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We considered of great clinical significance a recent report from Holmberg et al1 on the increased incidence of CMV disease after autologous CD34-selected peripheral blood stem cell (PBSC) transplantation. We reported previously an increased incidence of viral complications after autologous CD34-selected PBSC transplantation in 19 consecutive patients.2 We recently analyzed a cohort of 40 CMV-seropositive patients affected by hematological malignancies submitted to CD34-selected PBSC. CD34 selection was carried using the Ceprate SC (Cellpro, Bothell, WA, USA) in 25 patients and CliniMACS (Miltenyi Biotec, Bergisch-Gladbach, Germany) in 15 patients thereafter, both according to the manufacturer's specifications and we retrospectively evaluated the incidence of CMV disease and other viral complications within the first 100 days after transplantation. Results were compared to a cohort of 136 CMV-seropositive patients submitted to unfractionated PBSC and treated at the same institution over a period of 5 years. Overall 31 patients (77.5%) submitted to CD34-selected PBSC transplantation had weekly CMV screening studies performed including the CMV pp65 antigenemia assay (CMV Brite; Biotest Diagnostic Corp, Denville, NJ, USA) and viral culture monitoring from stools, urine and throat were performed weekly in 30 patients. CMV infection was defined as either the evidence of any level of quantitative pp65 antigenemia and/or a positive culture. CMV disease was defined as a conventional culture of bronchoalveolar lavage fluid, or gastric/duodenal biopsy in association with symptoms.3 Other viral infections were defined as the evidence of positive culture from urine, stools or throat in association with symptoms. Of the 40 patients, 39 were transplanted for hematological malignancies (97.5%) including NHL, MM and HD. The median number of CD34+ × 106/kg infused was 4.2 (0.86–16). The characteristics of the patients are shown in Table 1. Of the 136 patients transplanted with unfractionated PBSC, 134 were affected by hematological malignancies including NHL, MM, HD and AML. The CMV screening study was carried out in 105/136 patients (77%). In this group the median number of CD34+ × 106/kg infused was 10.35 (range 2–50.2) (P = 0.0014). Patients in both groups were transplanted with a variety of high-dose conditioning regimens not including total body irradiation. No patient required steroid therapy for regimen-related toxicities. Thirty-two patients after CD34-selected PBSC transplantation received G-CSF 5 μg/kg post transplant while in the group of patients submitted to unfractionated PBSC, G-CSF was not used as for institutional policy. All patients who were serologically positive for herpes simplex virus (100% in both groups) received acyclovir 500 mg/m2 every 8 h from day −1 to day 100 after transplantation. Patients were switched to oral high-dose acyclovir as soon as possible after autotransplantation. Antiviral therapy with gancyclovir or foscarnet was administered for documented CMV infection. Treatment with cidofovir or ribavirin was instituted when a documented adenovirus infection was diagnosed.
No significant differences were observed for neutrophil engraftment in both groups (13 vs 13 days) while platelet (21 vs 12 days, P = 0.0001) and reticulocyte (15 vs 12, respectively, P = 0.0001) engraftment were significantly delayed after CD34-selected PBSC transplantation producing a significantly higher requirement for platelet and RBC transfusions. The absolute number of lymphocytes and the count of CD4+ lymphocytes was significantly lower at 30 and 60 days in CD34-selected patients as reported elsewhere.4
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References
Holmberg LA, Boech M, Hooper H et al. Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation Blood 1999 94: 4029–4035
Ljungman P, De Bock R, Cordonnier C et al. Practices for cytomegalovirus diagnosis, prophylaxis and treatment in allogeneic bone marrow transplantation recipients: a report from the Working Party for Infectious Diseases of the EBMT Bone Marrow Transplant 1993 12: 399–403
Rutella S, Rumi C, Laurenti L et al. Immune reconstitution after transplantation of autologous peripheral CD34+ cells: analysis of predictive factors and comparison with unselected progenitor transplants Br J Haematol 2000 108: 105–115
Childs R, Sanchez C, Engler H et al. High incidence of adeno- and polyomavirus induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancies following T cell depletion and cyclosporine Bone Marrow Transplant 1998 22: 889–893
Sica, S., Sora, F., Chiusolo, P. et al. Early viral complications after autologous CD34-selected peripheral blood stem cell transplantation.
Bone Marrow Transplant26, 587–588 (2000). https://doi.org/10.1038/sj.bmt.1702550