Preemptive anti-CMV therapy during allogeneic bone marrow transplantation based upon blood PCR surveillance produces molecular evidence of effective viral clearance with absence of clinically detectable disease.

AJ Peniket, MR Howard, W Preiser, AR Perry, PD Kottaridis, N McKeag, NS Brink, S Mackinnon, AH Goldstone


Thirty two consecutive patients undergoing allogeneic bone marrow transplantation for a variety of haematological malignancies were incorporated into a CMV blood PCR surveillance/treatment protocol. The patients were transplanted between October 1996 and May 1997 and had the following diagnoses: AML 7, ALL 11, CGL 5, multiple myeloma 3, NHL 3, Hodgkin's disease 2 and MDS 1. Sixteen patients received HLA-identical unrelated donor transplants, 15 received HLA-identical sibling transplants and 1 received a haploidentical transplant from an uncle. There were three toxic deaths before Day 20 (Days 11, 12, and 18). The followup on the remaining patients was a median of 126 days (Range 65 to 267).The surveillance protocol consisted of weekly blood PCR for CMV DNA. If PCR was positive for 2 consecutive weeks then therapy was instigated with 2 weeks of ganciclovir 5 mg/kg bd (or foscarnet 90 mg/kg bd if blood counts were low). If at the end of this period CMV became undetectable then therapy was discontinued and routine surveillance resumed; if CMV PCR remained positive then therapy was switched from ganciclovir to foscarnet (or vice versa) until viral DNA became undetectable. A total of 382 samples were tested for the presence of CMV DNA with 79 (20.7%) positive samples. 14 patients (43.8%) became poitive at least once. 12 of 14 patients (85.7%) with seropositivity for CMV present in both donor and recipient became positive at least once. 2 of 5 seropositive patients with seronegative donors became positive at least once. None of the 13 seronegative patients (40.6%) with seronegative donors had a single positive sample. Thirteen patients (40.6%) underwent 22 treatment courses. Four patients (12.5%) required switching of therapy at two weeks because of persisting PCR positivity but all patients became PCR negative by the time therapy stopped. The longest course of therapy was 4 weeks. Five patients (15.6%) received two or more treatment episodes. There was no definite evidence of CMV disease in any of the patients but one patient died of an idiopathic pneumonitis (post-mortem request declined). There were six other deaths beyond 30 days not felt to be related to CMV disease [Disease progression (3 patients), Staphylococcal septicaemia (1 patient), gastrointestinal haemorrhage (1), systemic aspergillosis (1)]. Of 343 culture assays for CMV there were only two single positive results (0.6%). Of 344 CMV DEAFF tests of blood there were 81 toxic samples (23.6%) but no positive assays (0%). In conclusion, therapy according to our current protocol appears to produce a very low level of CMV disease and confirms effective clearance of viral DNA from the blood at a molecular level.

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Full conference title: 

39th meeting of the American Society for Haemotology
    • ASH 39th (1998)