Treatment of acute lymphoblastic leukaemia in adults

Abstract

Between 1972 and 1982, 112 consecutive previously untreated adults (aged 15-69 years, median 26) commenced therapy for acute lymphoblastic leukaemia (ALL) at St Bartholomew's Hospital. The first 63 patients entered into the study received initial treatment which comprised four cycles of adriamycin and vincristine, prednisolone and L-asparaginase with the first cycle (OPAL). In 1978, six cycles were given, with escalating doses of adriamycin and cyclophosphamide from cycle 3 (HEAV'D). Central nervous system (CNS) prophylaxis incorporated intrathecal methotrexate and cytosine arabinoside with cranial irradiation. Maintenance chemotherapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate for 3 years. Results obtained with the OPAL and HEAV'D regimens were not significantly different. The overall complete remission (CR) rate was 66% (73/111), factors correlating unfavourably with achievement of CR being advanced age (P less than 0.001) and L3 morphology/B-ALL immunophenotype (P less than 0.01). Fifty-three patients have relapsed, the bone marrow being the primary site in 43. Extramedullary relapse alone occurred in 10 (seven CNS, two testicular and one skin). Only three of the 64 patients who had complete CNS prophylaxis subsequently relapsed in the CNS as an isolated site. One patient died in CR, 19 remain in continuous CR between 2.5 and 10.5 years. The median duration of remission of the 73 patients who achieved CR was 18.5 months, factors correlating favourably with duration of CR being low blast cell count at presentation (P less than 0.002) and common ALL immunophenotype (P less than 0.04). Twenty-four patients remain alive, with a median survival of all patients of 18 months. Long-term survival is possible for approximately 20% of adults with ALL treated relatively intensively.

High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia

“…Overall, the remission duration curve is the same as that for patients treated in the previous study. However, there was a trend in favour of high blast cell count (> 10 x 109 li) and T-cell phenotype (data not shown) in contrast to the previous results when low blast cell count and C-ALL phenotype were found to correlate favourably with duration of remission (Barnett et al, 1986).…”

“…'Risk' Patients were grouped on the basis of prognostic factors derived from the previous analysis (Barnett et al, 1986). 'High risk': T, B, null-ALL or blast count> 10 x 10'1-' at presentation.…”

“…Comparison is made with the outcome for 111 patients of similar age distribution treated at SBH between 1972 and 1982 with two treatment programmes, 'OPAL' and 'HEAV'D', as previously reported (Lister et al, 1978;Barnett et al, 1986) (Bollum, 1979). The results were interpreted according to the following classification.…”

“…Complete remission (CR) can be achieved in the majority of adults with acute lymphoblastic leukaemia (ALL) with standard combination chemotherapy yet only a minority are cured (Willemze et al, 1975, Hoelzer et al, 1984Barnett et al, 1986). Intensive consolidation therapy resulting in more effective elimination of 'minimal residual disease' might thus be expected to reduce the frequency of relapse.…”

A rodent model for testicular involvement in acute lymphoblastic leukaemia

“…The testis is the third common (8-16% of cases) site of relapse after primary treatment of childhood acute lymphoblastic leukaemia (Ritzen, 1990;Gustafsson, 1991), but in adults only some testicular relapses (t 1% of cases) of acute lymphoblastic leukaemia have been reported (Barnett et al, 1986;Jensen et al, 1991). The mechanism of this difference in lymphoblast survival from chemotherapy between children and adults is largely unknown.…”