Extramedullary involvement in patients with acute promyelocytic leukemia

Liso, Vincenzo; Specchia, Giorgina; Pogliani, Enrico Maria; Palumbo, Gaetano; Mininni, D; Rossi, Vincenzo; Teruzzi, Elisabetta; Mestice, Anna; Coppi, Maria Rosaria; Biondi, Andrea

doi:10.1002/(sici)1097-0142(19981015)83:8<1522::aid-cncr6>3.0.co;2-4

Cited by 63 publications

(41 citation statements)

References 27 publications

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“…[23][24][25] In this study, we were unable to assess CD56 expression and FLT3-ITD mutation as predictive factors for CNS relapse in multivariate analysis because of an insufficient number of patients with adequate data. Other factors previously related to extramedullary relapse, such as age (< 45 years), 3 BCR3 isoform, 3,4 and development of differentiation syndrome 5 were not significant determinants of CNS relapse in our study. The low incidence of CNS relapse does not argue in favor of systematic CNS prophylaxis even in patients with high-risk APL.…”

Section: Discussioncontrasting

confidence: 51%

“…The reported incidence of CNS relapses in APL ranges from 0.6% to 2%. 2,3 Although CNS involvement is associated with age 3 and BCR 3 isoform, 3,4 and possibly with the use of ATRA and the development of differentiation syndrome, 5 high white blood cell (WBC) count at presentation appears to be the most consistent predictive factor. 3,6 For patients without leukocytosis, who have an extremely low risk of CNS relapse, there is a general consensus that CNS prophylaxis is not indicated.…”

Section: Introductionmentioning

confidence: 99%

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Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Montesinos

Dı́az-Mediavilla²,

Debén³

et al. 2009

Haematologica

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BackgroundThe prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and MethodsBetween 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. ResultsCentral nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. ConclusionsThis study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.Key words: acute promyelocytic leukemia, central nervous system relapse, all-trans retinoic acid, idarubicin, prognostic factors.Citation: Montesinos P, Díaz-Mediavilla J, Debén G, Prates V, Tormo M, Rubio V, Pérez I, Fernández I, Viguria M, Rayón C, González J, de la Serna J, Esteve J, Bergua JM, Rivas C, González M, González JD, Negri S, Brunet S, Lowenberg B, and

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Section: Discussioncontrasting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Montesinos

Dı́az-Mediavilla²,

Debén³

et al. 2009

Haematologica

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“…Because extramedullary APL occurred in 19 patients who had received ATRA as part of their anti-leukemia regimen, the suggestion was made that ATRA might possibly play a role in the development of extramedullary APL. Two years later, a report from Italy [2] documented the occurrence of extramedullary APL in seven patients out of 120 adults with APL referred to 2 institutions over a nine year period. The authors noted that the medical literature contained 37 well-documented cases of extramedullary APL.…”

Section: Discussionmentioning

confidence: 99%

“…Promyelocytic sarcoma is an extremely rare form of MS corresponding to the malignant promyelocytes of acute promyelocytic leukemia (APL). When present, it most often occurs as a manifestation of relapsed APL or at the time of diagnosis of systemic APL [1,2] . This report describes a patient with an isolated promyelocytic sarcoma causing spinal cord compression and treated successfully with decompression laminectomy followed by the PETHEMA chemotherapy regimen for APL [3] .…”

Section: Introductionmentioning

confidence: 99%

Promyelocytic sarcoma presenting with spinal cord compression and treated successfully with surgical debulking and the PETHEMA regimen for acute promyelocytic leukemia

Cornfield

Gheith

Barron

2015

CRCP

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A 52-year old woman presented with signs and symptoms of thoracic spinal cord compression caused by a spinal canal mass extending from the seventh to the ninth thoracic vertebra. Initial treatment consisted of high dose steroids and decompression laminectomy with subtotal resection of the abnormal mass. Sheets of immature myeloid cells which expressed the t(15;17)(q22;q21) of acute promyelocytic leukemia (APL) by fluorescence in situ hybridization (FISH) were present, consistent with promyelocytic sarcoma. Bone marrow examination showed no evidence of acute leukemia. She was then placed on the PETHEMA (Programa para el Tratamiento de Hematopatias Malignas, a Spanish cooperative chemotherapy group) regimen for APL for 15 months. There has been no evidence of local recurrence or of systemic APL at the 4.5-year mark, the longest follow-up of isolated promyelocytic sarcoma in the medical literature.

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“…[1,2] APL relapse in the bone marrow is common; however, an increasing number of extramedullary (EM) recurrences have also been reported. [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.…”

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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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Extramedullary involvement in patients with acute promyelocytic leukemia

Cited by 63 publications

References 27 publications

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Promyelocytic sarcoma presenting with spinal cord compression and treated successfully with surgical debulking and the PETHEMA regimen for acute promyelocytic leukemia

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

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