The long-standing debate of whether patients with acute myeloid leukemia (AML) should proceed to allogeneic hematopoietic cell transplantation (HCT) during first complete remission (CR1) remains ...unsettled. Although allogeneic HCT during CR1 used to be recommended for those with intermediate or poor cytogenetics if they had a matched sibling donor, the concept of indications for allogeneic HCT during CR1 has been evolving by virtue of advances in understanding of the molecular pathogenesis of AML and innovations in transplantation practice attained over the last few decades. The incorporation of molecular profiles of leukemia has been shown to contribute to further refinements of risk classification that had previously relied mostly on cytogenetics, while the progress in transplantation procedures has made it possible to perform transplantations more safely even for patients without a matched sibling donor. These significant changes have underpinned the need to reappraise indications for allogeneic HCT during CR1 of AML. Improvements in clinical applications of genetic and measurable residual disease information as well as in transplantation technology are expected to further refine indications for allogeneic HCT during CR1, and thus promote an individualized approach for the treatment of AML.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Allogeneic hematopoietic cell transplantation (HCT) is the most potent therapy for preventing relapse of acute myeloid leukemia (AML). Although its efficacy is compromised by a high risk of ...treatment-related morbidity and mortality, an accumulating body of evidence has led to the general recommendation favoring allogeneic HCT from a matched sibling donor during first complete remission (CR1) for younger patients with cytogenetically intermediate- or high-risk AML. Over the past few decades, this field has seen a great many advancements. The indications for allogeneic HCT have been refined by taking into account the molecular profiles of leukemic cells and the degree of comorbidities. The introduction of high-resolution human leukocyte antigen-typing technology and advances in immunosuppressive therapy and supportive care measures have improved outcomes in alternative donor transplantation, while the parallel growth of unrelated donor registries and greater use of umbilical cord blood and haploidentical donors have considerably improved the chance of finding an alternative donor. The development of reduced-intensity and non-myeloablative conditioning has made it possible to receive allogeneic HCT for patients who might once have been considered ineligible due to advanced age or comorbidities. Thanks to these advances, the role of allogeneic HCT during CR1 has become progressively more important in the treatment of AML.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The development of effective prophylaxis strategies against graft-versus-host disease (GVHD) has contributed to the widespread use of haploidentical related hematopoietic cell transplantation ...(Haplo-HCT). Currently, GVHD prophylaxis containing posttransplant cyclophosphamide (PTCY) is considered the standard of care in Haplo-HCT, and recent studies have shown comparable results for PTCY-based Haplo-HCT and HCT from other donor sources. The conditioning regimen plays an important role in eradicating tumor cells to prevent disease relapse and suppressing the recipient's immune system to facilitate engraftment. PTCY-based Haplo-HCT was initially developed using a nonmyeloablative conditioning regimen consisting of fludarabine, cyclophosphamide and low-dose total body irradiation, but high relapse rates reinforced the need to intensify the conditioning regimen. In this respect, various myeloablative and reduced-intensity conditioning regimens have been investigated. However, the optimal conditioning regimens for PTCY-based Haplo-HCT have not yet been established, and this issue needs to be addressed based on data from patients undergoing the procedure. In this article, we review the existing literature on conditioning regimens for PTCY-based Haplo-HCT and discuss future perspectives.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hematopoietic cell transplantation (HCT) represents a valuable therapeutic option for younger patients with mantle cell lymphoma (MCL). Despite the rarity of this disease, significant research ...efforts have been undertaken to improve the outcomes, and autologous HCT is currently considered an established treatment for younger patients who respond to induction therapy. The past 20 years have seen further progress by incorporating rituximab and high-dose cytarabine into induction therapy and adopting rituximab as posttransplant maintenance therapy. Allogeneic HCT is generally reserved for relapsed/refractory patients because of concerns about high toxicities; however, a fraction of relapsed/refractory patients can be salvaged at the expense of high non-relapse mortality. Although significant advances have been attained over the past decades, MCL treatment still has room for improvement. A risk-adapted approach based on measurable residual disease and genetic information will promote therapeutic optimization and individualization. Moreover, the recent development of molecularly targeted drugs is expected to alter the therapeutic landscape, and the incorporation of novel drugs into the current treatment scheme is another key issue. These ongoing and future advances will change the role of HCT in MCL treatment and contribute to further improvements in outcomes.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mutations in the FMS-like tyrosine kinase 3 (
FLT3
) gene are detected in approximately 30% of acute myeloid leukemia (AML). The high frequency of
FLT3
mutations, along with their adverse effect on ...prognosis, makes FLT3 a promising therapeutic target, and has spurred development of FLT3 inhibitors. First-generation inhibitors, including midostaurin and sorafenib, lack specificity for FLT3 and act on multiple kinases, whereas second-generation inhibitors, including gilteritinib, and quizartinib, are highly specific to FLT3 and are more potent than first-generation inhibitors. Several FLT3 inhibitors have recently gained regulatory approval worldwide, and several others are under development. The advent of FLT3 inhibitors has changed the standard treatment for
FLT3
-mutated AML in the frontline and relapsed/refractory settings and contributed to improved outcomes for this formidable AML subtype. However, numerous unresolved issues remain owing to rapid changes in practice. These include identification of optimum FLT3 inhibitors and combination therapies, the role of maintenance therapy, and the indication for allogeneic hematopoietic cell transplantation. Furthermore, strategies to overcome resistance to FLT3 inhibitors must be pursued. Results of ongoing and future studies will improve our ability to use FLT3 inhibitors more effectively, which should provide significant benefits to a wider range of patients.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
6.
Acute myeloid leukemia in older adults Yanada, Masamitsu; Naoe, Tomoki
International journal of hematology,
08/2012, Volume:
96, Issue:
2
Journal Article
Peer reviewed
Open access
Acute myeloid leukemia (AML) is predominantly a disease of older adults, with a median age at diagnosis of over 65 years. AML in older adults differs biologically and clinically from that in younger ...ones, and is characterized by stronger intrinsic resistance and lower tolerance to chemotherapy. The effects of age on both patient- and disease-related factors result in a higher incidence of early death during chemotherapy, a lower rate of complete remission, and a reduced chance of long-term survival. Treatment options for older adults with AML include intensive chemotherapy, less-intensive chemotherapy, best supportive care, or enrolment in clinical trials. Given the heterogeneous nature of AML in older adults, therapeutic decisions need to be individualized after systematic assessment of disease biology and patient characteristics. Regardless of treatment, however, outcomes for older AML patients remain in general unsatisfactory. In contrast with the progress made for younger adults, the treatment of AML in older adults has not improved significantly in recent decades. Development of less toxic and more targeted agents may well provide treatment alternatives for a majority of these patients. The overall dismal outcome with currently available treatment approaches has encouraged older AML patients to participate in prospective clinical trials.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia ...effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte antigen-matched related donor transplantation (MRDT). This study included 2451 adult patients with non-remission R/R AML who received CBT (1738 patients) or MRDT (713 patients) between January 2009 and December 2018. Five-year progression-free survival (PFS) and the prognostic impact of CBT were evaluated using a propensity score (PS) matching analysis. After PS matching, the patient characteristics were well balanced between the groups. The five-year PFS was 25.2% (95% confidence interval CI: 21.2-29.5%) in the CBT group and 18.1% (95% CI: 14.5-22.0%) in the MRDT group (P = 0.009). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69-1.00, P = 0.045); this was due to a more pronounced decrease in the relapse rate (HR: 0.78, 95% CI: 0.69-0.89, P < 0.001) than an increase in the NRM (1.42, 1.15-1.76, P = 0.001). In this population, CBT was associated with a better 5-year PFS than MRDT after allogeneic HSCT.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Conditioning regimens play a crucial role in preventing relapse of acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (HCT). In early times, myeloablative ...conditioning was used exclusively, but it was associated with significant toxicity. However, the advent of reduced-intensity conditioning has allowed allogeneic HCT to be performed more safely, leading to an expansion of our choices for conditioning regimens. As the transplantation methods have become highly diversified, it is reasonable to determine an optimal conditioning regimen in consideration of patient-, disease-, and transplantation-related factors. In this context, large-scale registry-based studies provide real-world data to allow for a detailed evaluation of the utility of individual conditioning regimens in specific clinical settings. The Japanese Society for Transplantation and Cellular Therapy has been conducting a nationwide survey for HCT since 1993 that currently covers >99% of all the transplantation centers nationwide, and >1,000 allogeneic HCTs performed for adults with AML are registered per year. We have been using the registry data to implement a number of studies focusing on adults with AML, and the large number of patients registered consecutively from nearly all transplantation centers nationwide represent real-world practice in Japan. This article reviews and discusses the results obtained from our registry-based studies pertaining to various conditioning regimens.
Autologous hematopoietic cell transplantation (HCT) is an effective therapy for patients with relapsed acute promyelocytic leukemia (APL). However, it remains unclear whether this procedure is ...equally effective for certain groups of patients. To address this question, we analyzed 296 patients with APL who had undergone autologous HCT during second or subsequent complete remission (CR2+) between 2006 and 2019. Among them, 24 patients were ≥65 years old, and 17 underwent autologous HCT during third or subsequent CR. Of the 286 patients whose measurable residual disease (MRD) data were available, 21 showed detectable MRD. The 5-year probabilities of relapse-free survival (RFS), overall survival, relapse, and nonrelapse mortality for the entire cohort were 85%, 88%, 9%, and 6%, respectively. The multivariate analysis revealed that the duration of first CR ( < or ≥2 years) was the sole factor associated with RFS (P = 0.002), but even those with CR1 duration <2 years showed a 5-year RFS of 76%. The other factors such as age, disease status, and MRD status were not predictive for the survival outcomes. Our findings demonstrate very favorable long-term results when autologous HCT is conducted during CR2 + across the various subgroups of patients with relapsed APL.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The aim of this study was to develop a comprehensive system for predicting non-relapse mortality after allogeneic hematopoietic cell transplantation (HCT) during first complete remission (CR) of ...acute myeloid leukemia (AML). After dividing 2344 eligible patients randomly into a training set and a validation set, we first identified and scored five parameters, that is, age, sex, performance status, HCT-comorbidity index (HCT-CI), and donor type, on the basis of their impact on non-relapse mortality for patients in the training set. The non-relapse mortality-J (NRM-J) index using the sum of these scores was then applied to patients in the validation set, resulting in a clear differentiation of non-relapse mortality, with expected 2-year rates of 11%, 16%, 27%, and 33%, respectively (P < 0.001). The estimated c-statistic was 0.67, which was significantly higher than that of the European Society for Blood and Marrow Transplantation score (0.60, P = 0.002) and the HCT-CI (0.57, P < 0.001). The NRM-J index showed a significant association with overall survival, but not with relapse. Our findings demonstrate that the NRM-J index is useful for predicting post-transplant non-relapse mortality for patients with AML in first CR, for whom the decision of whether to perform allogeneic HCT is critical.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
