Clinical characteristics, prognostic factors and multidrug‐resistance related protein expression in 36 adult patients with acute promyelocytic leukemia

Abstract

71% (24 of 34) of evaluable patients remain in CR at a median follow-up of 57 months (range 4-158 months) while 29% (10 of 34) relapsed at a median time of 12 months (range 8-43 months) and, of them, eight of 10 died early. The majority of patients that relapsed were in high-risk group. The overall survival (OS) of the whole population at 32 months was 66% and the DFS at 42 months was 62%. A statistically significant difference in terms of DFS was observed between HR and IR/LR patients (P = 0.04 by log-rank). DFS was not affected by age, sex, Hb levels, karyotype, and BCR isoform. At conclusion, our data confirm that despite the high rate of success with ATRA plus chemotherapy as induction (more than 90% of CR), about 30% of APL patients have a relapse (without a long-lasting second remission) and underline the importance of patient stratification in distinct risk groups at diagnosis in order to better adapt the type and intensity of treatment (risk-adapted therapy). Taking into account the high expression of CD33 and the low expression of MDR proteins in APL, new and investigational approaches like gemtuzumab-ozogamicin, with or without ATRA and other new drugs, should be strongly considered expecially in HR APL.

Clinical characteristics, outcome and early induction deaths in patients with acute promyelocytic leukaemia: a five-year experience at a tertiary care centre

“…A relapse rate of 30% was observed in our patients, which is in concordance with relapse rates ranging from 20% to 30% reported in other studies, despite consolidation and maintenance therapy. (6,11) In sharp contrast to the projected survival of patients with APL in most international studies, (31,32) the very low survival rate seen among our patients with APL at 42 months was probably related to the very high early death rates observed in our study. The worst outcome was observed in high-risk patients, with a survival of only 15.4% at 42 months.…”

“…PML-RARA). (6) There are two morphological variants of APL, with the most common being the hypergranular variant, in which promyelocytes are populated with abundant azurophilic granules and may contain multiple Auer rods, which is a classical finding. (4) Accounting for about 25% of patients with APL, the less common microgranular variant of APL (M3v) is more aggressive than the hypergranular variant, and on light microscopy is seen to be morphologically characterised by immature myeloid cells that lack azurophilic granules and have convoluted nuclei.…”

Antibody Drug Conjugates: Preclinical Considerations

“…It is hypothesized that this clinical activity is due to the high and homogenous expression of CD33 on APL blasts and very low expression levels of P-glycoprotein (103,104).…”

Antibody-Drug Conjugates of Calicheamicin Derivative: Gemtuzumab Ozogamicin and Inotuzumab Ozogamicin

“…In general, the results suggested clinical activity in relapsed AML with an acceptable safety profile, opportunity for first-line therapy, and remarkable activity in relapsed acute promyelocytic leukemia (APL; Tables 1 and 2). This type of AML combines a high and homogeneous expression of CD33 with low levels or absence of Pgp (32)(33)(34). GO has shown prolonged molecular remissions in APL, both as a single agent and in combination, without reports of VOD (35)(36)(37)(38)(39)(40).…”