Monthly Archives: August 2021

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About 250 miles above sea level, a unique laboratory circles the planet. Here in low-Earth orbit on the International Space Station (ISS), gravitys tug is faint enough that objects appear to be weightless. These microgravity conditions cause living things from people to organs and cells to function differently than on terra firma. Researchers from UPMC and the University of Pittsburgh aim to use the ISS U.S. National Laboratory (ISSNL) to conduct biomedical research not possible on Earth and advance space-based biomanufacturing.

In recent years, microgravity research has become more accessible through the ISSNL. At the same time, breakthroughs in gene editing, stem cell research and development of mini lab-grown organs have helped advance regenerative medicine, the discipline that focuses on replacing or repairing damaged or diseased body parts. Progress in these two areas means that now is the right moment to consider the future of biomanufacturing in space, according to Dr. William Wagner, director of the University of Pittsburghs McGowan Institute for Regenerative Medicine and distinguished professor of surgery, chemical engineering and bioengineering at Pitt.

Dr. William Wagner and Gary Rodrigue discuss the future of biomanufacturing in space.

We are truly blessed to be at a point in humankind where access to low-Earth orbit and access to microgravity is available, Wagner said during a fireside chat with Gary Rodrigue, director of programs and partnerships at the Center for the Advancement of Science in Space (CASIS), at the 10th annual International Space Station Research and Development Conference. The question is, how are we going to leverage the unique aspects of this environment?

To help answer this question, the McGowan Institute and CASIS, the organization that manages the ISSNL, brought together more than 100 experts in regenerative medicine, tissue engineering and aerospace for the Biomanufacturing in Space symposium last year. Originally planned as an in-person event, the symposium pivoted to a series of virtual meetings that took place weekly over several months.

In a review article recently posted to Preprints, symposium attendees identified areas that hold the greatest promise for space-based biomanufacturing for tissue engineering and regenerative medicine.

Its an incredible privilege to try to answer the question of what makes sense to do in microgravity, said Wagner. Its a similar feeling to being an explorer on a ship and heading to some uncharted land. I think many people who were on those calls shared that sense of exploration.

The researchers identified organs-on-a-chip miniature devices that mimic human organs as one important subject for future research in space. Because disease-like characteristics develop in these systems under microgravity, insight into disease pathways and development of drugs that block these pathways can be accelerated in low-Earth orbit.

Stem cell research is another area that could be advanced in microgravity, according to the article. Stem cells, which can be turned into any type of cell, have many potential applications for treating diseases, injuries and birth defects. Because these cells behave differently in low gravity, research on the ISS could improve stem cellbased treatments and enhance fundamental understanding of processes such as aging and organ development.

The third target area that the researchers identified is 3D printing of tissues for transplantation and disease modeling. The near absence of gravity on the ISS could enable more consistent deposition of complex molecules and reduce the need for structural support, which have been hurdles in the production of these 3D tissues.

The researchers also outline commercial opportunities and potential business models for developing a sustainable market for space-based biomanufacturing. According to Wagner, these considerations are important for ensuring that new therapies make it to patients.

We cant just run experiments; we cant just publish papers. We have to think about how it is going to get to the patient, said Wagner. If we dont get it to the patient, we always say that we havent succeeded in our mission.

Originally posted here:
Researchers Gaze into Space to Envision Future of Regenerative Medicine - UPMC & Pitt Health Sciences News Blog - UPMC

The umbrella term of leukemia encompasses several distinct types of leukemia, including acute myeloid leukemia (AML).

In 2021, its estimated that over 20,000 new cases of AML will be diagnosed, according to the National Cancer Institute (NCI). Since treatment varies depending on the specific kind of leukemia present, an accurate diagnosis is crucial.

There are a variety of treatments for AML. Your doctor will explain them and help choose a treatment plan based on the type of cancer you have and your individual situation.

Read on to learn more about the various treatment options for AML.

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It affects white blood cells (WBCs), making them abnormal. In some forms of AML, they may also multiply very quickly.

Other names for AML include:

Read this for more information about AML.

Once the diagnosis is confirmed, your healthcare team will develop a plan to treat AML. Depending on the specific type and stage of AML, you may receive one or more of these treatments:

Chemotherapy is the main form of treatment for AML. Its divided into two phases:

Since AML can progress quickly, treatment is usually started as soon as possible after diagnosis. Other treatments may be used as well.

Chemotherapy, also called chemo, is the use of anti-cancer drugs to treat cancer. This is the main treatment for AML.

These drugs can be injected into a vein or under the skin, allowing the chemotherapy to travel through the bloodstream to attack cancer cells throughout the body. If leukemia has been found in the brain or spinal cord, chemo medication may be injected into the cerebrospinal fluid (CSF).

Chemo medications most often used to treat AML include:

Other chemo medications may include:

Side effects of chemotherapy can vary depending on the drug, dosage, and duration. They can include:

While chemotherapy is the main treatment for AML, for a subtype of AML called acute promyelocytic leukemia (APL), other non-chemotherapy drugs are more effective.

APL is caused by a specific gene mutation that affects WBCs. Some medications work better than chemo to help those cells develop normally. Two of these medications are:

ATRA can be given with chemotherapy or with ATO for the initial treatment of APL. Both drugs can also be given during consolidation.

Side effects of ATRA include:

Side effects of ATO can include:

Radiation therapy uses high-energy radiation to kill cancer cells. While its not the main treatment for those with AML, it can be used in treating AML. In AML, the radiation used is external beam radiation, which is similar to an X-ray.

Radiation can be used in AML to treat:

Side effects of radiation can include:

Surgery is rarely used in AML treatment. Leukemia cells are spread through the bone marrow and blood, making the condition impossible to improve with surgery. On rare occasions, a tumor or mass related to leukemia may form that may be treated with surgery.

Prior to chemotherapy, a small surgery to place a central venous catheter (CVC) or a central line, is often done. During this procedure, a small flexible tube is placed into a large vein in the chest. The end of it is either right under the skin or sticks out in the chest or upper arm.

Having a central line installed allows the treatment team to give intravenous medication and chemotherapy through the CVC, and to draw blood from it, reducing the number of needle sticks an individual has to have.

While chemotherapy is the main treatment for AML, it has its limits. Since high doses of these medications are toxic, the dosage must be limited. A stem cell transplant allows for higher doses of chemotherapy medications.

In a stem cell transplant, very high doses of chemotherapy medications, sometimes combined with radiation, are given. All of the individuals original bone marrow is destroyed on purpose.

Once this stage of therapy is over, blood-forming stem cells are given. These stem cells will grow, rebuilding the bone marrow. Healthy, cancer-free stem cells replace the destroyed bone marrow.

Read this article for more information about a stem cell transplant.

Targeted therapy drugs are medications that target only certain parts of cancer cells. They can be very effective for some people with AML. Most targeted therapy drugs are taken orally, except for gemtuzumab ozogamicin (Mylotarg), which is given as an intravenous infusion.

Talk with your treatment team about the potential side effects of each drug and what you should watch for when taking it. Some targeted therapy medications include:

One type of targeted therapy medication called FLT3 inhibitors targets the FLT3 gene. In some people with AML, a mutation in the FLT3 gene causes the creation of a protein, also called FLT3, that enables cancer cells to grow. Drugs in this category include:

Side effects of these drugs may include:

In some people with AML, there is a mutation in the IDH2 gene. These mutations stop bone marrow cells from maturing in a normal way. Medications called IDH inhibitors block IDH proteins produced by these mutated genes, allowing these bone marrow cells to grow normally and remain healthy.

Drugs in this category include:

Side effects can include:

AML cells contain a protein called CD33. A medication called gemtuzumab ozogamicin (Mylotarg) attaches to this CD33 protein and helps deliver chemotherapy medications directly to cancer cells so that these drugs are more effective.

Common side effects include:

There are less common but serious side effects like:

Venetoclax (Venclexta) is a BCL-2 inhibitor. This drug targets BCL-2, which is a protein that helps cancer cells live longer. The drug stops the BCL-2 protein from helping cancer cells survive so that these cancer cells die sooner. This medication can be used along with other chemotherapy drugs.

Side effects include:

AML can cause cellular mutations that prevent cells like bone marrow cells from developing and functioning normally. These mutations may affect the pathway cells use to send necessary signals. This pathway is called hedgehog. For some people with AML, especially those over age 75, strong chemo medications may be so harmful that chemo is not an option. For these individuals, a medication called, Glasdegib (Daurismo), may help them live longer. This medication helps stop the mutations and allows bone marrow cells to function normally.

Side effects of this medication may include:

Refractory AML happens when an individual is not in remission even after one to two cycles of induction chemotherapy, which means they have a blast count of 5 percent or more. Ten to 40 percent of people with AML have refractory AML.

If treatment isnt successful with one course of chemo, another one may be done. If a person is still not in remission after the second course of chemo, they may be given other medications or an increased dose of their current chemotherapy medications.

Other treatment options include stem cell transplant or a clinical trial of new therapies.

When an individual has no evidence of disease after treatment, its called remission or complete remission. Remission means these three criteria are met:

If there is no evidence at all of leukemia cells in the bone marrow, using highly sensitive tests, its called complete molecular remission. Minimal residual disease (MRD) occurs when, after treatment, leukemia cells cannot be seen in the bone marrow with standard tests but more sensitive tests like PCR tests do find leukemia cells.

Even after an individual has entered remission, they will likely need follow-up care and will need to be monitored by their doctor and healthcare team. This may mean additional tests, more frequent physical exams, and other care.

Although chemotherapy is the main treatment for AML, there are a variety of treatment options, depending on the AML subtype or whether you have a specific mutation. Treatment also depends on your response to initial treatment and whether or not remission is sustained.

Your treatment team will explain all of your treatment options and help you choose the treatment plan that is best for you and your individual situation.

Follow this link:
Acute Myeloid Leukemia Treatment: What You Need to Know - Healthline

When utilizing a validated antibody assay against the SARS-CoV-2 spike protein, investigators revealed a high seroconversion rate of 94% among 200 patients with cancer in New York City who had received a full dose of 1 of the FDA-authorized COVID-19 vaccines.

Patients with solid tumors experienced an impressive seroconversion rate of 98% compared with a rate of 85% in those with hematologic malignancies, 70% in those who had received highly immunosuppressive therapies like anti-CD20 agents, and 73% in those who had previously undergone stem cell transplantation. Notably, patients who received treatment with immune checkpoint inhibitors or hormonal therapies experienced seroconversion rates of 97% and 100%, respectively, following vaccination.

We saw very encouraging [data] showing that most patients with a cancer diagnosis have a really high chance of responding to vaccinationsas long as the vaccinations are done in an appropriate manner, [with] both doses administered, Balazs Halmos, MD, MS, study author, director of Thoracic Oncology, and director of Clinical Cancer Genomics at Montefiore Medical Center, told OncLive in an exclusive interview on the research. This was [true] even for [patients who were receiving] active treatment with chemotherapy, targeted therapy, or immunotherapy.

Halmos and colleagues launched this study to develop a better understanding with regard to the immunogenicity of vaccines in a group of patients with a cancer diagnosis in New York City by examining the rates of anti-spike immunoglobulin G (IgG) antibody positivity after receiving 1 of the 3 authorized COVID-19 vaccines.

A total of 213 patients were enrolled to the study through an informed-consent process. Twenty-nine additional patients with cancer who received the SARS-CoV-2 spike IgG testing were identified through retrospective chart review.

A total of 18 patients did not have this test conducted following consent, and thus, they were excluded from the analysis. Twenty additional patients were excluded because they had their test done before having received full vaccination in accordance with FDA guidance. Four additional patients were excluded for other reasons.

As such, 233 patients with cancer were noted to have received all required doses of their COVID-19 vaccine; all these patients were included in the safety analysis. A subset of 200 patients received the IgG test and were included in the immunogenicity analysis. Serological information from these patients were utilized in association studies between cancer subtypes and therapies.

Investigators also examined the link between the quantitative titer of SARS-CoV-2 spike IgG and cancer subtypes and therapies. If the 200 patients, 185 had available IgG titers that were at least 2 days following the last vaccine dose. A total of 15 patients were excluded from the vaccination cohort with titers; these patients had received the vaccine, but titers were checked less than 1 week from their last dose.

Among those included in the efficacy analysis (n = 200), the median age was 67 years (range, 27-90), 58% were female, and 42% were male. The study population was noted to be representative of the diverse population that resides in the Bronx, New York, with 32% of patients identifying as African American, 39% as Hispanic, 22% as Caucasian, 5% as Asian, and 3% as other ethnicities.

Additionally, 67% of patients had a solid tumor diagnosis and 33% had a hematologic malignancy. Among those with solid tumors, 26% had breast cancer, 14% had gastrointestinal cancer, 9% had genitourinary cancer, 5% had gynecologic cancer, 13% had thoracic or head and neck cancer, 1% had skin or musculoskeletal cancer, and 1% had carcinoma of an unknown primary. Among those with hematologic malignancies, 13% had lymphoid disease, 9% had myeloid disease, and 11% had plasma cell disease.

Seventy-five percent of patients had an active malignancy and 67% were receiving active treatment at the time that they received the COVID-19 vaccine. Fifty-six percent of patients were on active chemotherapy. Moreover, 19% of patients were on active chemotherapy within 48 hours of receiving at least 1 of their COVID-19 vaccine doses.

Fifty-four percent of patients completed vaccination with the Pfizer vaccine, 31% with the Moderna vaccine, and 10% with the Johnson & Johnson vaccine. A total of 3 patients had received a complete mRNA vaccination series but the information regarding the type of vaccine (Pfizer vs Moderna) are not yet available.

Additional findings from the study showed that significantly higher titer values were observed in solid tumors vs hematologic malignancies among a subgroup of 185 patients with available IgG titers longer than 7 days post vaccination, at a median of 7858 AU/mL vs a median of 2528 AU/mL, respectively (P = .013).

When comparing patients who were receiving active cancer treatment vs those who were not, no significant differences in seroconversion were reported, at 96% and 93%, respectively. However, investigators did report lower seropositivity rates in those who were on active cytotoxic chemotherapy versus other treatments, at 92% vs 99%, respectively (P = .04). Moreover, significantly lower seroconversion rates were also noted in those who received immunosuppressive therapies like stem cell transplant (73%; P = .0002), CD20 antibody therapy (70%; P = .0001), or CAR T-cell therapy (all seronegative; P = .0002).

Significantly lower titer levels were observed in patients who received CD20 antibody therapy vs the overall patient population, which underscored the susceptibility of patients receiving these treatments during the pandemic.

No statistically significant associations between age, ethnicity, time since immunosuppressive therapy, steroid use, or treatment within 48 hours of a vaccine dose, and seropositivity were reported.

Although all patients who were receiving CDK4/6 inhibitor treatment demonstrated positive anti-spike IgG test results, notably antibody titers were noted to be very low in this subset (n = 5), at a median of 1242 AU/mL vs a median of 6887 AU/mL in the overall cohort. Given the known involvement of the CDK4/6 pathway in immune activation, this might be biologically plausible and warrants further studies into the impact of CDK4/6 inhibitors on vaccine efficacy, the study authors noted.

A trend to lower titers were also reported among subsets of patients who received BCL-2 or BTK inhibitors.

Among a subset of 22 patients with cancer who had previously been infected with COVID-19, the seroconversion rate was 95%. Notably, antibody titers in those who had prior infection with the virus were found to be significantly higher than those who did not have a known prior infection, at a median of 46,737 AU/mL and a median of 5296 AU/mL, respectively (P < .001).

Our study, along with other emerging data, strongly highlights the continued need to vaccinate patients with a cancer diagnosis urgently and broadly, as vaccinations are likely to be highly effective, the study authors concluded. On the other hand, our study highlights at-risk cohorts of patients, in particular patients with hematologic malignancies following receipt of immunosuppressive therapies such as stem cell transplantation, anti-CD20 therapies, and CAR T-cell treatments. These cohorts of patients could potentially benefit from passive immunization with anti-COVID antibodies in the face of the ongoing pandemic.

Read more from the original source:
Study Calls for COVID-19 Vaccination in Patients With Cancer to Enable Optimal Treatment Delivery During Pandemic - OncLive

As you may have heard, the Centers for Disease Control and Prevention (CDC)has recommended a third dose of the COVID-19 vaccine for people who are immunocompromised. This includes some but not all people with cancer.

Mini Kamboj

Mini Kamboj, Memorial Sloan Kettering Cancer CentersChief Medical Epidemiologist, has answers to your questions about who is eligible and how you can schedule an appointment to receive your third shot.

For a vaccine to protect you, it must activate your immune system. In some immunocompromised patients, this ability is impaired, so a third dose can boost the immune response.

According to the CDC, among severely immunocompromised people who had undergone solid organ transplant and had virtually no protection after receiving two doses of the Pfizer-BioNTech or Moderna vaccine, 30 to 50% developed antibodies protecting them from COVID-19 after getting an additional dose.

People who have moderate to severe immunosuppression qualify to receive an additional dose, usually because of an organ or stem cell transplant, HIV infection, steroid therapy, or certain cancer treatments that impair the bodys ability to fight infections.

Its important to know that not all cancer patients have a weakened immune system. Those cancer patients who are considered immunocompromised include:

These eligibility criteria cover the most common indications. Your provider will be able to order the third vaccine dose for other immunosuppressive treatments or conditions if they decide that the extra dose will benefit you.

If you meet the criteria, you can receive a third dose 28 days or later after completing your first vaccine series.

Only patients who completed their primary immunization with either Pfizer-BioNTech or Moderna vaccines can receive the third dose. MSK will offer the same vaccine brand to patients as they previously received. Mixing vaccines is not permitted at this time.

The CDC has not made any recommendations yet for people who received the Johnson & Johnson vaccine. We are closely following their guidance and will communicate any changes.

To find out if you should get a third dose, call your MSK doctors office or send a message through the MyMSK patient portal. If you are eligible for an additional vaccine, your doctor will schedule an appointment for you.

On Wednesday, August 18, MSK will begin offering the additional vaccines at the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, located at 530 East 74th Street.

Starting Monday, August 23, we will be scheduling appointments at:

These clinics will be open 9:00 a.m. to 5:00 p.m., Monday through Friday.

Additional dates and locations, including our New Jersey locations, will be added shortly.

If you think you meet the criteria for getting a thirdvaccine dose, you should call your providers office to confirm your eligibility, and a vaccine appointment will be scheduled for you. You should be prepared to share your vaccination card or a photo of it. Please present information from your card, rather than the Excelsior pass, which does not have the details about what vaccine brand you received and on what dates.

Yes, the Food and Drug Administration (FDA) hasgranted emergency use authorization for patients 12 and older to receive the Pfizer-BioNTech vaccine and 18 and older to receive the Moderna vaccine.

The side effects from a third COVID-19 vaccine are similar to those experienced after receiving the original vaccines. Scientists in Israel recently began giving a third dose of the Pfizer-BioNTech vaccine to people with compromised immune systems. Side effects were reported by 31% of people, the most common being soreness at the injection site. Other side effects included fatigue, headache, body aches, and fever. These symptoms dont last long about one to three days.

The safety of a third dose in people whove had COVID-19 breakthrough infections is not known, therefore an additional dose for those patients is not recommended at this time. Some patients in whom initial vaccine responses are expected to be severely blunted, such as stem cell transplant orCAR-T recipients or those treated with B-cell depleting therapies, may benefit from a third dose after breakthrough infection. Discuss your situation with your clinical care team.

Even after the third dose, people with weakened immune system must take precautions to protect themselves from COVID-19. You should:

If you develop symptoms of COVID-19, contact your clinical care team and get tested.

Not at this time.The vaccines remain very effective against severe disease for those who do not have compromised immune systems. In the future, third doses may be recommended for more people because immune protection tends to weaken over time. In addition, as new variants of COVID-19 emerge, it may be necessary to design new vaccines to protect against them.

August 16, 2021

See the rest here:
A Third Dose of the COVID-19 Vaccine Recommended for Some Cancer Patients With Weakened Immune Systems - On Cancer - Memorial Sloan Kettering