Eva Svarch

Evaluation of intensification and maintenance programs in the treatment of acute lymphoblastic leukemia.

This cooperative prospective study was designed to answer the following questions in cases with acute lymphoblastic leukemia induced to achieve complete remission with the combination of vincristine and prednisone (if by day 29 the bone marrow was not M1, daunorubicin was added to the former regimen) and who received preventive CNS therapy with 2400 rad of cobalt‐60 to cranio‐cervical region and simultaneously intrathecal methotrexate and dexamethasone: 1) Is a short intensification with cytosine‐arabinoside and cyclophosphamide immediately after complete remission useful? 2) Does the use of weekly doses of 6‐mercaptopurine and methotrexate have the same maintenance effect as daily 6‐mercaptopurine and twice weekly methotrexate? and 3) Do further 3 month‐doses of intrathecal methotrexate and dexamethasone help to decrease still more the incidence of meningeal leukemia? From October 1972 to December 1975, 473 previously untreated patients entered this study and 465 (390 children and 75 adults) are evaluated in this paper. Of them, 373 (80%) achieved complete remission (children 84% and adults 61%). Out of 109 “high risk”children (one or more of the following characteristics at diagnosis: marked organomegaly, mediastinal widening, leukocytosis above 50000/ mm3 and CNS involvement) 83 (76%) and out of 281 “standard risk”children (all the others) 244 (87%) achieved complete remission. The median duration of complete remission according to different prognostic factors was as follows: “high risk”children 10 months, adults 24 months and “standard risk”children 25 months. Duration of complete remission of the “standard risk”children in relation to with or without intensification, daily or weekly maintenance and additional intrathecal therapy or none, showed no significant difference; however, those who received intensification, daily maintenance and further intrathecal therapy behaved slightly better. Median survival for all the cases of this study was as follows: adults 10 months, “high risk”children 12 months and “standard risk”children 26. months. At 36 months, 13% of “high risk”children, 25% of adults and 39% of “standard risk”children are still alive. We conclude that the variables studied in this protocol did not show significant extension of complete remission, however the sum of them seems to offer some advantage. Moreover, what appears clear is the importance of prognostic factors which must be taken into account in future studies. Cancer 42:1730–1740, 1978.

Chemoimmunotherapy with levamisole in acute lymphoblastic leukemia

Patients with acute lymphoblastic leukemia (ALL) who were in two consecutive protocols and in complete remission (CR) with maintenance therapy, were randomized to receive or not receive levamisole. A total of 15 of 55 low‐risk patients of protocol 10‐LLA‐72 with levamisole had relapses, compared with 25 of 54 not receiving levamisole; 67 and 49%, respectively, remain in CR at 48 months (P < 0.025). In protocol 1‐LLA‐76, 14 of 91 low‐risk patients on levamisole and 25 of 93 patients not receiving levamisole had relapses; 78 and 61%, respectively, remain in CR at 36 months (P < 0.05). Seventeen of 39 high‐risk patients (children with a leukocyte count higher than 50,000 and adults) receiving levamisole had relapses compared with 37 of 61 not on levamisole. The DNCB skin test shows at 18 and 24 months a 74 and 85% positivity in the levamisole group vs. a 38 and 35% positivity in the control group (P< 0.025). We conclude that levamisole prolongs the duration of CR and survival in low‐risk patients with ALL.

59 CONTINUATION THEFAPY IN ACUTE LYMPHOBLASTIC LEUKEMIA: EVALUATION OF DIFFERENT REGIMENS

This investigation has the following scheme: Induction: vincristine (VCR)+daunorubicin+prednisone (PRED); CNS prevention: intrathecal methotrexate (MTX)+dexamethasone × 6 early doses followed by one trimesterly; and Continuation: 6-mercaptopurine daily and MTX twice weekly with reinforcement of pulse doses of VCR 1.5 mg/m2 × 1 + PRED 40 mg/m2/day × 7 (arm A) or VCR+PRED alternating with arab. cit. (Ara.C) 50 mg/m2/sc q. 12 h × 10 + cyclophosphamide (CTX) 600 mg/m2 × 1 (arm B). Pulses are performed in both arms at 1,2,3,4,6 mo, and trimesterly thereafter: In addition, half of the cases received levamisole (LEV) 120mg/m2/oral/daily and the other half, none.From Jan. 1976 to Dec. 1978, 378 patients entered this study. 282/322 (88%) children and 44/56 (78%) adults achieved complete remission (CR) (P<0.05). The % of CR at 30 mo. are, arm A > 20.000 leukocytes 46%, > 20.000 37% and arm B > 20.000 78%, > 20.000 33% (P < 0.01 between and > 20.000 leukocytes in both arms and P < 0.05 between arms A and B in patients with > 20.000 leukocytes). In addition, 59% of the LEV-treated patients and 50% of the control group are still in the first CR at 30 mo. (P < 0.05).We conclude that: 1) usefulness of alternating reinforcement pulses of VCR+PRED with Ara.C-CTX in relation to VCR+PRED alone, and 2) immunotherapy with LEV is effective in prolonging CR.

6 EFFECTIVENESS OF PREVENTION OF CNS LEUKEMIA WITH INTRATHECAL (IT) METHOTREXATE (MTX) AND DEXAMETHASONE (DMT) IN ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

A protocol was started in 1976 for the treatment of ALL. It included 3 injections of IT MTX-DMT during the induction, another 3 early in remission followed by one injection every 3 months as prevention of CNS disease.Thus far 24 (8,9%) CNS relapses were observed in 270 patients who achieved complete remission(median: 18 months, range: 1 to 33). Data from earlier protocols of our group, which included radiotherapy (RT) to cranium plus 5 doses of IT MTX showed 49 patients (11,6%) of a total of 443 who experienced CNS relapse. The comparison of the incidence of CNS leukemia of both preventive methods according to life table analysis is the following:We conclude that in comparison with earlier protocols which included RT the present regimen compares favourably in standard and high risk patients.