Relapse rates following cessation of chemotherapy during complete remission of acute lymphocytic leukemia

Abstract

The therapeutic benefit of maintenance chemotherapy beyond three years for children with acute lymphocytic leukemia (ALL) in continuous complete remission was evaluated by the investigators of Childrens Cancer Study Group (CCSG). Two hundred and twenty leukemic children in first remission for three years or longer and who had received at least three years of continuous chemotherapy were eligible. One hundred and one patients were randomized to either continue chemotherapy for an additional three years or to discontinue therapy, and 119 patients nonrandomly continued or discontinued therapy. The patients had received a variety of chemotherapy regimens. The study period extended from April 1970 until December 1977, with a median follow-up time of 25 months. Relapses occurred in 15 randomized patients (15%). Randomized patients remaining on chemotherapy experienced a statistically significant lower relapse rate than patients randomized to discontinue therapy. Also among randomized patients, bone marrow relapse was significantly more frequent in males than in females. Considering the total patient group, age and white blood count at diagnosis had no significance in predicting relapse. Of relapse events in males, 21% were isolated testicular relapses, identifying the testicles as a major risk site in males completing three years of continuous complete remission. This study demonstrates that continuing chemotherapy beyond three years results in a significant prolongation of remission in males, although the eventual survival outcome for later discontinuance of therapy will require longer follow-up.

Isolated Testicular Relapse Five Years After Cessation of Chemotherapy for Acute Lymphoblastic Leukemia

“…2,3,8,12 About 10 per cent of these patients have occult leukemic infiltration to the testes. 2,3,12 This patient had isolated testicular relapse 5 years after completing chemotherapy for ALL. In two large series of children having chemotherapy discontinued after 2.5 years or more of continuous remission maintenance therapy, none of them had bone marrow or extramedullary relapse 4.5 years after completing therapy.…”

“…1-3 Some of these patients will eventually relapse, with most recurring during the first year after discontinuation of therapy. [1][2][3] Extramedullary relapse may occur while the patient is still undergoing chemotherapy or after it has been discontinued. Since the introduction of CNS sanctuary therapy, leukemic infiltration of the testis has emerged as a more common site of extramedullary relapse in boys.…”

Current Therapeutic Strategies and New Treatment Paradigms for Follicular Lymphoma

“…The concept of maintenance chemotherapy has become a recurrent theme in hematology, which was initially pioneered in pediatric ALL with the POMP regimen that contributed to durable remissions [36]. As FL is an incurable disease, there have been attempts to improve OS and PFS.…”

Childhood Acute Lymphocytic Leukemia

“…Many of these children were treated prior to the development of cur rently accepted chemotherapy, so the results cannot be applied directly to chil dren now undergoing therapy. 69 In a Cancer and Leukemia Group B study, children were randomized to continue therapy for seven years or stop at five years and so far, no difference has ap peared in the number of relapses. 70 Thus, with currently available treat ment, continuing therapy past five years does not seem to be advantageous to the group as a whole, although continuing past three years may be advisable, at least in males.69 Means of identifying the patient who will benefit from further therapy are needed; one such method already in wide use is testicular biopsy, which identifies the male at high risk for testicular relapse and possibly relapse at other sites.…”

“…70 Thus, with currently available treat ment, continuing therapy past five years does not seem to be advantageous to the group as a whole, although continuing past three years may be advisable, at least in males.69 Means of identifying the patient who will benefit from further therapy are needed; one such method already in wide use is testicular biopsy, which identifies the male at high risk for testicular relapse and possibly relapse at other sites. 69 Optimal length of treatment will be clarified with longer follow-up, but will probably prove to be dependent not only on time but on the type and intensity of therapy. Decisions regarding individual children must take these background re sults into account in relation to the in tensity and toxicity of the maintenance therapy being administered.…”