Dr. Guillermo J. Ruiz-Argüelles (second from left) started the outpatient
HCT program at Clínica Ruiz. Three other members of the Ruiz-Delgado
family work for the clinic: Dr. Guillermo J. Ruiz-Delgado (left); Rodrigo J.
Ruiz-Delgado, MBA; and Manuel A. Ruiz-Delgado, MBA.
The U.S. is starting to see a shift in the treatment of hematologic malignancies to outpatient or even home-based settings, but one program in Mexico has been embracing this philosophy for decades.1
Mexico’s Clínica Ruiz has been a pioneer in outpatient hematopoietic cell transplantation (HCT) for 30 years, performing its first autologous HCT (AHCT) back in 1993. It began as a way to perform HCT in Mexico, a country that, like many other low- and middle-income countries (LMICs), lacked the hospital resources that high-income countries enjoy, but along the way, Clínica Ruiz found that outpatient HCT also reduced costs and improved patient outcomes.
According to Clínica Ruiz’s transplant coordinator, Juan Carlos Olivares-Gazca, MD, MPH, the clinic has treated 1,925 patients since the program began. While the majority were AHCTs (1,669 patients), the clinic has also performed allogeneic HCTs (alloHCT) for 256 patients.
“Today, Clínica Ruiz is the biggest HCT program in Mexico,” he said.
Establishing an Outpatient HCT Program
The outpatient HCT program got its start after Guillermo J. Ruiz-Argüelles, MD, MACP, the general director at Clínica Ruiz’s Centro de Hematología y Medicina Interna de Puebla, completed a post-doctoral research fellowship at Mayo Clinic and returned to Mexico to share what he had learned. He knew that hospitals in Mexico lacked units with laminar airflow, positive pressure, or high-efficiency filters needed to carry out an in-hospital program. Given that hospital stays are also typically about a month long, he knew the costs would be too high for the population to endure.
“When I came back, I decided to start a totally different way of grafting patients,” he said.
Dr. Ruiz-Argüelles created an outpatient HCT program in 1993 that relied on using peripheral blood-derived non-frozen hematopoietic cells to significantly reduce costs and make it a more feasible option for LMICs.
The facility began by performing AHCT in patients with multiple myeloma (MM).
Three years later, they developed an outpatient alloHCT program using reduced-intensity conditioning, offering a solution for those who may otherwise not have received HCT treatment.
Over the years, Clínica Ruiz has continued to expand the conditions they treat with HCT.
Today, Clínica Ruiz operates two facilities – one in Puebla and the other in Monterrey – and performs HCT in patients with acute leukemias, chronic leukemias, bone marrow hypoplasias, lymphomas, MM, inherited anemias, myelofibrosis, myelodysplasias, paroxysmal nocturnal hemoglobinuria, multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy, and myasthenia gravis.
Changing Industry Perceptions
According to Dr. Ruiz-Argüelles, the biggest challenge Clínica Ruiz faced while establishing the program was changing industry perceptions.
“One of the major challenges was to convince the scientific community that our method of doing bone marrow transplants on an outpatient basis was sensible and could be done,” he said.
To demonstrate the value of both their outpatient program and the efficacy of non-frozen hematopoietic cells, doctors at Clínica Ruiz began publishing their results, attending conferences, and sharing what they learned with others.
“Since we started doing [hematopoietic] cell transplants, we have made 165 papers,” Dr. Ruiz-Argüelles said.
Reducing Costs and Improving Outcomes
According to Dr. Ruiz-Argüelles’s son, Manuel Ruiz-Delgado, MBA, who serves as the financial director at Clínica Ruiz, an advantage of their outpatient program is often a reduction in costs.
“HCT can range between $30,000 and $100,000,” Mr. Ruiz-Delgado said. “Outpatient conduction of HCT can decrease the costs, but it depends on the country where the treatment is performed.”
In 2022, Dr. Ruiz-Argüelles and colleagues reported in Therapeutic Advances in Hematology that AHCT programs in high-income countries can have median costs ranging anywhere from $100,000 to $150,000.2 In addition, the cost associated with outpatient allografting in high-income countries can range anywhere from $150,000 to $400,000.
“Regarding autologous transplantation, we have shown that the costs of the procedure are reduced when done in the outpatient [setting] compared with in-hospital autografting,” Dr. Ruiz-Argüelles wrote in an article in The Lancet Haematology about lessons learned over the three decades of the program.3 “For allogeneic transplantation, we have shown that the long-term overall survival and the prevalence and severity of graft-versus-host disease (GVHD) are improved in those patients allografted outside the hospital compared with inpatients.”
In 2011, Dr. Ruiz-Argüelles and his colleagues reported in Blood that the incidence of GVHD after peripheral HCT (PHCT) appeared to decrease after non-myeloablative conditioning was used.4 Of the 304 patients with hematologic and non-hematologic malignancies who underwent outpatient PHCT during a 20-year period, 80% were successfully engrafted. A total of 154, or 64%, developed acute or chronic GVHD.
Dr. Ruiz-Argüelles theorized in The Lancet article that the reduced prevalence and severity of GVHD his team has seen in alloHCTs could be the result of the outpatient setting, which has a “lower prevalence of C. difficile infections.”3
“Although it is now clear that reduced-intensity conditioning is not the best choice in all settings, it seems to be the best option with which to start a (bone marrow transplant) programme because of its cost-effectiveness compared with conventional myeloablative conditioning, a point that is crucial to programmes organised in underprivileged settings,” he wrote.
Their outpatient program has also seen low hospitalization rates. Only about 4% of Clínica Ruiz’s patients who receive AHCT need to be hospitalized during the program, according to Dr. Ruiz-Argüelles, while the remaining 96% are fully outpatient. That percentage increases to 20% to 30% for alloHCT patients, primarily for those who receive haploidentical HCT, he said.
Although the HCT program at Clínica Ruiz began with patients with MM, today patients with MS make up the largest percentage of those treated.
Dr. Ruiz-Argüelles said the program to treat patients with MS on an outpatient basis ramped up in 2015. To date, they have grafted 1,518 patients with MS from all over the world, with many coming from the U.S. and the U.K.
“Patients do not go to the hospital unless they have a complication, and the complications are mainly fever, neutropenia, or some other complication, but that happens in our experience in less than 3% of cases,” he said.
The clinic has seen strong efficacy in outpatient HCT for those with MS, using peripheral blood-derived non-frozen hematopoietic cells and employing a non-myeloablative regimen.
“The outcomes are really good, about 75% to 80% of the patients respond to transplant, so that is really high compared to the 50% that has been reported with some of the other drugs for MS,” Dr. Olivares-Gazca said.
In one study of 286 patients with MS who received AHCT, only eight had to be sent to the hospital.5 Researchers also reported that patients recovered granulocyte and platelet counts within eight days after transplant. At 128 months, there was an overall survival rate of 100%.
Mr. Ruiz-Delgado credits the low hospitalization rate Clínica Ruiz typically observes to their decades of experience.
“I don’t think there is another center that has this experience,” he said. “We have treated many, many patients, we have been modifying or making small changes, and now we are experts at what patients need.”
Dr. Juan Carlos Olivares-Gazca (left); Dr. Guillermo J. Ruiz-Argüelles;
and Manuel A. Ruiz-Delgado, MBA, have worked together to establish
the biggest HCT program in Mexico.
Outpatient Program Requirements
To be included in Clínica Ruiz’s outpatient program, Dr. Ruiz-Argüelles said that patients need to have a sociocultural level “adequate to follow instructions,” have a caregiver who can be with them for the whole treatment, and agree to stay safely in a nearby location. If they don’t have those aspects in place, Clínica Ruiz can help.
“All of these barriers can be solved with a facility like ours, the Center for Outpatient Residents, where the patient can get a caregiver and be closely monitored,” Dr. Ruiz-Argüelles said.
For example, at the Puebla location, Clínica Ruiz has an apartment building especially designed for patients, complete with security, regular cleaning services, food, an on-site translator, and accessibility features built into the design.6 A similar facility is available in Monterrey.
Sharing the Knowledge
From the beginning, a central goal for Dr. Ruiz-Argüelles has been sharing what he’s learned with others, and he continues to do that today.
Dr. Ruiz-Argüelles laid out his recommendations for other LMICs to begin their own HCT programs in The Lancet Haematology in 2020.3
Much like his own start, he recommended that other LMICs begin their programs with autologous transplants for patients with MM using non-frozen hematopoietic cells. This strategy eliminates the need for costly cell-freezing capabilities.
“You can start autografting patients with multiple myeloma, lymphoma, or other haematological malignancies by using preparative regimens that do not require freezing the HSCs [hematopoietic stem cells],” he wrote. “The use of short preparative regimens for autologous HCT, such as high dose melphalan for patients with multiple myeloma, allows keeping HSCs in conventional blood banks at 4°C for up to seven days.”
Dr. Ruiz-Argüelles also recommended establishing the bone marrow transplantation program as an outpatient program to reduce costs and improve safety. After a center gains experience with hematologic malignancies, they can add autoimmune conditions, he said.
The advantage to autoimmune conditions is that they are “not at risk of GVHD, viral reactivation, or cytokine release syndrome.”
After achieving successful autologous transplantation, Dr. Ruiz-Argüelles believes that LMICs can then consider performing alloHCT using reduced-intensity conditioning treatments.
He noted that tissue culture facilities are not needed to start a program in LMICs. Instead, he suggested reserving resources for more essential aspects of a transplantation program, such as laboratory support, apheresis, and antibiotics and antifungals.
Dr. Ruiz-Argüelles also doesn’t believe blood product irradiation devices are necessary and said his clinic has found there is similar GVHD prevalence for patients who use irradiated blood products compared to those who use leukocyte-depleted products.
He also cautioned against starting a cord bank, noting that they could be unreliable in LMICs. Clínica Ruiz did several cord blood transplantations using domestic cord blood but found the cells were of poor quality and delivered poor outcomes. Importing the cord blood cells from high-income countries could yield better results, but it comes with a significant cost.
Because of the significant cost, Dr. Ruiz-Argüelles also advised against importing matched unrelated donor hemopoietic cells.
In a final effort to keep costs low, Dr. Ruiz-Argüelles recommended using generic drugs and biosimilars. For instance, in Mexico a vial of filgrastim is $300, whereas the biosimilar is $80 and has shown similar effectiveness, he noted in The Lancet article.
One of the biggest challenges to the program was getting the scientific community to embrace Clínica Ruiz’s ideas, but that’s no longer a struggle thanks to their long history and published results.
In a full-circle moment of sorts, Dr. Ruiz-Argüelles was given a distinguished alumni award from Mayo Clinic for his “tireless search to develop technologies that reduce the cost of health care delivery to underserved populations.”
He also received a lifetime achievement award from former Mexico President Felipe Calderón.
Perhaps even more notable, clinicians in other LMICs are already employing Clínica Ruiz’s strategies in their own institutions, making HCT a possibility for more patients worldwide.
“Our method of doing transplants without freezing the cells has been reproduced in Colombia, Venezuela, Argentina, even in Ecuador, and also in Chile,” Dr. Ruiz-Argüelles said. “It has been shown that it can be reproduced.”
As for Clínica Ruiz’s future, Mr. Ruiz-Delgado said they are “always looking for new things” and new treatment options.
Whatever they learn, Dr. Ruiz-Argüelles said an important aspect of their program is to share the knowledge with others so LMICs all over the world can benefit. Their methods for AHCT and alloHCT have been registered with clinicaltrials.gov of the U.S. National Institutes of Health and are available to everyone.
“By publishing our results, we want the scientific community all over the world to test our methods and find out if they can reproduce our results,” he said.
- Lawrence L. Ding dong: the doctor will see you (at home) now. ASH Clinical News. June 2023. Accessed Aug. 1, 2023. https://ashpublications.org/ashclinicalnews/news/7096/ding-dong-the-doctor-will-see-you-at-home-now.
- Gómez-Almaguer D, Gómez-De León A, Colunga-Pedraza PR, et al. Outpatient allogeneic hematopoietic stem-cell transplantation: a review. Ther Adv Hematol. 2022;13. doi:10.1177/20406207221080739.
- Ruiz-Argüelles, GJ. Lessons learned starting a bone marrow transplantation programme in a resource-constrained setting. Lancet Haematol. 2020;7(7);E509-E510.
- Cantú-Rodríguez O, Flores-Jiménez JA, Gutiérrez-Aguirre CH, et al. Low incidence and severity of graft-versus-host disease after outpatient allogeneic peripheral blood stem cell transplantation employing a reduced-intensity conditioning. Eur J Haematol. 2011;87(6):521-530.
- Ruiz-Argüelles GJ, León-Peña AA, León-González M, et al. A feasibility study of the full outpatient conduction of hematopoietic transplants in persons with multiple sclerosis employing autologous non-cryopreserved peripheral blood stem cells. Acta Haematol. 2017;137(4):214-219.
- Clínica Ruiz. Accessed Aug. 1, 2023. https://hsctmexico.com/index.php?lng=eng.