HIF, Hypoxia Research & Stem Cell News

ITALY – Tumor Institute: safer stem cell transplants

Fondazione IRCCS Istituto Nazionale Tumori di Milano

Methods to provide safer stem cell transplants to individuals who are not completely compatible with the donor are being developed. Encouraging results have come from a post-transplant cellular therapy, which strengthens the immune system against viral infections and tumors, developed for the first time at the National Tumor Institute (INT) in Milan. The INT conducted the first phase I-II study in the world, published in ‘Blood’, whose main objective was to assess the use of a low dose radiochemotherapy, followed by low dose post-transplant infusions CD8-depleted donor lymphocytes after a 50% compatible hematopoietic stem cell transplant.

The objective of the study was to reduce transplant toxicity and improve immune system function after the transplant to reduce mortality due to infections and relapses. Stem cell transplants from fully compatible donors (HLA-identical) are an option for many individuals with blood-borne cancers. However, only 50-60% of these patients are able to find a fully compatible donor in their families or on the international donor registry. For leukemia and lymphoma patients with a high risk for early relapse who are not able to find an identical donor, the only concrete alternative is a transplant from a 50% compatible family donor (haploidentical donor) or umbilical cord stem cell transplants for child or low weight patients.

In the past, the use of partially compatible donors was prevented by severe side effects. New strategies to improve results are increasingly necessary. Twenty-eight adult patients affected by advanced hematological neoplasias who had no other alternative treatment in order to survive took part in the study. Twenty-four of the patients were suffering from lymphoma and four from acute leukemia.

Transplant-related mortality after two years was reduced from 40-50% to 25%. The two-year global survival rate was 44% with a better result for patients with chemosensitive diseases (2-year survival rate of 75%).
On the whole, 54 CD8 depleted donor lymphocyte infusions were performed on 23 patients, using three different doses of cells with the objective of defining which dose favored an efficient reconstitution of immunity against infective agents and residual tumor cells, reducing the probability of inducing aggressive immune responses against the recipient. The infusions were well tolerated by the patients and did not reduce the transplant from taking root and did not induce acute toxicity.

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