Blood, 1 January 2003, Vol. 101, No. 1, pp. 370-370
CORRESPONDENCE
To the editor:
Leukocyte reduction and HTLV-I: is the glass half empty or half
full?
We read with interest the recent article by Pennington et
al.1 Based on the ability to detect Tax DNA in the
blood of asymptomatic carriers with proviral loads exceeding
108 DNA copies/L, the authors conclude that leukocyte
depletion (LD) may not provide complete protection from human T-cell
leukemia virus-I (HTLV-I) transmission by transfusion.
Lau et al2 proved that cytomegalovirus
(CMV)-infected blood, another example of a cell-borne viral infection,
transfected with as many as 3 × 108 infected cells,
contains a residual of 105 viral copies following
LD, consistent with the present study's observations. These findings
were confirmed in asymptomatic seropositive donors by Dumont et
al.3 However, in spite of the residual polymerase
chain reaction (PCR) detectability of the CMV DNA in the postfiltration
blood, little controversy exists concerning the ability of LD to
greatly reduce the potential for transfusion-transmitted CMV
infection.4,5
Okochi and Sato6 conclude that approximately
108 infected lymphocytes are required to transmit HTLV-I
infection by transfusion. This conclusion is further supported by the
fact that plasma derived simultaneously from donations of whole blood
whose red cells have transmitted HTLV-I infection have not transmitted
the infection nor, as stated by the authors, has plasma ever been
documented to transmit the infection. A unit of non-LD plasma delivers
an average 3 × 106 leukocytes to a
recipient.7 Kobayashi et al8 confirmed the
infectivity of 7 units of native red cells from HTLV-I-positive donors
using a syncytium induction assay in which cocultivation of
HTLV-I-permissive (ME-80) cells and donor lymphocytes effect the
development of multinucleated giant cells. Following LD, only 1 of the
7 filtered units showed infectivity using this assay.
Shinzato et al9 quantified the HTLV-I viral genome load in
the blood of 133 asymptomatic carriers and found that 95% of the
individuals had 10 infected cells per 100 peripheral blood mononuclear
cells (PBMCs), which approximates less than 108
cells per unit of blood. Levin et al found the number of
infected cells to be as low as 1 per 10 000 PBMCs in patients with
HTLV-I-associated disease.10 Accepting the findings of
the current study (ie, LD imposes a 3-4 log10 viral titer
reduction), the residual number of proviral genomes in the blood of
asymptomatic carriers is substantially less than that of plasma from
infected donors and the infectious viral load requirement of Shinzato
et al.9
As a final point, we believe use of MT2 cells as carriers of HTLV-I
underestimates the benefit of LD because filtration of these cells
results in a reduction of 1 log10 less than that of native leukocytes.
Only clinical experience can confirm the extent to which LD will be
effective in minimizing the incidence of transfusion-transmitted HTLV-I
infection. We agree with Pennington et al1 that
LD will not "provide complete protection" because no
precautions, including nucleic acid testing, can. However, based on the
information above, we believe LD will provide significant protection
and, perhaps as for CMV, protection comparable to that afforded by
serologic screening. Casting the conclusion this way appears more
consistent with the authors' own data taken within the
context of the available literature.
Barry Wenz and Girolamo A. Ortolano
Correspondence: Barry Wenz, Pall Corporation, 2200 Northern
Blvd, East Hills, NY 11548
References
1.
Pennington J, Taylor GP, Sutherland J, et al.
Persistence of HTLV-I in blood components after leukocyte depletion.
Blood.
2002;100:677-681[Abstract/Free Full Text].
2.
Lau W, Onizuka R, Krajden M.
Polymerase chain reaction based assessment of leukoreduction efficacy using a cytomegalovirus DNA transfected human T-cell line.
J Clin Virol.
1998;11:109-116[CrossRef][Medline]
[Order article via Infotrieve].
3.
Dumont LJ, Luka J, VandenBroeke T, Whitley P, Ambruso DR, Elfath MD.
The effect of leukocyte-reduction method on the amount of human cytomegalovirus in blood products: a comparison of apheresis and filtration methods.
Blood.
2001;97:3640-3647[Abstract/Free Full Text].
4.
Bowden RA, Slichter SJ, Sayers M, et al.
A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant.
Blood.
1995;86:3598-3603[Abstract/Free Full Text].
5.
Leukocyte reduction for the prevention of transfusion-transmitted cytomegalovirus (TT-CMV). Association bulletin 97-2. Vol 19. Bethesda, MD: American Association of Blood Banks.; 1997:10-12.
6.
Okochi K, Sato H.
Transmission of adult T-cell leukemia virus (HTLV-I) through blood transfusion and its prevention.
AIDS Res.
1986;2:S157-S161.
7.
Hiruma K, Okuyama Y.
Effect of leucocyte reduction on the potential alloimmunogenicity of leucocytes in fresh-frozen plasma products.
Vox Sang.
2001;80:51-56[Medline]
[Order article via Infotrieve].
8.
Kobayashi M, Yano M, Kwon K-W, Takahashi TA, Ikeda H, Sekiguchi S.
Leukocyte depletion of HTLV-1 carrier red cell concentrates by filters. In:
Sekiguchi S, ed.
Clinical Application of Leukocyte Depletion. Boston, MA: Blackwell Scientific Publications; 1993:138-148.
9.
Shinzato O, Ikeda S, Momita S, et al.
Semiquantitative analysis of integrated genomes of human T-lymphotropic virus type I in asymptomatic virus carriers.
Blood.
1991;78:2082-2088[Abstract/Free Full Text].
10.
Levin MC, Fox RJ, Lehky T, et al.
PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease.
J Virol.
1996;70:924-933[Abstract].
Response:
Infectious dose of HTLV-I in transfusion recipients
We certainly agree with Wenz and Ortolano that leukocyte
depletion (LD) reduces the risk of human T-cell leukemia
virus-I (HTLV-I) transmission by transfusion just as they agree with
us that this reduction does not equate zero risk. It is therefore important to be precise as to whether we consider LD to achieve risk
reduction or risk removal.
In their rebuttal of our conclusions, Wenz and Ortolano quote
studies regarding cytomegalovirus (CMV) and HTLV-I. We are
not convinced that CMV is a relevant model to compare with HTLV
because the biology of herpesviridae is radically different from human retroviruses. Specifically, retroviruses are integrated into the host
cell genome, whereas CMV is a cytoplasmic virus and thus could
potentially be released during LD processes if cellular damage occurs.
However, one aspect that posttransfusion HTLV-I and CMV transmission
have in common is that clinical infectivity and pathogenicity of
infection (or reactivation in the case of CMV) is more a function of
the competence of the host immune system than of viral load. The rare
development of clinical expression of HTLV-I infection after
transfusion may well be more likely to occur in immunodeficient
individuals.1 Similarly, the disastrous consequences of
CMV infection or reactivation have been observed essentially in
premature neonates and bone marrow or organ transplant recipients.
Although HTLV-I proviral load can be accurately measured, the threshold
of susceptibility of patients with various levels of immunodeficiency
cannot be predicted. It is therefore prudent to assume that, in these
immunocompromised individuals who are the primary recipients of
platelet concentrates, very low viral load can be not only infectious
but could lead to clinical sequelae. Under such circumstances, it is
likely that proviral loads considerably lower than the 108
infected cells calculated by Okochi and Sato in
immunocompetent recipients of red cells can be
infectious.2
We agree with Wenz and Ortolano that only clinical evidence
could solve the problem. However, the low prevalence of HTLV-I infection and the extreme rarity of posttransfusion clinical
consequences of HTLV-I infection make it doubtful that such evidence
would ever be provided. Only a systematic follow-up of transfusion
recipients in an area where anti-HTLV-I is not currently part of blood
screening may provide an answer; but who would be willing to bear the
massive cost involved?
Jean-Pierre Allain and Lorna M. Williamson
Correspondence: Jean-Pierre Allain, Division of Transfusion
Medicine, University of Cambridge, Cambridge, United Kingdom; e-mail:
jpa1000{at}cam.ac.uk
References
1.
Gout O, Baulac M, Gessain A, et al.
Rapid development of myelopathy after HTLV-I infection acquired by transfusion during cardiac transplantation.
N Engl J Med.
1990;322:383-388[Medline]
[Order article via Infotrieve].
2.
Okochi K, Sato H.
Transmission of adult T-cell leukemia virus (HTLV-I) through blood transfusion and its prevention.
AIDS Res.
1986;2:S157-S161.
