Two Men HIV-Free After Bone Marrow Transplants

Two HIV-positive men no longer have detectable virus in their blood after receiving bone-marrow transplants to treat Hodgkin's lymphoma. Timothy Henrich and Daniel Kuritzkes , from Brigham and Women's Hospital, Boston, USA, explained at the International AIDS Society Conference, Kuala Lumpur, Malaysia, that one patient has been off HIV medications for over fifteen weeks and the other seven weeks, and there are still no signs of the virus rebounding.

Completely ridding a patient of HIV is extremely difficult. The virus hides within human DNA in such a way as to become "untouchable". ART (anti-retroviral therapy) helps control the virus in the bloodstream. However, as soon as ART stops, HIV usually replicates rapidly.

The two patients had been HIV-positive for over thirty years. They had both developed Hodgkin's lymphoma, a blood cancer that requires a bone marrow transplant if chemotherapy and other treatments failed. Blood cells are made in the bone marrow - experts believe the bone marrow is a major HIV reservoir.

After undergoing the bone marrow transplants, one man has had no detectable HIV in his blood for four years, and the other for two years.

Lead researcher, Dr. Timothy Henrich warned against using the C-word (cure), saying it is still early days.

In an interview with the BBC, Henrich said:

"We have not demonstrated cure, we're going to need longer follow-up. What we can say is if the virus does stay away for a year or even two years after we stopped the treatment, that the chances of the virus rebounding are going to be extremely low."

Last year, Kuritzkes and Henrich announced that HIV was easily detected in the blood lymphocytes of the two patients before their transplants, but within eight months post- transplant the virus had become undetectable. At the time the patients were still on ART.

The two patients came off ART earlier this year. They are regularly monitored and have no detectable HIV virus. Henrich said "We demonstrated at least a 1,000 to 10,000 fold reduction in the size of the HIV reservoir in the peripheral blood of these two patients. But the virus could still be present in other tissues such as the brain or gastrointestinal track."

If the virus were to rebound, it would mean that the brain, GI tract, lymph nodes or some other sites are important reservoirs of infectious virus "(and) new approaches to measuring the reservoir at relevant sites will be needed".

Bone marrow transplant not the answer to HIV infection

Bone-marrow transplant as a way of curing people infected with HIV is unlikely to ever become standard clinical practice.

In this case, the two patients had blood cancer; the transplants were performed to treat the cancer, not the HIV infection.

Most HIV-positive people do not have blood cancer. Bone marrow transplants are costly and risky - patients face a 20% risk of death. Before undergoing a transplant, the patient's immune system needs to be weakened to minimize the risk of rejection.

A third patient, who also had lymphoma and was HIV-positive and had received the same transplant as the two Boston subjects, died from cancer.

With ART, a person with HIV can enjoy the same life expectancy as other people.

Doctors "cured" baby born with HIV infection

In March this year, doctors from Johns Hopkins Children's Center, the University of Mississippi Medical Center and the University of Massachusetts Medical School announced that an HIV-positive baby who was administered ART within 30 hours of being born had been "cured".

Deborah Persaud, M.D., explained that it is very uncommon to treat a baby for HIV-infection so soon after birth. She added that this was the first case of a functional cure in an HIV-positive infant. The medical team believes that the prompt administration of antiretroviral therapy led to the newborn's cure.

Dr. Persaud said "Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place."

First apparent HIV-infection cure probably occurred in Germany, 2010

In December 2010, researchers from Charite - University Medicine Berlin, Germany, wrote in the journal Blood than an acute myeloid leukemia patient, Timothy Brown, who was also HIV-positive had been cured of HIV infection after receiving a bone marrow transplant.

The scientists wrote "Our results strongly suggest that cure of HIV has been achieved in this patient."

In 2007 Timothy Brown stopped receiving ART, had his own immune system effectively wiped out with high-dose chemotherapy and radiation therapy, and received a bone marrow transplant.

In this case, the donor had a very rare gene mutation - CCR5-delta32 - which protected him from HIV infection, meaning that Brown acquired that protection. In July 2012, scientists in California found traces of HIV in his tissue. However, Brown says that any virus that remains in his body is completely inactive ("dead") and cannot replicate.

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Drug Shortage Linked To Cancer Relapse

A drug shortage appears to have caused a higher rate of relapse among children, teens and young adults with Hodgkin lymphoma, researchers form St. Jude Children's Research Hospital reported this week. The scientists say this is the first example of the tragic consequences of the current drug shortage. They emphasized that protecting patient access to lifesaving treatment must always be the number one priority in any health care system.

Children, adolescents, and young adults with Hodgkin lymphoma in a national clinical trial showed an estimated two-year cancer-free survival rate that dropped from 88 to 75 percent due to a drug shortage.

The study began before any reported drug shortages, however, the change started in 2009 after a shortage of mechlorethamine became apparent. The drug mechlorethamine was replaced by cyclophosphamide for treatment of patients with middle or high risk Hodgkin lymphoma.

No study patients are deceased, but those who relapsed had more rigorous therapy that was linked with higher risks of infertility and other health issues later.

The results of comparing these two groups two years after their cancer diagnoses are published in the New England Journal of Medicine. The outcomes demonstrate the first available evidence of a drug shortage that resulted in disadvantages in specific patients.

History Of Drug Shortages

Recently, many caregivers and patients have had their medical treatments compromised by drug shortages, like mechlorethamine and other injectable drugs. Available since the 1960's for cancer treatment, mechlorethamine just became obtainable again.

Cyclophosphamide is a safe and effective substitute for mechlorethamine, used for decades for treatment of children and adults with Hodgkin's lymphoma.

Monika Metzger, M.D., an associate member of the St. Jude Department of Oncology and the study's principal investigator, said:

"This is a devastating example of how drug shortages affect patients and why these shortages must be prevented. Our results demonstrate that, for many chemotherapy drugs, there are no adequate substitute drugs available."

Previous shortages have most frequently been solved using substitutions. This study has given a real face to the drug shortage problem, showing that it is real. There are actual therapies that are unable to be given because drugs are just not available.

Michael Link, M.D., the senior author and professor of pediatrics in hematology-oncology at Stanford, as well as a member of the pediatric hematology-oncology service at Packard Children's Hospital, explains:

"Despite heroic efforts by the drug shortage office of the Food and Drug Administration to solve the shortages of a number of medically necessary drugs, it is clear that patients are still suffering from the unavailability of life-saving drugs. A more systematic solution to the problem is needed."

Results of Drug Substitutions

Hodgkin lymphoma is cancer that attacks the lymph system and makes up approximately six percent of childhood cancers. Around 90 percent of patients in the United States with this cancer will become long-term survivors.

In 2002, the five institutions collaborating on this study worked as the Pediatric Hodgkin Consortium and accepted a seven-drug chemotherapy treatment course, which included mechlorethamine, to treat high risk child patients. The researchers aimed to avoid infertility and other issues and maintain high cure rates.

In 2006, a companion study started for patients with intermediate-risk disease. The risk groups are defined by how far the cancer has spread, the location and number of lymph nodes involved, as well as the experience of negative symptoms like night sweats, fever, and weight loss.

Patients underwent 12 weeks of the seven-drug chemotherapy treatment course. They also received radiotherapy with their dose given in accordance to their chemotherapy response. Once mechlorethamine was no longer available, the substitution cyclophosphamide was allowed in its place.

Results for cancer patients are calculated in terms of cancer-free survival, also known as the number of years patients live disease-free. When investigators looked at the substitution's influence, they saw that approximate disease-free survival was 88 percent for the 181 patients whose treatment included mechlorethamine.

For the 40 patients who were given cyclophosphamide, the rate was 75 percent. The variation prompted researchers to stop enrolling new patients in the trials.

As a whole, patients who had the cyclophosphamide experienced less negative symptoms and were more inclined to have intermediate-risk, rather than high-risk Hodgkin lymphoma. The authors note that there is no valid explanation for the significant difference in event-free survival besides the drug substitution.

The patients in the study were between the ages of 3 and 21, with half being under 14 years. Relapsed patients underwent additional therapy. Extra treatment included extensive chemotherapy and a stem cell transplant using the patient's own blood-creating stem cells.

The investigators said it is too early to determine whether these patients will experience the same long-term survival rates as those who did not get their cancer back.

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Five-Minute' Blood Cancer Injection Cuts Treatment Time By Two Hours

A new injection for blood cancer patients trialled at Southampton's teaching hospitals can deliver a two-hour dose of drugs in around five minutes.

Patients diagnosed with follicular non-Hodgkin lymphoma (NHL), a disease that attacks one specific type of infection-fighting cell, previously had rituximab administered via an intravenous drip.

Around 4,000 people, mainly in their 60s, are diagnosed with the condition in the UK every year and the majority of them will receive the drug, which targets and destroys specific proteins on the surface of cancerous cells, alongside chemotherapy to help eliminate all signs of the lymphoma and induce remission.

At the moment, most sufferers receive both treatments via a drip in a four-hour session once every three weeks. When the six-month course of chemotherapy ends, patients often require a further two years of rituximab given over two hours once every eight weeks.

Results of the multi-centre international study, presented at the annual meeting of the American Society of Hematology in Atlanta, showed that giving the drug by a quick injection under the skin was as safe and effective as the conventional intravenous treatment.

Dr Andrew Davies, a consultant in medical oncology at Southampton General Hospital and study lead, said: "This is a new formulation of a drug we are very familiar with and have been using for many years and the study demonstrates injection is equivalent to the intravenous drip method.

"In the near future, patients will be able to benefit from shorter, more convenient and potentially less complicated hospital visits, which will greatly reduce administration time for NHL patients and ease the capacity burden in busy chemotherapy day units."

Dr Davies, who is also a Cancer Research UK senior lecturer at the University of Southampton, added: "There is a high degree of patient preference and satisfaction with this new formulation of rituximab in Southampton and we hope to see it rolled out nationwide very soon."

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Bosulif Approved By The FDA For Treatment Of Chronic Myelogenous Leukemia

The US Food and Drug Administration approved Bosulif as treatment for a rare disease, found in older adults, which attacks the blood and bone marrow and is known as chronic myelogenous leukemia (CML).

Approximately 5,430 people will be diagnosed with CML in 2012. The majority of people with CML have the Philadelphia chromosome, a genetic mutation where the bone marrow produces an enzyme called tyrosine kinase. This enzyme sparks excess creation of unhealthy and irregular white blood cells named granulocytes, which fight infection.

Bosulif is aimed towards patients with chronic, accelerated, and blast phase (extremely high levels of granulocytes) Philadelphia chromosome positive CML and who are also not responding to other therapies. Bosulif works by obstructing the tyrosine kinase signal that helps produce the abnormal granulocytes.

"With the approval of tyrosine kinase inhibitors, we are seeing improvements in the treatment of CML based on a better understanding of the molecular basis of the disease," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research.

The FDA has approved other drugs such as imanitib, dasatinib, and nilotinib to treat many forms of CML. Bosulif was evaluated in a single clinical trial that included 546 adult patients who have chronic, accelerated, or blast phase CML. All patients in the study had CML that continued to progress after being treated with imanitib and dasatinib and/or nilotinib, or could not tolerate side effects of these treatments. Participants were all given Bosulif.

The effectiveness of Bosulif was determined by the amount of patients who experienced a major cytogenetic response (MCyR) within the first 24 weeks of treatment for chronic level CML. Findings showed patients who previously used imanitib reached MCyR after the initial 24 weeks. 52.8 percent of the patients who achieved MCyR at any time had a response that lasted 18 months or longer. Of the patients who were previously treated using imatinib, followed by dasatinib and/or nilotinib, 27 percent reached MCyR within 24 weeks. Among those who achieved MCyR at anytime, 51.4 percent had a response that lasted nine months or longer.

Of those patients with accelerated CML previously treated with at least imatinib, 33 percent had their blood counts return to normal, while 55 percent reached normal blood counts with no evidence of leukemia within the beginning 48 weeks of treatment. In addition, 15 percent of participants with blast phase CML achieved normal blood counts, while 28 percent achieved normal blood counts with no evidence of leukemia.

Common side effects seen associated with Bosulif are diarrhea, nausea, low levels of platelets in the blood, abdominal pain, anemia, vomiting, fever, and fatigue.

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