Less than a decade ago, when children with cancer arrived at the Angkor Hospital for Children (AHC) in Siem Reap in northwest Cambodia, the only treatment available to them was palliative care. Now, thanks to the determination and dedication of Cambodian physicians, along with assistance from Health Volunteers Overseas (HVO), a U.S.-based nonprofit dedicated to improving the availability and quality of health care in resource-scarce areas, receiving a malignant diagnosis at AHC is no longer an automatic death sentence.
"This evolution was based on the tenacity and bravery of the physicians at AHC who wanted to go from basically having a survival rate of 0% for any type of pediatric cancer because the patients weren't treated, to being able to treat more than half of the cases that come to them," Leslie S. Kean, MD, PhD, the Robert A. Stranahan Professor of Pediatrics at Harvard Medical School, Director of the Stem Cell Transplant Center at Boston Children's Hospital, and chair of the HVO Hematology Steering Committee, told ASH Clinical News.
Arriving at the point where Cambodian physicians had the training, resources, and support to treat patients with leukemia, other malignancies, and benign hematologic conditions has been a gradual process that required an innovative and continued partnership between physicians nearly half a world apart.
Dr. Kean is one of many hematologists who volunteer to provide educational support to staff at AHC and other institutions in Cambodia, Peru, and Tanzania as part of a collaboration between HVO and the American Society of Hematology (ASH). Through the program, ASH member volunteers commit to visiting a site for at least 2 weeks, working toward goals set collaboratively by the volunteers and the on-site physicians.
The collaboration has led to "huge steps forward" in blood disorder diagnosis and treatment in Cambodia, according to Ben Watkins, MD, Assistant Professor of Pediatrics at Emory University School of Medicine and a pediatric hematologist/oncologist at the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta. Dr. Watkins has volunteered with HVO since 2015 and now serves as the project director of its newest hematology site at Calmette Hospital at the National Cancer Center in Phnom Penh.
ASH Clinical News spoke with Drs. Watkins and Kean, as well as other ASH members volunteering with HVO's hematology program, about their experiences working with local health care workers and institutions in Cambodia to overcome barriers and improve outcomes for patients.
Overcoming Horrors of the Past
Cambodia is making great strides in providing health care for its citizens, which required surmounting numerous obstacles. More than 4 decades ago, an estimated 1.7 million Cambodians were killed in a mass genocide carried out by the Khmer Rouge regime under dictator Pol Pot. Political leaders systematically targeted the country's educated – wiping out an entire generation of doctors, teachers, musicians, and intellectuals. The devastating effects of this massacre are still being felt in the country.
"When I started going to [Siem Reap], there was nobody older than 30 in that hospital because much of the older generation of physicians had been killed," Dr. Kean said, who made her first trip to Cambodia as a volunteer with the HVO hematology program in 2009. Cambodia's new physicians, then, could not rely on the knowledge and expertise of their predecessors. Instead, the country's health-care system has been tasked with rebuilding a new pool of talented physicians.
For many years, hospitals in Cambodia also lacked the resources and expertise to treat childhood cancer. Because of this lack of expertise, ASH volunteers focus on offering educational and technological support, according to Katherine Tarlock, MD, Assistant Professor at the Center for Clinical and Translational Research at Seattle Children's Hospital. In addition to serving as a volunteer for the HVO program, Dr. Tarlock is a member of the HVO Hematology Steering Committee. "We have calls once a week with [the AHC staff]. We email every single day, going back and forth to help clinicians make treatment decisions," she explained. "They have no doctor whom they can turn to and ask, ‘Should I start this antibiotic?' or ‘Should I do the bone marrow biopsy today?'"
Physicians in the country also do not have formal in-country fellowship programs. "They finish the equivalent of pediatric residency, and the concept of training in a subspecialty just doesn't exist," she added.
Answering the Call
HVO has been helping low-resource countries across the globe build health worker capacity since its founding in 1986, according to April Pinner, MSPH, RD, HVO's Director of Program Design and Evaluation.
Ms. Pinner said volunteers with varying backgrounds in health care have been traveling to AHC since 2000 to help educate local clinicians across several specialties, including hematology, oncology, nursing, general pediatrics, and anesthesia. Hematology volunteers are encouraged to volunteer for both the AHC and Calmette sites in Cambodia. (Note: As of press time, HVO has suspended its volunteer placements until August 31 due to the COVID-19 pandemic. Visit the HVO website for more information.)
"HVO recruits highly skilled volunteers to provide teaching and training to local health workers, transferring knowledge and skills, which then remain in country to benefit the local patient population long after a volunteer's return home," Ms. Pinner explained.
The hematology project was launched at AHC in Siem Reap in 2008. In the 12 years since, 18 volunteers have gone to the country, completing a total of 38 assignments. A second hematology project in Phnom Penh was launched in 2019 and has already had 6 volunteers' complete 6 assignments, she added.
Establishing an Oncology Program
Dr. Kean was the second ASH volunteer to visit the country in 2009. At the time, she said, AHC had strict curricula it used for all their young doctors – the equivalent of residents in the U.S. medical training system. She was planning simply to go and teach some of the curriculum.
Just days before she was set to leave for Cambodia, a local physician mentioned that the hospital was hoping to start treating patients with leukemia as well. Dr. Kean, a bone marrow transplant specialist, consulted her colleagues specializing in leukemia before she embarked on the trip, and, although she had received helpful advice, she knew that building the capacity to treat leukemia in the country would need to be a long-term project that would take years of effort and coordination.
HVO hematology volunteers set out to help AHC reach this goal, but, because of the complex treatment regimens for treating leukemia, they initially focused on another area of pediatric oncology: retinoblastoma.
"Retinoblastoma was what we thought of as the ‘lowest-hanging fruit,'" Dr. Watkins said. "We'd seen a number of cases there and were fortunate to have an ophthalmologist who was willing to volunteer and educate the surgical staff on how to perform the surgeries."
Volunteers also worked to develop a chemotherapy regimen to help improve survival rates for these patients. Initially, retinoblastoma was the only cancer treated, but by 2016 and 2017, the oncology program at AHC had also started treating a few other solid tumors, such as Wilms and yolk sac tumors, as well as chronic myeloid leukemia, according to a 2017 report published in Blood Advances detailing the hospital's efforts to establish a pediatric oncology program in collaboration with HVO.
ASH members who have visited Cambodia say it is difficult to know the exact prevalence of hematologic and other disorders in the country because, for many years, patients weren't being treated and data on the prevalence of various conditions weren't being gathered.
However, as the volunteer team began their work, researchers were able to collect data on the most prevalent types of cancer seen at AHC. In 2016, for example, the hospital saw 23 retinoblastoma cases, 20 leukemia, 2 lymphoma, 1 neuroblastoma, 2 Wilms tumors, and 11 "other" cancers. Over the years, the ASH volunteers observed that acute leukemia was the most common cancer seen in Cambodian children, as in other countries. "But the treatments for acute leukemia are much more intense [than the first cancer treatments being delivered at AHC], and, according to U.S. protocols, can extend to 2.5 to 3 years for acute lymphocytic leukemia (ALL)," Dr. Watkins said. "We weren't prepared to treat those patients yet because we didn't have the supportive care that was really needed."
Facing Challenges Unique to Cambodia
In addition to the lack of supportive care, AHC was facing other unique challenges. For example, the hospital's oncology program launched with just one oncology fellow and one oncology nurse.
Cambodia struggles with limited resources and a lack of diagnostic capabilities to treat hematologic conditions. According to Dr. Tarlock, there often are not enough platelets to administer platelet transfusions and obtaining chemotherapy drugs at an affordable cost remains a challenge.
Diagnosing hematologic malignancies remains difficult, as the hospital does not have access to flow cytometry. To overcome that limitation, HVO established a partnership with a Seattle-based lab that agreed to provide free flow cytometry services for Cambodian patients suspected of having leukemia.
"It's great that we can now reach accurate leukemia diagnoses and see responses to therapy, but it's all been out of country," Dr. Tarlock said. "All the bone marrow biopsies and other biopsies are sent to partner labs in the U.S. where HVO volunteers are based."
Through the collaborative effort between local physicians and HVO volunteers – who participate in weekly conference calls and regularly travel to Cambodia – AHC was able to overcome those challenges and treat its first patient with ALL in 2018.
The treatment regimen for patients with ALL living in Cambodia is much different than that in the U.S., where clinicians rely on multiple treatment protocols based on an individual's risk and cytogenetic makeup and have easy access to a variety of chemotherapy drugs.
Dr. Watkins explained that the Cambodian physicians and HVO team have to develop more low-cost treatment options. The clinicians looked back at what treatments had worked in the U.S. before the introduction of more targeted – and more expensive – drugs.
In addition to treating patients with hematologic malignancies, the hospital also sees patients with thalassemia, immune thrombocytopenic purpura, hemoglobin E disease, and various forms of anemia.
Navigating a "Typical" Day
For an HVO volunteer, an average day on site at AHC often begins much like a shift at any hospital, starting with early morning rounds in the intensive care unit (ICU). Volunteers offer bedside training and one-on-one case reviews, and also identify any new hematologic patients who were admitted overnight.
"For patients who are on active treatment, we discuss their chemotherapy regimen, when their chemotherapy is due, or if the next dose has to be modified," Dr. Tarlock explained. "If a patient has gotten sick from chemotherapy, we talk about that, as well as any complicated infections and management. Often there are a few patients who don't have a diagnosis or just received a diagnosis, so we may work on setting up a treatment plan for them."
After rounding in the ICU, physicians typically go to the inpatient department to review cases, look through charts, and make sure there aren't any hematologic concerns that have not been previously identified.
In the afternoons, volunteers have more opportunities to conduct teaching rounds, where hematologists discuss specific cases or review overall care strategies with the Cambodia team.
"We are working on several initiatives with the AHC staff now, such as writing up our experiences with treating retinoblastoma or establishing treatment protocols," Dr. Kean said. "Much of what we've been doing lately is talking with nurses and working with the pharmacists to make sure they understand the safety parameters for chemotherapy."
Dr. Tarlock added that typical education topics are centered on transfusions, coagulation, or how to approach a bleeding patient. Volunteers also have been working with the team in Cambodia on quality-improvement initiatives and establishing a database to track patient outcomes over time. There is no one "regimented day," according to Dr. Kean, and volunteers need to be flexible and work with staff on-site to identify the how they can
make the most meaningful impact.
Envisioning a Promising Future
Following the success of the partnership at AHC, HVO opened the new previously mentioned partnership site at the Calmette Hospital in Phnom Penh in 2019, which offers volunteer opportunities for both pediatric and adult hematology.
The new facility has been designated as the country's National Cancer Center and is equipped with more resources than AHC. However, Dr. Watkins emphasized that staff will still need to be trained on how to use the equipment and developing standardized therapy regimens.
The ultimate goal is to form a national Cambodian oncology group, where the hospitals can work together to create standardized treatment protocols and provide support to one another, Dr. Watkins said. Volunteers with the program are asked to commit to visiting Cambodia for at least one 2-week period, but the experience has been so rewarding that many volunteers have chosen to make regular trips to the country to help accelerate progress.
"Working with the teams at Calmette and AHC, I can see how important volunteers are to that system," Dr. Watkins said. "As a volunteer clinician, your direct involvement leads to improved treatment of these patients, who otherwise had no prospect of a cure. It's extremely rewarding." —By Jill Sederstrom
