Anyone experienced Bone Marrow Transplant with TP53 mutation?

Hi
I’ve been recently diagnosed with high risk MDS. I have monosomes with 15,18,20,22. Missing chromosomes 5,7,17 and TP53 at 87%.

It was diagnosed when I went in for belly cramping, fever, chills.

I do have incredible care team. But there are so many factors, it’s frightening. Thoughts?

@bromlj1 - I’m deeply sorry you’re navigating a high-risk MDS diagnosis—it’s a lot to take in. Your chromosomal abnormalities (monosomies 15, 18, 20, 22, and missing 5, 7, 17) and 87% TP53 mutation indicate a complex situation, often linked to a higher risk of progressing to AML or complications like infections. What are you most concerned about at this time? Your symptoms—belly cramping, fever, chills—likely stem from low blood counts or spleen enlargement, common in MDS. Having a stellar care team is a huge asset, and here are some thoughts to help you manage the fear and complexity.
High-risk MDS with TP53 mutations and complex karyotype can feel overwhelming due to its tougher prognosis, but outcomes vary. Your team is likely using tools like IPSS-R or IPSS-M to guide treatment. Options may include hypomethylating agents (azacitidine, decitabine), though TP53 mutations can reduce their effectiveness, or clinical trials targeting TP53 (e.g., magrolimab or venetoclax combos). Has your team reviewed these topics with you? Stem cell transplant might be considered if you’re eligible—ask about this. Ensure your symptoms are addressed (e.g., imaging for spleen issues, infection checks). Emotionally, the uncertainty is heavy; connecting with the MDS Foundation or a counselor can help. Pace yourself with information—focus on one step at a time, like “What’s my next treatment?” You’re not alone, and research is advancing rapidly. Lean on your team, and let me know if you want specifics on trials, support, or just a space to process

What a terrific post of info by roywalton.
I cannot believe the journey i have been on since my transplant April 9th of 2024. In October of 2023 I had never heard of a 5q deletion or a TP53 mutation. I had been a relatively healthy 60-year-old with a shingles occurrence 4 years previously and a mix of colds, basil cell carcinomas and that sort of thing. I did not read medical terms. I had started donating blood in my mid-twenties while going to college. Talked into it by my older brother. In my mid-thirties, I switched to platelets. Twenty-five years later breast cancer. Chemo, different meds and the Lynparza pill.
On my 2nd visit to the City of Hope I was given an option by a person in the department of the genetics team to have the genetics test. My blood had been tested by the Red Cross for over 30 years. Why not I thought. More details would be helpful.
Then the interesting word of MDS was revealed. Caused by? Who knows exactly. Another genetic mutation, the chemo I received, a side effect of Lynparza pill I took? Blasts? 5q deletion? TP53? Before that the Brca2? What in the world. I read about other people having Brca2, but little else about mutations or blood disorders did I read. Besides that, it never occurred to me I would have anything like these mutations or something such as MDS.
To Julie.
Having a medical team which includes the Doctor, test departments and the nursing team is where you will find answers. This is what the hematology units do every single day. Evaluate where you are at. Study all that information you provided and come out with a treatment plan. Many tests will happen if they have not already.
This reminded me of my 25 plus days in the hospital last year in April. After my transplant with my new cells, I honestly wondered why my precious blood could be drawn 4 times per day every day. What would be left? I voiced this to a nurse one day and she let me know the quantity of blood vs what is in my body. I would be ok. My body will handle it.
Allow yourself to fill the fear but know your caring team is there to care for you. I found Lori and so many others on Mayo connect who have walked this journey and helped me see what I would walk through. I looked through that window of "What is going to happen" to find people who knew.
Keep us posted.

Just wanted to add...my oldest friend of 66 years was diagnosed with MDS 25 years ago....and it never progressed!

@katgob - you're in great hands at COH! Myelodysplastic syndromes (MDS) likely stem from a mix of factors, and your case—possibly tied to BRCA2, TP53, 5q deletion, chemotherapy, or Lynparza (olaparib)—is understandably confusing. MDS involves faulty bone marrow producing abnormal cells (blasts). Your BRCA2 mutation, known for breast/ovarian cancer, impairs DNA repair, potentially making bone marrow cells vulnerable to damage from chemotherapy (e.g., alkylating agents), which is a common cause of therapy-related MDS (t-MDS), often with 5q deletion or TP53 mutations. These occur in 15% and 5-40% of MDS cases, respectively, with TP53 linked to worse outcomes and higher blasts. Lynparza, a PARP inhibitor, rarely (< 2%) triggers MDS, especially in BRCA2 carriers post-chemotherapy, but it’s less likely the sole cause. Blasts reflect disease severity, not its cause, with >5% indicating higher-risk MDS. De novo MDS, driven by spontaneous mutations (e.g., SF3B1, TET2), is also possible, especially with age. Your BRCA2 knowledge likely focused on solid tumors, as its MDS link is less discussed but recognized in t-MDS (16-21% of cases). The shock of these mutations and MDS is valid—it’s often found late via bone marrow tests. Ask your doctor for cytogenetic/molecular results to clarify your subtype (e.g., del(5q), TP53-mutated) and guide treatment (e.g., lenalidomide for del(5q), hypomethylating agents for TP53). Clinical trials or support groups (e.g., MDS Foundation) may help. Share test details for deeper insights. Do you feel more in control as you learn more about genes and genetic testing?

roywalton. I had my transplant 1 year ago April 9th. Your knowledge and what you share is something i shall reread.
I knew next to nothing, and you just filled my inbox with so much more info! This is exactly why i love Mayo Clinic Connect!!!!

Roywalton,
Thank you for your note.

Yes, my care team is looking for a match. Good to know the MDS could cause the abdominal pain. They have eliminated at other potential issues.

The TP-53 is perplexing. I agree, best to just focus on next step…just finished second round of Vidaza. Time to build energy!

Thank you again

I hear from my Dr yesterday that there is a clinical trial for TP53 chemo.

Any thoughts?

@bromlj1 - Clinical trials targeting TP53 mutations are ongoing, focusing on cancers where this tumor suppressor gene is frequently altered, such as head and neck squamous cell carcinoma (HNSCC), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and solid tumors like ovarian and colorectal cancer. TP53 mutations, found in ~50% of human cancers, impair its tumor-suppressive function and often confer oncogenic properties, making them a key therapeutic target. Below is a summary of relevant clinical trials and approaches based on current data:
Key Clinical Trials and Therapies
APR-246 (Eprenetapopt):
Mechanism: A small molecule that reactivates mutant p53 by restoring its wild-type conformation.
Trials:
Phase Ib/II (NCT03072043): Combines APR-246 with azacitidine for TP53-mutated MDS/AML with 20–30% marrow blasts. Showed a high complete remission (CR) rate in patients with only TP53 mutations.
Phase II (NCT03588078): Tests APR-246 with azacitidine in TP53-mutated MDS/AML with >30% blasts.
Phase Ib/II (NCT02098343): Evaluates APR-246 with carboplatin and pegylated liposomal doxorubicin in platinum-sensitive recurrent high-grade serous ovarian cancer with mutated p53.
Phase Ib (NCT04383938): Combines APR-246 with pembrolizumab (an immune checkpoint inhibitor) for advanced/metastatic solid tumors. Well-tolerated but lacked sufficient sample size for efficacy assessment.
Phase II (NCT03268382): APR-246 with pegylated liposomal doxorubicin for platinum-resistant high-grade serous ovarian cancer.
Phase III (NCT03745716): Eprenetapopt with azacitidine in TP53-mutated MDS, with enrollment completed and results expected.
Status: Promising preclinical results, with some trials showing complete remission, but clinical efficacy is still under evaluation.
PC14586 (Rezatapopt):
Mechanism: Reactivates p53 Y220C mutant, restoring wild-type tumor suppressor function.
Trial: The PYNNACLE trial (NCT04585750) evaluates PC14586 in patients with advanced solid tumors harboring TP53 Y220C mutations. Recent posts on X highlight its potential to target this “undruggable” mutation, showing antiproliferative effects.
Status: Ongoing, with early data suggesting promise for specific TP53 mutations.
Lonsurf and Talzenna (Talazoparib):
Mechanism: Exploits TP53-mutant cells’ inability to handle DNA damage. Lonsurf (TAS-102) causes DNA breaks, while talazoparib (a PARP inhibitor) prevents repair, leading to cell death.
Trial: An ongoing trial (not specified by NCT number) tests this combination in advanced colorectal or gastroesophageal cancer, with plans to expand to TP53-mutant pancreatic and breast cancer if initial results are positive. Preclinical data showed enhanced tumor shrinkage in mice without increased side effects.
Status: Early-phase trial, with initial results expected soon.
Adavosertib (Wee1 Inhibitor):
Mechanism: Targets synthetic lethality in TP53-mutated cells by inhibiting the G2/M checkpoint, enhancing DNA-damaging agent effects.
Trials:
NCT03028766 and NCT02585973: Adavosertib with cisplatin and radiation in locally advanced HNSCC.
NCT04158336, NCT03968653, NCT04768868: Phase I studies for advanced solid tumors, including combinations with chemotherapy (carboplatin, paclitaxel, gemcitabine), durvalumab, or olaparib.
Adavosertib has been tested in 59 clinical trials, showing specificity for TP53-mutated colorectal cancer cells when combined with DNA-damaging agents like 5-FU or doxorubicin.
Status: Ongoing, with context-dependent efficacy; broader application needs further study.
Idasanutlin:
Mechanism: An MDM2 inhibitor that prevents wild-type p53 degradation, effective in TP53 wild-type cancers but limited in TP53-mutated cases.
Trial: Phase III (NCT01773408) combines idasanutlin with cytarabine in relapsed/refractory AML, showing a 35.6% CR rate in TP53 wild-type AML.
Status: More effective in wild-type TP53 cancers, limiting its use for mutant TP53.
ALRN-6924:
Mechanism: A stapled peptide dual inhibitor of MDM2 and MDM4, aiming to protect wild-type p53 and arrest the cell cycle in normal cells, reducing chemotherapy toxicity.
Trials: Multiple phase I trials for advanced solid tumors and as a chemoprotectant.
Status: Early-stage, with potential limited to wild-type TP53 cancers.
Arsenic Trioxide (ATO):
Mechanism: Rescues intact p53 structure in some TP53 missense mutations (e.g., R175H, R282W), but not DNA contact mutants like R248Q or R273H.
Trials: Ongoing in China for MDS, AML, refractory solid tumors, and recurrent/metastatic ovarian/endometrial cancer (NCT03855371, NCT04869475, NCT04489706, NCT04695223).
Status: Outcomes pending, with preclinical data showing tumor growth inhibition.
Gendicine:
Mechanism: A viral vector delivering the wild-type p53 gene for gene therapy, primarily tested in mesothelioma and other cancers.
Trials: Ongoing trials for mesothelioma, with no FDA approval yet; access is limited to clinical trials.
Status: Safe and effective in some preclinical and early human studies, with mild side effects like flu-like symptoms.
General Insights
Cancer Types: TP53 mutations are inclusion criteria in 164 clinical trials, with 107 open, targeting AML (112 trials), MDS (72 trials), non-small cell lung cancer, ovarian carcinoma, and solid tumors.
Challenges: TP53 mutations are not yet “clinically actionable” due to the lack of approved targeted therapies. The complexity of p53’s role as a transcription factor makes it difficult to drug, and many trials focus on synthetic lethality or restoring wild-type function.
Emerging Strategies:
Synthetic Lethality: Targeting pathways like Wee1 or PARP to exploit DNA repair deficiencies in TP53-mutated cells.
Gene Editing: CRISPR/Cas9 to correct TP53 mutations, though concerns about genomic instability limit clinical use.
Immunotherapy: Exploring mutant p53 peptides as immunotherapy targets.
Prognostic Impact: TP53 mutations are linked to worse outcomes in cancers like HNSCC (80% mutation rate in HPV-negative cases), AML, MDS, and DLBCL, necessitating tailored trials.
Accessing Trials
ClinicalTrials.gov: Search for trials using identifiers like NCT03072043 or NCT03745716.
Consultation: Patients should consult oncologists or services like Massive Bio for trial matching, especially for TP53-mutated or wild-type tumors.
Biomarker Testing: Essential for identifying TP53 mutation status to qualify for trials. Immunohistochemistry (IHC) is a rapid, cost-effective screening tool for TP53 mutations in AML/MDS, with high sensitivity (86%) and specificity (90%).
Notes
No p53-based therapies are FDA-approved yet, but APR-246 and PC14586 are among the most advanced.
Patients with inherited TP53 mutations (e.g., Li-Fraumeni syndrome) may qualify for specialized trials and should avoid radiation due to increased cancer risk

I was treated at City of Hope. I had a TP53 mutation. My trial was to prevent GVHD which can and does happen after transplants. I did not have any GVHD symptoms and i am 420 plus days past transplant.