Formulations against leukemia that do not work: study by the UIS

JEriling Arias Vargas, 24, still remembers when she desperately crossed the border between Colombia and Venezuela. She was carrying her son Moses in her arms. She had to take him to a medical center in Cúcuta.

It was August 2021, Jeriling and Moisés were on vacation at the home of their mother and grandmother Sandra Milena Vargas, in San Cristóbal in the state of Táchira, 40 kilometers from the Colombian border. They had traveled from Bogotá to spend a few weeks there with their family.

It was in those days that Jeriling began to notice that Moses was pale. He also had no strength in his legs when he tried to walk. “My little legs hurt, mommy, they hurt,” Jeriling recalls Moisés telling her during his stay in Venezuela. One more detail made her not hesitate to return to Colombia: she began to notice how Moisés’s hair tone was darkening, losing the blonde color that characterized him.

Jeriling went to a renowned hospital in Cúcuta. Moses was hospitalized for 20 days. The assessment response did not convince him: “The child is fine,” the woman recalls were the words with which they released him from the emergency department.

Rather than return to her mother’s house, Jeriling decided to stay with a relative in Cúcuta. She did not trust that initial medical report; If Moisés did not recover with the medicines he had been prescribed, she preferred to be close to the health center.

Four days later they returned with Moisés to the same hospital; The response this time, following the check-up and seven days of hospitalization, was different. “You must go to Bucaramanga to be examined, the child may have cancer.” That was the explanation that Jeriling heard before the new urgency that opened a new stage in their lives.

Not in vain, during 2021, Cúcuta was the city in the country with the longest waiting times for the care and diagnosis of children with cancer, according to the High Cost Account, with an average of 26 days.

At the end of September of that year, already in Bucaramanga, the opinion was forceful: Moisés had acute lymphoblastic leukemia, the most common type of childhood cancer in the world, and which in Colombia represents more than 30% of cancer cases in minors. old.

Moisés began a series of treatments that have kept him in Bucaramanga for more than 16 months. Jeriling does the math. Showing a smile, he notes that they have lived longer in the rooms of a clinic than in a house they rented north of the city.

One of the first drugs to appear in this cocktail of prescriptions was asparaginase, an essential drug for the treatment of this type of disease. However, the first few doses did not do Moisés any good.

“Her skin color changed, she trembled, vomited, she was very weak,” says Jeriling, explaining her reaction to the first brand of this medicine that her son was given. Later, they exchanged it for a higher quality one.

This initial situation may have an explanation in international and local investigations. The newspaper The country from Spain, in an article published last month, warns regarding the low quality of brands of the drug asparaginase and the danger that this situation entails at a global level.

That same report makes it clear that Colombia, in July 2022, was second on the list of importers of “low quality” asparaginase from India.

In the country, through a preclinical study carried out at the Industrial University of Santander, UIS, six researchers verified that three of the six brands of asparaginase used in the country are not completely effective.

A situation that requires attention

This information is important, not only for Moisés, but for many cancer patients: asparagine is one of the 20 essential amino acids for cells to divide; while asparaginase is the name by which the essential medicine is known to prevent cancer cells from multiplying in the body. This is how the researcher and university professor Arturo Gutiérrez, co-author of the preclinical study that required more than a year of joint work, explains it.

In the absence of asparagine, normal cells are capable of recycling and producing it, from similar components, therefore they can multiply; while cancer cells have “a deficiency in this process,” says Gutiérrez. That makes cancer cells unable to expand in the face of low levels of that amino acid.

How does asparaginase work? Professor Gutiérrez describes it as a “molecular scissors” that enters the body and reduces the amount of asparagine. Expected result? That normal cells survive by recycling other components and can multiply; while the cancerous ones cannot do so due to the lack of asparagine and, therefore, are destroyed.

The current problem? That half of the asparaginase formulations applied in the country are not so ‘sharp’ and do not reduce asparagine levels, at least that is what the aforementioned preclinical study showed. That is, three out of six formulations do not comply with what was promised.

“They are enzymes without control,” says Gutiérrez, a professor at the UIS School of Microbiology. “It’s not all formulations,” she clarifies.

“Without biosimilarity studies, these (low-quality) molecules have been admitted in the country,” he told Vanguard another of the co-authors of the investigation. In this sense, it is essential, according to the researchers consulted, that the National Institute for Food and Drug Surveillance, Invima, carry out a thorough review, as a health authority, of these drugs.

“Colombia is the second country in Latin America to have laboratories to measure asparagine levels,” says Diana Valencia, a pediatric hematologist-oncologist and member of the Colombian Association of Pediatric Hematology and Oncology, Achop, a non-profit scientific association. that works for the well-being of minors and their families who handle these cases.

This situation, says the oncologist Valencia, who is also the delegate for Colombia of the Latin American Society of Pediatric Oncology, should place the country in an advantageous situation to make effective decisions and verify that the asparaginase molecules that are marketed comply with the standards .

The evidence gathered by the UIS researchers is related to what was documented in Brazil, one of the first countries in which studies allowed to verify what some of the doctors in that country already suspected: the treatment was not being effective because various brands used low-quality molecules that, according to The countryflooded the market especially from low- and middle-income nations.

“Mechanisms for the entry of medicines into the country are not being efficient to corroborate what is entering. This affects the principle of equity because it is not only access to medicine, but also receiving the best medicine for a cure”, says the oncologist Valencia, who daily cares for children who face this disease.

“We can measure asparaginase levels and evaluate whether it is effective or not and, therefore, make a change in a timely manner; make the respective notification of non-effectiveness to the regulatory entity”, says one of the researchers who was in the process of reviewing the medical compounds in the laboratory, regarding the possibility of guaranteeing the expected quality of these drugs.

According to the World Health Organization, WHO, 80% of children diagnosed with cancer survive in high-income countries; while in lower and low income countries that hope of cure is barely 20%. For Colombia, according to the Ministry of Health, this survival rate was 61% in 2022.

a longed for sound

Moisés has continued with his chemotherapy treatment. He already finished his process with the asparaginase. Three days following finishing his radiotherapy, before the bone marrow transplant, Moisés had a relapse and that trip to Bogotá will have to wait, at least for a few days.

– I’m so bad? –Moses asks her mother when he sees her come out of the bathroom with red cheekbones.

“No, son,” Jeriling replies.

“Then why are you crying so much, mommy?” her son questions.

In the middle of these conversations, Jeriling and Moisés usually go to a song; a melody that reminds them, in her words, that they “heal little by little” and that “tomorrow everything will be more beautiful”.

Jeriling waits for Moises, smiling as usual, to ring the bell soon, signaling the end of his treatment. Maybe by then Jeriling will start telling Moses what the word ‘cancer’ means.

In 2022, 356 minors were reported who, like Moisés, were diagnosed with acute lymphoblastic leukemia in Colombia. This represents 38% of the cases of childhood cancer detected in the country during that period.

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