stem cell transplant

Patient achieves HIV and blood cancer remission three decades after HIV diagnosis through stem cell transplant at City of Hope

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  • Known as the City of Hope patient, he is the fourth patient in the world and the oldest to go into long-term remission of HIV without antiretroviral therapy (ART) for over a year after receiving stem cells from a donor with a rare genetic mutation. He is now 66 years old. He was 63 when he received the transplant. 
  • Among those patients, he also had HIV the longest, since 1988, before going into remission for HIV and leukemia.
  • Patient’s case opens up opportunities for older patients living with HIV and a blood cancer to receive a transplant and achieve remission for both diseases if a donor with rare genetic mutation can be identified.
  • Research presented today at AIDS 2022 press conference, highlighting the latest HIV research.
  • City of Hope is a global leader in stem cell transplantation for patients with blood cancers and patients with HIV/blood cancer.

LOS ANGELES — City of Hope, one of the largest cancer research and treatment organizations in the United States, announced today that a 66-year-old man who was diagnosed with HIV in 1988 has been in remission of the virus for over 17 months after stopping antiretroviral therapy (ART) for the disease following a stem cell transplant from an unrelated donor for leukemia, according to research presented today at the AIDS 2022 press conference by Jana K. Dickter, M.D., City of Hope associate clinical professor in the Division of Infectious Diseases. He received the transplant nearly 3 1/2 years ago at City of Hope. 

The man, known as the City of Hope patient, lived with HIV for over 31 years, the longest of any of the three previous patients with HIV who have gone into remission for a blood cancer and HIV. He was 63 years old when he received a transplant, the oldest patient to receive a transplant and go into remission for HIV and leukemia. 

The patient received a chemotherapy-based, reduced-intensity transplant regimen prior to his transplant that was developed by City of Hope and other transplant programs for treatment of older patients with blood cancers. Reduced-intensity chemotherapy makes the transplant more tolerable for older patients and reduces the potential for transplant-related complications from the procedure. 

The patient received a blood stem cell transplant at City of Hope in early 2019 for acute myelogenous leukemia from an unrelated donor who has a rare genetic mutation, homozygous CCR5 Delta 32. That mutation makes people who have it resistant to acquiring HIV. CCR5 is a receptor on CD4+ immune cells, and HIV uses that receptor to enter and attack the immune system. But the CCR5 mutation blocks that pathway, which stops HIV from replicating.

The City of Hope patient has not shown any evidence of having replicating HIV virus since the transplant. He stopped taking ART for HIV in March 2021. He might have been able to stop the therapies sooner but wanted to wait until he was vaccinated against COVID-19.

“We are proud to have played a part in helping the City of Hope patient reach remission for both HIV and leukemia. It is humbling to know that our pioneering science in bone marrow and stem cell transplants, along with our pursuit of the best precision medicine in cancer, has helped transform this patient’s life,” said Robert Stone, president and CEO of City of Hope and the Helen and Morgan Chu Chief Executive Officer Distinguished Chair. “The entire team at City of Hope is honored to make a difference every day in the lives of people with cancer, diabetes and other life-threatening diseases.” 

“We were thrilled to let him know that his HIV is in remission and he no longer needs to take antiretroviral therapy that he had been on for over 30 years,” Dickter said. “He saw many of his friends die from AIDS in the early days of the disease and faced so much stigma when he was diagnosed with HIV in 1988. But now, he can celebrate this medical milestone.”

“The City of Hope patient’s case, if the right donor can be identified, may open up the opportunity for more older patients living with HIV and blood cancers to receive a stem cell transplant and go into remission for both diseases,” Dickter added.

“When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence,” the man, who wishes not to be identified, said. “I never thought I would live to see the day that I no longer have HIV. City of Hope made that possible, and I am beyond grateful.”

City of Hope is a leader in treating patients with blood cancers, as well as patients with HIV and blood cancers with transplants. City of Hope has one of the nation’s leading transplant programs and is at the forefront of using transplants to treat older adults with blood cancers. The institution has performed nearly 18,000 transplants since 1976.

City of Hope was one of the first centers in the United States to perform effective, curative autologous transplants, which use a person’s own stem cells, for patients with HIV-related lymphoma. When many centers still treated patients with low-intensity, noncurative treatment approaches, City of Hope challenged that paradigm by demonstrating that autologous transplants could be used to cure patients with HIV-related lymphomas who would otherwise die.

City of Hope further pioneered the use of gene-modified blood stem cell transplants to evaluate the use of stem cells engineered to be resistant to HIV infection. The institution was also a primary national co-leader in two National Cancer Institute-sponsored trials for autologous as well as allogeneic stem cell transplantation, which use a donor’s stem cells, for patients with HIV and blood cancers. These trials led to a change to the national standards of care on how best to manage this vulnerable patient population.

Leveraging their expertise in cellular immunotherapy, City of Hope scientists have also developed chimeric antigen receptor (CAR) T cells that can target and kill HIV-infected cells and control HIV in preclinical research. They are working to start a clinical trial using CAR T cell therapy, which has the potential to provide HIV patients with a lifelong viral suppression without ART.

“The City of Hope patient is another major advancement. It demonstrates that research and clinical care developed and led at City of Hope are changing the meaning of an HIV diagnosis for patients across the United States and the world,” said John Zaia, M.D., Ph.D., director of City of Hope’s Center for Gene Therapy, Aaron D. Miller and Edith Miller Chair for Gene Therapy and a leader in HIV research. “City of Hope remains at the forefront of clinical research that changes people’s lives for the better.”

Under the care of City of Hope hematologist Ahmed Aribi, M.D., assistant professor in the Division of Leukemia, the patient received three different therapies to get him into remission before receiving a transplant. Most patients achieve remission after one therapy. The remission is necessary because a transplant is an intensive procedure that can cause serious complications.

For the transplant, Aribi and his team worked with City of Hope’s Unrelated Donor BMT Program — directed by Monzr M. Al Malki, M.D. — to find a donor who was a perfect match for the patient and had the rare genetic mutation, which is found in just 1-2% of the general population.

The patient did not experience serious medical issues after transplant.

“This patient had a high risk for relapsing from AML [acute myeloid leukemia], making his remission even more remarkable and highlighting how City of Hope provides excellent care treating complicated cases of AML and other blood cancers,” Aribi said. 

Source: City of Hope

Man is oldest person possibly cured of HIV after stem cell transplant

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A 66-year-old man is the oldest person yet to possibly be cured of HIV after undergoing a stem cell transplant, researchers announced Wednesday.

The man had HIV for more than 31 years when he received a blood stem cell transplant in early 2019 for acute myeloid leukemia (AML) using cells from a donor with a rare genetic mutation that prevents HIV from entering human cells, making people who have it resistant to most strains of the virus.

IDN0722Dickter_Graphic_01_WEB
Dickter J, et al.

The man has remained free of replicating HIV since his transplant — including for the last 17 months after stopping treatment for HIV, said Jana K. Dickter, MD, a physician at City of Hope National Medical Center in Duarte, California, where the patient was treated. His leukemia also is in remission.

“This research is particularly important because people with HIV continue to live longer thanks to advances in antiretroviral therapy,” Dickter said during a press conference announcing the findings ahead of the AIDS 2022 meeting in Montreal.

She said the case “opens possibilities for other older persons living with HIV and blood cancer to receive a transplant and achieve remission from both diseases if a donor with this rare genetic mutation can be identified.”

At 63 years old when he underwent the procedure, the “City of Hope patient” — as he is being called — was the oldest person with HIV and leukemia to undergo a transplant and go into remission for both, according to Dickter and colleagues.

He is at least the fourth person to have potentially been cured of HIV after receiving stem cells from someone with the CCR5-delta 32 mutation, and the second such case to be made public this year.

In February, researchers at the Conference on Retroviruses and Opportunistic Infections (CROI) announced that, for the first time, a woman had achieved sustained treatment-free remission this way. The so-called “New York patient” was said to be in remission for more than a year without treatment.

Two other cases were announced in past years at CROI, including the “Berlin patient,” later identified as Timothy Ray Brown, who died in 2020 following a recurrence of AML. Brown remained HIV free for the rest of his life after undergoing a bone marrow transplant in 2007.

A man known as the “London patient” who later identified himself as Adam Castillejo was reported in 2020 to have been in HIV remission for 30 months after undergoing allogeneic hematopoietic stem cell transplantation for Hodgkin’s lymphoma.

Experts have warned that stem cell transplantation is too risky and expensive to be a conventional cure for HIV. What these cases have done, however, is prove that it is possible to cure HIV, a complex virus that can be suppressed to undetectable levels with potent medication but remains notoriously difficult to eliminate, experts have said.

“Although a transplant is not an option for more people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” Sharon Lewin, MBBS, PhD, president-elect of the International AIDS Society and director of The Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, said during an earlier press briefing. Lewis was not involved in the case.

Before his transplant, the “City of Hope” patient had sustained an undetectable viral load on ART since the 1990s, according to Dickter and colleagues. He had HIV the longest of any of the four patients who have achieved long-term HIV remission via stem cell transplant.

He also received the least immunosuppressive regimen of any of them before his transplant. The regimen was designed for older and less-fit patients “to make transplantation more tolerable for them,” Dickter said.

“This patient’s outcome and the results of this research are profound,” Dickter said. “Because this patient was older, lived the longest with HIV prior to transplant and received the least immunosuppressive therapy compared to the previous patients who had achieved remission from HIV after stem cell transplantation, we now have evidence that some HIV patients with blood cancers may not need fully intensive immunosuppressive therapy prior to transplant in order to put them into remission.”

The man continued taking an ART regimen of emtricitabine, tenofovir alafenamide and dolutegravir for more than 2 years after his transplant, stopping in March 2021 after he was vaccinated against COVID-19.

References:

Dickter J, et al. Abstract 12508. Presented at: International AIDS Conference; July 27-Aug. 2, 2022; Montreal (hybrid meeting).

Patient achieves HIV and blood cancer remission three decades after HIV diagnosis through stem cell transplant at City of Hope. https://www.cityofhope.org/patient-achieves-hiv-and-blood-cancer-remission-three-decades-after-hiv-diagnosis-through-stem-cell. Published July 27, 2022. Accessed July 27, 2022.

Perspective

Paul A. Volberding, MD)

Paul A. Volberding, MD

There have now been several cases of long-term HIV control following aggressive treatment of cancer diagnosed after HIV was suppressed by ART. Although the inability to detect HIV in these cases doesn’t prove that the infection has been truly cured, the longer these remissions are followed, the more likely a true sterilizing eradication or cure has been affected. Each of these cases is important, and we continue to hope that by studying them as a group, we might discover unifying evidence that enables us to find ways to the same end in larger numbers of cases without the toxicity and risk for mortality associated with cancer therapy and stem cell transplantation. The current case extends these previous reports and again used marrow donation from an individual carrying the delta CCR5-delta 32 mutation, which confers HIV infection resistance. We look forward to longer term follow-up of this case and of others that we hope to see over time. HIV cure remains a tremendous goal of a large and dedicated research community.

Paul A. Volberding, MD

Chief Medical Editor, Infectious Disease News

Professor emeritus of medicine

University of California, San Francisco

US woman is third person to achieve sustained HIV remission after stem cell transplant

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A middle-aged woman from the United States is the third person — and first woman — to achieve sustained treatment-free HIV remission after undergoing a stem cell transplant, researchers announced Tuesday.

The unnamed woman of mixed race developed high-risk acute myeloid leukemia (AML) in 2017 — 4 years after being diagnosed with HIV — and received a haplo-cord stem cell transplant from a donor with a rare genetic mutation called CCR5-delta 32, the researchers reported at the virtual Conference on Retroviruses and Opportunistic Infections (CROI).

Bryson Y, et al. LB 65. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 12-16, 2022 (virtual meeting).
Bryson Y, et al. LB 65. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 12-16, 2022 (virtual meeting).

She ceased ART for HIV 37 months after receiving the transplant and has remained in HIV remission for 14 months, according to the researchers. Her leukemia is also in remission.

“This provides hope of cord blood cells or haplo cord [cells] to achieve HIV remission for individuals requiring transplantation,” Yvonne J. Bryson, MD, chief of pediatric infectious diseases at the David Geffen School of Medicine at the University of California, Los Angeles, said after presenting the findings at the conference.

The woman joined a short list of people who have potentially been cured of HIV after receiving stem cells from someone with the CCR5-delta 32 mutation, which creates natural resistance by preventing HIV from entering human cells.

“This is a natural mutation, but it’s rare,” occurring in less than 1% of people, Bryson said.

She said donated bone marrow is not routinely screened for the mutation, which is most common among northern Europeans and Caucasians.

The first two people who achieved long-term remission following a similar procedure were initially known as the “Berlin patient” and the “London patient.” Both of their cases were also presented at CROI.

According to NBC News, the woman is being called the “New York patient” because she was treated at New York-Presbyterian Weill Cornell Medical Center. A spokesman for CROI said he believes the name will stick.

The “Berlin patient” was later identified as Timothy Ray Brown, who died in 2020 following a recurrence of leukemia. After undergoing a bone marrow transplant in 2007, Brown remained free of detectable HIV without treatment for more than a decade before his death.

The “London patient” later identified himself as Adam Castillejo and was reported in 2020 to have been in HIV remission for 30 months after undergoing allogeneic hematopoietic stem cell transplantation for Hodgkin’s lymphoma.

Bryson said that the success of a third patient provides additional proof that HIV reservoirs can be cleared sufficiently for remission or cure in the setting of resistant target cells.

PERSPECTIVE

Paul A, Volberding

There is a limited amount we can learn from a single case that might help us understand any causes responsible for the outcome, but as we have additional cases, we might hope to find underlying conditions that are associated with remission. As we learn more, we might hope to find opportunities to predict this outcome or even design treatments to increase this possibility. Each case, then, is very interesting and potentially important.

Paul A. Volberding, MD

Chief Medical Editor, Infectious Disease News

Professor emeritus of medicine

University of California, San Francisco

Study shows stem cell transplant is better than drug therapy for scleroderma

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https://speciality.medicaldialogues.in/study-shows-stem-cell-transplant-is-better-than-drug-therapy-for-scleroderma/

THE BERLIN PATIENT, FIRST AND ONLY PERSON ‘CURED’ OF HIV, SPEAKS OUT

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Timothy Ray Brown, long known only as the “Berlin Patient” had HIV for 12 years before he became the first person in the world to be cured of the infection following a stem cell transplant in 2007. He recalls his many years of illness, a series of difficult decisions, and his long road to recovery in the first-person account, “I Am the Berlin Patient: A Personal Reflection,” published in AIDS Research and Human Retroviruses, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is part of a special issue on HIV Cure Research and is available free on the AIDS Research and Human Retroviruses website.

Brown’s Commentary describes the bold experiment of using a stem cell donor who was naturally resistant to HIV infection to treat the acute myeloid leukemia (AML) diagnosed 10 years after he became HIV-positive. The stem cell donor had a specific genetic mutation called CCR5 Delta 32 that can protect a person against HIV infection. The virus is not able to enter its target, the CD4 cells. After the stem cell transplant, Brown was able to stop all antiretroviral treatment and the HIV has not returned.

“This is the first time that we get to read this important story written by the man who lived it,” says Thomas Hope, PhD, Editor-in-Chief of AIDS Research and Human Retroviruses and Professor of Cell and Molecular Biology at Northwestern University, Feinberg School of Medicine, Chicago, IL. “It is a unique opportunity to share in the human side of this transformative experience.”

Nobel in action: Japanese woman undergoes revolutionary stem cell transplant .

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AFP Photo / Anne-Christine Poujoulat

A breakthrough stem cell transplant has been carried out in Japan for a woman suffering from an incurable eye illness. Japanese doctors say it’s the first-ever operation when adult cells were used to repair the damaged organ.

The two-hour surgery was completely successful, Japan’s Nikkei newspaper reported. It came seven years after the Kyoto University professor Shinya Yamanaka created induced pluripotent stem cells (iPS) – multifunctional stem cells that can be generated directly from adult tissues. The research later won him the 2012 Nobel Prize.

In this case, the cells were made from the patient’s skin, which prevents controversy over the use of embryos.

AFP Photo / Anne-Christine Poujoulat

The patient is in her 70s and suffered from age-related macular degeneration, a disease when blood vessels crowd the retina, entailing visual impairment and blindness.

The surgery took place at the Institute for Biomedical Research and Innovation Hospital in Kobe, and was carried out by Yasuo Kurimoto, the hospital’s head of ophthalmology, and Masayo Takahashi, the head of retinal regeneration projects at the Riken Center for Developmental Biology.

The patient is now reportedly in stable condition, according to the hospital, and is set to be discharged next week.

Due to the fact that so many vision cells died, the doctors don’t expect a major improvement in her eyesight – and if there is any, it’ll take a couple of years to show. However, the surgery could slow down the spread of the disease.

The possible side effect that concerns the scientists is that the implanted cells could become cancerous, so the primary goal of the operation was to prove that stem cells aren’t dangerous.

“We will have succeeded if cancer does not develop after a year,” Yasuo Kurimoto said.