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.

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.

KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia.

Killer cell immunoglobulin-like receptors (KIR) genotype and haplotype frequencies have been reported to vary distinctly between populations, which in turn contributes to variation in the alloreactivity of natural killer (NK) cells. Utilizing the diverse KIR genes to identify suitable transplant donors would prove challenging in multi-ethnic countries, even more in resource-limited countries where KIR genotyping has not been established. In this study, we determined the KIR genotypes from 124 unrelated Malaysians consisting of the Malays, Chinese, Indians, and aboriginal people through polymerase chain reaction sequence-specific primer (PCR-SSP) genotyping and employing an expectation-maximization (EM) algorithm to assign haplotypes based on pre-established reference haplotypes. A total of 27 distinct KIR haplotypes were discerned with higher frequencies of haplotype A (55.2%) than haplotype B (44.8%). The most frequent haplotypes were cA01:tA01 (55.2%), cB01:tB01 (18.1%), and cB02:tA01 (13.3%), while the least frequent haplotypes were cB03:tB01 (1.2%), cB04:tB03 (0.4%), and cB03:tA01 (0.4%). Several haplotypes were identified to be unique to a specific ethnic group. The genotype with the highest frequency was genotype AB (71.8%), followed by AA (19.4%), and BB (8.9%). The Indians exhibited the lowest genotype AA but the highest genotype BB, whereas genotype BB was absent in the aboriginal people. Despite the limitations, the genotype and haplotypes in the Malaysian population were successfully highlighted. The identification of ethnic-specific KIR genotypes and haplotypes provides the first step to utilizing KIR in identifying suitable transplant donors to further improve the transplant outcome in the Malaysian population.

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia.

Background: Immune thrombocytopenia (ITP) is well characterized in Western, European and other Asia-Pacific countries. Nevertheless, the clinical epidemiology, treatment pattern and disease outcome of ITP in Malaysia are still limited and not well known. Objective: This study aimed to describe the clinical epidemiology, treatment outcome and mortality of ITP patients in haematology tertiary multicentre in Malaysia. Methods: Clinical and laboratory data of newly diagnosed adults with ITP by a platelet count <100 × 109/L from January 2010 to December 2020 were identified and analyzed. Results: Out of 500 incident ITP, 71.8% were females with a striking age preponderance of both genders among those aged 18-29 years. The median age was 36 years. The median platelet count was 17.5 × 109/L, 23.0% had a secondary ITP, 34.6% had a Charlson's score ≥1, 53.0% had bleeding symptoms including 2.2% intracranial bleedings (ICB). Helicobacter pylori screening was performed in <5% of cases. Persistency and chronicity rates were 13.6% and 41.8%, respectively. Most (80.6%) were treated at diagnosis onset and 31.2% needed second-line treatment. Throughout the course of ITP, 11.0% of patients died; 3.0% and 8.0% with bleeding and non-bleeding related ITP. Conclusion: This study confirms the epidemiology of ITP is comparable with worldwide studies. Our incidence is high in the female, Malay ethnicity, primary ITP and events of cutaneous bleeding at ITP onset with 18-29 years predominance age group for both genders. The frequency of persistent and chronic ITP is inconsistent with published literature. Corticosteroids and immunotherapies are the most prescribed first-line and second-line pharmacological treatments. Thrombopoietin receptor agonist medications (TPO-RAs) usage is restricted and splenectomy is uncommon. Our mortality rate is similar but ITP related bleeding death is fourth-fold lower than previous studies. Mortality risks of our ITP patients include age ≥60 years, male, severe bleeding at presentation, CCI≥1 and secondary ITP.

Trends in disease indications for hematopoietic stem cell transplantation in the Asia-Pacific region: A report of the Activity Survey 2017 from APBMT.

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.

Autologous stem cell transplantation (ASCT) outcome for multiple myeloma in a tertiary referral centre in Malaysia.

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.

The 2016 APBMT Activity Survey Report: Trends in haploidentical and cord blood transplantation in the Asia-Pacific region.

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.