Long-term outcomes in patients with AML achieving first complete remission: confronting the double-hit of survivorship

2020 ◽  
Vol 61 (13) ◽  
pp. 3035-3037
Author(s):  
Strachan Mackenzie ◽  
Saar Gill
2017 ◽  
Vol 35 (20) ◽  
pp. 2260-2267 ◽  
Author(s):  
Daniel J. Landsburg ◽  
Marissa K. Falkiewicz ◽  
Joseph Maly ◽  
Kristie A. Blum ◽  
Christina Howlett ◽  
...  

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.


2019 ◽  
Vol 8 (5) ◽  
pp. 569 ◽  
Author(s):  
Masahiro Imamura ◽  
Akio Shigematsu

The outcome for adults with acute lymphoblastic leukemia (ALL) treated with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) is poor. Therefore, allogeneic HSCT (allo HSCT) for adults aged less than 50 years with ALL is performed with myeloablative conditioning (MAC) regimens. Among the several MAC regimens, a conditioning regimen of 120 mg/kg (60mg/kg for two days) cyclophosphamide (CY) and 12 gray fractionated (12 gray in six fractions for three days) total body irradiation (TBI) is commonly used, resulting in a long term survival rate of approximately 50% when transplanted at the first complete remission. The addition of 30 mg/kg (15 mg/kg for two days) etoposide (ETP) to the CY/TBI regimen revealed an excellent outcome (a long-term survival rate of approximately 80%) in adults with ALL, showing lower relapse and non-relapse mortality rates. It is preferable to perform allo HSCT with a medium-dose ETP/CY/TBI conditioning regimen at the first complete remission in high-risk ALL patients and at the second complete remission (in addition to the first complete remission) in standard-risk ALL patients. The ETP dose and administration schedule are important factors for reducing the relapse and non-relapse mortality rates, preserving a better outcome. The pharmacological study suggests that the prolonged administration of ETP at a reduced dose is a promising treatment.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3020-3020
Author(s):  
Philipp G. Hemmati ◽  
Gero Massenkeil ◽  
Theis H. Terwey ◽  
Stefan Neuburger ◽  
Philipp le Coutre ◽  
...  

Abstract Allogeneic hematopoietic stem cell transplantation (alloHSCT) is recommended for patients with high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Whereas conventional myeloablative conditioning is associated with a considerable treatment-related mortality (TRM), less intensive conditioning regimens may not be as efficient for long-term disease control, particularly in high-risk patients. Here, we present a retrospective single-institution analysis of 90 patients with median age of 39 years (range 17–66) with high-risk AML, i.e. based on non-favorable karyotype (not t(15;17), t(8;21) or inv(16)), blast persistence on day 16, the failure to achieve CR1 after two courses of induction therapy or the presence of secondary or therapy-induced AML, who underwent alloHSCT in CR1 between 1994 and 2007 (median follow-up 26, range 1–147 months). As stem cell source bone marrow (BM) was used in 17/90 patients (19%), whereas 73/90 patients (81%) received peripheral blood stem cells (PBSC). In 61/90 patients (68%) standard high-dose myeoloablative conditioning (12 Gy TBI + 120 mg/kg CY), (TBI group), was administered, whereas 29/90 (32%) patients received reduced-intensity conditioning (FLUD/BU/ATG)(RIC). A matched-related donor (MRD) was available for 62/90 patients (69%), whereas alloHSCT was performed from an unrelated donor (URD) in 28/90 patients (31%). Prevention of graft-versus-host disease (GvHD) consisted of CSA/MTX in the TBI group or CSA/MMF in the RIC group. 48/90 (53%) patients had a normal karyotype, whereas 39/90 patients (43%) displayed an aberrant karyotype. Projected overall survival (OS) and disease-free survival (DFS) of the whole cohort at 1, 3, and 5 years was 74%, 62%, and 57% and 72%, 58%, 54%, respectively. Causes of death were relapse (17/90 = 19%) or TRM (17/90 = 19%). The OS in the TBI group versus the RIC group was 72% vs. 79% at 1 year, 64% vs. 52 at 3 years, and 59% vs. 52% at 5 years (p = 0.78). Furthermore, there was no significant difference in the 1, 3, and 5-years DFS rates (72%, 62%, 57% vs. 75%, 50%, 49%) between the two groups. OS and DSF reached a plateau beyond 39 months (TBI group) and 33 months (RIC group). Relapse and TRM in the TBI group versus the RIC group were 21% vs. 14% and 16% vs. 24%. A comparison of the OS between the subgroups with a normal (n = 48) versus an aberrant (n = 39) karyotype revealed no significant difference at 1 year (83% vs. 65%), 3 years (70% vs. 47%), and 5 years (67% vs. 45%) (p = 0.06). Notably, there was no significant difference in the incidence of chronic graft-versus-host disease (cGvHD) between the TBI group and the RIC group (46% vs. 52%). Taken together, these results suggest that patients with AML in CR1 achieve a robust and durable long-term remission irrespective of the conditioning intensity (TBI vs. RIC) and the presence of an aberrant karyotype.


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