Advances in therapy for childhood non-B-lymphoblastic leukaemia.
The majority of therapeutic gains for patients with ALL have come from prospectively planned clinical trials. Beginning in the 1970s, series of well-designed protocols have produced valuable information that has permitted the development of curative therapy for more than two-thirds of patients. This success emphasizes the importance of controlled, carefully analysed therapeutic studies, which pay dividends for many years by providing a sound basis for future developments. Experienced biostatisticians should be involved early in the development of clinical trials to ensure that research questions can be reliably answered in terms of the size and composition of the patient sample and in terms of accrual time. Despite extensive pre-planning, a protocol may require early termination due to unexpected results that compromise the integrity of the initial design (Rivera et al, 1985). Thus, periodic treatment assessment of the trial is crucial to a successful outcome. Extended follow-up of patients is a requirement in every leukaemia study since relapses may occur many years after diagnosis, especially if patients have a lower risk of treatment failure (Rivera et al, 1979). The quality of long-term survival must also be well documented because all protocols include toxic therapy (Ochs and Mulhern 1988). Every physician treating children with ALL would like to select therapy that is both effective and well tolerated. Unfortunately, this is not always possible when patients have high-risk features. Secondary AML, deaths in remission and fatal organ toxicity (Steinherz, 1991c) are equally devastating complications of current chemotherapy for ALL, and no single protocol can be recommended over any other. Patients with ALL may be equally well served by any of several different protocols. The practice of administering 6MP + MTX alone and usually orally as continuation treatment has been virtually abandoned. Today, most children receive intensified chemotherapy in one schedule or another, including good-risk patients on POG protocols who, although treated largely with antimetabolite-based programmes, receive high-dose chemotherapy during the initial 6 months of treatment. In view of the more favourable results attained with reinduction therapy in recent CCG studies, these investigators also recommend such an approach for children with better-risk ALL. We fully agree. Regrettably, with the success of current regimens for higher-risk ALL, it has not been possible to exclude all toxic agents that may induce serious late complications.(ABSTRACT TRUNCATED AT 400 WORDS)
Rivera
G K
GK
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D005544:Forecasting; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017254:Leukemic Infiltration / Q000517:prevention & control; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008578:Meninges / Q000473:pathology; D015337:Multicenter Studies as Topic; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D012306:Risk; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome