Annals of Hematology

, Volume 91, Issue 3, pp 475–476

Acquired severe aplastic anemia after H1N1 influenza virus vaccination successfully treated with allogeneic bone marrow transplantation

Authors

    • Haematology Unit and Bone Marrow Trasplantation SectionUniversity of Florence and Careggi Hospital
  • Barbara Scappini
    • Haematology Unit and Bone Marrow Trasplantation SectionUniversity of Florence and Careggi Hospital
  • Stefano Guidi
    • Haematology Unit and Bone Marrow Trasplantation SectionUniversity of Florence and Careggi Hospital
  • Giovanni Longo
    • Haematology Unit and Bone Marrow Trasplantation SectionUniversity of Florence and Careggi Hospital
  • Alberto Bosi
    • Haematology Unit and Bone Marrow Trasplantation SectionUniversity of Florence and Careggi Hospital
Letter to the Editor

DOI: 10.1007/s00277-011-1278-0

Cite this article as:
Donnini, I., Scappini, B., Guidi, S. et al. Ann Hematol (2012) 91: 475. doi:10.1007/s00277-011-1278-0
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Dear Editor,

Here, we report a case of acquired severe aplastic anemia (SAA) which occurred in a young man potentially correlated to the administration of H1N1 influenza virus vaccine. On 30 November 2009, a 25-year-old man presented to ER with fever, headache, sore throat and diffuse bruises. Laboratory tests revealed severe pancytopenia (WBC 1.2 × 109/L, haemoglobin 11.2 g/dL and platelets 3,000 × 109/L).

He was immediately referred to our institution. Liver and renal functions were normal as well as coagulation parameters. Medical history was completely negative with the exception that he received vaccination for H1N1 virus few days before, on 15 November 2009 (Focetria, lot number # 090201). He was completely healthy before. The only reason why his family doctor suggested this specific vaccination was because he worked as a salesman, travelling abroad frequently.

All microbiological tests, including blood cultures, were repeatedly negative, and fever was responsive to a broad spectrum antibiotic therapy. On 5 December 2009, further worsening of parameters (WBC 0.56 × 109/L, haemoglobin 7.6 g/dL and platelets 3,000 × 109/L) was observed.

Evaluation tests for herpetic viruses (CMV, EBV, HHV-6 and HHV-8), hepatic viruses (HCV, HBV), HIV and parvovirus B19 performed by both serology and PCR techniques did not show any evidence of an active infection. Paroxysmal nocturnal haemoglobinuria was excluded by flow cytometry analysis, and screening for autoimmune diseases was negative.

A CT scan showed only splenomegaly with a splenic size of 16 cm. Bone marrow biopsy was compatible with the diagnosis of aplastic anaemia. Bone marrow immunophenotype demonstrated the absence of CD34+ cells with a relative increment in T lymphocytes. Cytogenetic analysis was not available for insufficient metaphases.

According to international guidelines, we decided to wait for human leukocyte antigen (HLA) typing of siblings and he received only supportive irradiated red blood cell and platelet transfusions and antibacterial, antiviral and antifungal prophylaxis with levofloxacin, aciclovir and itraconazole, respectively. After a febrile episode, he was treated with filgrastim subcutaneously (263 mcg) for 7 days, without any significant improvement of white blood cell count.

Patient underwent bone marrow HLA-identical sibling transplantation on 31 December 2009, after non-myeloablative conditioning with fludarabine 30 mg/m2 and cyclophosphamide 30 mg/Kg on days −6 to −3 and antithymocyte globulin 2.5 mg/Kg on days –4 and −3. The patient did not suffer any significant infectious complications after the transplantation.

At the last follow-up, 110 days since bone marrow transplant, the patient presented a near complete haematological recovery (WBC 3.7 × 109/L, haemoglobin 13.2 g/dL and platelets 136,000 × 109/L) with PCR-based microsatellite polymorphism analysis showing 8% host chimerism. Clinically, the patient has become fully asymptomatic and has been managed only with observation.

SAA is a rare disease with an incidence rate of 2–4/million/year in the general population [1]. Signs and symptoms are related to pancytopenia and marrow failure, with infections and bleeding as major complications.

Many clinical associations (pregnancy [2], eosinophilic fasciitis and seronegative hepatitis [3]) such as exposure to toxic substances (benzene) or various drugs (chloramphenicol, penicillamine or gold) have been reported [4, 5]. Aetiology remains in most cases unknown. In the majority of cases, SAA is an immune-mediated disease with a hematopoietic stem and progenitor cell destruction by an aberrant immune response involving the T cells [6, 7]. A response to immunosuppressive therapies represents the principal support for this hypothesis, even if why T cells are activated in SAA remain unclear: HLA-DR2 overexpression [8], polymorphisms in cytokine genes, mutation in PRF1 and the gene for perforin have been described [9, 10], suggesting genetic basis for aberrant T cell activation in SAA.

Interestingly, up to 10% of cases of acquired aplastic anaemia are preceded by a viral hepatitis [11] and temporary or sometimes permanent relapse of aplastic anaemia after an acute infection has been described [12]. Furthermore, a case of a relapse of SAA after influenza immunization has been previously reported [13].

These data support the hypothesis that generally any “immunological modification” might trigger SAA and more importantly might induce a relapse of the disease. On the basis of these considerations, in our opinion, in patients with SAA in remission, any type of vaccination should be administered only if strictly, medically indicated.

Our patient history is similar to many SAA cases, but in our opinion, this temporary relationship with H1N1 vaccine needs to be taken in consideration. Of course, a definitive correlation with the anti H1N1 vaccination could not be demonstrated, but in our opinion, vaccination might represent at least a trigger on a genetic predisposition for the induction of an abnormal immune response and consequent development of the disease. To our knowledge, no similar cases have been reported so far, no further information is still available about the incidence of aplastic anaemia after H1N1 vaccination in Italy or Europe.

Copyright information

© Springer-Verlag 2011