Extramedullary involvement in patients with acute promyelocytic leukemia: a report of seven cases.
BACKGROUND
Extramedullary involvement is only occasionally observed in patients with acute promyelocytic leukemia (APL) but has been said to occur more frequently after treatment with all- trans retinoic acid (ATRA) than after treatment with cytotoxic drugs. In the literature, 37 well-documented cases have been reported.


METHODS
The authors report 7 patients with extramedullary APL documented by cytologic, phenotypic, and molecular analyses among 120 adult APL patients referred to two different institutions during a period of 9 years.


RESULTS
In this APL series, extramedullary disease (EMD) occurred in 7 of 120 cases (5.8%). The extramedullary sites were the skin in five patients, the central nervous system in one, and the lymph nodes in one. Molecular analysis of the PML/RARalpha rearrangement was performed on four samples of skin and one of CSF; all patients exhibited the same molecular pattern in the bone marrow (BM) and EMD sites. Of 120 patients, 61 were treated with ATRA plus chemotherapy and 59 with chemotherapy alone. Relapses were observed in 38 patients, 6 of whom had EMD; 1 patient had developed EMD at the onset of APL. Of the relapsed EMD cases, 2 of 61 patients had received ATRA plus chemotherapy and 4 of 59 had received chemotherapy alone.


CONCLUSIONS
There is some controversy as to whether treatment of APL with ATRA may predispose patients to the development of extramedullary relapse. The data from this study do not contain evidence that EMD may occur more frequently in APL patients treated with ATRA.
Divisione di Ematologia, Università di Bari, Italy.
V
V
Liso
G
G
Specchia
E M
EM
Pogliani
G
G
Palumbo
D
D
Mininni
V
V
Rossi
E
E
Teruzzi
A
A
Mestice
M R
MR
Coppi
A
A
Biondi
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D014178:Translocation, Genetic; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D003561:Cytarabine; D014212:Tretinoin; D015255:Idarubicin; D003630:Daunorubicin