CORRESPONDENCE Response of Aleukemic Granulocytic Sarcoma to All-fra/w-retinoic Acid Plus Interferon Alfa-2a

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Granulocytic sarcoma (GS) is a rare extramedullary tumor consisting of immature myeloid precursors. It develops most commonly during the course of acute or chronic myeloid leukemias and myeloproliferative disorders (7) and more rarely in patients without evidence of blood or bone marrow hematologic malignancy. Fifty-two well-documented cases of aleukemic or primary GS have been reported in the English literature, but no standardized treatment has been identified. We report here the case of a patient with aleukemic GS who achieved a complete response after treatment with all-rranj-retinoic acid (ATRA) plus interferon alfa-2a (IFN a2a.) In July 1995, a 53-year-old man was referred to the National Institute for Cancer Research, Genoa, Italy, with a diagnosis of GS on the basis of histologic evaluation through cranial biopsy of a nodular mass arising in the right occipital region. No benefit had been achieved with polychemotherapy and radiotherapy on the right skull (4800 rads). Upon physical examination, the patient was found to have a large, thick mass in the right occipital region, and his symptoms (severe headache, intermittent bilateral dimness, asthenia, and loss of strength in the lower limbs) were worsening. Nuclear magnetic resonance (NMR) revealed a mass stretching from the cranial vault of the occipital level to the intra-cranial and extra-cranial compartments (Fig. 1, A); no chromosomal aberration was revealed by cytogenetic analysis of bone marrow. The diagnosis of isolated aleukemic GS was confirmed by a further cranial biopsy through immunocytochemical analysis (CD34 and CD68R expression and partial CD43 and CD 15 expression). ATRA is known to be active against promyelocytic leukemia, whereas experimental and clinical data support synergistic antiproliferative, differentiating, immunologic, and antiangiogenic effects of retinoids when they are combined with interferons to treat some hematologic and solid tumors (2). Therefore, after obtaining informed consent from the patient, we started an experimental treatment with ATRA (given orally at a dose of 45 mg/m per day, in two daily administrations, 3 consecutive days a week) plus IFN a-2a (3 x 10 IU given intramuscularly, three times a week). Blood samples were drawn from the patient for pharmacokinetic analysis before ATRA administration and during treatment. Combined therapy was given over 4 consecutive weeks, followed by IFN a-2a, which was administered alone for 12 more weeks. A clinical response was evident in the right occipital lesion. This response was associated with a complete remission of the painful symptoms. The cranial NMR was repeated in October 1995 and demonstrated a complete regression of the neoplastic lesion, which appeared to be replaced by bone tissue (Fig. 1, B). Treatment compliance was good, and toxicity was very low and quickly reversible (World Health Organization grade I, skin dryness, hypercholesterolemia, and hypertriglyceridemia). One year after the start of treatment, no evidence exists of loco-regional relapse or bone marrow involvement. Our pharmacokinetic data confirm that the combination of intermittent ATRA therapy and IFN a-2a results in prolonged exposure to effective ATRA concentrations, as previously reported (3-6). To our knowledge, this is the first reported case of GS treated by such a differentiating approach. The adopted regimen demonstrated a direct antitumor activity, toxicity was very low, and there was good patient compliance. We

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تاریخ انتشار 2005