High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is an effective treatment option for patients with AL amyloidosis. However, due to multi-organ involvement in this disease, HDM/ASCT is feasible in a minority of patients. Sixty-three patients received HDM/ASCT in our institution between 2006 and 2017. Of those, 51 patients are alive after a median follow-up of 46 months, and the 7-year estimated overall survival rate was 74%. Five patient died ≤100 days post-HDM/ASCT. Survival rate is significantly worse in patients with cardiac involvement. To maximize the benefit and minimize toxicity, careful patient selection and experienced management are important, especially for patients with cardiac involvement. In this review, evolution of HDM/ASCT and novel treatment strategies are discussed.
The number of hematologic malignancy cases in Japan is increasing every year, especially since technique improvements here have pushed up the upper age limit for hematopoietic stem cell transplantation (HSCT). Furthermore, recent research from outside Japan has demonstrated improved clinical results for elderly HSCT patients and older age alone isn’t thought to be contraindication to HSCT. In Japan, HSCT annual reports for 2015 revealed steady increase in elderly HSCT patients for 20 years. And data from the annual reports showed that HSCT for patients over 60 years of age is becoming a major indication. Regretfully, we have not yet researched HSCT carefully enough, so many HSCT problems remain for elderly patients. These problems include optimization of indication, conditioning regimens, method of immune-suppression, and analysis of HSCT cost-effectiveness, etc. Japan vitally needs further research on elderly HSCT because we have one of the oldest populations in the advanced nations and Asian countries. Elderly Japanese as well as senior hematologic malignancy patients worldwide will all greatly benefit from our efforts to improve elderly HSCT.
The results of hematopoietic stem cell transplantation (SCT) after reduced-intensity conditioning (RIC) have not been compared with those after myeloablative conditioning (MAC) in patients under 55 years old. To clarify the efficacy and safety of RIC, we retrospectively analyzed the outcomes of 24 patients with RIC and 136 patients with MAC. In univariate analysis, RIC recipients had a higher incidence of disease progression (3y progression: MAC 31.9% vs RIC 42.1%, P=0.09) and shorter overall survival (3y OS: 46.5% vs 40.6%, P=0.12), but these differences were not significant. Progression-free survival and non-relapse mortality were not different between the two groups. Based on the multivariate analysis, RIC increased the incidence of disease progression (HR 2.12, P=0.01) and shortened OS (HR 1.75, P=0.04). In patients with a high disease risk, SCT after RIC increased the incidence of disease progression. In conclusion, as OS and PFS were similar between RIC and MAC, RIC may be considered as a treatment option.
To elucidate late effects of reduced intensity stem cell transplantation (RIST) in childhood cancer survivors, we retrospectively examined late effects, primarily endocrine disorders, in 23 patients who underwent RIST and 12 patients who underwent myeloablative stem cell transplantation (MAST). After RIST, the overall rate of late effects was 69.6% and its severity mostly ranged from mild to moderate. After MAST, all patients had some late effects and its severity was severe or life threatening. The severity of late effects was clearly reduced in RIST. Endocrine late effects after RIST were growth disorders in eight patients (35.0%) and thyroid dysfunction in three patients (13.0%). After MAST, endocrine late effects were growth disorders in three patients (25.0%) and thyroid dysfunction in one patients (8.3%). There was no significant difference following RIST or MAST. Concerning gonadal dysfunction among patients who reached puberty, the prevalence rate was higher after MAST than after RIST. In girls after RIST, 37.5% were considered as having ovarian dysfunction on evaluation of anti-Müllerian hormone levels. We found that RIST reduced late effects; however, endocrine disorders such as gonadal dysfunction were still very common. Further improvement of transplantation conditioning and continued long-term follow-up are needed.
The purpose of this study was to clarify the influence of difference in exercise capacity before allogeneic hematopoietic stem cell transplantation (Allo-HSCT) on the change in physical function level in the transplantation treatment process. Thirty-two patients who had undergone Allo-HSCT participated and were evaluated by conducting physical function tests before Allo-HSCT, after departure from a clean room, and at discharge. All Allo-HSCT patients received physical therapy from 1 week before Allo-HSCT until they were discharged from the hospital. We divided these 32 patients into two groups as having higher or lower scores as compared to the median, based on their six-minute walk test (6MWT) scores obtained before HSCT. The change in physical function after Allo-HSCT showed similar trends in both groups. However, the high group showed significantly higher values in all physical function tests than the low group. This study showed the possibility that enhancing exercise capacity before Allo-HSCT might maintain physical function at the high level after Allo-HSCT.
Using standardized self-reporting instruments, we conducted a nationwide cross-sectional study evaluating the quality of life (QOL) of 2-year treatment-free survivors who received hematopoietic cell transplantation (HCT) under the age of 20 years from 1995 to 2009. A background comparison was conducted between 442 participating survivors (the analyzed group) and 1186 non-participating survivors (the non-analyzed group). The analyzed group included more allogeneic bone marrow or cord blood HCTs and fewer autologous HCTs, than the non-analyzed group. Recent HCTs were more common in the analyzed group, which may explain the more frequent use of reduced-intensity conditioning and tacrolimus for graft-versus-host disease (GVHD) prophylaxis. Overall, there were no statistical differences between the analyzed group and non-analyzed group in sex distribution, age at HCT, primary diseases, various adverse effects such as acute and chronic GVHD, engraftment, relapse, and other additional treatments. By analyzing these participating survivors, the QOL of Japanese survivors post-HCT in childhood can be better understood. (UMIN9546)
Hematopoietic cell transplantation (HCT) requires the comprehensive corporations of hematologists, nurses, radiologists, operation-room staffs, blood transfusion specialists, dermatologists, experts of respiratory diseases, gastroenterologists, pathologists pharmacologists, administrative office and the other almost entire functions of an institute. Because of that, “Harmonization of medical services” has been the key-word of HCT and it has become a good character of the persons who have participated in HCT. These persons have then created study group in each region, nation-wide academic society (Japan Society for Hematopoietic Cell Transplantation; JSHCT) and have obtained many national grants. They have also created Japan Marrow Donor Program and Japan Cord Blood Bank System under the collaboration with non-medical volunteers. They have made a good friendships with the people who have the similar good characters in oversea countries and organized international academic societies (APBMT and WBMT). As one who has worked in these period, I summarized what I have been involved and I sent a message that JSHCT, which is a “Technology-oriented society”, should advance toward the aims which are not only the further improvement of the current HSCT field but also the expansion of the targeted diseases.