ABSTRACT
Objective To investigate the clinical efficacy of pretreatment regimen containing idarubicin (IDA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk refractory leukemia. Methods A total of 116 patients with high-risk refractory leukemia who received allo-HSCT treated with 7 types of IDA-containing pretreatment regimes were enrolled in this study. The implantation rate of 116 recipients was summed up. The 2-year overall survival (OS), 2-year disease free survival (DFS), cumulative recurrence rate, recurrent mortality, transplantation related mortality (TRM), cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were statistically analyzed by Kaplan-Meier survival curve. Results All 116 recipients successfully implanted. The median follow-up time was 28 (7-70) months. Among them, 64 recipients survived, the 2-year OS was 55.2%, 2-year DFS was 51.7%, 2-year recurrent mortality was 23.3% and 2-year TRM was 18.1%. Among 116 recipients, 72 cases suffered from aGVHD. The 2-year cumulative incidence rate of aGVHD was 62.1% including 20 cases of grade Ⅲ-Ⅳ aGVHD, the 2-year cumulative incidence rate was 17.2%. Among 116 recipients, 59 cases presented with cGVHD. The 2-year cumulative incidence rate was 55.4%, of which the 2-year cumulative incidence rate of extensive cGVHD was 14.7%. Among 116 recipients, 30 cases recurred with a 2-year cumulative recurrence rate of 25.9%. Conclusions IDA-containingpretreatment regime has high safety and effectiveness, and can be used as an effective pretreatment regime for transplantation preprocessing in patients with high-risk refractory leukemia.
ABSTRACT
Several hot questions such as selection of patients and favorable time of transplantation, design of conditioning regimen, monitoring of chimerism and complication of graft versus host disease (GVHD) in allogeneic hematopoietic stem cell transplantation following reduced intensity regimen (RIC-HSCT) as salvage therapy for refractory leukemia are discussed in this article. More and more investigators began to recognize that it was not a fundamental to undergo transplantation in complete remission for patients with refractory leukemia, since it may expend patients' physical status. RIC-HSCT may be substantially considered as a kind of adoptive immunotherapy, so that immunologic attacking targets and the latency of immunoreactian must be considered when making the decision to use, lacking of attacking targets and rapidly growing diseases seemed to be less susceptible to control. Commonly used reduced intensity regimens differed significantly, but it was clear that dose intensity was very important in refractory leukemia. In fact, many investigators used intermediate dosage between criteria of non-myeloablative and conventional myeloablative regimens. Complete donor chimerism is the hallmark of engraftment but often delayed in RIC-HSCT. Since sustained complete donor chimerism induced persistent graft-versus-leukemia (GVL) effect play an important role in patients' long-term survival, it was recommended that sensitive techniques (eg. STR-PCR) should be used to analysis chimerism and should be measured more frequently (every 2-4 weeks), and lineage-specific chimerism (eg. T cell) analysis was also recommended. As compared with traditional HSCT, the incidences of acute and chronic GVHD are similar and the onset of GVHD is associated with the GVL effect. Decrease or interruption of immunosuppressive drugs early after transplantation and donor lymphocyte infusion may facilitate transformation to complete donor chimerism, so that it may benefit patients with advanced disease at time of transplantation from avoiding disease relapse in one hand, but may induce GVHD in the other hand.
ABSTRACT
It is difficult for the patients of refractory leukemia to complete remission (CR) and long-term disease-free survival (DFS), and it was always been the hot spots of research in the field of hematologic malignancies. The diagnostic criteria of refractory leukemia were adjusted constantly at domestic and foreign, the high-risk factors about refractory leukemia were found constantly too. New molecular markers that represent mutations or gene overexpression have been identified such as FMS-like tyrosine kinase-3 and nucleophosmin,which will enhance the ability to more accurately prognosticate for patients with acute myeloid leukemia. The treatment of patients with refractory or relapsed acute myeloid leukemia remains challenging. Multiple new agents with tremendous potential were in development and clinical trials. Such as applying resistance reversal agents,enhancing molecular targeted therapy, improving the technology of hematopoietic stem cell transplantation,empoldering the new drugs, and forming a new chemotherapy program etc. Monoclonal antibodies and peptide vaccination with leukemia-associated antigens also brought the hopes of increasing the remission and cure rates for patients with acute myeloid leukemia.