Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many disorders, including hematological malignancies and benign diseases, both acquired and congenital. Autologous, as well as allogeneic HSCT, have been used for more than 20 years,1 the first HSCT having been performed in Argentina in 1986.2 In recent years, significant changes have occurred in the transplant field, such as an improvement in the supportive care and the spectrum of the conditioning regimen, increasing the age for transplant, and the access to the transplant of patients with comorbidities; particularly in the allogeneic setting, a wide availability of donors, including mismatched donors, have been reported.3 In Argentina, the creation of a Registry of HSC Voluntary Donors in 2001 added more possibilities to increase the HSCT rate in our country.2 At present, more than 80,000 transplants are performed all over the world every year and this number is expected to rise.4,5

However, the HSCT is a highly specialized, technologically sophisticated procedure, which requires expensive resources and a multidisciplinary team of trained transplant personnel. For these reasons, access to the HSCT suffers great inequality across several regions of the world, including within the same country, even in developed countries.6,7 The rate of transplants in different nations has already been reported and this was found to be significantly correlated with economic indexes.8 A voluntary survey of members of the Latin American Bone Marrow Transplantation Group (LABMT) regarding transplant activity between 2009 and 2012 showed a median transplant rate (number of transplants per 10 million inhabitants) of 64 in 2012, which is 5- to 8-fold lower than the corresponding rate for North American and European regions. In this LABMT survey, the corresponding transplant rate for Argentina was 149 (38 for allogeneic and 110 for autologous transplants).9 However, there are no data available on the homogeneity of access to the transplant procedure in Argentina, where there is also a significant internal migration for this procedure.

We aimed to evaluate the temporal trends in HSCT transplant rates in Argentina from 2009 to 2018 and transplant rates across the country and to estimate the effect of age, period and birth cohort, using the national database from the National Central Coordinating Institute for Ablations and Implants (INCUCAI).

This study presented the first comprehensive report of the HSCT rate in Argentina. Using a National Database comprising all transplants performed in Argentina between 2009 and 2018, we found a steadily increasing HSCT rate, going from 153.3 HSCT/10,000,000 inhabitants in 2009 to 260.1 HSCT/10,000,000 inhabitants in 2018. This rate showed a significant increase throughout the studied period, mainly because of the autologous and related allogeneic transplants, without changes regarding unrelated allogeneic transplants. We also showed a large heterogeneity across the country, with rates ranging between 99 and 680 transplants for the year 2018.

According to the 2017 report, the highest transplant rate in Europe was registered for Germany (930), followed by Italy (850) and France (830) and the lowest rate was recorded by Romania (160).25 In the Asian-Pacific region, the highest HSCT rate was evidenced in Australia (714) and the lowest one in Myanmar (0.4) for the year 2015.26 Our transplant rate is lower than most European countries; however, the lowest rate for an Argentine province (99) is higher than the Latin American global rate (69).5

Overall, autologous HSCTs were more frequently reported than allogeneic HSCTs. This proportion is slightly higher than the global world perspective previously reported for the year 2006,27 but different from the Asian-Pacific region, where allo-transplants are more frequent; the main indication of the transplant in this population was hemoglobinopathy, which may account for the difference.26 Higher use of allogeneic, compared to autologous, HSCT was also reported for the East Mediterranean/African region.28 The highest proportion of autologous transplants explains that our main indication for transplant was plasma cell disorders, representing 45% of the diagnosis. Globally, 14% of transplants in the pediatric population is quite similar to the percentage previously reported.29 For 2018, the absolute number of patients transplanted after the age of 60 (23.6%) and after the age of 70 (2.1%) observed in our country was low, the majority being autologous transplants; however, when considering the age-sex HSCT rate, the highest was for the 60 to 69 years age group in the autologous transplant. The number of both autologous and allogeneic transplants for the treatment of malignant diseases in older patients continues to grow.4,30 According to the CIBMTR report, 39% of allogeneic transplant recipients were 60 years old and older and 55% of autologous transplant recipients for lymphomas and multiple myeloma were 60 or older in 2018. Likewise, patients ≥ 70 years old represented 9% of allogeneic transplants and 15% of autologous transplant activity in 2018, as per the CIBMTR data.31

An upward and predictable trend in the HSCT rate has been reported since 1999 from surveys in Europe.16 Additionally, according to the CIBMTR report for the United States in 2015, the number of autologous hematopoietic cell transplantations (HCTs) has steadily risen since 2000, mainly for the treatment of plasma cell and lymphoproliferative disorders and due to an increase in the age at transplant.32 In our report, joinpoint regression analysis indicated a significant trend towards increasing HSCT rates over time. A considerable period effect may reflect a global rise in the transplant rate since 2013, probably due to the access to novel agents in prevalent diseases for transplant, such as multiple myeloma (in the autologous rate), lymphoma and acute leukemias (in allogeneic cases), as well as the wide incorporation of the use of mismatched/haploidentical family donors for the allogeneic after 2014, overcoming unrelated donors since 2016. In the autologous transplant group, a sharp increase in the HSCT rate after the age of 40 was found, with an effect of birth cohorts before 1970 and without the effect of the period. In the allogeneic transplant setting, an increase in the HSCT rate with age is also found, with a probable change after 2013, without the birth cohort effect. In respect to unrelated donor transplants, no effect of age, period or cohort was found. Unlike the US and Europe, where unrelated donors surpassed related donors,33 in Argentina, this type of transplant remains the lowest (40% out of the allogeneic), despite the growth of unrelated donor registries all over the world. Our transplant rate for unrelated donors was 36.8 in 2018 (per 10 million inhabitants), which is less than a half than that reported for Switzerland and Germany (218 and 109 per 10 million inhabitants per year, respectively).33 This observation may reflect that probably not all patients in need of an allogeneic transplant have access to it, in addition to the growing use of mismatched/haploidentical family donors during the last years may have influenced this figure. Alternatively, the probability of finding a well-matched unrelated donor for our population may be lower than in Europe34 and this emphasizes the need to make major efforts to recruit donors in local registries.33

We showed a large heterogeneity across the country regarding HSCT rates. It is known that transplant rates are influenced by economic and sociodemographic factors, as well as by team density and team distribution.16,35 Among the macroeconomic factors, Gratwohl et al. identified governmental health care expenditures as the most closely associated with HSCT rates.27 A CIBMTR analysis showed that a higher percentage of individuals below the poverty line and patients with acute myeloid leukemia remained significantly associated with a lower transplantation rate and that the geographical location within the country (rural vs urban) was also associated with a lower transplant rate. These factors were not significant in the pediatric populations.36 In Europe, a wide regional difference in the access to the search for unrelated donors was found in Italy for patients with acute leukemia; furthermore, a considerable internal migration to obtain access to the transplant was found.8 A marked difference in transplant rates between regions was also described in Spain. In respect to the autologous transplantation rate, the only associated variable was the team density, whereas there was a strong influence of macroeconomic determinants in the case of allogeneic transplant rates.37 The high heterogeneity of transplant rates in Argentina may depend on these factors, but also on the variation in the insurance coverage of the transplant cost across the country. Access to transplants in our country may be affected by the team density and team distribution. The highest indicators are observed in CABA, the capital of the country; however, considering the whole country, the team density is lower than 10 (per 10 million inhabitants) and the team distribution is lower than 1 (per 10,000 km2), both suggested targets for establishing the HSCT in a country.16 In our study, the median number of transplants by team of ∼30 transplants per year is nearly half of the number reported by European centers.33 HSCT teams in Argentina are concentrated in five out of the twenty-four states in the country (four of them in the central region); therefore, in contrast to the US, most patients in Argentina will have to travel long distances to access a transplant center. However, the analysis of this factor is beyond the scope of this study.38

We used a careful statistical methodology to address our questions. However, the low number of observations in the analysis of the studied groups may limit the power of such analysis, as evidenced in the confidence intervals shown in the APC figures. In regard to HSCT rates by state, we assumed a similar disease incidence for all states and the lack of systematic national information precludes a further analysis, although it seems that there is no clear pattern of higher incidence in any particular Argentine region. Furthermore, the analysis of the outcome of the transplants was beyond the scope of this study.

In conclusion, age-sex standardized HSCT rates in Argentina have been increasing in recent years, mainly due to autologous and family donor allogeneic transplants. A wide variation in HSCT rates throughout the country was found, demonstrating differences in the access to transplantation among Argentine regions. This study will allow us to make a “situation diagnosis” (in order to know the country's reality) and, therefore, to guide programs aimed at ensuring accessibility through an equitable allocation of resources, the knowledge of the appropriate transplant application process, patient eligibility, the importance of timely planning and, as a final result, the quality of the procedure.