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A stem cell transplant is often the best option to treat blood cancers, such as leukemia,?lymphoma,?multiple myeloma?and?myelodysplastic syndrome, as well as bone marrow failure syndromes like aplastic anemia.

To understand the different types of stem cell transplants and how they work, we spoke with ?Here¡¯s what he had to say.

What are stem cells?

Stem cells are the ¡°seeds¡± that reside in our bone marrow and eventually mature into the cellular components of our blood:

• red blood cells carry oxygen to our tissues
• platelets form?clots to stop bleeding
• white blood cells fight off infections

How many different types of stem cell transplants are there?

Stem cell transplants fall into two categories: autologous and allogeneic.

An autologous stem cell transplant uses the patient¡¯s own cells for treatment. We collect healthy stem cells from the patient, treat the cancer with high-dose?chemotherapy, and then give the cells back. The patient will have low blood counts until the replaced stem cells become engrafted in the bone marrow and start replenishing the body¡¯s supply of normal, healthy cells.

An allogeneic stem cell transplant is similar, but we take cells from a donor. "Allo" means "other." The transplanted cells kill any remaining cancer cells and restore the patient¡¯s immune system.

Where do allogeneic stem cell transplant donor cells come from?

There are three different subtypes of allogeneic stem cell transplants:

• bone marrow transplants
• peripheral blood transplants
• cord blood transplants

With a bone marrow transplant, the donor receives general anesthesia, and the bone marrow is extracted in a 1-2-hour procedure. Once patients complete conditioning chemotherapy to prepare their body and destroy as much of the cancer as possible, they receive an infusion of the donor¡¯s healthy stem cells.

With a peripheral blood cell transplant, the donor receives growth factor shots to stimulate the bone marrow to push the stem cells out into the blood. This allows us to collect the stem cells from the blood using an apheresis machine (cell collection device).

The cells for a cord blood transplant come from an umbilical cord collected at birth by a cord blood bank, such as the MD Anderson Cord Blood Bank. For patients who don¡¯t have a well-matched, healthy donor, a cord blood transplant is often a good option.

What determines if a donor is a good match?

We all have protein structures called human leukocyte antigens (HLA) on our cells¡¯ surfaces.?These allow our immune systems to recognize our own tissues as ¡°self¡± and anything else as ¡°other.¡±

We try to find a donor whose antigens match the patient¡¯s antigens perfectly. Since antigens are inherited, family members -- especially siblings -- are a good starting point. But a family match isn¡¯t guaranteed. That's why many patients find unrelated donors through the .

The closer the match, the less risky the transplant. If the donor cells aren¡¯t a close enough match, the patient¡¯s body may recognize the donor cells as foreign and reject them. Or, the cells from the donor may recognize the new body as foreign and attack it. This is called graft-versus-host disease, or GVHD. But we also look at other factors, including the donor¡¯s:??

• age??
• sex??
• blood type??
• cytomegalovirus (CMV) exposure status???

And these are just a few. There¡¯s a long list of factors that go into that decision, beyond HLA type.

How do you decide what type of stem cell transplant a patient receives?

We consider the type of disease and how advanced it is. Most patients with multiple myeloma or lymphoma receive autologous transplants. Most leukemia patients receive allogeneic transplants.

Other factors we consider include:

• availability of a suitable donor
• previous treatments
• age and health of the patient and donor

Can a stem cell transplant be used in combination with other cancer treatments?

Technically, a stem cell transplant already is a combination treatment. A stem cell transplant has three phases. Infusing the cells is just one of them.

A week before the actual transplant, the patient receives conditioning chemotherapy to prepare the body for the new cells. This chemotherapy serves three purposes:

1. treating the cancer
2. suppressing the immune system to allow the donor cells to grow
3. making physical room in the bone marrow for the donor cells to implant themselves

The transplant repopulates the immune system with healthy cells. But patients may receive additional treatments in the third phase.

What are the latest developments in stem cell transplant research?

At one time, GVHD was the leading cause of death after a stem cell transplant. Today, we are successfully preventing that complication more and more with immunosuppressive therapy. This allows the donor cells to keep growing.????

Research has also enabled us to develop more effective conditioning chemotherapy regimens to treat patients¡¯ underlying cancers. This reduces both the type and degree of their possible side effects.??

Finally, we¡¯re able to do more transplants now in people who do not have a perfect tissue match. We can use bone marrow from half-match (haploidentical) relatives, or even mismatched unrelated donors successfully. And, we¡¯ve reduced the risks associated with that, so we can treat even more patients who wouldn¡¯t normally be eligible to receive a stem cell transplant.? We¡¯ve also developed better ways of treating infections, making the procedure even safer.

What¡¯s your advice to someone considering a stem cell transplant?

Learning that you need a stem cell transplant can be overwhelming. So, seek help from social work counselors if you need support. ??

Make sure you have all the resources you need, too, so that you can go into the process well-informed and know what to expect. There are many educational materials available, so seek them out and take advantage of them.?

Finally, line up your caregivers as quickly as possible. No one should have to undergo this process by themselves.???

Anything else you¡¯d like people to know about stem cell transplants???

Some people have been told that they¡¯re ¡°too old¡± to get a stem cell transplant. But that¡¯s not necessarily true. There¡¯s no longer any absolute cut-off age. Patients over age 65 are increasingly receiving transplants. Some recipients are well into their 70s and 80s. ??

As recently as 20 years ago, these same people would not have been considered good candidates. So, if you¡¯re ever told that, get a second opinion and be re-evaluated.

or call 1-877-632-6789.

Leukemia treatments have been constantly improving from the days when patients had to come to the hospital or clinic for intravenous doses of chemotherapy that caused unwanted side effects. Now, leukemia treatment often can be as convenient as a medication taken at home ¡ª a pill (or pills) with drugs highly customized to the person¡¯s?type of leukemia and even the genetic mutations present within those individual¡¯s cancer cells.

In research presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition, MD Anderson experts shared how different types of leukemia medication can be highly effective as oral treatments.

¡°It makes it much easier,¡± says leukemia specialist ¡°Rather than telling the patient to come every day for five days for an IV chemotherapy treatment, we can just prescribe a pill they can take at home.¡±

Drug combination showed early success for?CLL treatment

In 2019, Jain and his colleagues in the New England Journal of Medicine in which patients with chronic lymphocytic leukemia?(CLL) were given an oral treatment regimen combining two drugs: ibrutinib?and venetoclax. This combination included two separate approaches with medications that work through two different mechanisms of action: a BTK inhibitor and a B-cell lymphoma-2 (Bcl-2) protein inhibitor, respectively. One works more in the lymph nodes and the blood, and the other more in the bone marrow. ¡°We get the best out of this drug combination because they have complementary activity and synergy,¡± Jain says.

The patients ¡ª all of whom were older, high risk or both ¡ª took the drugs together for two years. ¡°We had high rates of deep remission for our patients,¡± Jain says. Most stopped taking both drugs after two years, although a few continued taking the combination therapy for a third year.

The researchers recently presented the results of a five-year follow-up at ASH (). ¡°Many are still in remission after five years,¡± Jain says. ¡°That is quite remarkable.¡±

Additional BTK inhibitors are in the pipeline for CLL and potentially other diseases, too

As effective as these drugs are, there is always room for improvement. ¡°There¡¯s this concept of a third-generation BTK inhibitor, which works in a different mechanism, non-covalently,¡± Jain says. An example is a new drug called AS-1763.

At ASH, senior research scientist Shady Tantawy, M.D., is presenting a poster (), coauthored with Jain, indicating the results of their investigation of AS-1763. It showed a highly selective profile for BTK and potent inhibitory activities for several forms of BTK. Based on this encouraging early data, the team is recruiting for a new clinical trial to test AS-1763 for patients for whom other treatments haven¡¯t worked. They hope that this will prove to be another oral drug possibility for patients when other treatments have failed.

New treatments for?AML with high response rates

Acute myeloid leukemia?(AML) can be thought of as a group of cancers, each with its own mutations. Therefore, the most effective treatments are personalized and targeted, based on both the type of AML and the patient¡¯s age and health status.

Previous research showed that an IV regimen of a hypomethylating agent combined with venetoclax was highly effective in older adults who weren¡¯t good candidates for a more intensive chemotherapy treatment. ¡°This was the first real breakthrough for AML in older patients in decades,¡± says leukemia specialist However, the patients have to come into the hospital or clinic every day for a week out of every month for treatment for the rest of their lives.

¡°We asked ourselves, ¡®How can we make this better?¡¯¡± Kadia says. He and his team in the leukemia department conducted a clinical trial on the use of the drug ASTX727 (which is the hypomethylating agent decitabine/cedazuridine plus venetoclax) in pill form. The results, which Kadia is presenting at ASH (), showed a response rate of 64% among patients in the trial who were newly diagnosed with AML, also known as the frontline patients. Among those with relapsed or refractory AML, the response rate was also high: 46%. The pill was about as effective as the IV form of treatment and had tolerable side effects.

¡°A 64% response rate, especially in a group of patients with a median age of 80 years, is excellent,¡± Kadia says. ¡°Overall, in this older and very high-risk population of patients, the regimen was effective and tolerable. Eventually, I hope having the oral option will make the treatment more accessible for people, as they won¡¯t have to come into the hospital or clinic as often.¡±

Although this study was open to all patients with AML over the age of 75 (in the frontline group) and with AML who hadn¡¯t responded to treatment or that had returned (in the relapsed/refractory AML group), research indicates that targeting the drug based on the specific mutations of the cancer can be even more effective.

Researchers explore treatments for IDH-mutated AML

MD Anderson researchers are also conducting a clinical trial of ASTX727 combined with venetoclax and a targeted therapy in patients with IDH-mutated AML (). These patients have a mutation in either isocitrate dehydrogenase (IDH) 1 or 2, which can be targeted with the inhibitors ivosidenib or enasidenib, respectively. Both drugs can be taken orally.

This study enrolled only patients with mutations in IDH 1 or IDH 2 and treated them with the all-oral triplet of decitabine/cedazuridine (ASTX727) combined with venetoclax and targeted mutant IDH inhibitors ivosidenib or enasidenib. Although the study is still ongoing, the results, presented at ASH by fellow Himachandana Atluri, M.D., so far show 96% of patients with newly diagnosed IDH mutated AML achieved composite remission. In addition, about 45% of patients with relapsed or refractory disease also achieved composite remission. In all groups, some of the patients did have side effects, but these were either mild or could be managed with other drugs, such as corticosteroids.

¡°The response rates were significantly higher, and the median overall survival was not reached, but is a plateau, and still ongoing,¡± Kadia says. ¡°In general, it is showing that this all-oral drug triplet regimen is effective and can also be used when other drugs have not worked.¡±

Looking to the future of leukemia treatment

¡°The current standards are not necessarily optimal,¡± Jain says. That¡¯s why he and others are conducting clinical trials to improve upon the efficacy of already-established treatment regimens for different types of leukemia and are enrolling even newly diagnosed patients.

¡°AML treatment has changed,¡± Kadia says. ¡°People used to apply a one-sized-fits-all treatment, but for decades now at MD Anderson, we take an individualized approach based on what the patient¡¯s bone marrow shows on molecular testing and genetic tests, such as the IDH mutations. Characterizing the leukemia before starting treatment is paramount.¡±

¡°We have made tremendous progress,¡± Jain says. ¡°Many patients with certain types of leukemia, especially CLL, have an almost-normal lifespan.¡±

or call 1-877-632-6789.