This is a complicated question,” said Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute at the University of Utah in Salt Lake City.
“An autologous stem cell transplant (ASCT) does not completely negate the adverse risk features of high-risk gene mutations,” Dr. Mohyuddin said. “However, the data suggests that ASCT may play a more important role for these patients, given that remissions are often short without a ASCT.”
Those high-risk gene mutations in MM include the presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutations. Some patients may have multiple mutations, with a cumulative risk as mutations are added.
“Patients with high-risk gene mutations often have very short remissions without transplant,” Dr. Mohyuddin explained.
As to whether the ASCT actually changes or fixes those mutations, Dr. Mohyuddin does not think that’s a correct line of thinking. “When relapse happens, patients often have the same gene mutations that they had prior to transplant – and sometimes even have new ones.”

A recent Johnson & Johnson Press Release projects MM to be a $29 Billion by 2032. SCTs are already a $6 Billion a year Industry. Why would they ever want to Cure MM and see all of this Income Vanish.

As for DNA mutations - I know of multiple people that after getting to MRD Negative at 10 -6, their future BMB no longer had any of their original High Risk Factors. For a few, they had multiple. For myself, my original t4;14 no longer existed in my BMB that was taken around 15 months after I was MRD Negative and Stopped All MM Meds.

Like myself, the others that I know of did have DarzFasPro as part of their Treatment and then at a point reached MRD Negative.

Much more research and clinical trials are needed though.

@A MyMyelomaTeam Member

A factor that I do believe plays into my t4;14 no longer existing after I became MRD Negative may very well be related to the fact that I never collected my Stem Cells and I never had a SCT.

My recent research with Perplexity AI found that the Chemicals involved with both do cause damage to the Bone Marrow Microbiome. The damage can be from years to possibly even permanent. It may also account for early on relapses.

Perplexity.AI
Question:
1) What is the lasting damage to the Bone Marrow's microenvironment due to the ASCT chemo used to completely kill-off the bone marrow

Answer:
The [chemotherapy] used in autologous stem cell transplant (ASCT), especially high-dose melphalan, causes substantial damage to the bone marrow (BM) microenvironment, but the extent and duration of this damage vary.
Lasting damage to the bone marrow microenvironment from ASCT conditioning chemo includes:

Reduced marrow cellularity: Total body irradiation (TBI) and myeloablative [chemotherapy] regimens cause a long-term reduction in marrow cellularity (the number of hematopoietic and stromal cells) that can persist for a year or more post-transplant. This means fewer bone marrow cells are present to support hematopoiesis initially.

Increase in marrow adipocytes: [Chemotherapy] and radiation induce expansion of fat cells (adipocytes) within the marrow space, which negatively affect hematopoietic stem cell niche function and post-transplant engraftment.
Disruption of hematopoietic niches: The microenvironment that supports stem cell survival and differentiation is structurally altered. There may be transient edema and fibrohistiocytic proliferation during early recovery that later resolves, but some injury to stromal and endothelial cells can persist.

Immunological changes: ASCT induces lymphodepletion and temporarily disrupts immune cell populations in the marrow microenvironment, including T cells, which may delay immune reconstitution. Dysfunctional T cell patterns post-ASCT correlate with worse outcomes.

Potential functional compromise despite peripheral blood recovery: Peripheral blood counts may normalize relatively quickly, but the marrow reserve and microenvironment remain compromised for longer periods, which could affect sustained hematopoiesis.

While the BM microenvironment is injured by myeloablative [chemotherapy] used in ASCT, much of the damage gradually improves over months to years. However, some deficits in marrow reserve and immune microenvironment reconstitution may persist longer, influencing hematopoietic capacity and immune surveillance.

Therefore, the [chemotherapy] "kill-off" in ASCT causes structural and cellular injuries to the BM microenvironment that can last months to years, primarily reflected by decreased cellularity and altered supportive niches, but without widespread irreversible damage in most cases.

End Part 1:

Mentioned Users

A MyMyelo...

Hey Angie. I was told thst once I had high risk genetics. I would always be high risk. My mutations do not show up on my FISH testing. Probably because my treatments are keeping my numbers down. Cloneseq still says I have the original clones I started with. Seven different ones. I hoping to get rid of them.