Late Differentiation Syndrome in Acute Promyelocytic Leukemia: A Challenging Diagnosis

Abstract

Detailed knowledge about differentiation syndrome (DS) has remained limited. There are 2 large studies conducted by the Spanish workgroup PETHEMA (Programa Español de Tratamientos en Hematología; Spanish Program on Hematology Treatments) and the European group trial (LPA 96-99 and APL 93) in which the incidence, characteristics, prognostic factors and outcome of patients developing DS are evaluated. Both have described the median time of DS development between 10 and 12 days. The severity of the DS has been evaluated in the study conducted by PETHEMA, and severe DS usually occurs at the beginning of the treatment (median of 6 days), as compared with moderate DS (median of 15 days). We report here in two cases of late severe DS, with late diagnosis due to both time and form of presentation. We discuss the physiopathology, clinical presentation, prophylaxis and treatment of DS.

Role of Prophylactic Steroids in Differentiation Syndrome

“…After the initiation of ATRA, DS usually occurs within two to 21 days [9]. Late presentations may also happen [8].…”

“…DS is characterized by dyspnea, fever, weight gain of >5 kg, peripheral edema, hypotension, acute renal failure, interstitial pulmonary infiltrates, and a leukocyte count greater than 10 x 10^9/L [7]. Severe DS is diagnosed when four or more of the above symptoms are present [8]. Early recognition of DS along with corticosteroid treatment can lead to decreased morbidity and mortality in these patients [6,7].…”