Prophylaxis of Symptoms of Hyperhistaminemia after the Treatment of Acute Promyelocytic Leukemia with <i>All-Tran</i><i>s</i> Retinoic Acid

Abstract

A 61-year-old man with acute promyelocytic leukemia (APL) is described in whom some leukemic promyelocytes contained granules similar to those of basophils, and hyperhistaminemia developed after treatment with all-trans retinoic acid. The symptoms of hyperhistaminemia, mediated via H₂ receptors, were prevented by the administration of an H₂-blocker, famotidine, but wheezing due to bronchospasms, mediated via H₁ receptors, developed and was improved by administration of chlorpheniramine. In APL, it is generally thought that the maturation of neutrophilic leukocytes is arrested at the level of abnormal promyelocytes. However, heterogeneity of leukemic promyelocytes has been described and in a few patients some leukemic promyelocytes have been known to show basophilic features. Marked basophilia and severe symptoms due to hyperhistaminemia have recently been reported after the treatment of APL with ali-trans retinoic acid. Our case presented similar basophilic features, but indicated that the symptoms of hyperhistaminemia after administration of retinoic acid can be prevented with antihistaminic drugs and suggested that both H₁ and H₂- blockers should be administered to such APL patients with basophilia.

Three-Way Translocation t(12;15;17) (p13;q24;q21) Found in Acute Promyelocytic Leukemia with Basophilic Differentiation

“…In basophilic APL, the leukemic promyelocytes probably differentiate into basophils, causing unusual differentiation syndrome symptoms due to the release of histamine, heparin and cytokines involved in anaphylaxis by basophils. We did not observe a basophils increase during the course of treatment, but our patient experienced various episodes of skin rash and itching, which were successfully treated with endovenous antihistamine therapy [ 26 ].…”

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy

“…In promyelocytic leukemia, detection of metachromatic basophilic granulation in the cytoplasm of leukemic promyelocytes, together with the development of hyperhistaminemia, after starting therapy [15,[38][39][40], have long suggested that basophil-associated vasoactive mediators (e.g., heparin, histamine) might be released by those leukemic promyelocytes upon spontaneous or chemotherapyinduced cell differentiation and/or death; thereby, such release of basophil-related contents by these leukemic cells might contribute, at least in part, to the development of an anticoagulant state and a higher risk for severe bleeding. In line with this hypothesis, maturation of leukemic promyelocytes toward the basophil lineage has been recurrently reported in the literature, particularly after all-trans retinoic acid therapy [15][16][17][18].…”