Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center. Between 2005 and 2015, the greatest increase in the number of HSCTs was observed in Vietnam. Allogeneic HSCT was performed more frequently than autologous HSCT, and a majority of cases involved related donors. Regarding allogeneic HSCT, the use of cord blood has remained steady, especially in Japan, and the number of cases involving related HLA non-identical donors has increased rapidly, particularly in China. The incidence of hemoglobinopathy, a main indication for allogeneic HSCT in India, China, Iran, and Pakistan, increased nearly six-fold over the last decade. Among the 18 participating countries/regions, the transplant rate per population varied widely according to the absolute number of HSCTs and the national/regional population size. We believe that this report will not only benefit the AP region but will also provide information about HSCT to other regions worldwide.
Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potential curative option for many patients with hematological malignancies (HM). However, the high rate of transplantation-related mortality (TRM) restricted the use of standard myeloablative HSCT to a minority of young and fit patients. Over the past few years, it has become evident that the alloreactivity of the immunocompetent donor cells mediated anti-malignancy effects independent of the action of high dose chemoradiotherapy. The use of reduced intensity conditioning (RIC) regimens has allowed a graft-versus-malignancy (GvM) effect to be exploited in patients who were previously ineligible for HSCT on the grounds of age and comorbidity. Retrospective analysis showed that RIC has been associated with lower TRM but a higher relapse rate leading to similar intermediate term overall and progression-free survivals when compared to standard myeloablative HSCT. However, the long term antitumor effect of this approach is less well established. Prospective studies are ongoing to define which patients might most benefit from reduced toxicity stem cell transplant (RT-SCT) and which transplant protocols are suitable for the different types of HM. The advent of RT-SCT permits the delivery of a potentially curative GvM effect to the majority of patients with HM whose outcome with conventional chemotherapy would be dismal. Remaining challenges include development of effective strategies to reduce relapse rates by augmenting GvM effects without increasing toxicity.
Allogeneic bone marrow or peripheral blood stem cell transplantation traditionally uses myeloablative regimen for conditioning to enable grafting of donor's stem cells. Animal experiments have shown that a milder non-myeloablative conditioning regimen does allow engraftment to occur. Nonmyeloablative conditioning regimens are low-intensity immunosuppressive treatment given to the recipient before infusion of donor's stem cells. It was reported to have decreased immediate procedural mortality, in particular those secondary to acute graft versus host reaction. However, it did give rise to higher risks of graft rejection, tumour tolerance and disease progression. Fortunately, appropriately administered donor lymphocyte infusion has been shown to establish full donor chimerism (complete donor stem cell grafting in the recipient's bone marrow) and potentiate antitumour effect (graft versus tumour reaction). The reduction of immediate transplant mortality allows the procedure to be carried out in older age groups, patients with concomitant diseases that otherwise would have made the patients unfit for the procedure, patients with non-malignant disorders such as congenital immune deficiencies, autoimmune disorders or thalassaemia majors. The regimen also allows transplantation of genetically manipulated haemopoietic stem cells (gene thrapy) to be carried out more readily in the immediate future. Lastly, the regimen may serve as a platform for immunotherapy using specific T cell clones for anti-tumour therapy with or without the knowledge of known tumour antigen.
Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2-6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2-6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT.
Allogeneic haemopoietic stem cell transplantation was initially considered as a means of delivering supralethal doses of chemotherapy with or without total body irradiation for the treatment of malignancy. However, it has become clear that this mode of therapy does not eradicate the malignancy in many patients and its benefit is largely due to the immune mediated graft versus malignancy effect. This has led to development of alternative strategy to utilize a less intensive preparative regimen pre-transplantation that provides sufficient immunosuppression to achieve engraftment of an allogeneic stem cell graft, thus allowing the evolution of a graft versus malignancy effect post-transplantation. Since September 1999, we had carried out 10 cases of allogeneic peripheral blood stem cell transplantation: one case of aplastic anaemia, four cases of acute myeloid leukemia (AML) in first remission, and five cases of chronic myeloid leukemia (CML) in chronic phase. The preparative regimen was non-myeloablative comprising Fludarabine with Cyclophosphamide or Busulphan. Recovery from transplantation was rapid with no or brief period of neutropenia or thrombocytopenia. Engraftment was established by determining donor's short tandem repeats in the recipient's bone marrow at day 30, 60 and 100 post-transplantation. Seven cases (70%) show partial or complete donor's chimerism by day 30 indicating successful engraftment. No treatment mortality was noted at day 100. Graft versus host disease was generally limited. Up to the date of reporting, two patients with CML had graft failure, one was successfully re-transplanted later. Two patients with AML had since relapsed and passed away. The others remain alive and well. The cost of transplantation on average was estimated to be about a quarter of that using a myeloablative regimen. It appears that this treatment strategy is a promising approach for the management of blood disorders.