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A CASE OF CYTOMEGALOVIRUS-INDUCED PANCYTOPENIA WITH CMV COLITIS
Author(s):
Olena Apanasenko
Affiliations:
Kiev center of bone marrow transplantation,KIEV,Ukraine
(Abstract release date: 05/17/18) EHA Library. Apanasenko O. 06/14/18; 216776; PB2062
Olena Apanasenko
Olena Apanasenko
Contributions
Abstract

Abstract: PB2062

Type: Publication Only

Background
     CMV infection is one of the important causes of morbidity and mortality after HSCT. It may manifest by involving multiple organs such as intestines, lungs, bone marrow, central nervous system involvement and others.

Aims

We describe a case of cytomegalovirus-induced pancytopenia with CMV colitis in patient after allogeneic stem cells transplantation from an unrelated donor for a secondary ALL.

Methods
     A 19-year-old man underwent an allogeneic HSCT following conditioning with fludarabine, ATG, thiosulphane. He had received cyclosporine and corticosteroids for acute, then chronic GVHD with skin, liver and gastrointestinal involvement. On D+150 serum CMV PCR was positive with 6.22x102 copies of DNA/105 cells without evidence of CMV disease, and the patient was started on valganciclovir preventive therapy. After the cancellation of immunosuppression (five months after transplantation), the patient's clinical course had worsened - appeared frequent watery stool, abdominal cramps, weight loss. Colonoscopy with colon biopsy was performed, which showed the presence of ulcerative colitis. СMV, EBV, human papillomavirus were negative, herpes simplex viruses 1 and 2 were positive in biopsy samples. Serum PCR CMV was not detected. He was started on antibiotics and antiviral therapy without any improvement. At D+270 PCR analysis showed that serum CMV was detectable, for which he again started treatment with valganciclovir 450 mg/day for 2 weeks. A gradual decrease in the number of leukocytes, platelets and hemoglobin level has been observed and watery liquid stool persisted. Differential diagnosis was conducted between CMV - enterocolitis and chronic intestinal GVHD. Biopsies from repeated colonoscopy showed positive PCR CMV. For increased watery stool, febrile fever, epistaxis due to cytopenia, patient received antibacterial and thrombocyte replacement therapy, G-CSF. But despite that, cytopenia persisted. Monitoring PCR CMV in the blood showed low viral load (4.26x102 copies of DNA / 105 cells). As possible causes of pancytopenia were considered recurrence of ALL, bone marrow failure, viral (CMV) infection. The patient's peripheral blood smear confirmed pancytopenia without any abnormal cells in bone marrow. 

Results
Based on these findings, diagnosis of CMV infection affecting the small intestine and colon was made and IV ganciclovir 10 mg/kg was started (despite of cytopenia -  WBC 1.6*109/l, Hb 86 g/l, Pl 22*109/l). The patient showed gradually improvement in pancytopenia, fever and frequency of stools. Quantitative PCR for CMV was repeated 2 weeks later and it became negative. 

Conclusion

     CMV infection could induce sustained and irreversible pancytopenia, despite normal findings in bone marrow aspiration. The pathogenesis is likely multifactorial, with both a central and peripheral effect. Several mechanisms have been proposed to explain the effect of CMV on human hematopoietic function. One indicates direct effect of CMV on bone marrow cells leading to cellular injury. Also alteration of accessory cell function by inducing the production of inhibitory cytokines resulting in a decreased production of hematopoietic factors or by altering cell surface adhesion molecule expression. Immunological mechanisms can be involved.

      The treatment of CMV viremia is not inconsequential and requires a close surveillance because first-line anti-CMV agents such as gancyclovir can further cause myelosuppression which may lead to superadded bacterial or fungal infection.

Session topic: 31. Infectious diseases, supportive care

Abstract: PB2062

Type: Publication Only

Background
     CMV infection is one of the important causes of morbidity and mortality after HSCT. It may manifest by involving multiple organs such as intestines, lungs, bone marrow, central nervous system involvement and others.

Aims

We describe a case of cytomegalovirus-induced pancytopenia with CMV colitis in patient after allogeneic stem cells transplantation from an unrelated donor for a secondary ALL.

Methods
     A 19-year-old man underwent an allogeneic HSCT following conditioning with fludarabine, ATG, thiosulphane. He had received cyclosporine and corticosteroids for acute, then chronic GVHD with skin, liver and gastrointestinal involvement. On D+150 serum CMV PCR was positive with 6.22x102 copies of DNA/105 cells without evidence of CMV disease, and the patient was started on valganciclovir preventive therapy. After the cancellation of immunosuppression (five months after transplantation), the patient's clinical course had worsened - appeared frequent watery stool, abdominal cramps, weight loss. Colonoscopy with colon biopsy was performed, which showed the presence of ulcerative colitis. СMV, EBV, human papillomavirus were negative, herpes simplex viruses 1 and 2 were positive in biopsy samples. Serum PCR CMV was not detected. He was started on antibiotics and antiviral therapy without any improvement. At D+270 PCR analysis showed that serum CMV was detectable, for which he again started treatment with valganciclovir 450 mg/day for 2 weeks. A gradual decrease in the number of leukocytes, platelets and hemoglobin level has been observed and watery liquid stool persisted. Differential diagnosis was conducted between CMV - enterocolitis and chronic intestinal GVHD. Biopsies from repeated colonoscopy showed positive PCR CMV. For increased watery stool, febrile fever, epistaxis due to cytopenia, patient received antibacterial and thrombocyte replacement therapy, G-CSF. But despite that, cytopenia persisted. Monitoring PCR CMV in the blood showed low viral load (4.26x102 copies of DNA / 105 cells). As possible causes of pancytopenia were considered recurrence of ALL, bone marrow failure, viral (CMV) infection. The patient's peripheral blood smear confirmed pancytopenia without any abnormal cells in bone marrow. 

Results
Based on these findings, diagnosis of CMV infection affecting the small intestine and colon was made and IV ganciclovir 10 mg/kg was started (despite of cytopenia -  WBC 1.6*109/l, Hb 86 g/l, Pl 22*109/l). The patient showed gradually improvement in pancytopenia, fever and frequency of stools. Quantitative PCR for CMV was repeated 2 weeks later and it became negative. 

Conclusion

     CMV infection could induce sustained and irreversible pancytopenia, despite normal findings in bone marrow aspiration. The pathogenesis is likely multifactorial, with both a central and peripheral effect. Several mechanisms have been proposed to explain the effect of CMV on human hematopoietic function. One indicates direct effect of CMV on bone marrow cells leading to cellular injury. Also alteration of accessory cell function by inducing the production of inhibitory cytokines resulting in a decreased production of hematopoietic factors or by altering cell surface adhesion molecule expression. Immunological mechanisms can be involved.

      The treatment of CMV viremia is not inconsequential and requires a close surveillance because first-line anti-CMV agents such as gancyclovir can further cause myelosuppression which may lead to superadded bacterial or fungal infection.

Session topic: 31. Infectious diseases, supportive care

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