Autologous hematopoietic stem cell transplantation activity for lymphoma and multiple myeloma in China

Autologous hematopoietic stem cell transplantation (AHSCT) is an important therapeutic strategy to improve the survival outcome of lymphoma and multiple myeloma (MM). The European Society for Blood and Marrow Transplantation reported that the number of AHSCT for MM increased sharply from 8032 to 37,743, the 5-year overall survival rate increased from 52 to 69% and the mortality decreased from 5.9 to 1.5% in 2015 – -2019

TO THE EDITOR Autologous hematopoietic stem cell transplantation (AHSCT) is an important therapeutic strategy to improve the survival outcome of lymphoma and multiple myeloma (MM). The European Society for Blood and Marrow Transplantation reported that the number of AHSCT for MM increased sharply from 8032 to 37,743, the 5-year overall survival rate increased from 52 to 69% and the mortality decreased from 5.9 to 1.5% in 2015--2019 compared with in 1995-1999 [1]. Limited data are available on the AHSCT performed in patients with lymphoma and MM stratified by age, sex and regions in the mainland of China. Therefore, we conducted the present study to provide epidemiological characteristics of AHSCT activity at national and provincial levels.
This retrospective study was organized by the autologous stem cell transplantation group of Chinese Society of Clinical Oncology which consisted of 211 AHSCT centers covering 29 provinces in mainland China. AHSCT centers were concentrated in the eastern region, including in Shandong (n = 22), Beijing (n = 19) and Guangdong (n = 18); few centers were located in the central and western regions including in Jilin (n = 2), Guizhou (n = 1) and Qinghai (n = 1). The AHSCT utilization rate was calculated by the number of AHSCT cases divided by the incident cases of the corresponding disease, and the incident data in national and provincial levels were extracted from the Global Burden of Disease Study 2019 using the standard source tool [2,3].
Our analysis identified 4556 transplantations, of which 2443 were performed for lymphoma and 2113 were performed for MM. The transplantation utilization rates were 2.4% for lymphoma and 11.3% for MM. As shown in Table 1, the median age was 52 years (range, 4-73 years) with a male/female ratio of 1.3:1. Higher proportion of inadequate hematopoietic stem cell yield with CD34 + cells <2 × 10 6 /kg was observed in patients aged over 60 years (10.9% vs. 8.6%). With respect to transplantation time, 85.6% (n = 3998) of transplantations were conducted in the front-line therapy and 14.4% (n = 658) were conducted as a part of salvage therapy. The 100-day non-relapse mortality rates were 1.3% and 0.3% for lymphoma and MM, respectively. In terms of geography, 55.8% (n = 2542) of transplantations were conducted in the eastern region, 24.1% (n = 1096) in the central region, and 20.1% (n = 918) in the western region.
The mean transplantation utilization rate was 3.8% in the overall patient group. The rate was over 5.0% in individuals 20-59 years with a peak of 9.4% in the age group of 45-49 years. For lymphoma, the transplantation utilization rate was very low (<1.0%) in individuals younger than 10 years, increased to more than 5.0% in individuals 20-50 years of age with a peak of 6.5% in the age group of 40-44 years, and decreased to less than 1.0% in individuals over 65 years old. For MM, the transplantation utilization rate was 0% in individuals younger than 25 years, increased to more than 10.0% in individuals 35-65 years with a peak of 33.8% in the age group of 45-49 years. Notably, the transplantation utilization rate was 3.5% for lymphoma and 17.2% for MM in the age groups younger than 70 years, and the rates were less than 1% for both diseases in the age groups older than 70 years.
The eastern region had a higher transplantation utilization rate than the central and western regions (4.6% vs. 3.0% vs. 3.3%). For lymphoma, the transplantation utilization rate for lymphoma was higher in the eastern region than that in the central and western region (2.9% vs. 1.9% vs. 2.2%). The highest transplantation utilization for lymphoma was observed in Beijing (12.6%), Tianjin (7.5%) and Chongqing (6.2%), while the lowest rate was observed in Inner Mongolia (0.4%), Guangxi (0.4%) and Heilongjiang (0.3%). Similarly, the transplantation utilization rate for MM was higher in the eastern region than that in the central and western region (13.7% vs. 9.3% vs. 9.3%). The highest transplantation utilization for MM was observed in Beijing (60.9%), Tianjin (44.0%), and Shanghai (23.8%), while the lowest rate was observed in Hainan (1.2%), Jiangsu (1.1%), and Guizhou (0.9%).
The AHSCT activity is increasing worldwide. A report by the Worldwide Network of Blood and Marrow Transplantation showed the number of AHSCT for lymphoproliferative disorders increased by 84.2% during 10 years period (21,655 in 2006 vs. 39,878 in 2016) [4]. The number of AHSCT was 2,723 in 2019 in China, with a median AHSCT rate of 13.2 per 10 million population, which was double the number in 2016 [5]. Additionally, the annual transplantation number increased by 8.8 fold from 2006 to 2015 in China, which was partly because of doubled number of transplantation centers [6].
AHSCT improves the prognosis of both younger and older patients with lymphoma and MM. A retrospective study demonstrated that the survival outcome of AHSCT was comparable in older and younger patients with MM (median progression-free survival, 33.5 vs. 33.8 months; median overall survival, 6.1 vs. 7.8 years) [7]. However, the application of AHSCT in older patients faces many barriers such as poor transplantation eligibility. In the present study, we observed a higher proportion of inadequate hematopoietic stem cell yield in the older patients, and a very low AHSCT utilization rate in the age group of more than 70 years. These findings suggest the need to establish a strategy to improve the stem cell harvest efficacy and to guarantee the treatment safety during AHSCT, especially in the older patient population.
The transplantation activity varies by many factors such as socioeconomic status and health service accessibility. AHSCT is widely used in developed regions. For example, the utilization rate of AHSCT for patients with MM aged <70 years was 52.2% in North America and 46.7% in Europe compared with 9.45% in Asia Pacific and 5.77% in Africa and the East Mediterranean [8]. In the present study, the AHSCT rate was low in the developing provinces because of fewer resources and transplantation teams. Notably, there was no AHSCT in two provinces including Tibet and Ningxia in the western region. These findings support the need to train transplantation teams and increase the application of AHSCT, especially in central and western regions.
The present study has several limitations. First, the number of AHSCT was not adjusted by the migration from residence to transplantation site. Second, many transplantation centers shared infrastructure for AHSCT and allogeneic hematopoietic stem cell transplantation, which may lead to underestimated or overestimated transplantation activity for each specific center. Third, we did not evaluate the AHSCT utilization rate in the transplanteligible patients because the incident data was secondary estimated data from the Global Burden of Disease 2019.
In conclusion, the present study was a comprehensive evaluation of AHSCT utilization for lymphoma and MM in the mainland of China. Developed regions and provinces had higher AHSCT utilization rates. These findings provide information on the BEAC carmostine, etoposide, cytarabine and cyclophosphamide, BEAM carmostine, etoposide, cytarabine and melphalan, BuCy busulfan and cyclophosphamide, CBV carmostine, etoposide, cyclophosphamide, TBI total body irradiation. a Carmostine could be substituted by bendamustine, semustine, fotemustine and so on.

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AHSCT activity for lymphoma and MM, which will be useful for