Chronic persistent parvovirus B19 bone marrow infection resulting in transfusion-dependent pure red cell aplasia in multiple myeloma after allogeneic haematopoietic stem cell transplantation and severe graft versus host disease.
BACKGROUND
We report a chronic persistent Parvovirus B19 (PVB19) infection despite long-term immunoglobulin substitution intravenous immunoglobulin (IVIG) and tapering of immune-suppressive therapy in a 41-year-old patient after allogeneic haematopoietic stem cell transplantation (alloHSCT) and long-term immune-suppressive therapy due to a steroid-refractory graft versus host disease (GvHD).


METHODS
More than 18 month after alloHSCT the patient acquired a de novo transfusion-dependent pure red cell aplasia (PRCA) due to a PVB19 infection. Despite prompt tapering of GvHD-directed therapy and application of various IVIG regimens, transfusion-dependent anaemia (fourerythrocyte concentrates a month) persisted, and a high PVB19 replication is still evident for more than 3.5 years. Virological analysis at different time points showed a very high PVB19 load in the blood (range: 6.79E9-1.56E11), as well as highly elevated PVB19-IgG (range: 1.95-3.34) and -IgM (range: 1.97-9.74) levels in serology testing. Other virological parameters were not significantly elevated. After 30 months, a bone marrow (BM) examination still revealed a highly dysplastic erythropoiesis without any cellular maturation, and a high-grade expression of PVB19 within the dysplastic erythropoietic progenitor cells, consistent with a PRCA due to a PVB19 infection of the BM. We suggest that PRCA was most probably caused by a primary PVB19 infection of unknown source following alloHSCT with a PVB19-negative donor.


CONCLUSIONS
PRCA due a PVB19 infection of the BM may persist over a long-time, despite prolonged administration of various IVIG regimen and tapering of GvHD-directed therapy. The case emphasizes the importance of PVB19 monitoring in heavily pre-treated haematological patients. Currently, PVB19-directed treatment options are extremely limited and optimized therapeutic strategies are urgently needed.
a Institute of Medical Microbiology , Jena University Hospital , Jena , Germany.
Matthias
M
Karrasch
b Dep. of Internal Medicine II, Hematology/Oncology , Jena University Hospital , Jena , Germany.|e Department of Hematology/Oncology/Hemostaseology , Helios Klinikum , Erfurt , Germany.
Volker
V
Schmidt
c Institute for Pathology , Jena University Hospital , Jena , Germany.
Andreas
A
Hammer
b Dep. of Internal Medicine II, Hematology/Oncology , Jena University Hospital , Jena , Germany.
Andreas
A
Hochhaus
b Dep. of Internal Medicine II, Hematology/Oncology , Jena University Hospital , Jena , Germany.
Paul La
P
Rosée
c Institute for Pathology , Jena University Hospital , Jena , Germany.
Iver
I
Petersen
d Institute for Virology and Antiviral Therapy , Jena University Hospital , Jena , Germany.
Andreas
A
Sauerbrei
a Institute of Medical Microbiology , Jena University Hospital , Jena , Germany.
Michael
M
Baier
e Department of Hematology/Oncology/Hemostaseology , Helios Klinikum , Erfurt , Germany.
Herbert G
HG
Sayer
a Institute of Medical Microbiology , Jena University Hospital , Jena , Germany.
Beate
B
Hermann
D000328:Adult; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000097:blood / Q000473:pathology / Q000628:therapy / Q000821:virology*; D010322:Parvoviridae Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D016732:Parvovirus B19, Human / Q000302:isolation & purification*; D012010:Red-Cell Aplasia, Pure / Q000188:drug therapy / Q000628:therapy / Q000821:virology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D016756:Immunoglobulins, Intravenous