The problem is this means many different things and many ways to do this are used, which makes it difficult when you are trying to assess risk verses benefit.
There are two main types (a) myoablative and (b) non-myoablative.
The aim of the (a) myoablative is to replace your immune system whereas (b) is to re-boot your immune system and so is the ultimate immunomodulator
Autologous Blood Stem Cells
First of all the infusions are with your own cells (autologous) because if they were from someone else when they arrive they would reject your organs and cause graft-verses host disease.
Autologous HSCT requires the extraction of haematopoietic stem cells (HSC) from you and storage of the harvested cells in a freezer. The person with MS is then treated with high-dose chemotherapy at the cost of partial or complete bone marrow ablation during myoablative treatment (destruction of patient’s bone marrow’s ability to grow new blood cells). The pwMS own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the pwMS normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of pwMS experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual.
Haematopoietic progenitor cell antigen CD34 is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells.Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as hematopoietic cells
Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes. In somes cases granulocyte-macrophage colony-stimulating factor (GM-CSF), also called sargramostim and molgramostim.GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells.
Melphalan is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents.
This chemical alteration inhibits DNA synthesis and RNA synthesis, functions necessary for cells to survive. These changes cause cytotoxicity in both dividing and non-dividing cells
This destroys the immune system and if you do not get stem cells to replace your immune system you cannot fight infection and there is a risk of a lethal infection.
Adverse drug reactions from cyclophosphamide include chemotherapy-induced nausea and vomiting, stomach ache, haemorrhagic cystitis, diarrhea, darkening of the skin/nails, alopecia (hair loss) or thinning of hair (in the BBC programe people lot their hair), changes in color and texture of the hair.
Therefore are you simply inducing side effects and not really targeting any thing extra. Although using stem cells may help in the re-booting process but this is not their function and the immune cells causing MS may not all be destroyed and relapses can occur.
The people doing the HSCT trials state a 1% mortality rate on their websites, but the trials indicate this risk may well be much lower
Some may have failed with a “big gun drug” and get the treatment option on a compassionate basis but in the trials Alemtuzumab is an exclusion criteria.
It would need a head to head trial of AHSCT verses Alemtuzumab (currently) or ocrelizumab (in the future).
If it takes until 2020-2022 to finish the trials and go to the regulators, the landscape may be different as some treatments may be out of patent and the cost constrainst will work against the cost-effectiveness. Will it get third line approval, as it is used now, or will it get first line useage
HSCT induces secondary Autoimmunity
People may also say that I don’t want the autoimmunity associated with Alemtuzumab, but this is occurring in HSCT also.
This includes ITP. People treated with Alemtuzumab are screened every month to detect this for up to 4 years after their treatment. Is this occurring following HSCT? Certainly the people doing health tourism are not getting follow-up treatment from their treating physician. Therefore ensure that you are followed up properly to mitigate this risk
In the Burt et al study in 2015
“Immune-mediated thrombocytopenia (ITP) developed in 3 of 22 (14%; 95% CI, 3%-35%) patients treated with alemtuzumab compared with 4 of 129 (3.1%; 95% CI, 0.9%-7.8%) patients treated with antithymocyte globulin (P = .07). Drug-free remission of ITP occurred in all cases after transient treatment with corticosteroids and intravenous immunoglobulin or rituximab.
Hypothyroidism was present in 9 patients (6.2%; 95% CI, 2.9%-11.4%) before receiving HSCT. After transplant, 7 additional patients developed hypothyroidism or hyperthyroidism. For patients with normal thyroid function before HSCT, thyroid dysfunction developed post-transplant in 2 of 20 treated with alemtuzumab (9%; 95% CI, 1%-32%) and 5 of 122 treated with anti-thymocyte globulin (4.0%; 95% CI, 1.3%-9.3%) (P = .26). The incidence rate of posttransplant immune dysfunction (ITP, hypothyroidism, or hyperthyroidism) was 22.7% (95% CI, 7.8%-45.4%) in 5 of 22 patients receiving alemtuzumab compared with 6.9% (95% CI, 3.2%-12.7%) in 9 of 129 patients receiving anti-thymocyte globulin (P = .03).
So are the risks any different.