PROPHYLACTIC USE OF RITUXIMAB TO PREVENT EBV REACTIVATION FOLLOWING HSCT IN PATIENTS WITH INHERITED

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PROPHYLACTIC USE OF RITUXIMAB TO PREVENT EBV
REACTIVATION FOLLOWING HSCTIN PATIENTS WITH
INHERITED METABOLIC STORAGE DISEASES  Attilio
Rovelli, Paola Corti, Adriana Balduzzi, Daniela
Longoni, Maria Dassi, Paolo Perseghin, Giuseppe
Gaipa, Andrea Biondi, Rossella Parini, Barbara
Bertagnolio, Graziella Uziel, Cornelio Uderzo
MOMIN Monza-Milano Network for Lysosomal and
Peroxisomal Diseases - Italy -
INTRODUCTION
RESULTS
GvHD has been correlated with a poor
neuropsychological outcome in patients with
inherited metabolic storage diseases (IMSD),
therefore we include T-cell depletion by MACS
technology (TCD) in the procedure for these
patients. Due to the amount of residual B-cell
after two-step negative selection (1 HSCT in this
series) and the increased number of B-cells in
the final product after T-cell addback following
positive selection (the other 11 HSCTs) (see BMT
2003, 31857-860 and 2004, 33353), a single dose
of rituximab on day 3 has been included in the
treatment plan since 1999 to carry out B-cell
depletion in vivo to prevent EBV-PTLD.
Engraftment occurred in all cases (see table 2)
the median number of cells infused (x106/kg) was
CD34 5.6, CD3 0.35 and 1.0 (at 1st and 2nd
HSCT, respectively). One pt. (n.6) died at a
median follow-up of 2.8 years (0.9 4.2) 9/10
pts. are alive with complete or partial (n.5 and
7) chimerism. All survivors, including those with
mixed chimerism, show stable or improved
neuropsychological condition, with the exception
of 2 patients (n.3 and 8). HSCT halted the
leukodystrophy progression in these 2 patients,
but they developed negative myoclonus, only
partially controlled by multiple drug treatment,
which seem to hinder the benefits achieved.
None of the pts. developed EBV
reactivation, with the surprising exception of
the only pt. (n.9) who did not receive rituximab
as prophylaxis and who was at that point (71
days) successfully treated with the anti-CD20
antibody (2 infusions). The pt. who developed EBV
reactivation and one who is only at 11 months
from HSCT are the only 2 pts. who have not yet
recovered CD19 cell count.
PATIENTS AND METHODS
Ten consecutive patients (see table 1) with
different IMSD who underwent 12 HSCTs (patients
n.1 and 2 who rejected successfully underwent a
2nd HSCT from a different unrelated donor) were
scheduled to receive the anti-CD20 monoclonal
antibody. Rituximab was administered to 9 pts.
following 11 HSCTs, but not to one (Pt.9) for
whom we did not receive parents consent.
Conditioning regimen included BuCy (7) or FluBuCy
(4) or TTCy (1) ATG. All patients were
monitored weekly for EBV reactivation by
quantitative PCR.
Table 2. Outcome
Table 1. Patients and HSCTs characteristics
CONCLUSION
Due to the rarity of IMSD and the limited number
of such a procedure/manipulation at our center, a
specific study was not feasible. Our observation
is intriguing and prompts for randomized studies
in settings where a higher number of pts. can be
recruited.
Legend MPS I-H mucopolysaccharidosis type I-H
GLD late-infantile globoid cell leukodystrophy
MLD adult-onset metachromatic leukodystrophy.