Complete remission in acute promyelocytic leukemia despite persistence of abnormal bone marrow promyelocytes during induction therapy: experience in 34 patients

Abstract

Thirty-four patients with acute promyelocytic leukemia (APL) (median age 37 years, range 20 to 69 years) received induction treatment between 1974 and 1985 with cytosine arabinoside (ara-C) and an anthracycline. Bone marrow hypercellularity was present at the time of diagnosis in all patients, although the median peripheral leukocyte count was 2,600/microL. A second course of induction therapy consisting of further ara-C and anthracycline was initiated 15 days after the start of treatment if bone marrow hypocellularity could not be documented. Karyotypic analysis of bone marrow blasts was performed on 15 of 34 patients; 11 of 15 had abnormalities in chromosomes 15 and/or 17. Twenty-nine of 34 (85%) patients had laboratory evidence of disseminated intravascular coagulopathy. Of the 29 patients surviving 14 days, 24 (83%) received a second course of induction therapy. Complete remission was achieved in 25 of 34 (74%) patients, with four of 25 (16%) requiring one course of induction chemotherapy and 21 of 25 (84%) receiving two courses. Bone marrow specimens obtained 15 days after the start of therapy from the 25 patients who eventually attained complete remission showed the continued presence of dysplastic promyelocytes in 21 cases; three specimens were technically inadequate and only one was truly devoid of promyelocytes. Seventeen of 25 (68%) patients still had persistence of abnormal bone marrow promyelocytes seven or more days after the second course of therapy. Patients in complete remission received various forms of postremission therapy. Ten of the 25 (40%) completely responding patients remain alive in continuous complete remission. Neither the absence of bone marrow hypocellularity nor the persistence of dysplastic promyelocytes during induction exerted any influence on the probability for survival. These findings confirm and extend prior reports that complete remission in APL, in contrast to other subtypes of acute nonlymphocytic leukemia (ANLL), can frequently be achieved without bone marrow aplasia. Whether this observation signifies that complete remission in APL is due to leukemic cell differentiation or selective cytotoxicity is unknown. The absence of therapy-induced bone marrow hypoplasia in APL is not an absolute indication of induction failure or a poor ultimate prognosis.

Complete remission in acute promyelocytic leukemia despite the persistence of the 15;17 translocation

“…In a recent retrospective series neither the absence of bone marrow hypocellularity nor the persistence of dysplastic progranulocytes immediately after induction chemotherapy adversely affected the likelihood of remission or survival. Although approximately one-half of the treated patients did not develop hypocellular marrows at any point during induction, 74% of patients entered remission and the median survival for responding patients was 34 months [5]. Similar clinical experiences in APL have been described previously [3,4].…”

“…Modern intensive management with clotting factor and platelet replacement with or without supplemental heparin has resulted in improvement in survival of patients with APL so that the remission rate and long-term disease-free survival of APL is now comparable to other subtypes of ANLL [3,5,10]. However, in contrast to other subtypes, remission has frequently been induced in patients with APL without a phase of marrow aplasia [3-51.…”

“…Consequently, in Case Report: CR in APL Despite Persistent t(15;17) 267 APL morphologic examination of early postinduction bone marrow fails to discriminate responsive from unresponsive patients. It has been suggested that serial cytogenetic studies may better identify early in the postinduction period patients with an adequate chemotherapeutic response [5]. We have had the opportunity to address this question directly.…”

“…Failure to achieve marrow hypoplasia or to eliminate leukemic cells is an indication for further chemotherapy [ 1,2]. However, in contrast to other ANLL subtypes, in patients with acute promyelocytic leukemia (APL), complete remission (CR) has been frequently attained without further therapy despite initial persistence of marrow hypercellularity and leukemic cells [3,4,5]. Consequently, morphologic assessment lacks diagnostic specificity in predicting CR in APL.…”

Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group

“…However, after chemotherapy, in APL, a slow disappearance of marrow blasts is encountered in some patients who will, however, subsequently achieve CR without further treatment. 16 Thus, if after courses I and 11, the day 20 marrow aspirate showed greater than 50% blasts, sequential bone marrow (BM) aspirates and coagulation studies were performed before concluding to resistant leukemia.…”