The roles of adoptive and active forms of immunotherapy in the cure of children suffering from acute lymphoid leukemia: a) underestimation of active immunotherapy benefit, b) its immunogenetic indications to select sensitive patients, hence prevent chemotherapy's late effects.
Children's acute lymphoid leukemia (ALL) chemotherapy started in 1948 with antimetabolites combined with steroids. It was enriched in 1959 with vincristine and cyclophosphamide and, in 1970, with daunomycin. It induced more and more apparently what were called complete remissions, and prolonged more and more the survivals without reducing however, until 1973, the (100%) mortality. It started to reduce it at the fifth year, to 20 and even 40% between 1973 and 1976, due to progressive and maximal intensification and duration of chemotherapy. It is in the same period that we proposed to apply in ALL remissions after relapses and in the first remissions of the most malignant type, allogeneic bone marrow grafts; we published the first success in human ALL in 1963, and clinically observed the same actions as those described experimentally: cytoablation of both leukemia and hematopoiesis, the latter being restored by the graft, whose reaction versus the residual neoplastic cells (called graft versus leukemia or GvL) appeared to be able to often eradicate them, at the cost however of a graft-versus-host reaction (both reactions sharing the same mechanism). One of us became a member of the Committee of the International Bone Marrow Transplant Registry, whose results showed the improvement in the prognosis of the aggressive form of ALL. The intensity and length established for chemotherapy for the most severe form of children's ALL have often been applied to the intermediary and to the least aggressive ones. The global 5-year survival increased to 60% between 1976 and 1984, and is around 80% today. But the registration of late debilitating or malignant effects of chemotherapy toxicities makes us wonder if some patients have not received an excessively intense and long application of cytostatics (often combined with ionizing radiations on CNS). In fact, the patients belonging to some HLA phenotypes (A33 and B17) have appeared to be especially often cured with active immunotherapy (killed leukemic cells and/or BCG), whose action was shown by specific cytotoxicity amplification, which was applied after short adjuvant chemotherapy, and hence is able to reduce the long chemotherapy incidence of debilitating or malignant late effects. Sakurai's group confirmed our absence of late relapses after ALL active immunotherapy, which contrasts with their risk after maintenance chemotherapy, whose minimal residual disease is a worrisome stumbling block to the cure.
Mathé
G
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Institut de Cancérologie et d'Immunologie & Hôpital Suisse de Paris, Issy les Moulineaux, France.
Amiel
J L
JL
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002908:Chronic Disease; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000628:therapy*; D011379:Prognosis
D000970:Antineoplastic Agents