ITALY – Tumor Institute: safer stem cell transplants

Posted on 25 March 2013 by Stem Man

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.

In search of stem cells with a perfect tissue match

Posted on 10 March 2012 by Stem Man

The extensive research on stem cells has revolutionised the way life-threatening diseases like leukaemia and aplastic anaemia can be treated.
But there are several steps before these diseases can be treated using stem cells.

To begin with, the Human Leukocyte Antigen (HLA)-typing of the patient is done. Doctors then get into the process of finding a matched donor from the computerised list made available to them by National Marrow Donor Programme (NMDP), U.S., and New York Cord Blood Bank.
If registration of potential bone marrow donors has been in place for a long time, the emergence of a number of cord blood banks, both public and private, which store the stem cells has gone a long way in helping doctors.

Finding a match is just the first step. However, it takes at least three months to procure matched bone-marrow stem cells. It takes just two weeks in the case of cord blood stem cells.
The three-month waiting period in the case of bone marrow arises as locating the matched donor very often becomes difficult.

It requires a minimum of one to three working days to import the stem cells once the match has been found.
“We transfuse blood and platelets to aplastic anaemia patients to sustain them till such time matched stem cells are located, procured and transplanted,” said Dr. Revathy Raj, Consultant Paediatric Haemato Oncologist, Apollo Speciality Hospital, Chennai. “In the case of leukaemia, patients undergo a cycle of chemotherapy in the interim period.”

An important point worthy of mention is that the bone marrow donor is not required to come to the hospital where the patient is, but rather could go to a nearest hospital in the U.S. to donate his stem cells.
In India there are not enough registered bone marrow donors, nor are there proper facilities to harvest bone marrow. Hence the bone marrow cells have to be obtained from organisations like NMDP. The lack of adequate number of donors also results in very slim chances of finding a match in India.

India fares better in the case of cord blood banks. India has two public banks — Reliance in Mumbai and Jeevan Stem Cell Bank in Chennai. But even these banks have only a handful of units. This makes the chances of finding a match very remote.
Though there are a good number of private cord blood banks in the country, they are of little use to the public. Stem cells banked in these places are made available only to the immediate relative of the donor.

from The Hindu

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Thalassemia cured using cord blood stem cells

Posted on 24 June 2009 by Stem Man

Bond strengthened: Eight-year-old Thamirabharuni, holding her brother who donated the stem cells, did not suffer from rejection or graft versus host disease as the tissue match was perfect - Photo: V. Ganesan

Eight-year-old Thamirabharuni and her one-year-old brother Pugazhendhi share a special kind of bond not commonly seen among siblings. Thanks to her brother, Thamirabharuni no longer suffers from thalassemia disease.

The stem cells transplanted in March helped her get rid of thalassemia. And hundred days after the procedure, one can safely say that her disease has been cured.
The stem cells that were transplanted came from two different sources — her brother’s cord blood, which was harvested during the time of his birth, and his bone marrow. Stem cells from the bone marrow had to be transplanted as there was insufficient number of stem cells in Pugazhendhi’s cord blood.

In the absence of cord blood stem cells, about 200 ml of bone marrow would have been required. It is difficult to get this quantity of bone marrow from a nine-month-old baby.
The cord blood was collected by and stored at Chennai based LifeCell International Pvt. Ltd., a private cord blood bank.

Risk of infection

So is it all over? “One has to be still careful. There is a risk of infection till the end of the first year [after transplantation],” said Dr. Revathy Raj, Consultant Paediatric Haemato Oncologist, Apollo Speciality Hospital, Chennai. Dr. Raj had done the transplantation for Thamirabharuni and two other cord blood transplantations for thalassemia before this.
The fact that patients are on immuno suppressing drugs for one year makes them vulnerable to infections. The risk of rejection of the transplanted stem cells, and the graft versus host disease (GVHD) reduce with time.

Thalassemia arises when red blood corpuscles (RBC) production is defective. A person suffers from the disease only when he inherits a defective gene from both parents. He becomes a carrier when he inherits a defective gene from only one parent. The diseased person has to undergo blood transfusion once every month for the rest of his life.

Gold standard

Though stem cells separated from bone marrow have been used for more than 30 years to treat thalassemia, and is a gold standard in treating the disease, cord blood stem cells are slowly becoming an attractive alternative.
Contrary to what is projected by some cord blood banks, doctors are very reluctant to use cord blood stem cells to treat thalassemia in the absence of a full tissue match.

Perfect match

“We need a 6/6 [perfect match] for thalassemia. Even a 5/6 match is not sufficient,” asserted Dr. Raj. And doctors refrain from using stem cells from unrelated donors, even if there is a perfect match.

Apart from infections, there are two major challenges from transplantation — graft versus host disease (GVHD) and rejection of the donated stem cells. “There is a 30 per cent chance of having graft versus host disease even when it is from a fully matched related (sibling) donor.” This risk increases to 50 per cent when it is from an unrelated donor, even if there is 6/6 tissue match.

Rejection rate becomes an issue even when there is a perfect tissue match. According to her, in the case of thalassemia, the rejection rate can be up to 20 per cent even with related donors, and up to 40 per cent in the case of unrelated donors.
But why should rejection and GVHD be an issue at all when there is a perfect 6/6 tissue match, and why should it be so high when stem cells are from unrelated donors?

Minor HLAs not tested

“There are several minor HLA antigens that are not tested. So if we use stem cells from people belonging to some other ethnic background, there are greater chances of [minor] HLA differences,” Dr. Raj stressed. “And this causes rejection and GVHD.”
In general, greater the tissue match and higher the stem cell count in cord blood, lesser are the chances of rejection and GVHD.

“So why undertake procedures that are risky when thalassemia can be treated through monthly transfusions,” she noted.
Private banking of cord blood for use by the family therefore becomes important when one of the siblings is suffering from a disease that can be cured using it.

Case for public banking

Despite the risk of rejection and GVHD, a less than perfect sample can be used to treat children suffering from life threatening diseases such as leukaemia and aplastic anaemia. This is where public cord blood banking gains significance.
There is a strong case for promoting public banks as depending solely on bone marrow samples will not be wise.

Even if a perfectly matched bone marrow donor is found, chances are that the person may no longer be interested in donating.
Collecting cord blood samples is easy, the number of samples that can be banked is limited only by resources, and samples can be made available at very short notice.

from The Hindu

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