Prognostic Impact of the Detection of the WT1 Gene mRNA with Peripheral Blood in Adult Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3289-3289
Author(s):  
Shuichi Miyawaki ◽  
Nahoko Hatsumi ◽  
Toshiharu Tamaki ◽  
Tomoki Naoe ◽  
Keiya Ozawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Consolidation Therapy

Abstract Background: Approximately 70–80% of all newly diagnosed patients with adult AML achieve a complete remission (CR). However, only about one third of those pts remain free of disease for more than 5 years. It is therefore important to predict which pts are most likely to suffer a relapse and thus perform alternative treatments such as stem cell transplantation in order to improve the prognosis of AML. We evaluated the impact of the detection of Wilms’ tumor gene1 (WT1) mRNA in the peripheral blood on the prognosis of AML pts. Patients and Methods: From June 1, 2001 to October 30, 2003 a study was performed on 191 pts with AML which evaluated the clinical usefulness of a WT1 mRNA assay kit for the early detection of relapse in AML pts (submitted in Rinsho Ketsueki). From these 191 pts, we selected the subjects for this study. All selected subjects achieved a complete remission, and also had their WT1 expression analyzed after consolidation therapy. The pts were excluded if they had received a stem cell transplantation before relapse. The WT1 mRNA levels were determined using the WT1 mRNA assay kit (Otsuka Pharmaceutical Co. Ltd) in accordance with the standard operating procedures using peripheral blood. The lower limit of detection was 50 copy/μgRNA. Therefore, less than 50 copy/μgRNA was judged as negative. All induction, consolidation and maintenance therapies were performed according to institutional standards. Results: Of 118 pts who achieved a complete remission, 50 pts (median age: 56 yrs 22–86) were evaluable. Their median WT1 mRNA levels before induction therapy was 48327 copy/μgRNA (137–329185). The WT1 mRNA levels at diagnosis did not correlate with either the relapse rate, DFS or OS, respectively. After CR, the WT1 mRNA level ranged from <50 copy/μg to 30732 copy/μgRNA. Thirty-four (69.4%) pts were positive and 15 pts (30.6%) were negative for the WT1 mRNA. The relapse rate of the positive pts and of the negative pts was 73.5% and 40.0% (P=0.0248 sensitivity=80.6 % specificity=50.0%), respectively. The OS rate at 3 years was 53.1% in the positive pts and 79.0% in the negative pts (P=0.1227), respectively. The DFS rate at 3 years was 30.0% in the positive pts and 60.0 % in the negative pts (P=0.0906), respectively. After consolidation therapy, the WT1 mRNA level ranged from <50 copy/μgRNA to 49174 copy/μgRNA. The WT1 positive pts numbered only 15 pts (32.6%) and the negative pts numbered 31 (67.4%). The relapse rate of the positive pts and the negative pts was 80.0% and 54.8% (P=0.0974), respectively. The OS of rate at 3 years was 42.8% in the positive pts and 69.8% in the negative pts (P=0.0381), respectively. The DFS rate at 3 years was 20.0% in the positive pts and 50.0% in the negative pts (P=0.0116). The rate of relapse within 1 year was 73.3% in the positive pts and only 33.3% in the negative pts (P= 0.0116). Conclusion: This study shows that the detection of the WT1 mRNA in the peripheral blood after treatment closely correlated with the prognosis in AML.

Low Incidence of Hepatic Veno-Occlusive Disease after Fractionated Doses of Mylotarg and Autologous or Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5300-5300
Author(s):  
Hassan Farhat ◽  
Emmanuel Raffoux ◽  
Francoise Isnard ◽  
Nathalie Contentin ◽  
Anne Laure Taksin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Conditioning Regimen ◽  
Consolidation Therapy ◽  
Hepatic Toxicity ◽  
First Relapse ◽  
Median Interval

Abstract Background. Gemtuzumab ozogamicin (GO, Mylotarg®) is a humanized calicheamicin-conjugated monoclonal antibody targeted to the CD33 antigen present on myeloblasts. A 28% response rate in acute myeloblastic leukaemia (AML) in first relapse was reported in phase 2 single agent trials using Mylotarg at a dose of 9 mg/m2 for two doses at 14 days interval. Significant hepatotoxicity was observed and an increased risk (up to 60%) of developing veno-occlusive disease (VOD) was also reported in patients receiving stem cell transplantation (SCT) after GO exposure. Risk of VOD was correlated with a short interval, less than 3,5 months from GO administration to SCT. We report here the feasibility of an intensive consolidation therapy followed by autologous or allogeneic SCT in patients with AML in complete remission after a reduced and fractionated salvage therapy with GO. Patients and methods. We retrospectively collected the results from 10 consecutive patients (median age 47 years; 18 years to 62 years) treated in 4 haematological centers. All patients received 3 infusions of GO 3 mg/m2/d at day 1, day 4 and day 7 during the induction course. Consolidation modalities and conditioning regimens before HSCT were adapted in each center. Results. Eight patients were in relapse (first relapse, n=4; second and subsequent relapses, n=4) and 2 were primary refractory to induction therapy. After GO salvage therapy, 6 patients achieved a complete remission (CR) and 4 a CR without normalization of the platelets counts (CRp). A grade 1 toxicity and a non severe VOD were recorded during salvage therapy. Consolidation therapy was administered in 6 cases (based on Ara-C chemotherapy in 5 cases and GO administration (3 mg/m2 day 1) in 1 case). Five patients received an allogeneic SCT (genoidentical donors n=2, phenoidentical donors n=3, one of those after a non myeloablative conditioning regimen) and five patients received an autologous SCT after a conditioning regimen with busulfan and melphalan. Median interval between the last chemotherapy and the graft was 47 days (16 to 61 days) and median interval from the last dose of GO and the graft was 108 days (16 to 221 days). Three cases (30%) of hepatic toxicity were recorded (grade 1, n=1; grade 2, n=1; grade 3, n=1), including 2 cases with VOD (20%), one of them confirmed by liver biopsy. The two patients with VOD were successfully treated with defibrotide and normalization of the hepatic tests was obtained. In both cases, the conditioning regimen was TBI/EDX and the interval from the last GO infusion to SCT was short (30 days and 16 days). Of note, the patient who experienced hepatic toxicity during the fractionated induction course did not experienced hepatic toxicity during the intensive SCT phase. Overall, median DFS and OS post SCT were 6.4 months and 8.6 months respectively. Conclusion. This retrospective study argues in favour of a lower hepatotoxicity with fractionated doses of GO leading to a lower risk of VOD when stem cell transplant is used as post remission therapy.

Decitabine As Induction Therapy For Median-To-High-Risk Myelodysplastic Syndromes(MDS) and Acute Myeloid Leukemia(AML) Before Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5044-5044
Author(s):  
Jin Zhou ◽  
Wu Depei ◽  
Chengcheng Fu ◽  
Aining Sun ◽  
Huiying Qiu ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Low Dose ◽  
Survival Advantage ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentiallycurative therapy for patients with MDS and AML, especially with refractory and relapsed disease. The leading cause of the failure of Allo-HSCT lies in that critical organ disfunction and related complications are common in elderly patients .There’s no matched donor available and high relapse rate were additional risk factors for higher mortality of Allo-HSCT. Decitabine is the only demethylation drugs approved in China for treatment of median-to-high-risk MDS. Treatment with decitabine before Allo-HSCT could reduce tumor burden, keep the disease stable, and allow patients enough time to select a suitable donor. 46 patients with MDS (n=14)and AML (n=32)were admitted in hematological Dept. of First Affilated Hospital of Soochow University who all received treatment with decitabine alone or combined with chemotherapy followed by allo-HSCT between September 2009 andFebruary 2013. Disease classifications of 46 patients (median age 39ys, range 9-54ys) were as follows: RCMD (n=3), RAEB-1(n=2), RAEB-2 (n=9), refractory and relapsed acute leukemia (n=28) and MDS-AML (n=7). All MDS patients were median risk 2 according to IPSS. 57.1% MDS and 68.8% AML patients have chromosomal abnormalities. Patients were treated with decitabine 20mg/m2 for 3-5d alone (n=14) or plus CAG chemotherapy (n=32) prior to modified BuCY condition regimen. Acute graft-versus-host disease (GVHD) prevention regimen were cyclosporine-A (CsA) plus low-dose methotrexate (MTX) for allo-HSCT from HLA-identical sibling donor, anti-thymocyteglobulin (ATG), CsA,Mycophenolate mofetil(MMF) and low-dose MTX for HLA matched allo-HSCT from unrelated donor and HLA haplo-identical allo-HSCT from related donor. The overall response rate and complete remission rates of decitabine treatment before transplantation were 85.7%, 71.4% in MDS patients and 78.1%, 53.1% in AML patients respectively. 91.3% patients obtained successful engraftment. After a median follow-up of 8 months (2-33 months), the overall survival (OS) rate was 76.1%. Treatment-related mortality was 16.8% within 100 days. The incidences of acute and chronic GVHD among evaluable patients were 5.4% and 29.7%. Cumulative relapse rate was 39.1% after transplantation. The 33-months DFS rates and OS rates were 62.5% and 90% in patients who had achieved complete remission treated with decitabine induction prior to transplantation, while median DFS and OS were only 5 ms (p=0.008)and 12.4 ms(p=0.0004)in patients who had not. The survival advantage had nothing to do with the HLA typing and donor. Decitabine induction is an effective therapy to bridge time to HSCT in MDS and AML patients with low treatment-related mortality. Its Improving therapeutic efficacy before transplantation will allow people obtain survival advantage post transplantation. Disclosures: No relevant conflicts of interest to declare.

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