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Purging e alte dosi di chemioterapia con reinfusione di cellule staminali autologhe in linfomi non Hodgkin follicolari resistenti/refrattari

In the era of monoclonal antibodies the role of autologous stem cell transplantation (ASCT) in the
management of follicular lymphoma (FL) is still debated.
To evaluate the safety and efficacy of myeloablative therapy with rescue of purged or unpurged
harvests in FL pts.
At our institution form 1997 to 2007 28 pts with refractory/resistant FL were eligible for ASCT.
Before high dose therapy they received 2-3 cycles of CHOP-like regimen (ACOD), followed by
Cyclophosphamide 4g/mq to mobilize the stem cells (SC). After SC collection the pts underwent 3
cycles of subcutaneous Cladribine at a daily dose of 0,14-0,10 mg/Kg for Day 1-5 every 3-4 weeks.
The conditioning regimen was based on Mitoxantrone 60mg/mq + Melphalan 180 mg/mq, followed
by SC re-infusion 24-hours later and G-CSF starting 24 hours after re-infusion.
In 19 pts the SC underwent purging: in 10 harvests the CD34+ were selected by immunomagnetic
beads, while in the other 9 pts, only Rituximab was used as “purging in vivo” agent. The remaining
9 pts received unpurged SC. Before ASCT 11 pts were in complete response (CR), 9 in partial
response (PR) and 2 in stable disease. Two pts were not eligible for ASCT because of progressive
disease (PD). The remaining 25 pts were eligible for ASCT. The engraftment was at a median of 11
days for leucocytes and 14 days for platelets (>20.000/mmc), with a delay of one day in the pts,
who received purged SC. Grade 3-4 mucositis was described in 8 pts. During aplasia a 48%
infection rate was reported, without differences between pts with purged or unpurged SC. One
patient in CR presented myelodysplastic syndrome at 18 months from ASCT.
After ASCT 22 pts were in CR, 2 in PR and one patient were not valuable, because died before
response assessment. Nine pts in CR showed PD at a median time of 14 months from ASCT. With a
median follow up of 5 years (range 2 months -10 years), 22 pts are alive and 11 (44%) in CR. Ten
pts died, 5 for progressive disease and 5 for treatment-related causes; in particular 7 of them
received in-vitro purged SC.
Conclusions: Our chemotherapy regimen, which included the purine analogue Cladribine in the
induction phase, seems safe and feasible. The high rate of CR reported and the sustained freedom
from progression up to now, makes such modality of treatment a valid option principally in
relapsing FL patients. In our experience, the addition of a monoclonal antibody as part of treatment
confirms its role “in vivo purging” without observing an increased incidence of infection.

Identiferoai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:807
Date16 June 2008
CreatorsBassi, Simona <1973>
ContributorsZinzani, Pier Luigi
PublisherAlma Mater Studiorum - Università di Bologna
Source SetsUniversità di Bologna
LanguageItalian
Detected LanguageEnglish
TypeDoctoral Thesis, PeerReviewed
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess

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