“Fulminant” Acute Promyelocytic Leukemia: Clinical and Biological Features.

Acute promyelocytic leukemia (APL) is associated with severe hemorrhagic coagulopathy, which is the main cause of early death. The introduction of ATRA ameliorated the complete remission rate and improved the overall survival compared to treatment with chemotherapy alone. However, the pioneristic large randomized trials comparing ATRA alone versus chemotherapy alone in previously untreated patients failed to demonstrate a significant reduction of early hemorrhagic deaths, notwithstanding ATRA capability to quench the ongoing coagulopathy. Nevertheless, the incidence of such very early deaths remains unsettled, leading to a bias in the evaluation of real impact of ATRA in clinical outcome of APL. We have retrospectively collected and examined a total of 31 very early deaths from APL from the database of 7 Italian Centres. Very early death was defined as death occurring within 72 hours from the first clinical observation. The incidence was 9.7% (31 of 318 APL enrolled in the same period in GIMEMA APL trials). Median age was 53 years (21–88), M/F ratio 0.9, 13 were variant forms of APL, median peripheral blood cell count was: WBC 41.2 ×10⁹/L (0.68–181), with 94% of blast cells, platelets 24 ×10⁹/L (6–96); BCR type 1, 2, 3 were observed in 10, 2, and 7 cases, respectively; clinical features of disseminated intravascular coagulopathy (DIC) were present in all but two patients, while median WHO grade of hemorrhage was 3. Median time from symptoms onset to diagnosis and from diagnosis to death was respectively 72 and 44 hours. One third of the patient did not receive any therapy, the others received some doses of ATRA with or without chemotherapy. The majority of these patients was not enrolled in any clinical trial. These preliminary data suggest that a relevant percentage of APL patients died before starting any effective treatment. Every clinical trial should include this slice of patients to give realistic clinical outcome of APL therapies. Seventy-two percent of patients showed WBC≥10×10⁹/L and variant form was more frequent (42%) than expected (usually 20–25% of APL). Based on the possible confused morphological features with monocytic leukaemia, diagnosis required rapidly confirmative molecular methods and heavy supportive and transfusional therapies. Moreover, underlying APL should be considered as a differential diagnosis when apparently spontaneous cerebral hemorrhage occurs; in some instance, a prompt supportive and differentiating therapy could be lifesaving.