Blood Beyond Borders
remained high compared with those among children in
higher-income countries.
Treating pediatric ALL was not a priority when
limited resources might go further in treating patients
with simpler, more common diseases, Dr. Vasquez
explained.
Beginning With Twinning
After the mother’s appeal, St. Jude agreed to support
a program in El Salvador for one year. The group
conducted a site visit and developed a plan to deliver
high-quality treatment for pediatric ALL at the Benjamin
Bloom Hospital.
During this 12-month period, researchers and
clinicians from St. Jude communicated with doctors in
Benjamin Bloom’s new leukemia program, providing
guidance for patients’ individual treatment plans through
phone calls and emails. Blood and bone marrow samples
were sent to the U.S. for immunophenotyping and
classification.
The partnership also provided funding for an essential
component that was missing from Benjamin Bloom:
specialized staff. The hospital could not justify spending
more on one department at the expense of its others,
so St. Jude supplemented salaries for some physicians.
“Overall, our investment totaled $100,000, more or less,”
Dr. Ribeiro recalled. He noted that the hospital’s physi-
cians were eager to take on extra work and responsibility.
Along with the constant communication, St. Jude sent
members of the Salvadoran hospital staff to Mexico to
train in pediatric oncology and gave them opportunities
to visit St. Jude in Memphis for additional guidance on
specific techniques.
Next, the group set up a training program for staff
physicians and nurse specialists at Benjamin Bloom. 2
After the collaboration’s initial 12 months, securing
sustainable financing remained the biggest challenge. The
program was backed by St. Jude, but in the long term,
the country would have to find ways to rely on minimal
outside support.
“[After hearing about the new leukemia program],
people came to our center to be treated,” said Dr. Vasquez.
“We actually had not only families, but also churches and
communities bringing children in just to ensure that the
children would have the chance to be treated.”
Once the program gained the support of the
surrounding community, it became easier to show the
local government the importance of funding the care. The
program’s early success was “a very energizing thing for
the locals, and that spread to the government,” said Dr.
Ribeiro.
Now, El Salvador’s public health-care system covers
ALL treatment for all children. This support is crucial, Dr.
Vasquez explained, because, without it, most patients would
not be able to complete the multiple rounds of therapy.
In the subsequent years, the Benjamin Bloom
Hospital began performing immunophenotyping and
flow cytometry on site. The results are still shared with
doctors in Tennessee, but the Salvadoran team no longer
needs to send the samples to the U.S. via express mail.
The newly established infrastructure also helped
patients with cancers outside of ALL. “We could now
treat other pediatric cancers that are also curable with
chemotherapy,” said Dr. Ribeiro, including Hodgkin
and non-Hodgkin lymphoma.” The longstanding stigma
around a cancer diagnosis in childhood was reduced, as
residents had contact with more and more survivors.
Customizing Treatment Plans
The gains in survival are undeniable, but establishing
a team of specialists and increasing funding are only
46
ASH Clinical News
the first steps toward the goal of raising survival rates
in El Salvador to those in higher-income countries.
Researchers at St. Jude and in El Salvador have been
working together to identify other barriers to successful
treatment.
One study published in 2015 showed that, even
when treatment was provided at no cost to patients, 13
percent of families still neglected appointments. 6 To
address this issue, researchers from San Salvador and
Memphis designed a treatment-adherence tracking
system: Families were contacted any time a patient
missed an appointment and were interviewed about their
reasons for treatment abandonment and nonadherence. If
clinicians were unable to contact families of patients who
missed appointments but who had a good prognosis, they
turned to law enforcement to connect with the family.
The most common reasons for missing appointments
or stopping treatment were “financial needs,” “unforeseen
barriers,” and “domestic needs.” After identifying the
cause for treatment abandonment, clinicians worked with
families to develop plans or allocate aid to help patients
and families avoid these issues in the future.
After two years of diligent follow-up, the Benjamin
Bloom doctors substantially reduced treatment abandon-
ment, from 13 percent to 3 percent.
However, according to Dr. Ribeiro, the treatment itself
proved to be an obstacle, after it proved toxic to certain
patients. Even those who received timely and consistent
therapy were less likely to be cured than their higher-
income counterparts.
At the program’s launch in 1993, the St. Jude team
began using a relatively simple outpatient chemotherapy
protocol. The regimen had been well tolerated in the U.S.,
but the outreach team quickly noticed abnormally high
rates of adverse events in El Salvador. Seven of the first 25
patients treated in El Salvador died from toxicities. 2
“You have to adapt the treatment intensity to the
support and care capabilities of the local area,” Dr. Ribeiro
commented. “You can’t just go to a lower-income country
and say, ‘We’re going to do this very intensive chemo-
therapy.’ You will end up killing people.”
Through constant telecommunication with a doctor
in Memphis, clinicians at Benjamin Bloom altered the
protocol, in particular by eliminating the drug dauno-
mycin and its potentially fatal adverse effects.
Treatment-related mortality has been decreasing since
the 1990s in certain lower-income countries, Dr. Ribeiro
noted, but even in 2011, its prevalence remained greater
in lower-income Central American countries (ranging
from 11 to 21 percent) than in higher-income countries
(ranging from 1 to 3 percent). 7 To describe the incidence,
timing, and predictors of treatment-related mortality,
researchers followed patients in El Salvador, Guatemala,
and Honduras who were diagnosed with ALL between
2000 and 2008, when the St. Jude protocol had been
implemented in El Salvador.
They found that, while treatment-related mortality
decreased overall during the eight-year study period
(from 11.2% to 7.9%; p=0.02), it remained high during
certain therapeutic timepoints. Of all instances of
treatment-related mortality, the majority (59%) occurred
during induction and one-quarter during maintenance.
According to the authors, this “contrasts sharply with
the patterns observed in [high-income countries], where
treatment-related mortality in maintenance is considered
a rare event.”
of St. Jude board of directors: With an investment of
$100,000 – the same amount of money that it cost to treat
one child in the U.S. – the group treated more than 100
children in El Salvador.
“That is consistent with the hospital mission that no
child should die in the dawn of life – and it doesn’t say
‘in Memphis,’ or ‘in El Salvador,’ or in any place else,” he
said. Thus, the International Outreach Program expanded
beyond El Salvador. St Jude is now working with hospitals
in 17 low- and middle-income countries to improve
cancer treatment for children using a similar model.
A cost analysis in 2018 showed that the price of
running the pediatric oncology unit at Benjamin Bloom
in 2016 was $5.2 million, which included seeing an
average of 90 outpatients per day and covering 1,385
inpatient stays per year. 8 The El Salvador government
covered 52.5 percent of that cost and charitable donations
made up another 44.2 percent. The last 3.4 percent came
from social security contributions. The estimated cost to
add one year of healthy life was $1,624, which the authors
considered “under the threshold considered to be very
cost effective.”
The success of the El Salvador model has spawned
other global programs. In September 2018, St. Jude
announced a collaboration with the World Health
Organization (WHO), with a goal of curing at least 60
percent of children with six of the most common kinds of
cancer worldwide by 2030. 9
“I knew firsthand the situation in lower-income coun-
tries, and I just said, ‘Well, this is may be my contribution
to the field. It may not be discovering a new molecule or
a new treatment, but I can help translate that progress to
other countries,’” said Dr. Ribeiro, recounting his involve-
ment with the global outreach program.
But St. Jude and the WHO will have to be selective
about where they focus their life-saving efforts. Countries
must meet certain criteria for these kinds of programs
to be successful; treating childhood cancers can’t be a
priority everywhere.
Lower-income countries recovering from war or
natural disasters will not be able to use their limited
resources for long, complicated cancer treatments, Dr.
Ribeiro noted. Establishing “twinning programs” requires
investment “not only in international agencies’ efforts, but
also in the infrastructural development of the countries,”
he added. “At this point, there are things we can do, and
some things that we can’t.” —By Emma Yasinski ●
REFERENCES
1. National Cancer Institute. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–
Health Professional Version. Accessed March 29, 2019, from https://www.cancer.gov/types/
leukemia/hp/child-all-treatment-pdq.
2. Ribeiro RC, Bonilla M. A leukemia treatment programme in El Salvador. Lancet. 2000;356
Suppl;s7.
3. The New York Times. A promising step in tackling childhood cancer. Accessed March 29,
2019, from https://www.nytimes.com/2018/09/29/opinion/sunday/childhood-cancer.
html.
4. Keegan THM, Alvarez E, Li Q, et al. Inpatients costs of cancer treatment among children and
young adults with acute lymphoblastic leukemia (ALL) treated at specialized cancer centers
in California. Abstract #324. Presented at the 2018 ASH Annual Meeting, December 4, 2018;
San Diego, CA..
5. Gupta S, Rivera-Luna R, Ribeiro RC, Howard SC. Pediatric oncology as the next global child
health priority: the need for national childhood cancer strategies in low- and middle-income
countries. PLOS Medicine. 2014;11:e1001656.
6. Salaverria C, Rossell N, Hernandez A., et al. Interventions targeting absences increase
adherence and reduce abandonment of childhood cancer treatment in El Salvador. Pediatr
Blood Cancer. 2015;62,1609-15.
7. Gupta S, Antillon FA, Bonilla M, et al. Treatment‐related mortality in children with acute
lymphoblastic leukemia in Central America. Cancer. 2011;117:4788-95.
8. Fuentes-Alabi S, Bhakta N, Vasquez RF, et al. The cost and cost-effectiveness of childhood
cancer treatment in El Salvador, Central America: a report from the Childhood Cancer 2030
Network. Cancer. 2018;124:391-7.
9. St. Jude Children’s Research Hospital. Collaborating to cure. Accessed March 29, 2019, from
https://www.stjude.org/global/collaborating-to-cure.html.
Expanding Borders
As Dr. Ribeiro calls it, the “true test” of the international
collaboration came when the doctors presented the
results of the program’s first few years to the members
May 2019