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Khoj et al.

, J Leuk 2013, 1:3


http://dx.doi.org/10.4172/2329-6917.1000120

Leukemia
Case Report

Open Access

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 and Jalil Ur Rehman3*
1
2
3

Postgraduate Student, Faculty of medicine,Saudi Arabia


Department Of Oncology, Student Investigator Program (SIP), Saudi Arabia
KFSHRC Jeddah Branch, Saudi Arabia

Abstract
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
feverinduced severe AA (SAA) salvaged by an allogeneic bone marrow transplant (BMT).

Keywords: 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 virusspecific 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 mol/L (normal range, 0-17 mol/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
patients 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

J Leuk
ISSN: 2329-6917 JLU, an open access journal

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.

Discussion
Only 2 cases of dengue feverinduced SAA have been reported in

*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: jaliljeddah@yahoo.com, jrehman@kfshrc.edu.sa
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 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.

Volume 1 Issue 3 1000120

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 1: 120. doi:10.4172/2329-6917.1000120

Page 2 of 2
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
feverinduced 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 feverinduced 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 B19induced 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 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.

Conclusion
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.
References
1. Segel GB, Lichtman MA (2010) Aplastic anemia: acquired and inherited.
(8thedn). Williams Hematology. McGraw Hill Professional, New York.
2. Ramzan M, PrakashYadav S, Sachdeva A (2012) Post-dengue fever severe
aplastic anemia: a rare association. Hematol Oncol Stem Cell Ther 5: 122-124.
3. Albuquerque PL, Silva Jnior GB, Digenes SS, Silva HF (2009) Dengue and
aplastic anemia--a rare association. Travel Med Infect Dis 7: 118-120.
4. Ullah K, Satti TM, Ahmed P, Raza S, Tariq WU, et al. (2007) Successful
allogeneic stem cells transplantation in severe aplastic anaemia complicated
by dengue Fever. J Coll Physicians Surg Pak 17: 635-636.
5. Young NS, Scheinberg P, Calado RT (2008) Aplastic anemia. Curr Opin
Hematol 15: 162-168.
6. Young NS (1996) Parvovirus infection and its treatment. Clin Exp Immunol 104
Suppl 1: 26-30.
7. Osaki M, Matsubara K, Iwasaki T, Kurata T, Nigami H, et al. (1999) Severe
aplastic anemia associated with human parvovirus B19 infection in a patient
without underlying disease. Ann Hematol 78: 83-86.
8. Lu J, Basu A, Melenhorst JJ, Young NS, Brown KE (2004) Analysis of T-cell
repertoire in hepatitis-associated aplastic anemia. Blood 103: 4588-4593.
9. Pham AM, Langlois RA, TenOever BR (2012) Replication in cells of
hematopoietic origin is necessary for Dengue virus dissemination. PLoS
Pathog 8: e1002465.

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 1: 120. doi:10.4172/2329-6917.1000120

J Leuk
ISSN: 2329-6917 JLU, an open access journal

Volume 1 Issue 3 1000120

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