The cost of hematopoietic stem cell transplantation in the real world

Abstract

In Brazil, the majority of the population does not have private health insurance and the government provides universal health care. Our ‘Unique Healthcare System’ pays for 95% of the 1500 hematopoietic stem cell transplants (HSCT) performed in the country every year. Hospitals are reimbursed a flat rate, ranging from US$13 000 for autologous to US$40 500 for unrelated donor transplants, excluding expenses with donor search and acquisition of the graft. The actual cost of the procedure is not captured routinely. Because unrelated donor recipients may have many clinical complications, most HSCT centers offer few or no beds to perform such transplants. The Pediatric Oncology Institute — GRAACC — is a non-profit organization that provides comprehensive care at no cost to the families, including unrelated donor HSCT. We are evaluating retrospectively the unrelated donor transplant costs to have data to present to the health authorities, looking for an appropriate funding formula for HSCT.

Keywords:

• Hematopoietic stem cell transplantation
• Costs
• Unrelated donors
• Pediatrics

Socio-economic Overview of Brazil

Brazil has 191 million inhabitants according to the 2010 census1 and almost 10% of the national population lives in the metropolitan area of Sao Paulo City.2 One-third of the Brazilian population is younger than 19 years of age1 and cancer has emerged in recent years as one of the most important causes of death.3 The country’s economy continues to improve despite the global crisis. The minimum wage in Brazil is US$311/month4 (US$1 = 1·75 Reais/BRL5) and most families’ monthly income ranges from 1–3 minimum wages per month (i.e. up to about US$1000/month). All children have at least the first 2 years of basic education but many adults cannot read fluently.

Basic Health Care Provisions

Every Brazilian has the right to have basic health care provided by the government in primary care facilities (Unidade Básica de Saúde) and in public hospitals under the ‘Unique Healthcare System’ (Sistema Único de Saúde). The public university hospitals are paid a fixed monthly amount (Orçamentação) based on the range of services and number of patients that were seen in the early 2000s. However, despite the higher number of patients that are seen nowadays, this amount has not been adjusted for many years. The public hospitals struggle to deliver good health care due to these financial constraints.

The Brazilian states have a public program to help the patients to travel when the appropriate health care is not available in their hometown (‘Out of Hometown Treatment’ Program). This program pays for transportation (airline or bus fare for the child and one parent), and a fixed small amount per day while the child is an outpatient. Should the patient die, this program also helps with the costs of transporting the body back home.

The Evolution of GRAACC

At the Federal University of Sao Paulo (Universidade Federal de São Paulo — Unifesp), pediatric oncology was part of the pediatric ward of the Sao Paulo University Hospital and had two dedicated beds. In 1991, the pediatric oncology professor, Dr Sergio Petrilli, other pediatric oncologists, volunteers, and parents of former patients founded the Support Group for Children and Adolescents with Cancer (Grupo de Apoio a Criança e ao Adolescente com Câncer — GRAACC) to improve the infrastructure for the University’s pediatric oncology program.

Over the years, GRAACC became more organized, increased fund raising and, in 1998, built the Pediatric Oncology Institute (Instituto de Oncologia Pediátrica), a non-profit organization that works as a product of the partnership between the University and GRAACC. Large companies helped to fund each of the 10 floors in the building. All professors are allowed to work at GRAACC as if they were at the main University Hospital, but all employees are paid by GRAACC. GRAACC also has a separate administration and independent finances.

GRAACC has grown to provide a comprehensive care program, including all diagnostic tests and imaging studies, nutrition, physical therapy, occupational therapy, psychology, ophthalmology, dentistry, and social work. Hospital teachers work in close contact with the patient’s school to bring to the hospital all lessons they should learn to help them succeed in school throughout treatment. None of these initiatives is paid by the public healthcare system. Altogether, the government pays about half of the hospital’s expenses. The other half comes from many fund raising events and, more importantly, from hundreds of small monthly donations.

Pediatric Oncology at the Pediatric Oncology Institute — GRAACC — Unifesp

Around 300 new patients are admitted every year. GRAACC is opened to any pediatric oncology patient, with or without insurance, and serves as a referral center for the treatment of pediatric brain tumors, retinoblastoma, and bone tumors. However, the hospital has only 23 beds for pediatric oncology; therefore, almost all patient care is delivered in the day-hospital (Quimioteca). There are specific nursing protocols, e.g. for administering chemotherapy in the outpatient setting with intravenous/oral hydration, urine alkalinization, and monitoring methotrexate levels, as well as administering antibiotics and blood products.

The patients must either live close to the hospital or stay in the Ronald McDonald House during chemotherapy or when they present with neutropenic fever, because most families do not have a car and would have to rely on very crowded public transportation.

Hard Realities

The majority of the patients seen at GRAACC have a monthly household income of less than US$900, a very low income by US standards.6 Household composition typically include parents and two to three children. On average, these Brazilian families spend 36% for accommodation (usually to pay rent), 20% for food, 20% for transportation, 7% for health care, 5% for clothing, and 3% for education.7 Treatment failure due to abandonment is very problematic in Brazil because the families cannot afford to live in Sao Paulo or in any other large city to have their children treated.

As one of its first initiatives, GRAACC rented a house for the children to stay in town with their mothers, including all meals, at no cost. Now, in partnership with the Ronald McDonald Institute, we can offer free housing, meals, and transportation for more than 30 children at the same time at a cost of US$400 000/year (R$695 428), an average of US$18/person (child plus one parent)/day. Because the families cannot afford most of the oral medications, if they are not given them through public programs, GRAACC also helps them with the cost of outpatient medications.

Hematopoietic Stem Cell Transplantation (HSCT)

In Brazil, around 1500 transplants are performed every year8 and 95% of them are paid for by the government,9 although with an unequal distribution; 4% of autologous and allogeneic related transplants are paid by private health insurance, compared to 15% of the transplants with unrelated donors.

The national transplant rate is 78·5 per 10 million inhabitants and 60% of them are autologous. Among the allogeneic transplants, 25% use unrelated donors (Table 1). None of these numbers is broken down by age.

Table 1. Number of HSCT performed in Brazil 2003–2010 and their distribution according to donor type

Year	2003	2004	2005	2006	2007	2008	2009	2010
Autologous	454 (45%)	628 (51%)	667 (55%)	833 (59%)	864 (59%)	858 (58%)	889 (59%)	916 (58%)
Allogeneic-related	545 (53%)	548 (44%)	468 (38%)	509 (36%)	497 (34%)	512 (34%)	493 (33%)	504 (32%)
Allogeneic-unrelated	22 (2%)	60 (5%)	82 (7%)	78 (5%)	96 (7%)	124 (8%)	118 (8%)	161 (10%)
Total	1021	1236	1217	1420	1457	1494	1500	1581

HSCT at GRAACC

In May 1999, the Pediatric Hematopoietic Stem Cell Transplantation Center started its activities at GRAACC with funding from the Ronald McDonald Institute. Over 300 transplants have been performed at GRAACC since then, now at a rate of 40–50 transplants per year. Half of the transplants performed are autologous, usually to treat high-risk neuroblastoma in first remission or relapsed (non-lymphoblastic) lymphomas and germ cell tumors. We do not have any current program for tandem autologous transplants. The HSCT unit is small with only four rooms and a total of six beds with HEPA-filtered air and positive pressure ventilation.

The number of unrelated transplants has increased every year, a total of 42 as of October 2011, most of them using cord blood from Brazilian cord banks as well as banks from other countries. Nineteen of these 42 children are alive at a median of 323 days after the transplant; the most important causes of treatment failure were relapsed disease, followed by graft failure and transplant-related toxicities. Most allogeneic transplants are performed for acute leukemia in second or subsequent remission.

The Economics of Transplantation

The government’s ‘Unique Health System’ (Sistema Único de Saúde) pays a fixed amount per transplant for the duration of the first admission10 (independent of the actual cost, and independent of the number of clinical complications and amount of supportive care used) (Table 2). It ranges from US$13 000 for autologous to US$40 500 for unrelated donor transplants. However, if the patient has graft failure and has to undergo a second stem cell infusion, it is paid as another transplant.

Table 2. Hospital reimbursement by Sistema Único de Saúde for HSCT in Brazil

	Reais	US dollars
Autologous	R$23 000	US$13 000
Allogeneic-related	R$55 000	US$31 500
Allogeneic-unrelated	R$71 000	US$40 500

Note: *Values are rounded.

Most Brazilian HSCT services cannot afford to offer transplant to the sickest patients, those who are likely to stay for long periods of time, or who need expensive medications, as is the case with most transplants using unrelated donors. In contrast, because GRAACC’s mission is to help any child while providing the highest possible standard of care, no patient with the potential to have a benefit from HSCT is refused.

The government pays separately (with no financial involvement of the transplant center) for the HLA-typing, for unrelated donor procurement, for confirmation of tissue type, and for the unrelated donor graft, either adult or cord blood unit(s). Therefore, these costs are not captured in the hospital system. The bone marrow or peripheral blood stem cell harvests, either related or unrelated, also have a separate reimbursement. Pre-transplant work-up may be performed in the hospital or by the primary care physician and these costs do not have any specific reimbursement.

If patients need to be readmitted or when they need intravenous medications at the day-hospital, reimbursement is also at a flat rate of US$77 (R$135) per day for ‘transplant related complications’, no matter the type of transplant or the timing of the re-admission, and it is the same amount for all complications. In a study from Sweden,11 fungal pneumonia, acute graft-versus-host disease, and graft rejection were among the most expensive post-transplant complications, and the cost of the first year following transplant was as high as US$981 000.

At GRAACC, the hospital costs are controlled very tightly and all expensive medications must be justified and their use defended case by case. However, because the reimbursement is a flat rate, the budget is based on the monthly expenditures of the transplant unit, not the actual cost per patient. Under a flat rate, reimbursements for transplants are paid to the hospital on top of the monthly payment for pediatric oncology care.

Children usually stay in the hospital for 1 week for the preparative regimen and between 2 and 4 weeks to recover before they are discharged to the day-hospital. The criteria to be discharged are having recovered counts, being afebrile, able to drink and eat, and need for intravenous medications for less than 12 hours. When beds are available, children may choose to stay in the hospital during the night in the inpatient unit, receiving all medications while they sleep, or in the day-hospital. The duration of outpatient care varies, between 2 weeks and 6 months, depending on the complications the patient experiences.

Most patients need readmissions after the first discharge following transplant to receive antibiotics when febrile, until bacteremia is ruled out, or to treat viral infections such as herpes zoster or upper respiratory tract infection. Cytomegalovirus antigenemia is frequent, since most Brazilian patients are cytomegalovirus-positive,12 but usually treated in the day-hospital. Whichever is the complication, reimbursement is always a flat rate of US$77 per day.

Study Design

Because of the complexity of the transplant procedure and the increasing possibility of clinical complications by transplant type (unrelated allogeneic/matched related allogeneic/autologous), we will have to evaluate the adequacy of the government rates separately by transplant type. We have initiated a project to evaluate the cost of the last 10 transplants from unrelated donors, in which there may be a larger discrepancy between the total costs and hospital reimbursement than in other transplant types.

Costs will be grouped in four categories: therapeutic costs [medications, blood support, central line, other (e.g. total parenteral nutrition, surgical procedures, oxygen, plasmapheresis — performed for patients with major ABO incompatibility, dialysis)], diagnostic costs (laboratory tests, radiological investigations), healthcare professionals, and hospital costs (e.g. room and board). All healthcare professionals are paid fixed salaries and there is no direct fee per patient. Therefore, costs for professional services will be estimated, dividing the salary of the professionals working in the ward (physicians, nurses, etc.) and in the cell processing laboratory by the number of transplants performed within the same time-frame. The ward costs are estimated also, based on the cost of maintenance of the air-handling system, water, telephone and electricity bills (a proportion of the total hospital cost), and a proportion of the administrative costs. All costs will be converted to the dollar value at the time of discharge.

All clinical characteristics of the patients, type of transplant, length of hospital stay, and use of medications and supplies will be extracted from the hospital computer system and checked manually in the clinical charts.

Indirect costs (e.g. from parents not working during the transplant process) and intangible costs (cost of pain and suffering13), as well as quality of life, were not evaluated prospectively and cannot be included in the retrospective review.

In conclusion, Brazil has a unique program to pay for unrelated HSCT. These transplants are performed in public hospitals in which the actual cost of the procedure is not captured routinely. We will estimate these costs retrospectively to have data to present to the Brazilian government in order to suggest a more appropriate funding formula for HSCT.

I would like to acknowledge that this work started as an initiative by Dr Carmen Vergueiro, the head of the AMEO — Bone Marrow Association in Brazil. I thank Dr Susan K. Parsons for reviewing the manuscript and making many valuable suggestions. I am very grateful to Dr Ronald Barr for his invitation to present the Brazilian experience, for all his suggestions, and for reviewing and editing the manuscript.