Intensive Retreatment of Childhood Acute Lymphoblastic Leukemia in First Bone Marrow Relapse

We devised a plan of intensive chemotherapy to address the problem of inadequate results of treatment in children with acute lymphoblastic leukemia in first bone marrow relapse. Immediately after remission was induced with four conventional drugs, a two-week intensification course of teniposide and cytarabine was given to eradicate subclinical leukemia. Patients in remission were then treated for two years with rapid rotation of pairs of drugs that were not cross-resistant and periodic courses of the same agents used to induce remission. A second complete remission was induced in 31 of the 39 patients in whom response to chemotherapy could be assessed. The probability of maintaining bone marrow remission in these patients for one year was 0.38±0.19 (95 percent confidence interval); the two-year probability was 0.29±0.17. Seven patients completed the treatment program, five of whom have been in continuous second complete remission 17 to 20 months after the cessation of therapy. Children whose initial bone marrow remission lasted less than 18 months had significantly poorer responses to retreatment than did those with a longer first remission (P = 0.004). Intensive chemotherapy, as described here, may save half of the children with acute lymphoblastic leukemia in whom bone marrow relapse occurs after a relatively long initial remission. (N Engl J Med 1986; 315:273–8.), THE prognosis for children with acute lymphoblastic leukemia (ALL) in whom relapse in bone marrow occurs during initial therapy or shortly thereafter has been dismal. Most of these patients do not have long-lasting second remissions and eventually die.^{1 2 3} By contrast, among children in whom relapses occur more than six months after elective cessation of therapy, the prospects for inducing and maintaining a new remission are clearly better.^4,5 Our working hypothesis is that the length of first hematologic remission directly reflects the degree of drug sensitivity or perhaps the intrinsic growth potential of leukemic cells. Hence, therapy effective in patients with…