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ISSN: 2329-6917
Journal of Leukemia
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A Case of Dengue Fever-Induced Severe Aplastic Anemia Salvaged by Allogeneic Bone Marrow Transplant

Lujain Khoj1 Rawan Baksh2 Mohammad Aslam3 Mohammad Kelta3 Bassim Albeirouti3 Jalil Ur Rehman3*
1Postgraduate Student, Faculty of medicine,Saudi Arabia
2Department Of Oncology, Student Investigator Program (SIP), Saudi Arabia
3KFSHRC Jeddah Branch, Saudi Arabia
Corresponding Author : Dr. Jalil Ur Rehman, MBBS, MRCP, MRCP
Assistant Consultant Hematology/BMT, MBC-J-64
Department of Oncology, King Faisal Specialist Hospital
Po Box 40047, Jeddah 21499, Kingdom of Saudi Arabia
Tel: 00966-555212399
E-mail: [email protected], [email protected]
Received June 29, 2013; Accepted August 09, 2013; Published August 12, 2013
Citation: Khoj L, Baksh R, Aslam M, Kelta M, Albeirouti B, et al. (2013) A Case of Dengue Fever-Induced Severe Aplastic Anemia Salvaged by Allogeneic Bone Marrow Transplant. J Leuk (Los Angel) 1:120 doi:10.4172/2329-6917.1000120
Copyright: © 2013 Khoj L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Aplastic anemia (AA) is a type of bone marrow failure characterized by peripheral pancytopenia and bone marrow hypoplasia. The complications of AA include infections and bleeding. A rare association between dengue fever and AA has been reported. Dengue fever is a disease endemic to the western region of Saudi Arabia. In the literature 8 cases of Dengue fever induced Aplastic anemia has been reported and treated conservatively, but none has received allogeneic bone marrow transplant .In the context of this background, we report the first case of dengue fever–induced severe AA (SAA) salvaged by an allogeneic bone marrow transplant (BMT).

Dengue Fever; Aplastic Anemia (AA); Allogeneic Bone Marrow Transplant (BMT)
Case Presentation
A 17-year-old male patient without any apparent prior diagnosis of an illness presented to our emergency department with heavy epistaxis, purpuric rash, and gum bleeding as well as severe symptoms of anemia. The patient had a history of fever and headache 1 month prior to presentation, but no history of drug abuse or exposure to possible toxic agents or radiation and no family history of diseases similar to dengue fever. The patient resided in an area where dengue fever is prevalent. On physical examination, the patient looked pale and had a purpuric rash on the limbs and active epistaxis, but no lymphadenopathy or organomegaly. The patient was pancytopenic and laboratory tests revealed the following: white blood cell (WBC) count, 1.7 (normal range, 4.5-11.5); lymphocytes, 88% (normal range, 20-45%); hemoglobin, 5.2 (normal range, 14-18); mean corpuscular volume, 72.3 (normal range, 80-94); mean corpuscular hemoglobin, 23.5 (normal range, 32-36); platelet count, 6 (normal range, 150-450); absolute neutrophil count, 0.2 (normal range, 2-7.5); reticulocyte count, 0.009; and schistocyte, +1. Rouleaux formation of red blood cells was present, and dengue virus–specific immunoglobulin (Ig) G and IgM antibodies were positive. Tests for hepatitis B and C, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, and parvovirus B19 were all negative, as well as for Coombs’ test. Vitamin B12 level was 150.6 pmol/mL (normal range, 145-660 pmol/mL), folate level was 31.3 nmol/L (normal range, 7-40 nmol/L), ferritin level was 495 ng/mL (normal range, 30-400 ng/ml), total and direct bilirubin level was 16 µmol/L (normal range, 0-17 µmol/L), and lactate dehydrogenase level was 156 U/L (normal range, 100-190 U/L). Bone marrow biopsy and aspiration revealed that there was marked hypocellularity (<5% hematopoietic cells), the bone marrow trabeculae were replaced by fat, there were very few bone marrow elements, and there was predominant lymphocytosis. A diagnosis of SAA [1] was made. The patient received a transfusion of packed RBCs and platelets several times and was initially given intravenous Immunoglobulin (IVIG) plus folic acid, iron, and vitamin B12 for presumed idiopathic thrombocytopenic purpura. The patient’s laboratory parameter values did not improve, and he became transfusion dependent after 2 months; therefore, he was referred to King Faisal Specialist Hospital and Research Centre Jeddah Branch to be considered for an allogeneic BMT. Our reevaluation of the patient confirmed our diagnosis of AA, and chromosomal and breakage studies did not reveal any evidence of Fanconi anemia or paroxysmal nocturnal hemoglobinuria (PNH). Human leukocyte antigen (HLA) typing was done, and the patient had a full matched related donor, his 5-year-old sister. The patient was conditioned with 50 mg/kg of IV cyclophosphamide started on D-5 and continue till D-2, total of 4 days, along with Mesna to avoid the cytotoxic effects of Cyclophosphamide on uroepithelium and 30 mg/kg of horse antithymocyte Globulin started on D-5 and continue till D-3 for the total of 3 days with necessary pre medications to avoid the serum sickness with ATG, followed by the allogeneic BMT on D0(15/10/2012) with bone marrow harvested stem cells (dose infused 3.57 × 106 CD34 cells) . He was started on GVHD prophylaxis with Intravenous cyclosporine 2.5 mg/kg q 12 hourly on D-1 and received the dose of methotrexate 15 mg/m2 on D+1 and 10 mg/m2 on D+3 and 6. The engraftment was considered successful on D15 with absolute neutrophil counts more than 1000 and platelets reach above 50,000 without support and the patient was discharged home and given immunosuppression therapy with cyclosporine and prophylaxis for bacterial, fungal and viral infection with Ciprofloxacin 500 mg bid, Fluconazole 200 mg daily and Acyclovir 400 mg twice daily. Post bone marrow transplantation course was uneventful except for nausea, mild mucositis and rise in liver enzyme, with no acute or chronic graft verses host disease The patient currently has a normal healthy life with 90 % Donor Chimerism as per the report on D210. He continues on cyclosporine to complete a year with Septrin-DS 1 tab twice daily, 3 times in a week as a PCP prophylaxis till discontinuation of immunesuppressive treatment.
Only 2 cases of dengue fever–induced SAA have been reported in the literature in patients aged 8 and 11 years [2,3] both patients were diagnosed with AA following a dengue virus infection, and both were successfully treated with chemotherapy alone. In the first case, BMT was planned but could not be done because an HLA-matched donor was not available [2]. However, to our knowledge, the present case is the first ever case where allogeneic BMT was performed for dengue fever–induced SAA. The patient tolerated the transplant well, with no major complications or graft-versus-host disease. There are only a few reported cases of AA due to dengue fever in the literature. Albuquerque et al. reported similar cases from Latin America, and Ramzan et al. reported a case from India [2,3]. In both articles, the diagnosis of AA was confirmed by IgG and IGM; however, none of the patients received a BMT. Hemorrhagic episodes in patients with aplastic anemia occur usually secondary to thrombocytopenia and require frequent support with platelet concentrates and other blood products. Infection with dengue virus (particularly dengue sero type-2 of South Asian genotype) is associated with dengue hemorrhagic fever. Dengue infection further worsens the disease process in patients with aplastic anaemia due to uncontrolled hemorrhagic diathesis and major organ failure, which may prove fatal in these already immunocompromised patients, if not treated appropriately [4].
In our case, the patient presented with bleeding due to thrombocytopenia. Upon investigation, the patient was found to be pancytopenic, the dengue virus serology was positive for both IgG and IgM, and the bone marrow biopsy showed SAA. Other causes of AA, such as PNH and myelodysplastic syndrome, were excluded from consideration. Hence, a diagnosis of dengue fever–induced AA was made. The defects could be the result of an autoimmune response mediated by cytotoxic T lymphocytes (CD8), which are detectable in the blood and bone marrow of AA patients. As is known in many autoimmune diseases, an acute viral illness can trigger this autoimmune response.
Most acquired AA is the result of an immune-mediated destruction of hematopoietic stem cells that causes pancytopenia and aplastic bone marrow. The severe form of aplastic anemia is a life-threatening bone marrow failure disorder that, if untreated, is associated with a very high mortality rate. An immune response dominated by oligoclonal expanded cytotoxic T cells targets hematopoietic stem and progenitor cells, inducing their cell death via apoptosis and hematopoietic failure [5]. Again, this can be triggered by a dengue virus infection.
Other viruses causing SAA, including parvovirus B19 and hepatitis, also share the same immunologic pathogenesis outlined above. Two hypotheses can be made concerning the pathogenesis of parvovirus B19–induced AA. The first hypothesis involves the direct effect of parvovirus B19, suggesting that all 3 precursor cell lines in the bone marrow might become the target cells [6]. The second hypothesis is based on immunologic mediation. In virus-associated hemophagocytic syndrome with an acute parvovirus B19 infection, raised levels of cytokines such as interferon γ would impair regulation of the phagocytic system, resulting in pancytopenia and/or decreased hematopoiesis [7]. In hepatitis, activation of circulating cytotoxic T cells increases, with the T cells tending to accumulate in the liver, and therefore there is a large amount of T cell infiltration from the liver parenchyma [8]. Recovery of autologous hematopoiesis in patients whose stem cell transplant engraftment failed and responsiveness to immunosuppressive therapies support the hypothesis that the immunologic pathophysiology underlying an immune response triggered by acquired AA leads to bone marrow failure [5].
The other mechanism in which a dengue virus infection causes aplastic anemia is the replication of the virus in the hematopoietic cells, which directly damages these hematopoietic cells peripherally or in the bone marrow [9]. This supports the association between dengue fever and AA as reported in our case.
Allogeneic BMT is the transplant method of choice for SAA in younger patients, and it was achieved successfully in our case. The transplant was done following a priming regimen with cyclophosphamide and antithymocyte Globulin and was made feasible because of a well-established collaboration and good organization between different health institutions. In addition, finding an HLAmatched donor in our country is not challenging because most patients have a large number of siblings. Regarding the serious association between dengue fever and SAA, the importance of eradicating the Aedes aegypti mosquito, which is the main carrier of dengue fever, cannot be overemphasized. Efforts should be placed to decrease morbidity and mortality related to dengue virus, and this could be established by proper sanitation and by having an effective vaccine and specific antiviral treatment.

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