Successful Treatment with Erwinia l -Asparaginase for Recurrent Natural Killer/T Cell Lymphoma

Abstract

We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT) and was successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase. A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed as having nasal type NK/T cell lymphoma on the basis of histopathological and flowcytometric findings of tumor, revealing diffuse infiltration of atypical lymphoid cells into blood vessels and expression of CD7 and CD56 antigens, but not CD3. He had tumor infiltration in the bone marrow and at the right lower lung field. After five cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy, the patient achieved complete remission and received high-dose chemotherapy with auto-PBSCT, although the tumor recurred in the right leg 10 months later. Despite salvage chemotherapy, followed by local irradiation and surgical amputation, a tumor recurred at the left upper gingiva 10 days after. Using E. coli L-asparaginase (6000 U/m2/day), the tumor regressed, fever was alleviated and the serum lactate dehydrogenase decreased to normal range after several days. The asparagine synthetase expression in tumor cells was immunohistochemically negative on paraffin-embedded tissues. Because of the anaphylactoid reaction developing after E. coli L-asparaginase, alternative Erwinia L-asparaginase (6000 U/m2/day) was administered, resulting in regression of tumor and fever lysis. L-asparaginase is a promising agent for the treatment of NK/T cell lymphoma.

Leukemia and Lymphoma of Natural Killer Cells

“…Although the treatment schedule was not uniform, 18 CHOP refractory patients were treated with this regimen from one to six courses with intervals of 21 to 28 days, followed by radiotherapy of 50 to 70 Gy (median : 56 Gy). In addition, several case reports claim an excellent efficacy of L-asparaginase in the treatment of refractory NKcell malignancies 246,255,256 . Recently, the NK-cell Tumor Study Group started a phase I trial of a new combination chemotherapy named SMILE.…”

Natural killer-cell malignancies: diagnosis and treatment

“…At 6000 U/day for 7 days, L-asparaginase induced a CR in a case of relapsed non-nasal NK-cell lymphoma. 63 Together with vincristine and steroids, L-asparaginase (4000-6000 U/day for 7 days) was reported to lead to CR in 56% of patients with nasal NK-cell lymphoma. 62 Common side effects included allergic rashes, liver function derangement and hyperglycemia.…”

“…The drug L-asparaginase has been reported to be effective in refractory diseases. [61][62][63] L-asparaginase depletes asparagines, and as lymphoid cells lack L-asparagine synthetase, they are susceptible to L-asparaginase-induced inhibition of protein, DNA and RNA synthesis. At 6000 U/day for 7 days, L-asparaginase induced a CR in a case of relapsed non-nasal NK-cell lymphoma.…”

Nasalis típusú extranodalis natural killer T-sejtes lymphoma hazai előfordulása és kezelésével szerzett tapasztalatok

“…Egy másik tanulmány szerint 40 Gy sugárdózis heti 30 mg/m 2 cisplatin után három ciklus VIPD alkalmazásával a CR-arány, hároméves OS és PFS tovább javítható, a szisztémás relapsus előfordulása pedig csökkenthető [19]. 2003-ban Matsumoto és mtsai ENKTL autológ őssejt-transzplantációt követő relapsusának sikeres L-aszparagináz-kezeléséről számoltak be [20]. Ezt követően Jaccard és mtsai, valamint Yamaguchi és mtsai az L-aszparagináz különböző kemoterápiás protokollokba való beépítésével nagymértékben javuló összreagálást (OR) és CR-arányt figyeltek meg (OR 87/80%, CR 47/50-60%) nyugat-európai és távol-keleti betegcsoportban [21,22].…”