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Fulltext Allogeneic Hematopoietic Stem Cell Transplantation in Severe Aplastic Anemia: A Single Centre Experience in Malaysia

Wilfred G, Ong TC, Sh Shahnaz SAK, Wah HK, Carlo ES, Jameela S, et al.

Blood Cell Ther, 2022 May 25;5(2):45-53.
PMID: 36710947 DOI: 10.31547/bct-2021-018

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) provides curative therapy in almost 90% of patients with severe aplastic anemia (SAA). Older age, long duration of disease with consequent heavy exposure to transfusion, and active infection at the time of HSCT have a negative influence on the outcomes, causing graft failure (GF) and graft versus host disease (GVHD).
PURPOSE: To describe the outcomes of all patients with SAA who received hematopoietic stem cell transplantation at a tertiary center in Malaysia.
MATERIALS AND METHODS: We included a 20 y cohort of patients who underwent transplantation from January 1, 1999 to December 31, 2019. Data were obtained from electronic medical records. Demographics, clinical characteristics, and treatment outcomes were analyzed using descriptive statistics. Overall survival (OS) was analyzed using Kaplan-Meier curves. All analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 25.
RESULTS: Eighty patients were analyzed. The median age at diagnosis was 19 years, and 59% patients were male (n = 47). Malay ethnicity was the highest (52.5%), followed by Chinese (20.0%) and Native Sabah (15.0%). The median duration from diagnosis to transplantation was 13.5 weeks. A majority of patients received Cy-ATG conditioning (n = 51, 63.8%). Forty-one patients (51.2%) used peripheral blood as stem cell source, 36 patients (45.0%) used granulocyte colony stimulating factor (G-CSF) primed marrow graft and 3 patients (3.8%) used both. The mean nucleated mononuclear cell and CD34 cell doses were 4.7 ± 1.7 × 108/kg and 4.6 ± 1.9 × 106/kg, respectively. Median engraftment for WBCs and platelets was 14 and 15 days, respectively. There was no difference in WBC and platelet engraftment in patients who received peripheral blood stem cell transplantation or bone marrow transplant. At a median follow-up of 54 months, 49 patients (61.3%) achieved complete remission and 8 patients (10.0%) achieved partial remission. The estimated 5 y OS was 63% and higher among those who received HSCT within 3 months of diagnosis. Twenty-two patients (27.5%) died within 100 d of transplantation, and a majority of these died due to pre-engraftment death.
DISCUSSION AND CONCLUSIONS: Our study found that patients who received early allogeneic transplantation for SAA had better outcomes. Pre-engraftment failure was the major cause of transplant-related mortality within 100 d. Further studies are required to identify the factors responsible for delaying transplantation to improve treatment outcomes.
Fulltext The 2016 APBMT Activity Survey Report: Trends in haploidentical and cord blood transplantation in the Asia-Pacific region

Iida M, Dodds A, Akter M, Srivastava A, Moon JH, Dung PC, et al.

Blood Cell Ther, 2021 May 25;4(2):20-28.
PMID: 36712901 DOI: 10.31547/bct-2020-013

This report describes the results of the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) Activity Survey 2016, focusing on the trends of haploidentical and cord blood (CB) transplants in the Asia-Pacific region. Mongolia and Nepal submitted their first activity data in this survey, and the number of countries/regions participating in the activity survey grew to 20. The annual number of transplants exceeded 20,000 for the first time in 2016, and the total number of centers increased to 686. About 87.9% of all hematopoietic stem cell transplantations (HSCTs) were performed in China, Japan, Korea, India, and Australia with China performing the highest number. Beginning with the 2016 survey, APBMT modified the survey forms and initiated the collection of the exact number of haploidentical transplants. The total number of such transplants was 3,871, and 66.0% of those were performed in China. Meanwhile, cord blood transplants in this region remained high (1,612), and 81.8% of them (1,319) were performed in Japan. The number of facilities and transplants, the ratio of haploidentical transplants to related transplants, the ratio of CB transplants to unrelated transplants, and proportions of haploidentical and CB transplants per capita significantly differed among countries/regions in the Asia-Pacific region. Data collection and analysis revealed the transition and diversity of transplants in this region. This report also shows a dramatic increase in haploidentical transplants as seen in other parts of the world, while revealing uniquely that the activity of cord blood transplant remains high in this region.
Fulltext Autologous stem cell transplantation (ASCT) outcome for multiple myeloma in a tertiary referral centre in Malaysia

Liam CCK, Boo YL, Lee YL, Law KB, Ho KW, Shahnaz SAKS, et al.

Blood Cell Ther, 2021 Feb 25;4(1):1-8.
PMID: 36712843 DOI: 10.31547/bct-2020-009

BACKGROUND: Multiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission.
PURPOSE: This is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital.
MATERIALS AND METHODS: We included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages.
RESULTS: 139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n＝78). The most common subtype is IgG Kappa (n＝67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n＝31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n＝119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS.
DISCUSSION AND CONCLUSIONS: Our study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.
Fulltext Evolution of Hematopoietic Stem Cell Transplant Programs in Malaysia

Saidon N, Anuar NA, Meng CK, Chuan OT, Mui TS, Gin GG, et al.

Blood Cell Ther, 2020 Aug 25;3(3):44-47.
PMID: 36714175 DOI: 10.31547/bct-2019-017

Hematopoietic stem cell transplantation (HSCT) is now widely practiced worldwide. It has the potential to cure many hematological diseases, such as acute leukemia and thalassemia. As an emerging country, Malaysia has made advancements despite many challenges. HSCT has evolved rapidly since the first pediatric allogeneic HSCT case in 1987. The first adult HSCT was performed 5 years later in 1993. Currently, a total of 13 hospitals offer HSCT services throughout Malaysia. These include private healthcare services, substantially funded government hospitals governed by the Ministry of Health, and partially funded teaching hospitals governed by the Ministry of Education. Until 2015, 1,987 allogeneic and 1,648 autologous HSCT procedures were performed. This article narrates the history and development of HSCT in Malaysia and briefly discusses the challenging issues in this area.
Fulltext Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey

Iida M, Liu K, Huang XJ, Huang H, Kuwatsuka Y, Moon JH, et al.

Blood Cell Ther, 2023 Nov 25;6(4):114-123.
PMID: 38149021 DOI: 10.31547/bct-2023-015

The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.
Fulltext Challenges in Global Access to CAR-T cells: an Asian Perspective

Hwang WY, Takahashi S, Choi B, Huang H, Kawamata S, Ng SC, et al.

Blood Cell Ther, 2024 Feb 25;7(1):10-13.
PMID: 38486827 DOI: 10.31547/bct-2023-023

The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.
Fulltext Trends in disease indications for hematopoietic stem cell transplantation in the Asia-Pacific region: A report of the Activity Survey 2017 from APBMT

Iida M, Liu K, Huang XJ, Depei W, Kuwatsuka Y, Moon JH, et al.

Blood Cell Ther, 2022 Nov 25;5(4):87-98.
PMID: 36713681 DOI: 10.31547/bct-2022-002

The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.