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Romiplostim reverts the 160 in den-g gue hemorrhagic fever 140

120 To the Editor: First-genera-t /L) tion thrombopoietic agents were 9 100 recombinant forms of human (TPO), but their 80 development was discontinued due to the onset of neutralizing auto- 60 count (×10

antibodies cross-reacting with 40 endogenous TPO. Second-gen-e eration thrombopoiesis-stimulat-i 20 ing molecules (romiplostim and 0 ), have completed 0 10 20 30 40 50 55 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 phase III trials in primary im-m Time in days mune thrombocytopenia, whereas 9 phase II and III trials are ongoing Figure 1. Platelet count (x10 /L) by day. Arrows denote doses of romiplostim (4 µg/kg). in other conditions characterized by thrombocytopenia.1 Dengue gen and IgM antibodies were pres-e DHF in which romiplostim has is the most prevalent arthropod- ent; the had hypo-p been successfully used. An immune borne virus affecting humans to-d plasia and no evidence of myeloma mechanism of thrombocytopenia day causing a spectrum of disease, was found. The patient was treated due to increased platelet destruct- ranging from a mild febrile illness with intravenous hydrocortisone tion appears to be operative in pa-t to a life-threatening dengue hem-o (300 mg/day) and subcutaneous tients with DHF;9 however, in the orrhagic fever (DHF).2 The main (300 ug/day), with the case that we are reporting, the previ-o hematological findings of dengue neutropenia resolving 4 days later. ous stem cell transplant and the use are leukopenia, thrombocytopenia, The thrombocytopenia did not re-s of thalidomide led to a hypoplastic lymphocytopenia and the presence solve and was later treated unsuc-c marrow which most likely was un-a of atypical lymphocytes; in DHF, cessfully with oprelvekin and plate-l able to compensate the peripheral the thrombocytopenia is more pro-l let transfusions. Fifty-two days platelet destruction. longed, while the other hematolog-i after the thrombocytopenia en-s Romiplostim has been shown to ical abnormalities are not;3 DHF is sued, subcutaneous romiplostim (4 be effective in ameliorating throm-b endemic in México.4,5 ug/Kg/week) was started, and the bocytopenia in patients with chronic Multiple myeloma was identi-f platelet count increased promptly idiopathic thrombocytopenic pur-p fied in November 2007 in a 54-year (Figure 1). The patient remained pura and other thrombocytopenic old woman; she was initially treated with >100×109/L , 230 conditions.10,11 Its usefulness in this with thalidomide/dexamethasone days after starting romiplostim. case may stem from the combined /bortezomib until achieving a very Treatment of dengue fever, origin of the thrombocytopenia, on good partial response and then whether in its uncomplicated form one hand the platelet destruction autografted using high-dose mel-p or with hemorrhagic manifestations caused by the dengue virus and on phalan.6 After the autograft, she remains symptomatic. Steroids have the other a hyploplastic marrow was given thalidomide, 100 mg/ proved useful when DHF compli-c derived not only from the viral inf- day. Thirty-six months later she cates with septic shock7 and even fection, but also from the previous developed headache, gastrointesti-n though thrombocytopenia resolves stem cell allograft and the chronic nal symptoms, retro-orbital pain, spontaneously frequently, may be use of thalidomide. myalgia, joint pain, petechiae, pur-p prolonged in certain circumstanc-e pura and gum bleeding. The blood es.8 There are reports of anti-D S. Margarita Rodríguez- cell count disclosed thrombocy-t immune globulin in DHF cases Mejorada,a C. Gonzalo Rosel- topenia (2×109/L), leukopenia with severe and prolonged thromb- Gómez,a Rilke A. Rosado-Castro,a (0.7×109/L) and granulocytopenia bocytopenia9 but to the best of our Manuel Domingo-Padilla,a (0.05×109/L); dengue virus antig- knowledge, this is the first case of Guillermo J. Ruiz-Delgado,b-d

48 Hematol Oncol Stem Cell Ther 4(1) First Quarter 2011 hemoncstem.edmgr.com letter

From the aClínica de Mérida, Nasal extranodal periph-e started on CHOP chemotherapy Yucatan, bLaboratorios Clínicos eral NK/T-cell lymphoma but after two cycles, he had a poor de Puebla, Clínica Ruiz, Puebla, treated by the protocol response with a significant increase cCentro de Hematología y NK/T-cell high-dose-meth-o of the initial lesion and extension to Medicina Interna, Clínica Ruiz, otrexate L-asparaginase the right upper lip. A repeat biopsy Puebla, dUniversidad Popular dexamethasone showed a diagnosis of extranodal Autónoma del Estado de Puebla, NK/T-cell lymphoma, nasal type To the Editor: Puebla, México Extranodal NK/ with EBV+. T cell lymphoma, a nasal type lym-p The patient was switched to Correspondence: phoma, is a distinct entity by the combined treatment with metho-t 1 Guillermo Jose Ruiz-Arguelles WHO classification of lymphomas trexate 3g /m2 on day 1, L-asparagi 2 Centro de Hematologia y with a frequency of less than 1% of nase 6000U/m on day 2, 4, 6 and 8 Medicina Interna all non-Hodgkin lymphoma (NHL) with dexamethasone 40 mg day 1 to 2 3 8B Sur 3710 in the West and the North Africa day 4 on 21 days cycle for a total of 4 Anzures Puebla, and an increased incidence in Asia. three cycles. The patient responded Puebla 72530, México Standard treatment is not well estab-l nicely and the tumor regressed after [email protected] lished and anthracycline containing the first cycle. The patient achieved combination chemotherapy (CHOP) a complete clinical response after a had less than 30% survival at 5 years second cycle (Figure 3). One month REFERENCES in localized disease.5 We report a case after the third cycle, he started ir-r 1. Stasi R, Bosworth J, Rhodes E, Shannon MS, of extranodal NK/T cell lympho-m radiation, 30 Gy to the initial site Willis F, Gordon-Smith EC. Thrombopoietic agents. ma, nasal type, treated initially with of the disease. At the time of last Blood Rev. 24;179-90. 2. Ross TM. Dengue virus. Clin Lab Med 2010; CHOP as a large cell lymphoma and follow up at 24 months, he was 30:149-160 then with high-dose methotrexate, in complete remission (Figure 4). 3. Oliveira EC, Pontes ER, Cunha RV, Froes IB, Nascimento D. Hematological abnormalities in L-asparaginase and dexamethasone In conclucion, extranodal NK/T- patients with dengue. Rev Soc Bras Med Trop. as part of a multicenter phase II clini-c cell lymphoma nasal type is a rare 2009;42:682-5. 4. Ramirez-Zepeda MG, Velasco-Mondragon HE, cal trial (GELA-GOELAMS) for entity. Diagnosis may be difficult Ramos C, Penuelas JE, Maradiaga-Cecena MA, extranodal NK/T cell lymphoma. without an appropriate panel of im-m Murillo-Llanes J, Rivas-Llamas R, Chain-Castro R. Clinical and epidemiologic characteristics of A 34-year-old man, a welder by munohistochemistry that may not dengue cases: the experience of a general hospi-t profession for 17 years, was seen in be available in all hospitals, especially tal in Culiacan, Sinaloa, Mexico. Rev Panam Salud Publica. 2009;25:16-23. September 2008 for a right unilateral the detection of cytoplasmic expres-s 5. Navarrete-Espinosa J, Gomez-Dantes H, Celis- nasal obstruction associated with re-c sion (CD3ε), EBV expression and Quintal JG, Vasquez-Martinez JL. Clinical profile of dengue hemorrhagic fever cases in Mexico. Salud current epistaxis (Figures 1,2). There molecular biology techniques. Cases Publica Mex. 2005; 47:193-200. were no associated B symptoms and with clinical suspicion of extranodal 6. López-Otero A, Ruiz-Delgado GJ, Ruiz-Argüelles GJ. A simplified method for stem cell autografting performance status was 1. Anterior NK/T-cell lymphoma should have in multiple myeloma: A single institution experi-e rhinoscopy revealed a right nasal a full panel of immunohistochemis-t ence. Bone Marrow Transplant 2009; 44:715-9 7. Min M, U T, Aye M, Shwe TN, Swe T. Hydrocor-t cavity ulcerated mass with bleeding try from a tertiary referral center if tisone in the management of dengue shock syn-d on touch. There was no other abnor-m needed. Conventional anthracyclin- drome. Southeast Asian J Trop Med Public Health. 1975; 6:573-9. mal finding on physical examination based thereapy (CHOP) has a poor 8. Patil VD. Persistent thrombocytopenia after with no peripheral adenopathy or outcome. This could be related to dengue hemorrhagic fever. Indian Pediatr. 2006; 43:1010-1. hepatosplenomegaly. The diagnosis the overexpression of PGP (multi- 9. de Castro RA, de Castro JA, Barez MY, Frias MV, of NHL was established after several drug resistance) by NK/T tumor Dixit J, Generaux M. Thrombocytopenia associ-a 6 ated with dengue hemorrhagic fever responds to attempts at biopsy due to secondary cells. Chemosensitivity to L-aspara- intravenous administration of anti-D (Rh(0)-D) im-m infection and necrosis. The pathology aginase and high-dose methotrexate mune globulin. Am J Trop Med Hyg. 2007;76:737- 42. was reported as consistent with large has encouraging results and should 10. Molineux G, Newland A. Development of cell NHL and available immunohis-t be tested in future prospective stud-i romiplostim for the treatment of patients with 7-8 chronic immune thrombocytopenia: from bench to tochemistry showed lack of expres-s ies. Our patient had 17 years of bedside. Br J Haematol. 2010; 150:9-20. sion of CD20, CD3, and cytokeratin. occupational exposure to iron dusts 11. Ruiz-Delgado GJ, Lutz-Presno J, Ruiz-Argüelles GJ. Romiplostin may revert the thrombocytopenia Patient was staged as Ann Arbor and galvanized metals (welding) in graft versus host disease. Hematology 2011, in stage IEA with no poor prognostic that may had contributed to the de-v the press. factors according to the International velopment of this type of NHL In Prognostic Index. The patient was our patient .

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