Ear involvement in acute promyelocytic leukemia at relapse: a disease-associated ‘sanctuary’?

Breccia, Massimo; Mc, Petti; Testi, A. M.; Specchia, Giorgina; Ferrara, Felicetto; Diverio, Daniela; Romano, Angela; Guerrisi, V.; Greco, Antonio; Fiorella, ML; Vincentiis, Marco de; Mandelli, Franco; Coco, Francesco Lo

doi:10.1038/sj.leu.2402497

Cited by 29 publications

(16 citation statements)

References 23 publications

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“…[26][27][28] However, those presenting features may also be absent in case of ear involvement. 18 Finally, it has been suggested that occurrence of RA syndrome might be associated with an increased risk of EM relapse. 14 In our study, patients with EM relapse had significantly higher WBC counts at diagnosis, a higher incidence of bcr3 PML-RARa isoform but, also, were significantly younger than the other APL patients included in the study.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8] Although very rare in APL in the past, [9][10][11] cases of extramedullary (EM) relapse have been increasingly reported in the last few years. [12][13][14][15][16][17][18] Those EM relapses largely predominate in the central nervous system (CNS) and the skin, followed by other sites (testes, sites of vascular access, external ear and auditory canal). [12][13][14][15][16][17][18] It has been suggested that EM relapse may be associated with initial adverse prognostic features (including high WBC counts, microgranular morphology and bcr3 isoform), 12,15,17 but risk factors for EM relapse have not been precisely defined.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15][16][17][18] Those EM relapses largely predominate in the central nervous system (CNS) and the skin, followed by other sites (testes, sites of vascular access, external ear and auditory canal). [12][13][14][15][16][17][18] It has been suggested that EM relapse may be associated with initial adverse prognostic features (including high WBC counts, microgranular morphology and bcr3 isoform), 12,15,17 but risk factors for EM relapse have not been precisely defined. Because of its rarity, the outcome of patients with EM relapse remains undetermined and only one study reported that the outcome was similar to that of patients who experienced isolated BM relapse.…”

Section: Introductionmentioning

confidence: 99%

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Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Botton¹,

Sanz

Chevret³

et al. 2005

Leukemia

152

120

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We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26 950/mm 3 (7700-162 000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age o45 years (P ¼ 0.05), bcr3 PML-RARa isoform (P ¼ 0.0003) and high WBC counts (X10 000/ mm 3 ) (Po0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P ¼ 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P ¼ 0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (X10 000/mm 3 ) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC X10 000/mm 3 at diagnosis remains to be established.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Botton¹,

Sanz

Chevret³

et al. 2005

Leukemia

152

120

View full text Add to dashboard Cite

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“…70 A growing body of evidence, however, shows that an extramedullary relapse of APL is frequently observed among patients who have been induced into CR by ATRA regimens, including some hitherto rare relapse sites such as the external auditory canal. [71][72][73][74][75] There are a couple of explanations why extramedullary relapse is more common in patients treated with ATRA. First, ATRA reportedly upgrades the transcription of some leukocyte adhesion molecule genes, and thus ATRA-treated leukemia cells may show increased expression of adhesion molecules.…”

Section: Extramedullary Leukemia and Its Managementmentioning

confidence: 99%

Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate

2003

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“…[3,4] Central nervous system, skin, testicle, vascular access, external ear, and auditory canal are the most common EM relapse sites. [3][4][5][6][7][8] Before the ATRA era, the large majority of first relapses in APL occurred within 3 years of complete remission, and only 2% to 3% of patients relapsed after 4 years. [9] Disclosures Peer-review: Externally peer-reviewed.…”

mentioning

confidence: 99%

Testicular and Cutaneous Relapse in Acute Promyelocytic Leukemia Treated with All-trans Retinoic Acid and Chemotherapy

Erkek¹,

Demir²,

Ozkan³

et al. 2017

EJMO

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A 32-year-old man presented at the hematology department with bilateral testicular enlargement and multiple, painless, purple cutaneous nodules on both upper extremities and the trunk (Figure 1). He had been diagnosed with acute promyelocytic leukemia (APL) 7 years earlier.Complete remission was achieved with all-transretinoic acid (ATRA) and idarubicine therapy, and maintenance therapy had continued for 2 years since remission.Complete blood count and biochemical test results were normal, and peripheral blood smear (PBS) revealed no specific features. Bone marrow biopsy was performed, and did not demonstrate any leukemic infiltration. Real time polymerase chain reaction (RT-PCR) assay to detect t (15;17) (PML-RAR alpha) in blood samples was negative. Skin biopsy, however, revealed acute myeloid leukemic infiltration. Skin sample evaluated using RT-PCR for t (15;17) was positive. Bilateral, heterogeneous, hypervascular, irregular limited area was detected with testicular ultrasonography, indicative of testicular infiltration. Two weeks after confirmation of diagnosis, increase in D-dimer (>5000 μ/mL) and hypofibrinogenemia had developed. At the start of induction therapy, idarubicin (12 mg/m 2 /day, D2, 4, 6, 8), ATRA (45mg/m 2 ), arsenic trioxide (ATO) (0.15 mg/kg/day for 22 days) was administered and methylprednisolone was added for ATRA syndrome prophylaxis. On the 20 th day of therapy, after observing leukocytosis in his blood count, PBS and flow cytometry were reperformed. PBS demonstrated promyelocytes, and flow cytometry showed cell population CD13, CD33 positive, CD14 dim positive, and CD34 and HLA-DR negative. On the 30 th day of therapy, ATRA and ATO therapy was interrupted due to respiratory distress, prolonged QT, and fever. Dexamethasone 20 mg/day and intravenous imipenem 2 g/day was initiated for differentiation syndrome and pneumonia. Bilateral, subpleural consolidation areas; peribronchovascular infiltration; and ground glass opacity in the right middle lung zone was seen on tho-

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Ear involvement in acute promyelocytic leukemia at relapse: a disease-associated ‘sanctuary’?

Cited by 29 publications

References 23 publications

Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate

Testicular and Cutaneous Relapse in Acute Promyelocytic Leukemia Treated with All-trans Retinoic Acid and Chemotherapy

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