CliniMACS - The Haploidentical Tale
‘The glass is always half full’
All success begins with failures
Based on principles of Darwinian laws of inheritance, every individual inherits one HLA haplotype from each parent and share a haplotype with a sibling in 90% of cases. Thus, a Haploidentical donor is available for almost every individual. However, attempts at Hematopoietic Stem Cell Transplantation (HSCT) from Haploidentical family members were met with disastrous results in the 1980s with almost all patients succumbing to graft versus host disease (GVHD) or graft failure (GF).
Why do we need to keep some cells or get rid of some
The concept of Haploidentical family donor lied in the back burner until painstaking research by Reissner, Martelli and Aversa found a way to avert both these problems. The presence of T cells and B cells in the graft contributes to GVHD and EBV associated lymphoproliferative disorders. To overcome these problems, different techniques were employed since 1980, which include physical separation, immunological techniques and combination of both.
The revolution called CliniMACS
The physical methods were labour intense and time consuming, whereas the immunological methods, lack the precision as it is dependent on an antigen presentation on the cell surface and avidity of antibodies. The drawbacks of these methods were overcome by CliniMACS
technique which incorporated both the methods in a closed system in combination with magnetic separation.
Selecting only Stem Cells for BMT
Incorporating this technique, the Perugia group developed the first successful program for Haploidentical transplantation, selecting highly purified CD34 cells in a large numbers. However, the new immune system takes a long time to develop from donor stem cells. Patients undergoing such Haploidentical BMT were at high risk of dying from infections.
Getting rid of T and B cells
Rather than positively selecting stem cells only, getting rid of T and B cells was developed, using the CliniMACS technology. Negative selection of T cells (CD3) and B cells (CD19) was equally successful in both adults and children. However,the major problem of such transplants was related to relapse of leukemia or death from infections due to poor T cell immune reconstitution.
Can we have a BMT by having no GVHD, no infection and no recurrence/relapse of leukemia
technology has raised the bar further by enabling selective isolation or depletion of T cell subtypes. They have developed selective depletion of TCR αβ positive T cells
which depends on T gamma delta cells
and NK cells
to carry out anti infective or antileukemic functions. These developments have ushered a new era in the field of Haplo-identical BMT.
A new Hope for India
Dharamshila BMT Center
has started the first such Haploidentical BMT Program in India.
Based on the credentials of Dr. Sarita Jaiswal
as the only BMT physician in India, trained in the CliniMACS
based TCRalfabeta depleted BMT procedures and the perfect infrastructure Dharamshila BMT Centre hosts for these patients, Miltenyi Biotech in India has announced the installation of the CLINIMACS Technology at Dharamshila BMT centre to initiate this program.
CliniMACsbased TCRα / β depleted Haploidentical BMT is challenging and expensive for the following reasons:-
- CliniMACs is an extremely expensive imported technology.
- The Reagents required are also imported and therefore are very expensive.
- The technology also requires a very expensive infrastructure.
- Last but not the least, the expertise to handle this machine comes at a very high cost.
- Yet it is cheaper and safer than unrelated donor marrow or cord blood from registries.
- Patients generally do not require any immune suppression drugs and antibiotics, after they move out from BMT unit.
- However, patients require close monitoring and thus it becomes cost neutral in 2 yrs.
Who requires CliniMACS based TCRalfabeta depleted BMT
All patients who are fit to withstand the high doses of chemotherapy are eligible for this procedure. However, our team of experts decides the suitability of a child or a young adult to undergo this procedure.
CliniMACS based Haploidentical BMT Program at Dharamshila Hospital
As Dharamshila BMT centre has the right expertise and technology to develop this Haploidentical program for the first time in India, this might be the right step forward for children with Leukemia, Thalassemia
and Aplastic Anemia
without matched family donors. This program has been initiated for children with these diseases and enrolment has started
. Subsequently, this shall be extended to the adult patients.