44&25%)andDadmarz&Cawley (53&25%).However. in contrast to the latter group we found no correlation between CD 23 expression and clinical stage: 5 7 f 2 5% for Rai stage 0-11 (n=35) and 5 8 f 2 6 % for Rai stage 111-IV (n=12) (P<0.01). Furthermore, comparison of CD23 with CD25 also supports the preliminary findings of Gibson et a1 (1 989) in that when CD23 expression is high (>SO%) the CD25 receptor is also increased 49&29%. Whereas low CD23 expression (< 50%) is accompanied by low CD2 5 receptor expression (2 3 f 20%). B-CLL cases can be divided into three distinct groups according to the expression of the two activation antigens, CD25 and CD71, namely, CD25-/CD71CD25+/CD71-’+ and CD25-/CD71+ (Barnett et al, 1989). Morphologically changes in cytoplasm and nucleus are associated with the expression of one or both antigens, including an increase in cell size and the appearance of a nucleolus. Stark et a1 (1986), while reporting a correlation between FMC-7 expression and SmIg density in cases with prolymphocytoid transformation, found no relationship with clinical stage. Our results of FMC7 expression support this finding, stage 0-11 ( n = 3 5 ) 25f22% and stage 111-IV ( n = l l ) 32&25% (P<O.O1). We conclude therefore that the expression of activation antigens in B-CLL, namely CD23. CD25, CD71, FMC-7 and SmIg correlates with differentiation, i.e. prolymphocytoid morphology, and not with clinical stage as defined by the Rai system.

Patterns of survival in patients with advanced Hodgkin's disease (HD) treated in a single centre over 20 years.

A total of 164 consecutive adults with newly confirmed stage IIIB, IVA or IVB Hodgkins disease (HD) commenced cyclical combination chemotherapy comprising mustine, vinblastine, prednisolone and procarbazine (MVPP) every 6 weeks (145 patients) or minor variants (19) at St Bartholomews Hospital between 1968 and 1984. The median follow-up period is 14 years. Complete remission (CR) was achieved in 97/164 (59%) and partial remission (PR) in 23/164 (14%) with lesser responses or death being documented in 44. Achievement of CR correlated with stage, serum albumin and serum beta2 microglobulin level at presentation on univariate and multivariate analysis; 55/97 (58%) remain in continuous CR, the median duration of remission not having been reached. Twelve patients died in first remission; there have been 30 recurrences, one occurring after 13 years. Second remission was achieved in 17/30; 6/17 remain in continuous second remission and two have died in second remission. There have been nine second recurrences, third remission being achieved in 6/9. Two continue in third remission, two patients have died in third remission: 82/164 patients are alive with a minimum follow-up of 6 years. Eighty-two patients have died; 66 with evidence of HD, six with second malignancy, one each of haemorrhage and infection, eight of unrelated causes, the cause of death was unknown in one. The overall median survival from presentation is 14 years, being the same for patients in CR and PR with minimal residual abnormality (good partial remission, GPR), and being better for those for whom remission was achieved than those for whom it was not. The median survival following first recurrence is 4 years, being significantly longer for younger patients (less than 50 years). These results emphasise the importance of long-term follow-up to determine the clinical course of HD and are vital for planning experimental chemotherapy at the time of early treatment failure or recurrence.

Intensive chemotherapy for acute lymphoblastic leukaemia in adults

High-dose cytosine arabinoside (HD Ara-C) has been shown to induce complete remission in acute lymphoblastic leukaemia (ALL) which is refractory to, or which has recurred following conventional therapy [1–5]. This study was undertaken to determine whether the incorporation of HD Ara-C at a dose of 2 g/m2 twice daily for 6 days into the treatment previously used at St. Bartholomew’s Hospital (OPAL) [6] would improve the prognosis of adults with ALL.

Response to Fludarabine in Patients with Low Grade Lymphoma

Eighty-eight adults with low grade lymphoma were treated with Fludarabine phosphate at a dose of 25 mg/m2 intravenously, daily for five days, every three to four weeks. The response rate was 44% for those who had received prior treatment and 69% for those who had not. The major toxicity was myelosuppression, neutropenia (< 1.0 × 109/l) occurring in 55% of previously treated and 31% of previously untreated patients respectively. Further studies will determine the precise role of Fludarabine in the therapy of low grade lymphoma.

Treatment of recurrent acute myelogenous leukaemia at a single centre over a 10-year period.

Complete remission (CR) may be achieved in the majority of younger adults with acute myelogenous leukaemia (AML). However, with conventional treatment, only 25% are cured since most will subsequently relapse and die. The results of treatment in 232 newly diagnosed patients referred to St. Bartholomew’s Hospital over the past 10 years illustrate these points and highlight the difficulties inherent in the treatment of AML at relapse. All patients were initially treated with curative intent with “short-term therapy” according to one of four protocols as described previously [1]. Complete remission was achieved in 144/232 (62%) patients; 86/144 (60%) subsequently relapsed. The management and outcome of the latter patients form the basis of this report.