Allografting for patients with advanced hematological malignancies: non-myeloablative conditioning followed by the reinfusion of lymphocytes engineered with hsv thymidine kinase gene

Paolo Corradini, Corrado Tarella, Marco Bregni, Paola Carrera, Magda Marcatti, Alessandra Pescarollo, Fabio Ciceri, Andres Ferreri, Alessandro M. Gianni, Claudio Bordignon

Research output: Contribution to journalArticlepeer-review

Abstract

Allogeneic transplantation is a curative treatment for several advanced hematological tumors. Transplant efficacy, however, is frequently hampered by its toxicity, and this is particularly true when candidates are older than 45 yrs, heavily pretreated, or affected by other comorbidities. In order to decrease transplant-related mortality (TRM), and enhance the graft-vs-tumor effect, we have designed a program in which a non-myeloablative conditioning (thiotepa 10 mg/kg, fludarabine 60 mg/ms, cyclophosphamide 60 mg/kg) is associated with low dose GVHD prophylaxis, and programmed reinfusions of HSV-tk+ engineered donor lymphocytes (CyA tapering at d+90: reinfusion of Ix 10e7 CD3/kg for pts with molecular disease, or 1x1Oe8 CD3/kg for those with clinical disease). We have tested the feasibility of this program in a pilot study, enrolling 18 pts not eligible for conventional conditioning: 9 NHL, 2 HD, 1 ALL, and 6 AML. Median age was 49 yrs (range 32 - 65). Pts were considered at high-risk of TRM because they were old, heavily pretreated (16 of 18 received more than 2 lines or high-dose CT), and/or with concomitant organ disfunctions. Nine pts received BM and 9 PBPC grafts. All pts engrafted, median time to achieve 500 ANC was 13 days, median time to 20,000 PLTS was 19 days; myeloid and lymphoid chimerisms at day +30 and +90 were full donor in all pts achieving marrow remission. Acute GVHD grade 2-4 was scored in 4 pts (22%), I pt experienced WHO organ toxicity >2 (5%), 1 pt had CMV disease; 3 of 17 évaluable pts have ext cGVHD (17%). Overall TRM is 5% with a median follow-up of 290 days (range 66 - 668). Two pts died; 1 of disease progression and 1 of respiratory failure during GI endoscopy. Twelve of 18 pts (66%) showed a disease response: 10 CR (including 4 molecular remissions) and 2 PR; 4 of 12 responding pts already relapsed. Four pts received DLI for disease persistence after transplant or recurrence: 1 minimal and 1 complete response were observed. In conclusion, engraftment is prompt and stable, treatment toxicity and aGVHD incidence are lower than expected with conventional conditioning, but disease response in chemorefractory pts is still disappointing.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART II
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hematology

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