Before the Stem Cell or Bone Marrow Transplant

Your health care provider will ask about your medical history and do a physical exam. You will have many tests before treatment begins.
Before transplant, you will have one or two tubes, called catheters, inserted into a blood vessel in your neck or arms. This tube allows you to receive treatments, fluids, and sometimes nutrition.
Your doctor or nurse will likely discuss the emotional stress of having a bone marrow transplant. You may want to meet with a mental health counselor. It is important to talk to your family and children to help them understand what to expect.
You will need to make plans to help you prepare for the procedure and handle tasks after your transplant:

• Complete an advance care directive
• Arrange medical leave from work
• Take care of bank or financial statements
• Arrange care of pets
• Arrange for someone to help with household chores
• Confirm health insurance coverage
• Pay bills
• Arrange for care of your children
• Find housing for yourself or your family near the hospital, if needed

Complications of a Bone Marrow Transplant can included

• Anemia
• Bleeding in the lungs, intestines, brain, and other areas of the body
• Cataracts
• Clotting in the small veins of the liver
• Damage to the kidneys, liver, lungs, and heart
• Delayed growth in children who receive a bone marrow transplant
• Early menopause
• Graft failure, which means that the new cells do not settle into the body and start producing stem cells
• Graft-versus-host disease, a condition in which the donor cells attack your own body
• Infections, which can be very serious
• Inflammation and soreness in the mouth, throat, esophagus, and stomach, called mucositis
• Pain
• Stomach problems, including diarrhea, nausea, and vomiting

Complications of a Bone Marrow Transplant depend on many things

• The disease you are being treated for
• Whether you had chemotherapy or radiation before the bone marrow transplant and the dosages of such treatments 
• Your age
• Your overall health
• How good of a match your donor was
• The type of bone marrow transplant you received (autologous, allogeneic, or umbilical cord blood)

Risks of a Bone Marrow Transplant

A bone marrow transplant may cause the following symptoms:

• Chest pain
• Chills
• Drop in blood pressure
• Fever
• Flushing
• Funny taste in the mouth
• Headache
• Hives
• Nausea
• Pain
• Shortness of breath

Why the Procedure is Performed

A bone marrow transplant replaces bone marrow that either is not working properly or has been destroyed (ablated) by chemotherapy or radiation. Doctors believe that for many cancers, the donor's white blood cells can attach to any remaining cancer cells, similar to when white cells attach to bacteria or viruses when fighting an infection.
Your doctor may recommend a bone marrow transplant if you have:

• Certain cancers, such as leukemia, lymphoma, and multiple myeloma
• A disease that affects the production of bone marrow cells, such as aplastic anemia, congenital neutropenia, severe immunodeficiency syndromes, sickle cell anemia, thalassemia  
• Had chemotherapy that destroyed your bone marrow

Donor stem cells can be collected in two ways

• Bone marrow harvest. This minor surgery is done under general anesthesia. This means the donor will be asleep and pain-free during the procedure. The bone marrow is removed from the back of both hip bones. The amount of marrow removed depends on the weight of the person who is receiving it.
• Leukapheresis. First, the donor is given 5 days of shots to help stem cells move from the bone marrow into the blood. During leukapheresis, blood is removed from the donor through an IV line in a vein. The part of white blood cells that contains stem cells is then separated in a machine and removed to be later given to the recipient. The red blood cells are returned to the donor.

Before the transplant, chemotherapy, radiation, or both may be given

• Ablative (myeloablative) treatment: High-dose chemotherapy, radiation, or both are given to kill any cancer cells. This also kills all healthy bone marrow that remains, and allows new stem cells to grow in the bone marrow.
• Reduced intensity treatment, also called a mini transplant: Patients receive lower doses of chemotherapy and radiation before a transplant. This allows older patients, and those with other health problems to have a transplant.

A stem cell transplant is usually done after chemotherapy and radiation is complete. The stem cells are delivered into your bloodstream usually through a tube called a central venous catheter. The process is similar to getting a blood transfusion. The stem cells travel through the blood into the bone marrow. Most times, no surgery is needed.

Bone marrow transplants cancer treatment

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cells.
There are three kinds of bone marrow transplants:

• Autologous bone marrow transplant: The term auto means self. Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer (cryopreservation). After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make (regenerate) normal blood cells. This is called a rescue transplant.
• Allogeneic bone marrow transplant: The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match your genes. Special blood tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you may be found through national bone marrow registries.
• Umbilical cord blood transplant: This is a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for matching. But blood counts take much longer to recover.

New tool to guide Cancer Care in patients

Researchers must show that the drug predictions that seem so promising in a dish actually work in patients. They also will need to deal with technological issues, such as the time it takes to grow patients’ tumor cells in a dish, between two and six months in the study, and not every attempt was successful.

“For decades, literally decades, people have wanted to do patient-specific chemotherapy sensitivity testing, and it’s been a very hard problem,” said Dr. James Eshleman, a professor of pathology and oncology at Johns Hopkins University School of Medicine, who was not involved in the work. “One problem which is totally counterintuitive is that cancers grow in patients just fine, but” in a dish, “it’s relatively hard to generate cell lines, and specific cancers are extraordinarily difficult, largely for reasons that we don’t understand.”

The researchers believe that with time, those technological issues can be resolved. The study used an imperfect source of cells, leftovers taken from biopsies that had been done for other purposes. If the biopsies were taken with the idea of growing cells and testing drugs, it is likely that the process could be quicker and more efficient.

A far bigger question looms: Sometimes, therapies that seem like a home run in laboratory tests or even animal models of cancer do not work in people.

“This is really setting up the criteria for what we have to look at next,” Schlegel said. “Someone has to figure out if we grow up these cells, how many times is this going to be an adequate predictor of patient response?”

Engelman said he already is beginning to work on the answer to that question.

His team will start by reexamining clinical trials in which patients received drugs and their responses were known. Researchers will then grow cells harvested from their tumors in a dish to see whether the people who had the best responses to the drug also happened to have cells that were more sensitive to the treatment, as researchers would expect.

If that work shows promise, it will help provide the evidence needed to begin using the tool to guide cancer care in patients.

Study points to new Direction for Cancer Therapies

In the new study, the researchers started with 55 samples of cancer cells that had developed resistance to a targeted drug. Nearly half of the cells had been harvested directly from lung cancer patients whose cancer had returned.

The researchers then used a relatively new technique to grow those cancer cells in a dish, establishing a population of cells that could be used to screen for possible treatments.

Next, the scientists bombarded those cancer cells with an array of 76 different drugs and watched to see which ones would be effective. In 45 cases, they found that a novel drug combination worked; the cancer cells became resensitized to the initial drug that had stopped working.

Outside researchers said the study pointed to a future direction for care and was exciting because some of the drug combinations could not have been predicted by genetic testing alone. Dr. Richard Schlegel, director of the Center for Cell Reprogramming at Georgetown University School of Medicine, said the work was “a mirror into the future” of cancer care.

But significant hurdles still exist before the tool could be used to direct a drug regimen.

Doctors look to personalize Cancer Care

A group of Boston physicians and researchers has taken a crucial step toward personalized cancer treatment, identifying novel drug combinations that show promise against cancer cells that have developed a resistance to therapy.

The technology is not yet ready for the ultimate test, in which the promising drug combinations are given directly to patients. However, the researchers saw tantalizing hints of the potential of the approach when they grew a handful of the drug-resistant cancers in mice and observed that in all cases, the new drug regimens were effective at shrinking tumors.

“You could imagine in the future, maybe the not-too-distant future, we could start to do this as clinical trials where we would assign patients to treatments based on the results of what their cancer cells showed susceptibility to,” said Dr. Jeffrey Engelman, director of thoracic oncology at Massachusetts General Hospital, who co-led the work published Thursday in the journal Science. A revolution in medicine has made genetic testing of tumors almost routine when selecting treatment for many types of cancer. However, resistance to targeted therapy almost invariably develops and genetic clues, though powerful, have not always been sufficient to identify the best treatment.

That has spurred a range of efforts to personalize treatment and monitor cancer’s evolution. This summer, a Mass. General team showed that it was possible to isolate rare tumor cells circulating in the blood and analyze them to understand how a patient’s cancer was changing. Other researchers have been working on developing mouse avatars, in which a patient’s tumor is grown in a lab animal in which new therapies can be tested.

A new method using a Patient’s drug-resistant tumor cells to screen for effective Therapies

In collaboration with Cyril Benes, also at Massachusetts General, Engelman’s team developed a method using a patient’s drug-resistant tumor cells to screen for effective therapies. Starting with a tiny amount of tumor tissue from a biopsy, the scientists grew patient cells in a dish until they had enough to perform drug screening. They then tested those cells against 76 cancer drugs.
By combining the drug screening and traditional genetic analyses, the team successfully identified treatment combinations that killed cells in 45 of 55 drug-resistant tumor cell lines tested.
The team didn’t use the resulting drug combinations to alter or guide any patient’s treatment regimens, Engelman said. Before that can be done, the method needs to be evaluated in a randomized clinical trial to see whether the drug combinations that kill cancer cells in a dish are similarly effective in patients, he said.
In addition, the team spent months coaxing the patient cells to grow into large enough populations for the drug screening. To be useful to a cancer patient undergoing treatment, that process needs to take weeks, not months.
“What we’ve done is quite modest,” Engelman said. “What’s exciting now is whether we can take it to that next step -- use it to inform how we treat patients.”

New Cancer Technique Outsmarts Cells Resisting Treatment

By directly screening patient cancer cells, researchers have created a new way to identify potential treatments to effectively attack drug-resistant tumors.
While the screening system has only been used on tumor cells in a dish and in mice, the method could someday lead to individualized drug treatment strategies that adapt even as a patient’s tumor changes.
“The results have been promising enough where we are looking to see if we can develop this now to direct patient treatments,” said Jeffrey Engelman, a medical oncologist at Massachusetts General Hospital in Boston and co-senior author of the study released online today by the journal Science.
Targeted therapies are drugs that interfere with specific cancer-promoting pathways in tumor cells. They have been more effective than traditional chemotherapy drugs against tumors, though the effect usually lasts only one to two years. Tumors rapidly mutate to use alternate pathways, like back alleys, to bypass the original pathways blocked by the medicines.
To combat that resistance, researchers typically analyze DNA from a biopsy of a drug-resistant tumor to try and identify the resistance-causing mutation, then pick a new drug to block that alternate pathway as well. This approach has met with limited success because most genetic results are ambiguous or don’t directly point to treatment strategies, Engelman said.

Is it better to get Cancer Therapy at night?

“The study developed out of a mistake. We accidentally omitted a synthetic steroid…from the medium in which we routinely grow mammary gland cells,” “And we noticed that the cells acquired a faster rate of migration when we followed them under a microscope.”
Intrigued, they turned to mice to answer some more questions. Knowing that steroid levels peak during the day and drop off during sleep, Yarden and his colleagues wondered whether the timing of anti-tumor drugs would affect tumor growth. So they gave a group of mice with breast cancer tumors lapatinib at different times over a 24-hour period and tracked any differences in the size and growth of the tumors.
Indeed, the mice given the drug while they slept showed significantly smaller tumors after seven days than those who received the drug during the day. Yarden suspects that the lower levels of steroid hormones circulating at night allows more of the EGF-targeting drug to hone in on its receptors on the tumor cells and inhibit their growth. Not only that, but the tumors in the mice taking the drug at night looked different; they showed less blood vessel infiltration which meant they were less robust.
Does that mean it’s better to get cancer therapy at night? So far, the results only apply to animal models, and to cancers driven by EGF. More work needs to be done, but if it’s validated, shifting therapies to just before bed “seems logical,” says Yarden. Especially since drugs like lapatinib come in pill form, so it would be relatively easy to take medications before turning in rather than in the morning.

The body doesn't process drugs in the same way throughout the day

It’s news to no one that your body works differently when you’re awake and when you’re sleeping. But could the different states also affect how your body processes certain life-saving drugs? Researchers, reporting Friday in the journal Nature Communications, found that when it comes to cancer drugs, the answer may be yes.
Researchers at the Weizmann Institute of Science discovered—by happy accident—that some of the body’s molecular functions during the day may interfere with the effectiveness of certain cancer medication. Specifically, they found that the normal day-time production of some steroid hormones in the body actually inhibited the work of epidermal growth factor (EGF) receptors—which are the proteins targeted by a class of anti-cancer drugs. Tumor cells plant these receptors on their surfaces to attract nutrients that help them survive and grow. Drugs, including the breast cancer agent lapatinib, can block these receptors on tumors, and such medications are a popular way to treat breast cancers expressing epidermal growth factor.
But Yosef Yarden, a professor in the department of biological regulation, and his team found that when the tumor cells simultaneously bind to something else—such as steroid hormones—the EGF receptors are less active, making drugs like lapatinib less potent.
The findings are still preliminary, but there is other evidence that the day-night cycle may be a potentially important factor in determining cancer treatment dosing in coming years. Some studies showed, for example, that when the 24-hour rest and activity cycle is broken metabolically, and the EGF receptors aren’t given enough time to be active, certain tumors in animals grow two to three times faster.

Why Cancer Drugs May Work Better While You Sleep

The combination, he says, may be more effective since one drug works to suss out tumor cells, like shining a molecular spotlight on them, while the other builds up the body’s defenses against them, allowing immune cells to better target and eliminate cancers.
The time that both groups of patients enjoyed before their melanoma recurred, however, was similar. But Hodi and his team note that the inflammation caused as a side effect of the drugs could be interpreted as early tumor sites, leading researchers to record the presence of tumors that may not be there.
Teasing apart that issue and determining the safe and optimal doses of the combination will require more studies, says Hodi. The dose of ipilimumab he used, for example, was higher than the one approved by the FDA in 2011, since this study was begun before the agency approved the drug. But the idea that a combination of powerful immune-based drugs could help cancer patients fight their disease and survive longer is encouraging. “This world of [new cancer treatments] is moving fast, and there are a slew of possible combinations that others are studying now,” he says. “It’s where the future of cancer therapy will be.”

Promising New Cancer Treatment Uses Immune Cells

Cancer researchers are pumping out study after study trying to figure out how best to use the body’s own immune system to fight cancer tumors.
Scientists led by Dr. F. Stephen Hodi at Dana Farber Cancer Institute show for the first time that combining two drugs that target the immune system in different ways could help melanoma patients survive longer. From 2010 to 2011, 245 patients with advanced skin cancer who had not responded to at least one previous treatment were randomly assigned to get a newly approved drug, ipilimumab, designed to help the immune system better target tumors, either alone or in combination with another drug. Ipilimumab (marketed as Yervoy), was among the first anti-cancer medications that allows immune cells to “see” tumors better; since tumors grow from originally normal cells, the immune system often gives them a pass and doesn’t attack them as foreign. But drugs like ipilimumab, called checkpoint blockade inhibitors, help immune cells to look past cancer’s disguise and target abnormally growing tumors.
In the study, those who received the combination of ipilimumab and sargramostim, another drug that gives the immune system a laser-like focus on the proteins found on tumors, survived an average of 17.5 months after the study began, compared to 12.7 months for those who took ipilimumab alone. At the end of a year, nearly 70% of those receiving the combination were alive, while 53% of those in the ipilimumab alone group were.
“We show that the combination improves survival, and at the same time decreases side effects,” says Hodi. The patients receiving the two drugs reported fewer gut and respiratory complications, two of the organ systems most affected by checkpoint inhibitor drugs like ipilimumab.

Scalability and cost,Pfizer's reason for different approach

“We would like to take it to the next level, where CAR therapies become a more standardized, highly controlled treatment,” said Mikael Dolsten, Pfizer’s head of global research and development.

Working with French biotech Cellectis SA, ALCLS.FR -2.65% Pfizer wants to develop a generic CAR therapy for use in any patient, potentially lowering its cost. But its research is still preclinical, and may not work in humans.

Stephen McGarry, global head of health-care research at Société Générale, agrees the treatments being developed by Novartis and Juno could justify “astronomical” prices, although he thinks health-care payers and patients might fight back.

“When you look at the initial data with the Novartis therapy, you’re getting cures in some kids—what do you charge for that?” he asks

Juno-backed Sloan-Kettering trial, recruiting patients!

There are still big unanswered questions about CAR therapies: one is how long they last.

That is hard to tell because of the small numbers of patients treated so far, and because many of those whose cancer went into remission after the CAR therapies subsequently became eligible for stem-cell transplants which can themselves prolong survival.

Another concern is a potentially dangerous side effect called “cytokine-release syndrome,” an immune response which shows the therapy is working, but which can cause a sharp drop in blood pressure and surge in the heart rate.

The deaths of two patients in a Juno-backed Sloan-Kettering trial in March caused a temporary halt in the study because of worries over these immune responses.

“Patients need to be healthy enough to combat that side effect,” says Mr. Bishop, who thinks it is now manageable. The trial is recruiting patients again, excluding those with a risk of heart failure, and giving those with very advanced leukemia fewer modified cells.

New Costly Cancer Treatments Face Hurdles Getting to Patients

But the biggest hurdle yet may be the cost of the therapies.

The genetic engineering involved means CAR therapies are very complex to manufacture, and each is a unique personalized treatment using a patient’s own blood cells. The inability to mass-produce them has likely implications for how much companies will charge for them.

“What we’re talking about here is a single, very expensive therapy that’s used once for a specific patient and is not generalizable,” says Dr. Malcolm Brenner, director of the Center for Cell and Gene Therapy at the Texas Children’s Hospital in Houston.

Dr. Brenner signed a deal in March to commercialize his own CAR research with Celgene.

Novartis and Juno say it is too early to speculate on price, although Dr. Usman agrees the challenge is getting the manufacturing process to “a viable level where it’s both affordable and attractive.”

While most analysts think it is too early to estimate potential revenue or price, Citigroup believes CAR therapies could cost in excess of $500,000 per patient, which it notes is roughly in line with the cost of a stem cell transplant.

“This technology needs to be widely developed and accessible to patients,” says Dr. DeAngelo. “If the cost is going to be a hindrance, it’s going to be a really sad day.”

Novartis, Juno Conduct New Studies on Leukemia Therapies

Cancer treatments that genetically modify patients’ blood cells to target the disease have shown amazing results in clinical trials. Now drug companies and biotechs must overcome big hurdles to get them into hospitals, including their potential cost.

In two separate clinical trials—sponsored by Novartis AG NOVN.VX -0.51% of Switzerland and Seattle-based biotech Juno Therapeutics Inc.—almost 90% of patients saw their leukemia disappear after being given experimental so-called CAR T-cell therapies. The results were published in December and February, respectively.

Both trials were in small numbers of patients: 22 children in the Novartis trial and 16 adults in the Juno trial. The patients had acute lymphoblastic leukemia—the most common childhood cancer—and had exhausted standard treatments. Both companies are now conducting larger trials.

“CAR T cells are probably one of the most exciting concepts and fields to come out in cancer in a very, very long time,” says Dr. Daniel DeAngelo, a Boston-based hematologist and associate professor of medicine at Harvard Medical School, who wasn’t involved in either study.

Usman Azam, head of cell and gene therapies at Novartis, calls the therapies “critically important” for Novartis. “I think that a cure for cancers such as leukemia and lymphoma through a CAR technology is plausible,” said Dr. Azam in an interview with The Wall Street Journal. “Our job is to get this into patients as soon as we feasibly can.”