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.

Histone Deacetylase Inhibitors Antagonize Distinct Pathways to Suppress Tumorigenesis of Embryonal Rhabdomyosarcoma

“…The success of differentiation therapy was first demonstrated in acute promyelocytic leukemia (APL), which was nearly universally lethal before the introduction of all-trans-retinoic acid-induced differentiation therapy. The cure rates now approach approximately 80% [ 30 ]. Differentiation therapy in solid tumors has shown clinical promise in the past decade [ 31 – 33 ].…”

Modeling dynamics and alternative treatment strategies in acute promyelocytic leukemia

“…The dynamics in the peripheral blood compartment and bone marrow compartment are assumed to be equivalent, which means that the population behavior in the peripheral blood represents the population behavior in the bone marrow. This simplification is intended to reduce the model complexity, and is plausible because the clinical outcome in APL patients is assessed by peripheral blood analysis [21].…”

The Double Hazard of Thrombophilia and Bleeding in Acute Promyelocytic Leukemia

“…7 Early after the initial descriptions of patients with APL, it was recognized that most patients have evidence of widespread bleeding in the skin, as well as visceral organs. [2][3][4][5][6][7][8] Historically, intracerebral hemorrhage (ICH) has been the major cause of ED even in patients with modest thrombocytopenia or minimal evidence of apparent perturbed coagulation by routine tests. For example, Fig.…”

“…Approximately 20 to 30% of patients died of hemorrhage, most often intracerebral in location, either at presentation or after the initiation of chemotherapy. [2][3][4][5][6] Deciphering the pathogenesis of the bleeding diathesis became a major focus of research because the outcome of patients with APL appeared to be more favorable compared with that of patients with other subtypes of AML, provided that patients survive the first several weeks after the diagnosis.…”

“…Historically, in the pre-ATRA era, the disease-free survival rate was 30 to 40%. [2][3][4][5][6] However, with contemporary treatment strategies, depending on prognostic factors and risk classification, 70 to 95% of patients can be expected to be cured of their disease. Furthermore, the introduction of ATRA has provided the opportunity to investigate the coagulopathy associated with APL more thoroughly because both clinical bleeding and biochemical evidence of perturbed coagulation are corrected rapidly with ATRA.…”